Acta Scientific Nutritional Health (ASNH)(ISSN: 2582-1423)

Research Aticle Volume 7 Issue 7

Nutrition and Breast Cancer in the Provincial Hospital Jason Sendwe, in Lubumbashi: A Case Control Study, January 2019 to December 2020

Junichiro Yamamoto1*, Wataru Shioyama2, Hideo Ikarugi3, Yoshinobu Ijiri4 Muneshige Shimizu5, Tomoya Takashima6, Hiroyuki Kikukawa7, Masahiro Murakami6, Kazunori Otsui8, Jaap Jan Zwaginga9 and Kjell S Sakariassen10

1Kobe Gakuin University, Kobe, Japan
2Department of Internal Medicine, Division of Cardiovascular Medicine, Shiga University of Medical Science, Japan
3School of Economics and Management, University of Hyogo, Kobe, Japan
4Department Of Health and Nutrition, Osaka Shoin Women’s University, Osaka, Japan
5Department of Fishers, School of Marine Science, Japan
6Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, Japan
7The Faculty of Contemporary Social Studies, Kobe Gakuin University, Kobe 650-8586, Japan
8Department of General Internal Medicine, Kobe University Hospital, Kobe 650-0017, Japan
9Department of Hematology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands; CCTR, Sanquin Blood Supply, 1066 CX Amsterdam, The Netherlands
10I-13900 Biella, BI, Italy

*Corresponding Author: Junichiro Yamamoto, Kobe Gakuin University, Kobe, Japan.

Received: May 10, 2023; Published: June 29, 2023


Ex vivo shear-induced and in vivo helium-neon laser-induced thrombosis/fibrinolysis tests were compared in animal models. The results of this paired ex vivo global thrombosis test (GTT) and in vivo thrombosis test comparison showed that both tests were wellmatched. Thrombotic disorders are classified as type I, II, or III. Type I is due to increased thrombotic and decreased fibrinolytic activity, while type II is caused only by decreased fibrinolytic activity. Type III is caused by endothelial dysfunction which is independent of thrombotic and fibrinolytic activities of blood. Based on these animal experiments, specific medications can be considered also for humans. Daily intake of an antithrombotic diet and suitable individual-matched exercise may prevent thrombotic episodes and aid rehabilitation.

Keywords: Endogenous Fibrinolysis; Platelet Aggregation; Shear-Induced Thrombosis; Cancer-Associated Thrombosis; Antithrombotic Drug; Physical Exercise; Antithrombotic Diet


  1. Yamamoto J., et al. “Prevention of thrombotic disorders by antithrombotic diet and exercise: evidence by using global thrombosis tests”. Future Science OA.4 (2018): FSO285.
  2. Yamamoto J., et al. “Reevaluation of antithrombotic fruits and vegetables: great variation between varieties”. Drug Discoveries and Therapeutics 3 (2016): 129-140.
  3. Murakami M., et al. “Global thrombosis test for assessing thrombotic status and efficacy of antithrombotic diet and other conditions”. Future Science OA3 (2022): FSO788.
  4. Paniccia R., et al. “Platelet function tests: a comparative review”. Vascular Health and Risk Management 11 (2015): 133-148.
  5. Anghel L., et al. “From classical laboratory parameters to novel biomarkers for the diagnosis of venous thrombosis”. International Journal of Molecular Sciences 6 (2020): 1920.
  6. Kim AS., et al. “Mechanisms and biomarkers of cancer-associated thrombosis”. Translational Research 225 (2020): 33-53.
  7. Gorog DA., et al. “Current and novel biomarkers of thrombotic risk in COVID-19: a consensus statement from the international COVID-19 thrombosis biomarkers colloquium”. Nature Reviews Cardiology 7 (2022): 475-495.
  8. Kovacs IB., et al. “Evans blue: an ideal energy-absorbing material to produce intravascular microinjury by HE-NE gas laser”. Microvascular Research 1 (1975): 107-124.
  9. Yamamoto J., et al. “Effect of physical training on thrombotic tendency in rats: decrease in thrombotic tendency measured by the He-Ne laser-induced thrombus formation method”. Haemostasis 5 (1989): 260-265.
  10. Ratnatunga CP., et al. “High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation”. Circulation 3 (1992): 1077-1082.
  11. Yamamoto J., et al. “Effect of leucocyte products on platelet thrombus formation, coagulation and spontaneous thrombolysis, as measured from native human blood, in vitro”. Thrombosis Research 4 (1993): 281-287.
  12. Ikarugi H., et al. “Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans”. Journal of Applied Physiology 1 (1999): 133-138.
  13. Gorog D., et al. “Thrombotic status analyser. Measurement of platelet-rich thrombus formation and lysis in native blood”. Thrombosis and Haemostasis 3 (1995): 514-520.
  14. Nakajima S., et al. “A global platelet test of thrombosis and thrombolysis detects a prothrombotic state in some patients with non-insulin dependent diabetes and in some patients with stroke”. 11.8 (2000): 459-466.
  15. Yamamoto J., et al. “Gorog Thrombosis Test: a global in-vitro test of platelet function and thrombolysis”. Blood Coagulation and Fibrinolysis1 (2003): 31-39.v
  16. Yamamoto J., et al. “Global thrombosis test (GTT) can detect major determinants of haemostasis including platelet reactivity, endogenous fibrinolytic and thrombin generating potential”. Thrombosis Research5 (2014): 919-926.
  17. Sakariassen KS., et al. “Recollections of the development of flow devices for studying mechanisms of hemostasis and thrombosis in flowing whole blood”. Journal of Thrombosis and Haemostasis 10 (2004): 1681-1690.
  18. Taomoto K., et al. “Platelet function and spontaneous thrombolytic activity of patients with cerebral infarction assessed by the global thrombosis test”. Pathophysiology of Haemostasis and Thrombosis 1 (2010): 43-48.
  19. Shioyama W., et al. “Effect of cancer chemotherapy on platelet reactivity and thrombolytic activity”. Presented at the 25th Kinki Thrombosis Research Society Meeting. Osaka, Japan (2020).
  20. Kovacs IB., et al. “Spontaneous thrombolysis: a forgotten determinant of life or death”. Clinical and Applied Thrombosis/Hemostasis 3 (2006): 358-363.
  21. Kovacs IB., et al. “Enhanced spontaneous thrombolysis: a new therapeutic challenge”. Journal of Thrombosis and Thrombolysis 3 (2006): 221-227.
  22. Gorog DA. “Prognostic value of plasma fibrinolysis activation markers in cardiovascular disease”. Journal of the American College of Cardiology24 (2010): 2701-2709.
  23. Kawano M., et al. “Adjuvant effect of argatroban on staphylokinase induced thrombolysis of platelet rich thrombi in rat mesenteric venules in vivo”. Thrombosis Research 2 (1997): 115-126.
  24. Yamashita T., et al. “Conjunctive effects of the 5HT (2) receptor antagonist, sarpogrelate, on thrombolysis with modified tissue plasminogen activator in different laser-induced thrombosis models”. Haemostasis 6 (2000): 321-332.
  25. Hashimoto M., et al. “Enhanced thrombolysis induced by argatroban or activated protein C in the presence or absence of staphylokinase, measured in an in vivo animal model using mesenteric arterioles”. Haemostasis2 (2001): 80-89.
  26. Hashimoto M., et al. “Enhancement of endogenous plasminogen activator-induced thrombolysis by argatroban and APC and its control by TAFI, measured in an arterial thrombolysis model in vivo using rat mesenteric arterioles”. Journal of Thrombosis and Thrombolysis 1 (2002): 110-113.
  27. Sakariassen KS., et al. “A perfusion chamber developed to investigate platelet interaction in flowing blood with human vessel wall cells, their extracellular matrix, and purified components”. Journal of Laboratory and Clinical Medicine 4 (1983): 522-535.
  28. Sakariassen KS., et al. “Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-von Willebrand factor bound to the subendothelium”. Nature 5714 (1979): 636-638.
  29. Sakariassen KS., et al. “Platelet adherence to subendothelium of human arteries in pulsatile and steady flow”. Thrombosis Research 4-5 (1980): 547-559.
  30. Sakariassen KS., et al. “Factor VIII-von Willebrand factor requires calcium for facilitation of platelet adherence”. Blood 5 (1984): 996-1003.
  31. Sakariassen KS., et al. “Differentiation of patients with subtype IIb-like von Willebrand`s disease by means of perfusion experiments with reconstituted blood”. British Journal of Haematology 3 (1985): 459-470.
  32. Sakariassen KS., et al. “Mediation of platelet adhesion to fibrillar collagen in flowing blood by a proteolytic fragment of human von Willebrand factor”. Blood 5 (1986): 1515-1518.
  33. Sakariassen KS., et al. “Growth and stability of thrombi in flowing blood: Assessment of platelet-surface interactions with computer-assisted morphometry”. Thrombosis and Haemostasis3 (1988): 392-398.
  34. Sakariassen KS., et al. “Upstream thrombus growth impairs downstream thrombogenesis in non-anticoagulated blood: Effect of procoagulant artery subendothelium and non-procoagulant collagen”. Thrombosis and Haemostasis 5 (1991): 596-600.
  35. Roux SP., et al. “Effect of aspirin and epinephrine on experimentally-induced thrombogenesis in dogs: a parallelism between in vivo and ex vivo thrombosis models”. Arteriosclerosis, Thrombosis, and Vascular Biology5 (1991): 1182-1191.
  36. Fressinaud E., et al. “Shear rate-dependent impairment of thrombus growth on collagen in nonanticoagulated blood from patients with von Willebrand disease and hemophilia A”. Blood 4 (1992): 988-994.
  37. Sakariassen KS., et al. “The impact of blood flow on thrombogenesis”. Journal of Blood Rheology 7 (1993): 33-36.
  38. Roald HE., et al. “Clopidogrel - a platelet inhibitor which inhibits thrombogenesis in human non-anticoagulated blood independently of the blood flow conditions”. Thrombosis and Haemostasis5 (1994): 665-672.
  39. Diquélou A., et al. “Effect of blood flow on thrombin generation is dependent on the nature of the thrombogenic surface”. Blood 7 (1994): 2206-2213.
  40. Barstad RM., et al. “A perfusion chamber developed to investigate thrombus formation and shear profiles in flowing native human blood at the apex of well-defined stenoses”. Arteriosclerosis, Thrombosis, and Vascular Biology 12 (1994): 1984-1991.
  41. Sakariassen KS., et al. “The impact on blood shear rate on arterial thrombus formation”. Future Science OA 4 (2015): FSO30.
  42. Sakariassen KS. “Thrombus formation on apex of arterial stenoses: the need for a fluid high shear diagnosis device”. Future Cardiology 2 (2007): 193-201.
  43. Taka T., et al. “Platelet reactivity in spontaneously diabetic rats is independent from blood glucose and insulin levels”. Platelets 5-6 (2002): 313-316.
  44. Taka T., et al. “Thrombotic tendency of a non-insulin dependent diabetic rat OLETF”. Research Conference on OLETF Rats 2 (1996): 75-79.
  45. Iwasaki M., et al. “Are all wines made from various grape varieties beneficial in the prevention of myocardial infarction and stroke?” Future Science OA 2 FSO649 (2021).
  46. Yamamoto J., et al. “The antithrombotic effects of carrot filtrates in rats and mice”. Blood Coagulation and Fibrinolysis8 (2008): 785-792.
  47. Noguchi T., et al. “Enhanced thrombogenicity and altered hemodynamics in the cerebral microvasculature of stroke-prone spontaneously hypertensive rats”. Haemostasis5 (1997): 237-245.
  48. Taka T., et al. “Impaired flow-mediated vasodilation in vivo and reduced shear-induced platelet reactivity in vitro in response to nitric oxide in prothrombotic, stroke-prone spontaneously hypertensive rats”. Pathophysiology of Haemostasis and Thrombosis4 (2002): 184-189.
  49. Tamura Y., et al. “Impaired endothelial function may be due to decreased aortic tetrahydrobiopterin, assessed by a new flow-mediated vasodilation in vivo in hypercholesterolemic/atherogenic mice”. Blood Coagulation and Fibrinolysis 8 (2009): 699-705.
  50. Ijiri Y., et al. “Dietary diacylglycerol extenuates arterial thrombosis in apoE and LDLR deficient mice”. Thrombosis Research 4 (2006): 411-417.
  51. Ijiri Y., et al. “Mechanism of the antithrombotic effect of dietary diacylglycerol in atherogenic mice”. Pathophysiology of Haemostasis and Thrombosis 5 (2006): 380-387.
  52. Noma K., et al. “Cilostazol for treatment of cerebral infarction”. Expert Opinion on Pharmacotherapy 15 (2018): 1719-1726.
  53. Seong-Joon Lee., et al. “Cilostazol improves endothelial function in acute cerebral ischemia patients: a double-blind placebo controlled trial with flow-mediated dilation technique”. BMC Neurology 1 (2017): 169.
  54. Hiroyoshi M., et al. “The Effect of Cilostazol on Endothelial Function as Assessed by Flow-Mediated Dilation in Patients with Coronary Artery Disease”. Journal of Atherosclerosis and Thrombosis 10 (2016): 1168-1177.
  55. Takase B., et al. “Combined therapeutic effect of probucol and cilostazol on endothelial function in patients with silent cerebral lacunar infarcts and hypercholesterolemia: a preliminary study”. Medical Principles and Practice 1 (2014): 59-65.
  56. Jacobsen AP., et al. “Lifelong aspirin for all in the secondary prevention of chronic coronary syndrome: still sacrosanct or is reappraisal warranted?”. Circulation16 (2020): 1579-1590.
  57. Peng S., et al. “A long-acting PAI-1 inhibitor reduces thrombus formation”. Thrombosis and Haemostasis 7 (2017): 1338-1347.
  58. Noguchi N., et al. “Fibrinolytic potential of DS-1040, a novel orally available inhibitor of activated thrombin-activatable fibrinolysis inhibitor”. Thrombosis Research 168 (2018): 96-101.
  59. Sansilvestri-Morel P., et al. “S62798, a potent TAFIa inhibitor, accelerates endogenous fibrinolysis in a murine model of pulmonary thromboembolism”. Thrombosis Research 204 (2021): 81-87.
  60. Violi F., et al. “Statins as antithrombotic drugs”. Circulation 2 (2013): 251-257.
  61. Bonetti PO., et al. “Statin effects beyond lipid lowering--are they clinically relevant?”. European Heart Journal 24(3 (2003): 225-248.
  62. Oppelt P., et al. “Approach to chemotherapy-associated thrombosis”. Vascular Medicine 2 (2015): 153-161.
  63. Phillippe HM. “Overview of venous thromboembolism”. The American Journal of Managed Care 23 (2017): S376-S382.
  64. Morishita M., et al. “Mechanism of the experimental antithrombotic effect of some apple varieties involves enhanced endogenous thrombolytic activity”. Interventional Medicine and Applied Science3 (2012): 115-124.
  65. Kondo K., et al. “Trans-fatty acid promotes thrombus formation in mice by aggravating antithrombogenic endothelial functions via toll-like receptors”. Molecular Nutrition and Food Research4 (2015) 729-740.
  66. Ikarugi H., et al. “Impaired spontaneous thrombolytic activity in elderly and in habitual smokers, as measured by a new global thrombosis test”. Blood Coagulation and Fibrinolysis8 (2003): 781-784.
  67. Yamamoto J., et al. “Tomatoes have natural anti-thrombotic effects”. British Journal of Nutrition6 (2003): 1031-1038.
  68. Naemura A., et al. “An experimentally antithrombotic strawberry variety is also effective in humans”. Pathophysiology of Haemostasis and Thrombosis5 (2006): 398-404.
  69. Ijiri Y., et al. “Diet of fruits and vegetables with experimental antithrombotic effect may be beneficial to humans in the prevention of arterial thrombotic diseases”. International Journal of Drug Development and Research3 (2016): 12-16.
  70. Ikarugi H., et al. “High intensity exercise enhances platelet reactivity to shear stress and coagulation during and after exercise”. Pathophysiology of Haemostasis and Thrombosis3 (2003): 127-133.
  71. Baba Y. “Effects of exercise and diet interventions modeled on Healthy Japan 21 on thrombus formation”. Master’s Thesis, Kobe Gakuin University (2012).
  72. Baba Y., et al. “Changes in platelet reactivity, thrombolytic activity and other physical activities by habitual exercise”. Presented at the at the 51st Japan Society of Nutrition and Food Science Kinki Meeting. Hyogo, Japan (2012).
  73. Ikarugi H., et al. “The exercise paradox may be solved by measuring the overall thrombotic state using native blood”. Drug Discoveries and Therapeutics 1 (2017): 15-19.
  74. Gorog DA., et al. “First direct comparison of platelet reactivity and thrombolytic status between Japanese and Western volunteers: possible relationship to the “Japanese paradox”. International Journal of Cardiology1 (2011): 43-48.
  75. Gue YX., et al. “Thrombotic profile and oral anticoagulation in Asian and non-Asian patients with nonvalvular atrial fibrillation”. Journal of the American College of Cardiology 22 (2019): 2822-2824.


Citation: Junichiro Yamamoto., et al. “Investigations into the Pathomechanism of thrombotic Disorders with an Ex Vivo Global Test Performed from Non-Anticoagulated Blood: From Animal Experiments to Bedside Application".Acta Scientific Nutritional Health 7.7 (2023): 119-129.


Copyright: © 2023 Junichiro Yamamoto., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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