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1995 Fiscal Year Final Research Report Summary

Studies on the cause of HELLP syndrome

Research Project

Project/Area Number 05454443
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

TERAO Tosihiko  Hamamatsu University School of Medicine, Professer, 医学部, 教授 (60022852)

Co-Investigator(Kenkyū-buntansha) KANAYAMA Naohiro  Hamamatsu University School of Medicine, Assistant, 医学部附属病院, 講師 (70204550)
Project Period (FY) 1993 – 1995
KeywordsHELLP syndrome / sympathetic ganglion / vasospasm / endothelin / cytokines
Research Abstract

Aim : To determine the role of vasospasm of celiac artery, we have also performed several animal and clinical experiments. Materials and Methods : Immunostaining with anti TNF-alpha, anti neutrophil elastase, anti IL-1, anti IL-8 antibodies was done on hepatic tissues obtained from eclamptic and preeclamptic HELLP syndrome patients to understand the role of neutrophil or some cytokines in tissue damage in such disease. ET-1 was injected in pregnant and nonpregnant rabbits and their different blood parameters were investigated and analyzed. Endotoxin, potassium chloride, and saline solution were superposed on the celiac ganglion in pregnant or non-pregnant rats. Endotoxin was also superposed on bifurcation of the abdominal aorta. The blood pressure, proteinuria and various blood parameters were measured. Results : Periportal hemorrhage and ischemic necrosis with marked infiltration of neutrophils in liver tissues were found in HELLP syndrome cases. Those tissues were stained strongly to TNF-alpha and neutrophil elastase and moderately with polyclonal IL-1beta and IL-8 antibodies indicating that cytokine production induced by vasospasms occurred. Vasoconstriction of the hepatic artery following a bolus injection of 0.25 nmol/kg of ET-1 into the celiac artery occurred in rabbits. HELLP syndrome like biochemical parameters were obtained after the ET-1 injections and stimulation of celiac ganglions. Histological examination of liver tissues treated with injections of endothelin and stimulation of celiac ganglions showed varying degrees of ischemic necrosis of hepatocytes similar to human HELLP syndrome. Conclusion : This study suggests that injections of endothelin-1 and an exogenous stimulation of the celiac ganglion causes an increase in the blood pressure and liver ischemia, resulting in HELLP syndrome-like disease in pregnant and non-pregnant rats. We suggest that ET-1 and abdominal sympathetic nerve might play a causative role in HELLP syndrome.

  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 金山 尚裕: "HELLP症候群の病態と解析" 腎と透析. 39. 748-752 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 寺尾 俊彦: "HELLP症候群" 臨床婦人科産科. 49. 594-596 (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Halim A.: "Activated neutrophil by endothelin-l caused tissue damage in human umbilical cord" Thromb.Res.77. 321-327 (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Halim A.: "Pregnant Rabbits with Endothelin-l Injections" Gynecol,Obstet.Invest.39. 1-7 (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Halim A.: "Coagulation in vivo microcirculation and in vitro caused by endothelin-1" Thromb.Res.72. 203-209 (1993)

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      「研究成果報告書概要(和文)」より
  • [Publications] Halim A.: "HELLP Syndrome-like biochemical Parameters obtained with endothelin-1 injection in rabbits" Gynecol.Obstet,Invest.35. 193-198 (1993)

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  • [Publications] Halim A., Kanayama N., Machara K., Takahashi M., and Terao T.: "HELLP syndrome-like biochemical parameters obtained with endothelin-1 injections in rabbits." Gynecol. Obstet. Invest.35. 193-198 (1993)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Halim A., Kanayama N., El Maradny E., Machara K., and Terao T: "Coagulation in vivo microcirculation and in vitro caused by endothelin-1." Thromb.Res. 72. 203-209 (1993)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Halim A., Kanayama N., El Maradny E., Machara K., Shimoyama I., Sumimoto K., and Terao T: "Eclampsia-like seizures and electroenccphalographic changes in pregnant rabbits with endothelin-1 injections." Gynecol. Obstct. Invest.39. 1-7 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Halim A., Kanayama N., El Maradny E., Machara K., and Terao T.: "Activated neutrophil by cndothelin-1 caused tissue damage in human umbilical cord." Thromb. Res.77. 321-327 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Halim A., Bhuiyan A.B., Azim F.A., Khatun S., Kanayama N., El Maradny E., Machara K., Kobayashi H., and Terao T.: "Blood coagulation and fibrinolysis in eclamptic paticnts and thcir correlation with the clinical signs." Gynecol. Obstet. Invest.39. 97-102 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Halim A., Kanayama N., El Maradny E., Machara K., Hirano M., and Terao T.: "Endothelin-1 increased immunoreactive von Willebrand factor in endothelial cells and induced micro thrombosis in rats." Thromb. Res.76. 71-78 (1994)

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  • [Publications] Halim A., Kanayama N., El Maradny E., Machara, K., Bhuiyan A.B.and Terao, T.: "Correlated Plasma Elastase and Sera Cytotoxicity in Eclampsia : a Possible Role of Endothelin-1 Induced Neutrophil Activation in Preeclampsia-eclampsia." Am J Hypertension. (in press). (1995)

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  • [Publications] Halim A., Kanayama N., El Maradny E., Nakashima, A., Khatun, S., Bhuiyan A.B.and Terao T.: "Plasma P-selectin (GMP-140) and Glycocalicin are elevated in preeclampsia and eclampsia : their significances." Am J Obstet Gynecol. (in press). (1995)

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  • [Publications] Halim A., Kanayama N., El Maradny E., Maehara K., Hirano M., Kobayashi T., and Terao T.: "Endothelin-1 evoked an increase and oscillations in cytosolic calcium concentration in adherent single platelets and increase GMP-140 (P-selectin) in platelet suspension." Thromb. Res.80. 105-112 (1995)

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  • [Publications] Kanayama N., Kobayashi H., Yamamoto Y., Halim A., Machara K., and Terao T.: "Case of HELLP syndrome associated with hepatic artery spasms." Jpn. Obstet. Gynecol. Hematol.3. 43-44 (1993)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kanayama N., Halim A., Machara K., Kajiwara Y., Fujie M., and Terao T.: "Kunitz-type trypsin inhibitor prevents LPS-induced increase of cytosolic free Ca2+ in human neutrophils and HUVEC cells. Biochem." Biochem. Biophys. Res. Commun.207. 324-330 (1995)

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  • [Publications] Kanayama N., El Maradny E,Halim A,Maehara K,Kajiwara Y,Terao T.: "Urinary trypsin inhibitor suppresses premature cervical ripening." Eur.J.Obstet. Gynecol. Reprod. Biol.60. 181-186 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kanayama K,El Maradny E,Halim A,Liping S,Machara K,Kajiwara Y,Terao T.: "Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of Ca^<2+> influx." Am J Obstet Gynecol. 173. 192-199 (1995)

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  • [Publications] Kanayama N., Nakajima A., Maehara K., Halim A., Kajiwara Y., Isoda H., Masui T., and Terao T.: "Magnetic resonance imaging angiography in a case of celampsia." Gynecol. Obstet. Invest.36. 56-58 (1993)

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  • [Publications] El Maradny E., Kanayama N., Halim A., Maehara K., Sumimoto K., and Terao T.: "Interleukin-8 induces cervical ripening in rabbits." Am.J.Obstset. Gynecol.171. 77-83 (1994)

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  • [Publications] El Maradny E., Kanayama N., Halim A., Maehara K., and Terao T.: "Urinary trypsin inhibitor may have a protective effect on endothelial cells in preeclampsia." Acta Obstet. Gynecol. Scand.73. 755-757 (1994)

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  • [Publications] El Maradny E., Kanayama N., Halim A., Machara K., and Terao T.: "Urinary trypsin inhibitor has a protective effect on the amnion." Gynecol. Obstet. Invest.38. 169-172 (1994)

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  • [Publications] El Maradny E., Kanayama N., Halim A., Maehara K., Sumimoto K., and Terao T.: "Effects of neutrophil chemotactic factors on cervical ripening." Clin. Exp. Obstct. Gynecol.22. 76-85 (1995)

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  • [Publications] El Maradny E., Kanayama N., Halim A., Maehara K., Sumimoto K., and Terao T.: "The effect of interlcukin-1 in rabbit cervical ripening." Eur.J.Obstet. Gynecol. Reprod. Biol.60. 75-80 (1995)

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  • [Publications] El Maradny E,Kanayama N,Halim A,Maehara K,Sumimoto K.Terao T.: "Regulatory effect of aminopeptidase inhibitor (Bestatin) on the cervix during induction of ripening by interlcukin-8." J Leuko Biology. 57. 832-836 (1995)

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  • [Publications] El Maradny E., Kanayama N., Halim A., Maehara K., and Terao T.: "Endothelin has a role in carly pathogenesis of amniotic fluid cmbolism." Gynecol. Obstet. Invest.40. 14-18 (1995)

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  • [Publications] Maehara K., Kanayama N., Halim A., El Maradny E., Oda T., Fujita M., and Terao T.: "Down-regulation of interleukin-8 gene expression in HL60 cell line by human Kunitz-type trypsin inhibitor." Biochem. Biophys. Res. Commun.206. 927-934 (1995)

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  • [Publications] Kanayama N., She L,Maehara K., Kajiwara Y and Terao T.: "HELLP syndrome-like biochemical parameters obtained with stimulation of celiac ganglion in rats." J Hypertens. (in press). (1996)

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Published: 1997-03-04  

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