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2.
Eur J Obstet Gynecol Reprod Biol ; 168(2): 161-6, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23398725

ABSTRACT

OBJECTIVES: To investigate the effect of morphine on the reduced uteroplacental perfusion pressure (RUPP) model of pre-eclampsia in rats. STUDY DESIGN: The abdominal aorta and ovarian arteries of pregnant rats were isolated and clipped on gestational day 14. The chronic morphine treatment group received naltrexone 5 mg/kg 1h before each dose of morphine. L-nitromonomethylarginine 2 mg/kg was administrated in the same pattern. The control group received saline 10 ml/kg. Systolic blood pressure, blood urea nitrogen (BUN), creatinine, creatinine clearance, urinary protein, urinary nitrite/nitrate excretion, and fetal and placental weights were determined. RESULTS: Morphine significantly reduced systolic blood pressure, fetal and placental weights, plasma BUN, creatinine and urinary protein in RUPP rats compared with control rats. Urinary nitrite/nitrate excretion and creatinine clearance were significantly increased in response to morphine treatment. CONCLUSION: Morphine reduced blood pressure and improved renal function in the RUPP model of pre-eclampsia, but this was associated with reduced fetal and placental weights.


Subject(s)
Antihypertensive Agents/therapeutic use , Disease Models, Animal , Morphine/therapeutic use , Nitric Oxide/metabolism , Placental Circulation/drug effects , Pre-Eclampsia/drug therapy , Receptors, Opioid, mu/agonists , Animals , Antihypertensive Agents/adverse effects , Antihypertensive Agents/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Female , Fetal Development/drug effects , Kidney/drug effects , Kidney/metabolism , Kidney/physiopathology , Morphine/adverse effects , Morphine/antagonists & inhibitors , Narcotic Antagonists/pharmacology , Nitrates/urine , Nitric Oxide Synthase/antagonists & inhibitors , Nitrites/urine , Placentation/drug effects , Pre-Eclampsia/metabolism , Pre-Eclampsia/physiopathology , Pregnancy , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/antagonists & inhibitors , Renal Insufficiency/etiology , Renal Insufficiency/prevention & control , Up-Regulation/drug effects
3.
Eur J Med Chem ; 44(4): 1554-69, 2009 Apr.
Article in English | MEDLINE | ID: mdl-18782645

ABSTRACT

This is a first case ever reported on the fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) designed for targeted delivery of the paramagnetic magnesium stable isotope to the heart muscle providing a sharp clinical effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 h after a single injection (0.03-0.1 LD(50)). A whole principle of this therapy is novel: (25)Mg(2+)-magnetic isotope effect selectively stimulates the ATP overproduction in the oxygen-depleted cells due to (25)Mg(2+) released by the nanoparticles. Being membranotropic cationites, these "smart nanoparticles" release the overactivating paramagnetic cations only in response to the metabolic acidic shift. The resulting positive changes in the heart cell energy metabolism may help to prevent and/or treat the local myocardial hypoxic disorders and, hence, protect the heart muscle from a serious damage in a vast variety of the hypoxia-caused clinical situations including both doxorubicin and 1-methylnicotineamide cardiotoxic side effects. Both pharmacokinetics and pharmacodynamics of the drug proposed make it suitable for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes.


Subject(s)
Adenosine Triphosphate/biosynthesis , Fullerenes/pharmacology , Magnesium/chemistry , Magnetics , Myocardium/metabolism , Nanoparticles/chemistry , Porphyrins/chemistry , Animals , Drug Discovery , Fullerenes/chemistry , Fullerenes/metabolism , Fullerenes/pharmacokinetics , Heart/drug effects , Hydrogen-Ion Concentration , Hypoxia/chemically induced , Hypoxia/metabolism , Isotopes/chemistry , Magnesium/metabolism , Male , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Mitochondria/drug effects , Mitochondria/metabolism , Myocardium/ultrastructure , Neutron Diffraction , Oxygen/metabolism , Rats , Rats, Wistar , Scattering, Small Angle
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