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1.
Congenit Heart Dis ; 13(1): 118-123, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28880458

ABSTRACT

OBJECTIVES: Congenital heart defects are common noninfectious causes of mortality in children. Bleeding and thrombosis are both limiting factors in the management of such patients. We assessed the frequency of thrombocytopenia in pediatric patients with congenital cyanotic heart disease (CCHD) and evaluated determinants of platelet count including immature platelet fraction (IPF) and their role in the pathogenesis of thrombocytopenia. METHODS: Forty-six children and adolescents with CCHD during pre-catheter visits were studied; median age was 20.5 months. Complete blood count including IPF as a marker of platelet production and reticulated hemoglobin content (RET-He) as a marker of red cell production and iron status were done on Sysmex XE 2100 (Sysmex, Japan). C-reactive protein, prothrombin time (PT), Activated partial thromboplastin time (APTT) were also assessed. RESULTS: Thrombocytopenia was found in 6 patients (13%). PT was prolonged (P = .016) and IPF was significantly higher in patients with thrombocytopenia compared with patients with normal platelet count (14.15 ± 5.2% vs 6.68 ± 3.39%; P = .003). Platelet count was negatively correlated with IPF while significant positive correlations were found between IPF and hemoglobin, red blood cells (RBCs) count, hematocrit (Hct), PT, reticulocytes count, and immature reticulocyte fraction. CONCLUSIONS: We suggest that elevated IPF in CCHD patients with thrombocytopenia may denote peripheral platelets destruction as an underlying mechanism. Hemoglobin level, RBCs count, Hct, and RET-He were not significant determinants for platelet count in CCHD.


Subject(s)
Blood Platelets/metabolism , Heart Defects, Congenital/blood , Thrombocytopenia/blood , Blood Coagulation Tests , C-Reactive Protein/metabolism , Child, Preschool , Cross-Sectional Studies , Echocardiography, Doppler , Female , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/epidemiology , Homeodomain Proteins/blood , Humans , Infant , Infant, Newborn , Japan , Male , Morbidity/trends , Partial Thromboplastin Time , Platelet Count , Prognosis , Prothrombin Time , Survival Rate/trends , Thrombocytopenia/epidemiology , Trans-Activators/blood
2.
Arch Pharm (Weinheim) ; 348(2): 113-24, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25664629

ABSTRACT

A novel series of cyclic 2-oxindole derivatives incorporating 2-amino-tetrahydroquinolin-5-one were prepared. The structures of the prepared compounds were elucidated using different spectral tools. The regio-orientation of the reaction products was elucidated through NOE difference experiments and through using substituents on the ortho position to affect further cyclization. Antitumor and antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibited high to moderate antimicrobial activity. With respect to the antitumor activity, the compounds showed more potent cytotoxic effect only toward the human breast cancer cell line MCF-7. Also, we found that derivatives containing an ester group (8c, 11b, 14b, and 15b) are more active than those containing a cyanide group (8a, 11a, 14a, and 15a). Moreover, compounds 15b and 8b are the most active derivatives in this group. These two compounds showed apoptotic inhibition of the proliferation of human breast adenocarcinoma MCF-7 cells through DNA fragmentation, induction of the tumor suppressor protein p53, induction of caspase-9, and finally the inhibition of angiogenesis by decreasing vascular endothelial growth factor expression and secretion.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/pathology , Drug Design , Indoles/chemical synthesis , Indoles/pharmacology , Quinolones/chemical synthesis , Quinolones/pharmacology , Angiogenesis Inhibitors/chemical synthesis , Angiogenesis Inhibitors/pharmacology , Breast Neoplasms/metabolism , Caspase 9/metabolism , Cell Proliferation/drug effects , DNA Fragmentation , Disk Diffusion Antimicrobial Tests , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , MCF-7 Cells , Molecular Structure , Neovascularization, Pathologic , Oxindoles , Signal Transduction/drug effects , Structure-Activity Relationship , Tumor Suppressor Protein p53/metabolism , Vascular Endothelial Growth Factor A/metabolism
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