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1.
Talanta ; 205: 120077, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31450395

ABSTRACT

Implantable medical devices are an integral part of primary/critical care. However, these devices carry a high risk for blood clots, caused by platelet aggregation on a foreign body surface. This study focuses on the development of a simplified approach to create nitric oxide (NO) releasing intravascular electrochemical oxygen (O2) sensors with increased biocompatibility and analytical accuracy. The implantable sensors are prepared by embedding S-nitroso-N-acetylpenacillamine (SNAP) as the NO donor molecule in the walls of the catheter type sensors. The SNAP-impregnated catheters were prepared by swelling silicone rubber tubing in a tetrahydrofuran solution containing SNAP. Control and SNAP-impregnated catheters were used to fabricate the Clark-style amperometric PO2 sensors. The SNAP-impregnated sensors release NO under physiological conditions for 18 d as measured by chemiluminescence. The analytical response of the SNAP-impregnated sensors was evaluated in vitro and in vivo. Rabbit and swine models (with sensors placed in both veins and arteries) were used to evaluate the effects on thrombus formation and analytical in vivo PO2 sensing performance. The SNAP-impregnated PO2 sensors were found to more accurately measure PO2 levels in blood continuously (over 7 and 20 h animal experiments) with significantly reduced thrombus formation (as compared to controls) on their surfaces.


Subject(s)
Electrochemical Techniques/instrumentation , Nitric Oxide Donors/chemistry , Oxygen/blood , S-Nitroso-N-Acetylpenicillamine/chemistry , Vascular Access Devices , Animals , Electrochemical Techniques/methods , Equipment Design , Femoral Artery , Luminescent Measurements , Nitric Oxide/pharmacokinetics , Rabbits , Silicones , Swine
2.
Pharmacogenomics J ; 15(3): 241-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25266680

ABSTRACT

CYP3A4 has an important role in the metabolisms of many drugs used in acute lymphoblastic leukemia (ALL) therapy; still, there are practically no publications about the role of CYP3A4 polymorphisms in ALL pharmacogenomics. We genotyped eight common single-nucleotide polymorphisms (SNPs) in the CYP3A4 and CYP3A5 genes in 511 children with ALL and investigated whether they influenced the survival of the patients. We involved additional 127 SNPs in 34 candidate genes and searched for interactions with respect to the survival rates. Significant association between the survival rates and the common rs2246709 SNP in the CYP3A4 gene was observed. The gender of the patients and the rs1076991 in the MTHFD1 gene strongly influenced this effect. We calculated new risk assessments involving the gender-rs2246709 interaction and showed that they significantly outperformed the earlier risk-group assessments at every time point. If this finding is confirmed in other populations, it can have a considerable prognostic significance.


Subject(s)
Cytochrome P-450 CYP3A/genetics , Polymorphism, Single Nucleotide/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Adolescent , Child , Child, Preschool , Female , Gender Identity , Genotype , Humans , Infant , Male , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Minor Histocompatibility Antigens , Retrospective Studies , Survival Rate
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