Info

Neto JS, Nakao A, Toyokawa H, Nalesnik MA, Romanosky AJ, Kimizuka K, et al. Low-dose carbon monoxide inhalation prevents development of chronic allograft nephropathy. Am J Physiol Renal Physiol 2006 290 F324-F334. Nakao A, Neto JS, Kanno S, Stolz DB, Kimizuka K, Liu F, et al. Protection against ischemia reperfusion injury in cardiac and renal transplantation with carbon monoxide, biliverdin and both. Am J Transplant 2005 5 282-291. Sass G, Soares MC, Yamashita K, Seyfried S, Zimmermann WH,...

Types of Probes

FISH probes several hundreds or thousands of nucleotides long complementary to nearly the entire 16S or 23S rRNA and containing multiple fluorophore labels have long been used to detect microorganisms in environmental samples because such lengthy probes offer reliable hybridization and intense signal. These probes are prepared enzymatically, typically by PCR 112 or in vitro transcription 113, 114 , at which time multiple fluorophores are incorporated. Although polynucleotide probes allow the...

Summary

Primary and secondary prevention of MI is still a major challenge for healthcare systems and is the subject of numerous studies worldwide. During the recent years, CYP enzymes received more attention from cardiologists not only because they are involved in the metabolic clearance of numerous cardiovascular drugs but also because they play a major role in vascular homeostasis, the development of atherosclerosis and CVD. Thus, therapeutic activation or inhibition of specific CYPs might become a...

Proposed Roles for COX2 in Carcinogenesis

To date, at least six mechanisms by which COX-2 contributes to tumorigen-esis and the malignant phenotype of tumor cells have been identified, including induction of proliferation, inhibition of apoptosis, increased angiogenesis, enhanced invasiveness, immune modulation, and increased mutagenesis. Although COX-2-derived PGE2 in colorectal carcinoma cells stimulates cell proliferation 11 , the downstream signaling pathways involved in PGE2-induced proliferation are still unknown. Forced...

Ho

Pathways are essentially opposite in their biological properties. The C-16a hydroxylation leads to the formation of 16a-hydroxyestrone (16aOHE1) and estriol (E3), which retain proestrogenic activity 15 , whereas the 2-hydroxylation results in formation of 2-hydroxyestrone (2OHE1) and 2-methoxyestrone (2MeOE1) that are devoid of estrogenic activity or even antiestrogenic in some systems 16 . Because these two pathways are mutually exclusive, the dominance of one pathway over the other would...

CYP Gene Variants Interacting with Vascular Homeostasis

ECs take a central place in the regulation of vascular homeostasis and in the pathogenesis of CVD and MI. Endothelial dysfunction occurs very early in CVD, is associated with altered endothelial gene and protein expression patterns, and is promoted by a multitude of factors that modulate vascular homeostasis. During the last years, CYP activity has been recognized as an important aspect in cardiovascular (patho)physiology 18, 32, 178, 303, 304 . A key molecule in vascular homeostasis is AA 34,...

Cytochrome P450 Enzymes

CYPs represent a superfamily of membrane-bound heme-containing enzymes that catalyze phase I biotransformation of a variety of endogenous and exogenous compounds. They oxidize, peroxidize, and or reduce cholesterol, steroids, arachidonic acid (AA), bradykinin, vitamins, xenobio-tics, and numerous therapeutic substances in an oxygen- and NADPH-dependent manner 29-31 . Whereas CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 5 account for the metabolism of almost half of all clinically used drugs,...

Regulation of CYP Enzyme Activity

Genetic and numerous epigenetic factors 45, 52, 54, 55, 60 regulate CYP activity and contribute to drug metabolism and disease development and or progression 19, 31, 32, 47-49, 59, 61 . Genetic variations in CYP genes and receptors and regulatory proteins involved in the regulation of CYP expression activity influence the metabolism of endogenous or exogenous CYP substrates 45, 50, 52, 55, 57, 58, 61 . The frequency of these variants substantially differs between populations, an aspect to be...

Role of Estrogen Hydroxylation in Bone Density and Osteoporosis

The importance of estrogen metabolism in the pathogenesis of hormone-related diseases has come primarily from studies on breast cancer. For example, a lower circulating 2OHE1 16aOHE1 ratio is associated with an increased risk of breast cancer 67-70 , whereas high serum 16aOHE1 is a strong predictor of breast cancer risk 67 . In vitro studies showed that breast tissues obtained from women with breast cancer have increased 16-hydroxyl-ation. Furthermore, the addition of E2 to MCF-7 cell lines...

Introduction

Identification and classification of cells in environmental and clinical samples can be critical for determining both prophylactic and curative responses. In dealing with contamination of food or water supplies by microorganisms, bacterial infections in tissues, and cancer-causing mutations in biopsy samples, a rapid diagnosis may be a life or death issue. Standard detection of cells in clinical or environmental samples requires any of a number of methods including culture, antigen detection,...

Computational Metabolism Methods

Enzymes such as the P450s have high structural homology yet with distinct roles in xenobiotic metabolism even though their active sites enable a wide array of structurally diverse substrates to bind 67 . Naturally, the substrate selectivity of human P450s is related to the molecule structure and the key molecular-binding features of the active sites. The amino acid residues around the heme are thought to have a key role for substrate binding 68 . For a long time in the absence of x-ray crystal...