Minimally Invasive Cardiac Surgery Using a 3D High-Definition Endoscopic System.

We describe a minimally invasive heart surgery application of the EinsteinVision 2.0 3D high-definition endoscopic system (Aesculap AG, Tuttlingen, Germany) in an 81-year-old man with severe tricuspid valve insufficiency. Fourteen years ago, he underwent a Ross procedure followed by a DDD pacemaker implantation 4 years later for tachy-brady-syndrome.

Freezing Equals Freezing? Performance of Two Cryoablation Devices in Concomitant Mitral Valve Repair.

 Recent guidelines have recommended the addition of ablation in cardiac surgery for patients presenting with atrial fibrillation (AF). Currently available cryoablation devices use either nitrous oxide or argon gas as cooling agent. Our study aimed to compare success rates of two different devices currently available on the market and applied during concomitant cardiac surgery.

Plasma levels of apolipoprotein M in normal and complicated pregnancy.

Apolipoprotein M (apoM) is mainly associated with high-density lipoprotein in human plasma. Despite several studies suggesting apoM as an anti-atherogenic, its function is not yet fully understood. Plasma apoM was measured in normal pregnancies at four different gestational ages and in the postpartum period to investigate whether the concentration of apoM changes during pregnancy.

Development of the Berlin Symptom Checklist Ovary (BSCL-O) for the measurement of quality of life of patients with primary and recurrent ovarian cancer: results of a phase I and II study.

Goals Of Work: Quality of life (Qol) represents a relevant end point in the clinical management of advanced ovarian cancer (AOC). However, there exist only a few specific instruments which have been designed for patients with ovarian cancer. The aim of this study was to develop a systematic checklist (Berlin Symptom Checklist Ovary (BSCL-O)) as an instrument of Qol for patients with AOC and to discriminate between the frequency and the importance of symptoms.

Bioavailable flavonoids: cytochrome P450-mediated metabolism of methoxyflavones.

Methoxylated flavones were recently shown to be promising cancer chemopreventive agents. Their high metabolic stability compared with the hydroxylated analogs was shown in our laboratory using the human hepatic S9 fraction with cofactors for glucuronidation, sulfation, and oxidation. In the present study, the resistance of methoxylated flavones toward oxidative metabolism was investigated with human liver microsomes and recombinant cytochrome P450 (P450) isoforms.

Novel methoxylated flavone inhibitors of cytochrome P450 1B1 in SCC-9 human oral cancer cells.

Dietary polyphenols, including flavonoids, have been implied to have cancer preventive properties. Suggested mechanisms include inhibition of carcinogen-activating cytochrome P450 (CYP) transcription and activities. These studies have focused mainly on CYP1A1.

Improving metabolic stability of cancer chemoprotective polyphenols.

Dietary flavonoids and other polyphenols have the potential to be developed as effective food supplements as well as drugs for the prevention, as well as treatment of, cancer and other disease conditions. However, their very poor oral bioavailability, mainly due to extensive conjugation by glucuronidation and sulfation, is a severe limiting factor. First, this review shows the use of a simple, commercially available model system, the human hepatic S9 fraction, by which metabolic stability can be assessed effectively and accurately.

Cancer chemopreventive properties of orally bioavailable flavonoids--methylated versus unmethylated flavones.

Poor oral bioavailability has been a major limitation for the successful use of dietary flavonoids as cancer chemopreventive agents. In this study, we examined fully methylated flavones as promising improved agents. In the human oral SCC-9 cancer cells, 5,7-dimethoxyflavone and 5,7,4'-trimethoxyflavone were both 10 times more potent inhibitors of cell proliferation (IC(50) values 5-8 microM) than the corresponding unmethylated analogs chrysin and apigenin.

Benzo[A]pyrene-induced oral carcinogenesis and chemoprevention: studies in bioengineered human tissue.

Oral cancer, originating from smoking-induced lesions of the basal cells in the complex stratified oral epithelium, is difficult to treat. Early detection of premalignant lesions, e.g.

Flavonoid glycosides inhibit oral cancer cell proliferation--role of cellular uptake and hydrolysis to the aglycones.

Epidemiologic evidence supports the view that dietary flavonoids exert protective effects in oral diseases, including cancer. However, the dietary forms of flavonoids, the flavonoid glycosides, are thought to be inactive, thus they must first be hydrolysed to their active aglycones. This may occur in the saliva in the oral cavity.

S-adenosyl-L-methionine: transcellular transport and uptake by Caco-2 cells and hepatocytes.

S-adenosyl-L-methionine (SAMe) is an endogenous molecule that is known to be protective against hepatotoxic injury. Although oral SAMe appears to be absorbed across the intestinal mucosa, its systemic bioavailability is low. The reason for this is unknown.

Covalent binding of the flavonoid quercetin to human serum albumin.

Quercetin is an abundant flavonoid in the human diet with numerous biological activities, which may contribute to the prevention of human disease but also may be potentially harmful. Quercetin is oxidized in cells to products capable of covalently binding to cellular proteins, a process that may be important for its biological activities. In the present study, using radiolabeled drug and quantifying the products after electrophoretic separation, proteins to which oxidized quercetin is binding irreversibly were identified.

5,7-Dimethoxyflavone downregulates CYP1A1 expression and benzo[a]pyrene-induced DNA binding in Hep G2 cells.

The objective of this study was to examine the ability of dietary polyphenols to inhibit cytochrome P450 (CYP) 1A1 expression and activity and benzo[a]pyrene (BaP) DNA binding, with the main emphasis on prevention of chemical-induced hepatic carcinogenesis. For this purpose we used Hep G2 cells, a good model of the normal human hepatocyte for CYP1A1 cell signaling. First, when these cells were exposed to a low concentration (1 microM) of BaP, DNA binding occurred, which dramatically increased after 6 h of treatment.

Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans.

Increasing epidemiological evidence supports the view that dietary flavonoids have protective roles in oral diseases, including cancer. However, the dietary forms of flavonoids, the flavonoid glycosides, must first be hydrolyzed to the aglycones, which is thought to occur mainly in the intestine. In the present study we tested whether this hydrolytic activity occurs in the oral cavity.

High absorption but very low bioavailability of oral resveratrol in humans.

The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v.

The beta-D-glucoside and sodium-dependent glucose transporter 1 (SGLT1)-inhibitor phloridzin is transported by both SGLT1 and multidrug resistance-associated proteins 1/2.

Phloridzin, a glucoside of the flavonoid-like polyphenol phloretin, has long been known to be a specific nontransportable inhibitor of the sodium-dependent glucose transporter SGLT1. The objective of this study was to determine whether efflux by multidrug resistance-associated protein (MRP) transporters might have masked the absorption by SGLT1 in previous studies. Various cells used as transport models were incubated with phloridzin (50 microM) in the absence and presence of 50 microM 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK-571), a highly selective MRP1/MRP2 inhibitor, and the cellular uptake of phloridzin was measured by high performance liquid chromatography.

Evidence of covalent binding of the dietary flavonoid quercetin to DNA and protein in human intestinal and hepatic cells.

Quercetin-rich foods have the potential to prevent human disease. However, knowledge of its biological fate and mechanism of action is limited. This study extends previous observations of the oxidation of quercetin by peroxidases to quinone/quinone methide intermediates and, for the first time, demonstrates covalent binding of [14C]quercetin to macromolecules.

Resveratrol transport and metabolism by human intestinal Caco-2 cells.

Resveratrol is a dietary constituent suggested to have protective effects against cancer as well as cardiovascular disease. The purpose of the study was to learn whether this agent could be absorbed in man and enter the systemic circulation. This was examined by measuring transport and metabolism of resveratrol (5-40 microM) by the human intestinal epithelial cell line Caco-2 cultured in Transwells.

Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements.

Recent studies in our laboratory in the human hepatic and intestinal cell lines Hep G2 and Caco-2 have demonstrated induction of UGT1A1 by the flavonoid chrysin (5,7-dihydroxyflavone) using catalytic activity assays and Western and Northern blotting. In the present study, we examined which features of the flavonoid structures were associated with induction of UGT1A1 and whether common drug-metabolizing enzyme inducers also produce this induction. We also determined whether flavonoid treatment affected sulfate conjugation and CYP1A1 activity.

Carbon dioxide is the major metabolite of quercetin in humans.

A previous study in ileostomy patients indicated that dietary glucosides of the flavonoid quercetin are hydrolyzed efficiently in the intestinal lumen, followed by absorption of a large fraction of the quercetin aglycone. To determine the fate of quercetin, we administered 1.85 MBq (50 microCi) of (14)C-quercetin both orally (100 mg, 330 micromol) and intravenously (iv; 0.

Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in Caco-2 cells--potential role in carcinogen bioinactivation.

Purpose: Dietary flavonoids, present in fruits, vegetables and beverages have been demonstrated to be protective in cancer. Recently, we showed that the flavonoid chrysin induced UDP-glucuronosyltransferase (UGT) activity and expression in the human intestinal cell line Caco-2. In the present study, we determined the specific UGT isoform(s) induced and whether this induction facilitates glucuronidation and potential detoxification of the colon carcinogen 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP).

Disposition and metabolism of the flavonoid chrysin in normal volunteers.

Aims: To describe the oral disposition of the dietary flavonoid chrysin in healthy volunteers.

Methods: Oral 400 mg doses of chrysin were administered to seven subjects. Chrysin and metabolites were assayed in plasma, urine and faeces by h.

Quercetin and resveratrol potently reduce estrogen sulfotransferase activity in normal human mammary epithelial cells.

Estrogen sulfotransferase (EST) is the sole sulfotransferase expressed in normal human breast epithelial cells and has an important function in determining free estrogen hormone levels in these cells. In the present study we examined the inhibitory effect of the dietary polyphenols quercetin and resveratrol on EST activity, i.e.

Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption.

Flavonoids, dietary components in vegetables, fruits and beverages, may protect against coronary heart disease, stroke and cancer. However, the bioavailability of these compounds is questionable. A previous study in ileostomy patients of the most abundant flavonoid, quercetin, suggested a 52% absorption of its major dietary forms, monoglucoside (QMG) and diglucoside (QDG), from an onion meal.

Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in the human hepatoma cell line hep G2.

The UDP-glucuronosyltransferases (UGTs) have long been known to be inducible by various chemicals, including drugs, although the extent of induction in general has been modest. In the present study, we determined the ability of the dietary flavonoid chrysin to induce UGT activity, protein and mRNA. When pretreating human hepatoma Hep G2 cells with 25 microM chrysin, the glucuronidation of chrysin itself increased 4.