Effects of TCDD on Ah receptor, ARNT, EGF, and TGF-alpha expression in embryonic mouse urinary tract

Lipoprotein(a) [Lp(a)] biogenesis was examined in primary cultures of hepatocytes isolated from mice transgenic for both human apolipoprotein(a) [apo(a)] and human apoB. Steady-state and pulse-chase labeling experiments demonstrated that newly synthesized human apo(a) had a prolonged residence time (approximately 60 min) in the endoplasmic reticulum (ER) before maturation and secretion. Apo(a) was inefficiently secreted by the hepatocytes and a large portion of the protein was retained and degraded intracellularly. Apo(a) exhibited a prolonged and complex folding pathway in the ER, which included incorporation of apo(a) into high molecular weight, disulfide-linked aggregates. These folding characteristics could account for long ER residence time and inefficient secretion of apo(a). Mature apo(a) bound via its kringle domains to the hepatocyte cell surface before appearing in the culture medium. Apo(a) could be released from the cell surface by apoB-containing lipoproteins. These studies are consistent with a model in which the efficiency of post-translational processing of apo(a) strongly influences human plasma Lp(a) levels, and suggest that cell surface assembly may be one pathway of human Lp(a) production in vivo. Transgenic mouse hepatocytes thus provide a valuable model system with which to study factors regulating human Lp(a) biogenesis.     

Modulation of cardiac sodium current by alpha1-stimulation and volatile anesthetics

BACKGROUND: Alpha1-adrenoceptor stimulation is known to produce electrophysiologic changes in cardiac tissues, which may involve modulations of the fast inward Na+ current (I(Na)). A direct prodysrhythmic alpha1-mediated interaction between catecholamines and halothane has been demonstrated, supporting the hypothesis that generation of halothane-epinephrine dysrhythmias may involve slowed conduction, leading to reentry. In this study, we examined the effects of a selective alpha1-adrenergic receptor agonist, methoxamine, on cardiac I(Na) in the absence and presence of equianesthetic concentrations of halothane and isoflurane in single ventricular myocytes from adult guinea pig hearts. METHODS: I(Na) was recorded using the standard whole-cell configuration of the patch-clamp technique. Voltage clamp protocols initiated from two different holding potentials (V(H)) were applied to examine state-dependent effects of methoxamine in the presence of anesthetics. Steady state activation and inactivation and recovery from inactivation were characterized using standard protocols. RESULTS: Methoxamine decreased I(Na) in a concentration- and voltage-dependent manner, being more potent at the depolarized V(H). Halothane and isoflurane interacted synergistically with methoxamine to suppress I(Na) near the physiologic cardiac resting potential of -80 mV. The effect of methoxamine with anesthetics appeared to be additive when using a V(H) of -110 mV, a potential where no Na+ channels are in the inactivated state. Methoxamine in the absence and presence of anesthetics significantly shifted the half maximal inactivation voltage in the hyperpolarizing direction but had no effect on steady-state activation. CONCLUSION: The present results show that methoxamine (alpha1-adrenergic stimulation) decreases cardiac Na+ current in a concentration- and voltage-dependent manner. Further, a form of synergistic interaction between methoxamine and inhalational anesthetics, halothane and isoflurane, was observed. This interaction appears to depend on the fraction of Na+ channels in the inactivated state. (Key words: Anesthetics, volatile: halothane; isoflurane; methoxamine. Patch clamp: whole-cell configuration; sodium current; ventricular guinea pig myocytes.)     

Thermionic Emission as a Tool to Study Transport in Undoped nFinFETs

Thermally activated subthreshold transport has been investigated in undoped triple-gate MOSFETs. The evolution of the barrier height and of the active cross-sectional area of the channel as a function of gate voltage has been determined. The results of our experiments and of the tight-binding simulations we have developed are both in good agreement with previous analytical calculations, confirming the validity of the thermionic approach to investigate transport in FETs. This method provides an important tool for the improvement of device characteristics.      

Fatty Acids Released from Milk Fat by Lipoprotein Lipase and Lipolytic Psychrotrophs

ABSTRACT: The ability of 13 different strains of psychrotrophs to release free fatty acids in milk was evaluated by using GC analysis. The 13 strains could be categorized into 3 groups: Group 1 consisted of bacteria that grew well and released large quantities of free fatty acids, group 2 consisted of bacteria that grew well but released low amounts of free fatty acids, and group 3 consisted of bacteria that did not grow well nor released large quantities of fatty acids. In group 1, 3 strains were determined to be highly lipolytic, releasing short‐chain fatty acids in amounts greater than reported threshold values. Group 3 consisted of 2 strains, which did not grow well in heat‐treated milk, and the subsequent release of free fatty acids was minor during the 10‐d monitoring time. The other 8 strains tested showed no specific pattern of fatty acid release and quantities of short‐chain fatty acids were not large, despite the ability to grow to high numbers in the treated milk. This work indicates that the lipolytic activity of psychrotrophs common in raw milk is specific to the species and a general prediction of free fatty acid release may not be possible.     

Hypertonic-hyperoncotic solutions in open-heart surgery

PURPOSE: To examine relationships between tobacco use and use of other substances among U.S. high school students, by gender and racial/ethnic subgroups. METHODS: Data about tobacco and other substance use were analyzed from the 1995 national Youth Risk Behavior Survey implemented by the Centers for Disease Control and Prevention. RESULTS: Compared to nonsmokers, current smokers were significantly more likely to report use of all other substances we examined, including lifetime use of cocaine, inhalants, other illegal substances, and multiple substances and current alcohol use, episodic heavy drinking, marijuana use, and cocaine use. A strong dose-dependent relationship between current cigarette smoking and other substance use was identified. Among smokeless tobacco users, a strong dose-dependent relationship was found for all examined substances with the exception of lifetime and current cocaine use. Finally, a pattern of risk emerged suggesting that the likelihood of other substance use increases as students move from no tobacco use to smokeless tobacco use only, to cigarette smoking only, and to use of both smokeless tobacco and cigarettes. CONCLUSIONS: Programs designed to prevent tobacco or other substance use should consider that such use often occurs concomitantly.     

Effects of forage level and canola seed supplementation on site and extent of digestion of organic matter, carbohydrates, and energy by steers

The objective of this study was to determine the effects of fat supplementation from canola seed (CS) on ruminal fermentation and postruminal digestion of OM, carbohydrates, and energy of diets containing different levels of forage. Six ruminally and duodenally cannulated beef steers (354 kg +/- 18) were given ad libitum access to six isonitrogenous diets that were offered twice daily in a 6 x 6 Latin square design. Treatments were arranged as a 2 x 3 factorial with two forage levels (70 vs 30% of dietary DM as corn silage) and three forms of CS supplementation including no CS or CS added at 10% of dietary DM as whole CS treated with alkaline hydrogen peroxide or untreated crushed CS. Fat from CS provided 5% of dietary DM. The remaining dietary ingredients were corn, canola meal, molasses, and urea. No interactions (P > .05) between dietary forage level and CS supplementation were observed for ruminal characteristics or digestion of OM, carbohydrates, and energy in the rumen, postruminally, or in the total tract. Fat supplementation from CS did not affect (P > .05) DMI. With few exceptions, fat supplementation did not affect (P > .05) ruminal, postruminal, or total tract digestibilities of OM, structural and nonstructural carbohydrates, and GE. Ruminal disappearance of GE was decreased (P < .05) when diets were supplemented with fat from whole treated CS, and total tract digestibilities of OM and GE were decreased (P < .05) when diets were supplemented with fat from CS in either form. Ruminal pH, concentrations of NH3 N and total VFA, and molar proportions of acetate, propionate, and butyrate were not affected (P > .05) by fat supplementation. Results suggest that fat supplementation from CS (at 5% of dietary DM) as whole treated or untreated crushed had no negative effects on ruminal fermentation of OM, carbohydrates, or energy when steers were given ad libitum access to diets containing high or low forage.     

Prospective, randomized trial of prolonged intracoronary urokinase infusion for chronic total occlusions in native coronary arteries

OBJECTIVES: The purpose of this study was to determine the safety and efficacy of three dosing regimens of intracoronary urokinase for facilitated angioplasty of chronic total native coronary artery occlusions. BACKGROUND: Percutaneous transluminal coronary angioplasty of chronically occluded (>3 months) native coronary arteries is associated with low initial success secondary to an inability to pass the guide wire beyond the occlusion. METHODS: Patients were enrolled if a chronic total occlusion >3 months old could not be crossed with standard angioplasty equipment. Of the 101 patients enrolled, 41 had successful guide wire passage and were excluded from urokinase treatment. The remaining 60 patients were randomized to receive one of three intracoronary dosing regimens of urokinase over 8 h (group A = 0.8 million U; group B = 1.6 million U; group C = 3.2 million U), and angioplasty was again attempted after completion of the urokinase infusion in 58 patients. RESULTS: Coronary angioplasty was successful in 32 patients (53%) (group A 52%, group B 50%, group C 59%, p = 0.86). This study had a 90% power to detect at least a 50% difference between dosing groups at alpha 0.05. Bleeding complications requiring blood transfusion did not differ significantly among the dosing groups (A 0%, B 15%, C 6%, p = 0.14), although major bleeding episodes were less common in group A (p < 0.05). There were no major procedural or in-hospital complications. Angiographic follow-up in 69% of the patients with successful angioplasty revealed target vessel patency in 91% but an angiographic restenosis rate of 59%. CONCLUSIONS: A prolonged supraselective intracoronary infusion of urokinase can be safely administered and may facilitate angioplasty of chronic total occlusions. Lower doses of urokinase are equally effective and result in fewer bleeding complications than do higher dosage regimens. Vessel patency is frequently maintained, but restenosis remains a problem.