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Chronic Effects (chronic + effects)
Selected AbstractsCHRONIC EFFECTS OF ANGIOTENSIN II and AT1 RECEPTOR ANTAGONISTS IN SUBFORNICAL ORGAN-LESIONED RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2005John P Collister SUMMARY 1.,Angiotensin (Ang) II is known to exert some of its effects centrally via circumventricular organs. These unique central nervous system areas lack the normal blood,brain barrier and, therefore, allow peptide hormones access to the brain. Of these, the subfornical organ (SFO) has been shown to be involved in many of the acute dipsogenic and pressor effects of AngII, but much less is known about the role of the SFO in the chronic effects of AngII. We hypothesized that the SFO is a central site involved in the chronic hypotensive effects of endogenous AT1 receptor blockade, as well as the chronic hypertensive effects of exogenously administered AngII. 2.,In order to test these hypotheses, SFO-lesioned (SFOx) or sham Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers for intravenous administration of losartan or AngII and continuous measurement of blood pressure and heart rate. Rats were given 3 days of saline control infusion (7 mL/day of 0.9% NaCl) and were then infused with either losartan (10 mg/kg per day) or AngII (10 ng/kg per min) for 10 days. 3.,By day 4 of losartan treatment, arterial pressure had decreased 24 ± 2 and 18 ± 2 mmHg in sham (n = 9) and SFOx (n = 10) rats, respectively. Furthermore, by day 5 of AngII infusion, arterial pressure had increased 12 ± 3 mmHg in sham rats (n = 9), but only by 4 ± 1 mmHg in SFOx rats (n = 9). In each treatment group, these attenuated pressure responses in SFOx rats continued through day 10 of treatment. 4.,These results support the hypotheses that the SFO plays a role in both the hypotensive effects of chronic AT1 receptor blockade and the chronic hypertensive phase of exogenously administered AngII. [source] Stress, Breast Cancer Risk, and Breast Self-Examination: Chronic Effects of Risk and Worry,JOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 2 2004Donna M. Posluszny Identifying the risk factors for breast cancer allows targeted prevention and surveillance of women with higher than average risk. Moreover, aggressive, regular surveillance is necessary if mortality is to be reduced by finding disease in its early, more treatable stages. However, learning that one is at risk may cause stress as women worry about developing breast cancer and the severity of its effects. This study examined the distress associated with breast cancer risk by measuring perceived stress, breast cancer worry, risk perception, and surveillance behavior in women with average and higher than average risk profiles. Women at higher risk reported more worry, intrusive thoughts, and emotional upset throughout the year of the study than did women with average risk. In addition, stress reduced adherence to regular breast self-examination. [source] Acute and Chronic Effects of Nitrite on White Shrimp, Litopenaeus vannamei, Cultured in Low-Salinity Brackish WaterJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2004Amit Gross The marine white shrimp Litopenaeus vannamei is widely cultured. Recently, farmers have begun to culture this shrimp in low-salinity brackish water (< 6 g/L). The intensification of shrimp culture often results in occurrences of elevated nitrite concentration during the growing season. Nitrite is toxic to shrimp and exposure to high concentrations may cause retarded growth and mortalities. The current study was aimed at investigating the acute and chronic toxicity of nitrite to L. vannamei grown in low-salinity (2 g/L) brackish water. Studies of the 96-h EC50 and LC50 values of nitrite were performed to determine the acute toxicity, and an aquarium growth study (2 d post exposure to elevated nitrite concentrations) was conducted to evaluate the chronic effects of nitrite on shrimp production. The 96-h EC50 and LC50 values for juvenile L. vannamei grown in water of 2 g/L salinity was about 9 mg/L NO2 -N, suggesting a safe concentration for shrimp production in ponds to be less than 0.45 mgIL NO2 -N. Exposing shrimp to nitrite concentration of 4 mg/L for 2 d reduced their growth but did not affect their survival. [source] Acute and Chronic Effects of Extensive Radiofrequency Lesions in the Canine Caval Veins: Implications for Ablation of Atrial ArrhythmiasPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 12 2006GUILHERME FENELON M.D. Background: Although radiofrequency (RF) ablation within the caval veins has been increasingly used to treat a variety of atrial tachyarrhythmias, the consequences of RF ablation in the caval veins are unknown. We explored the acute and chronic angiographic and pathological effects of extensive RF ablation in the caval veins. Methods: Under fluoroscopy guidance, conventional (4 mm tip, 60°C, 60 seconds) RF applications (n = 6,7) were delivered in each vena cava (from ±2 cm into the vein to the veno-atrial junction) of 15 dogs (10 ± 3 kg). Animals were killed 1 hour and 5 weeks after ablation for histological analysis. Angiography was performed before ablation (acute dogs only) and at sacrifice to assess the degree of vascular stenosis. Results: In acute dogs (n = 5), luminal narrowing was noted in 10/10 (100%) targeted veins (mild in two; moderate in three and severe in five, including two total occlusions). In the six chronic animals that completed the protocol (four died during follow-up), stenosis was also observed in 12/12 (100%) ablated veins (mild in six; moderate in four and severe in two). Of these, one superior vena cava was suboccluded with development of extensive collateral circulation. Histologically, acute lesions displayed typical transmural coagulative necrosis, whereas chronic lesions revealed intimal proliferation, necrotic muscle replaced with collagen, endovascular contraction, and disruption and thickening of the internal elastic lamina. Conclusion: In this model, extensive RF ablation in the caval veins may result in significant vascular stenosis. These findings may have implications for catheter ablation of arrhythmias originating within the caval veins. [source] Chronic effects of silver exposure on ion levels, survival, and silver distribution within developing rainbow trout (Oncorhynchus mykiss) embryosENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2001Christine M. Guadagnolo Abstract Rainbow trout embryos were chronically exposed to silver (as AgNO3) in moderately hard water (120 mg CaCO3/L, 0.70 mM Cl,, 1.3 mg/L dissolved organic matter, 12.3 ± 0.1 °C) at nominal concentrations of 0.1, 1, and 10 ,g/L (measured = 0.117 ± 0.008, 1.22 ± 0.16, and 13.51 ± 1.58 ,g/L, respectively) to investigate the effects on mortality, ionoregulation, and silver uptake and distribution of the embryo. Mortalities in the low concentrations (0.1 and 1.2 ,g/L) were not significantly different from controls throughout embryonic development (days 1,32 postfertilization). Mortalities of embryos in the 13.5-,g/L treatment reached 56% by day 32 postfertilization (33% when accounting for control mortality), by which time more than 50% of surviving embryos had hatched. Accumulation of silver in whole embryos of 1.2- and 13.5-,g/L treatments reached the highest concentrations of 0.13 and 0.24 ,g/g total silver, respectively, by day 32, but whole embryo silver burden was not correlated with mortality. Silver concentrations in different compartments of the whole embryo (chorion, dissected embryo, and yolk) were greatest just before hatch and were higher in the chorion for all experimental treatments. Up to 85% of total whole embryo silver content was bound to the chorion, which acts as a protective barrier during silver exposure. Whole embryo Na+ concentration in the 13.5-,g/L treatment was significantly reduced relative to controls from days 23 to 32 postfertilization, and levels in the embryo were reduced by 40% at day 32 postfertilization, indicating that silver toxicity in the whole embryo is associated with an ion regulatory disturbance that is similar to the acute effect of AgNO3 in juvenile and adult trout. [source] Chronic effects of type 2 diabetes mellitus on cardiac muscle contraction in the Goto-Kakizaki ratEXPERIMENTAL PHYSIOLOGY, Issue 6 2007F. C. Howarth Type 2 diabetes mellitus accounts for more than 90% of all cases of diabetes mellitus, and cardiovascular complications are the major cause of mortality and death in diabetic patients. The chronic effects of type 2 diabetes mellitus on heart function have been investigated in the Goto-Kakizaki (GK) rat. Experiments were performed in GK rats and age-matched Wistar control rats at 18 months of age. The progressive effects of diabetes on glucose metabolism were monitored periodically by application of the glucose tolerance test. Ventricular action potentials were measured in isolated, perfused heart. Shortening and intracellular Ca2+ were measured in electrically stimulated ventricular myocytes. The GK rats displayed mild fasting hyperglycaemia and progressively worsening glucose tolerance. At 18 months of age and 180 min after intraperitoneal injection of glucose (2 g (kg body weight),1), blood glucose was 436 ± 47 mg dl,1 in GK rats compared with 153 ± 18 mg dl,1 in control animals. Heart weight to body weight ratio was significantly increased in GK rats (4.10 ± 0.09 mg g,1, n= 5) compared with control animals (3.36 ± 0.22 mg g,1, n= 4). Spontaneous heart rate was slightly reduced in GK rats compared with control rats. Although the amplitude of shortening was not altered, the amplitude of the Ca2+ transient was significantly increased in myocytes from GK rats (0.78 ± 0.11 ratio units) compared with control rats (0.50 ± 0.06 ratio units). Despite progressively worsening glucose metabolism, at 18 months of age the contractile function of the heart appears to be well preserved. [source] Chronic effects of low to moderate alcohol consumption on structural and functional properties of the brain: beneficial or not?,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2009Marinus N. Verbaten Abstract Objective Some studies suggest that the effects of low to moderate drinking (about 1,3 standard glasses of alcohol per day) on the brain and cognitive performance are positive. In the present study this hypothesis is investigated. Methods For this purpose studies on the effects of low to moderate drinking on brain structure (Magnetic Resonance Induction (MRI) studies) and on cognitive performance were analysed and discussed Results In MRI studies, a linear negative effect of alcohol consumption on brain volume was found. Furthermore, a linear decrease in grey matter concurring with a linear increase in white matter volumes as a function of number of drinks was reported in males, but not in females. Only in elderly low to moderate drinkers (aged,>,65 years) there appeared to be an U-shaped relationship between alcohol consumption and white matter integrity (grade) on the one hand and cognition on the other hand. Conclusions The changes reported in brain shrinkage, grey matter and white matter volume, as a result of low to moderate alcohol consumption sooner offer support for the contention that such drinking decreases brain health than for its beneficial effect. An exception might hold for elderly light and moderate drinkers where less white matter damage was found than in abstainers concurring with better cognitive performance. However, methodological problems impose limits on this conclusion. Copyright © 2009 John Wiley & Sons, Ltd. [source] Chronic effects of polychlorinated dibenzofurans on mink in laboratory and field environmentsINTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 2 2009Matthew J Zwiernik Abstract Mink are often used as a sentinel species in ecological risk assessments of chemicals such as polychlorinated biphenyls (PCBs), dibenzo- p -dioxins (PCDDs), and dibenzofurans (PCDFs) that cause toxicity mediated through the aromatic hydrocarbon receptor. Considerable toxicological information is available on the effects of PCBs and PCDDs on mink, but limited toxicological information is available for PCDFs. Thus, exposure concentrations at which adverse effects occur could not be determined reliably for complex mixtures in which PCDFs dominate the total calculated concentration of 2,3,7,8-tetrachlorodibenzo- p -dioxin equivalent (TEQ). Two studies were conducted to evaluate the potential toxicity of PCDFs to mink. The first was a chronic exposure, conducted under controlled laboratory conditions, in which mink were exposed to 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF) concentrations as great as 2.4 × 103 ng 2,3,7,8-TCDF/kg wet-weight (ww) diet or 2.4 × 102 ng TEQ2006-WHO-mammal/kg ww diet. In that study, transient decreases in body masses of kits relative to the controls was the only statistically significant effect observed. The second study was a 3-y field study during which indicators of individual health, including hematological and morphological parameters, were determined for mink exposed chronically to a mixture of PCDDs and PCDFs under field conditions. In the field study, there were no statistically significant differences in any of the measured parameters between mink exposed to a median estimated dietary dose of 31 ng TEQ2006-WHO-mammal/kg ww and mink from an upstream reference area where they had a median dietary exposure of 0.68 ng TEQ2006-WHO-mammal/kg ww. In both studies, concentrations of TEQ2006-WHO-mammal to which the mink were exposed exceeded those at which adverse effects, based on studies with PCDD and PCB congeners, would have been expected. Yet in both instances where PCDF congeners were the sole or predominant source of the TEQ2006-WHO-mammal, predicted adverse effects were not observed. Taken together, the results of these studies suggest that the values of the mammalian-specific toxicity equivalency factors suggested by the World Health Organization overestimate the toxic potency of PCDFs to mink. Therefore, hazard cannot be accurately predicted by making comparisons to toxicity reference values derived from exposure studies conducted with PCBs or PCDDs in situations where mink are exposed to TEQ mixtures dominated by PCDFs. [source] Lithium isotopes: differential effects on renal function and histologyBIPOLAR DISORDERS, Issue 4 2001Peter M Stoll Objectives: Reduction in renal concentrating ability has been reported in patients undergoing chronic lithium treatment. Prior work has demonstrated differences in physiological effects of the stable lithium isotopes, 6Li and 7Li. Here, we measured the degree of polyuria, polydipsia and kidney histological changes induced in rats by equimolar amounts of 6LiCl, 7LiCl and the commercially available mixture of both isotopes. Methods: Rats were given 1.0 mEq/kg of either 6LiCl, 7LiCl or ,nLiCl' (isotope mixture, 93% 7LiCl) by subcutaneous injection twice daily for up to 49 days. Twenty-four-hour urine volume and water intake were measured daily. Kidneys from rats treated for 7 days with 1.5 mEq/kg 6LiCl, 7LiCl and vehicle were examined under light microscopy and histopathologic changes graded on a 4-point scale of severity. Results: All rats showed loss in renal concentrating ability manifested by increasing urine volume and water intake. Peak effects occurred after 9,13 days treatment, then declined to stable levels at two to three times pre-treatment level. Mean peak effect was significantly greater for 6LiCl than for 7LiCl. Chronic effects of 6LiCl (weeks 3,7 of treatment) on polyuria and polydipsia were persistently higher than that of 7LiCl. nLiCl effect was intermediate. Kidneys from rats treated for 7 days with 6LiCl showed more frequently severe lesions in renal tubules than did 7LiCl-treated rats. Conclusions: Our current data and prior studies suggest that elimination or reduction of 6Li from pharmaceutical preparations may merit further evaluation as a possibly less potentially nephrotoxic form of lithium treatment. [source] Acute and chronic toxicity of imidazolium-based ionic liquids on Daphnia magnaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2005Randall J. Bernot Abstract Room-temperature ionic liquids (ILs) are considered to be green chemicals that may replace volatile organic solvents currently used by industry. However, IL effects on aquatic organisms and ecosystems are currently unknown. We studied the acute effects of imidazolium-based ILs on survival of the crustacean Daphnia magna and their chronic effects on number of first-brood neonates, total number of neonates, and average brood size. Lethal concentrations of imidazolium ILs with various anions (X,) ranged from a median lethal concentration (LC50) of 8.03 to 19.91 mg L,1, whereas salts with a sodium cation (Na+ X,) were more than an order of magnitude higher (NaPF6 LC50, 9,344.81 mg L,1; NaBF4 LC50, 4765.75 mg L,1). Thus, toxicity appeared to be related to the imidazolium cation and not to the various anions (e.g., CI,, Br,, PF,6, and BF,4). The toxicity of imidazolium-based ILs is comparable to that of chemicals currently used in manufacturing and disinfection processes (e.g., ammonia and phenol), indicating that these green chemicals may be more harmful to aquatic organisms than current volatile organic solvents. We conducted 21-d chronic bioassays of individual D. magna exposed to nonlethal IL concentrations at constant food-resource levels. Daphnia magna produced significantly fewer total neonates, first-brood neonates, and average neonates when exposed to lower concentrations (0.3 mg L,1) of imidazolium-based ILs than in the presence of Na-based salts at higher concentrations (400 mg L,1). Such reductions in the reproductive output of Daphnia populations could cascade through natural freshwater ecosystems. The present study provides baseline information needed to assess the potential hazard that some ILs may pose should they be released into freshwater ecosystems. [source] A multivariate biomarker-based model predicting population-level responses of Daphnia magnaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2003Wim M. De Coen Abstract A multivariate model is proposed relating short-term biomarker measurements in Daphnia magna to chronic effects (21-d exposure) occurring at the population level (time to death, mean brood size, mean total young per female, intrinsic rate of natural increase, net reproductive rate, and growth). The results of the short-term exposure (48h-96 h) to eight model toxicants (cadmium, chromium, mercury, tributyl tin, linear alkylsulfonic acid, sodium pentachlorophenolate, lindane, and 2,4-dichloro-phenoxyacetic acid) on the following biomarkers were used for the multivariate model: digestive enzymes (amylase, cellulase, ,-galactosidase, trypsin, and esterase), enzymes of the intermediary metabolism (glycogen phosphorylase, glucose-6-phosphate de-hydrogenase, pyruvate kinase, lactate dehydrogenase, and isocitrate dehydrogenase), cellular energy allocation (CEA) (protein, carbohydrate, and lipid content and electron transport activity), and DNA damage and antioxidative stress activity. Using partial least squares to latent structures (PLS), a two-component model was obtained with R2 of 0.68 and a Q2 value of 0.60 based on the combined analysis of a limited number of the 48- and 96-h biomarker responses. For the individual population-level responses, the R2 values varied from 0.66 to 0.77 and the Q2 values from 0.52 to 0.69. Energy-related biomarkers (cellular energy allocation, lipid contents, anaerobic metabolic activity,pyruvate kinase, and lactate dehydrogenase), combined with parameters related to oxidative stress (catalase) and DNA damage measured after 48 and 96 h of exposure, were able to predict long-term effects at higher levels of biological organization. [source] The further development of ionoregulatory measures as biomarkers of sensitivity and effect in fish speciesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2002S. J. Croke Abstract Extensive season-by-season sampling was used to establish the normal range of whole-body Na+ and Cl, and Na+ uptake in healthy populations of two fish species, rainbow trout, Oncorhynchus mykiss, and fathead minnow, Pimephales promelas, of known differences in sensitivity to ionoregulatory toxicants (low pH, trace metals). These data together with responses of both species to six different ionoregulatory challenge tests of increasing severity (mild handling, exposure to low Ca2+ water, epinephrine injection, net-confinement stress, exposure to copper, and osmotic shock) were evaluated for their potential as biomarkers of sensitivity and of effect of ionoregulatory toxicants. There were no obvious biomarkers of sensitivity in the ion measures themselves, but four of the six challenges (exposure to low Ca2+ water, epinephrine injection, exposure to copper, and osmotic shock) produced a significantly greater effect in the more sensitive of the two species, fathead minnow. Based on the responses of both species, this article makes a number of recommendations for the application of ion measures alone and in combination with challenge tests to the assessment of chronic effects in populations experiencing sublethal ionoregulatory stress. [source] REVIEW: Impulsivity as a determinant and consequence of drug use: a review of underlying processesADDICTION BIOLOGY, Issue 1 2009Harriet De Wit ABSTRACT Impulsive behaviors are closely linked to drug use and abuse, both as contributors to use and as consequences of use. Trait impulsivity is an important determinant of drug use during development, and in adults momentary ,state' increases in impulsive behavior may increase the likelihood of drug use, especially in individuals attempting to abstain. Conversely, acute and chronic effects of drug use may increase impulsive behaviors, which may in turn facilitate further drug use. However, these effects depend on the behavioral measure used to assess impulsivity. This article reviews data from controlled studies investigating different measures of impulsive behaviors, including delay discounting, behavioral inhibition and a newly proposed measure of inattention. Our findings support the hypothesis that drugs of abuse alter performance across independent behavioral measures of impulsivity. The findings lay the groundwork for studying the cognitive and neurobiological substrates of impulsivity, and for future studies on the role of impulsive behavior as both facilitator and a result of drug use. [source] Ethanol preference in C. elegansGENES, BRAIN AND BEHAVIOR, Issue 6 2009J. Lee Caenorhabditis elegans senses multiple environmental stimuli through sensory systems and rapidly changes its behaviors for survival. With a simple and well-characterized nervous system, C. elegans is a suitable animal model for studying behavioral plasticity. Previous studies have shown acute neurodepressive effects of ethanol on multiple behaviors of C. elegans similar to the effect of ethanol on other organisms. Caenorhabditis elegans also develops ethanol tolerance during continuous exposure to ethanol. In mammals, chronic ethanol exposure leads to ethanol tolerance as well as increased ethanol consumption. Ethanol preference is associated with the development of tolerance and may lead to the development of ethanol dependence. In this study, we show that C. elegans is a useful model organism for studying chronic effects of ethanol, including the development of ethanol preference. We designed a behavioral assay for testing ethanol preference after prolonged ethanol exposure. Despite baseline aversive responses to ethanol, animals show ethanol preference after 4 h of pre-exposure to ethanol and exhibit significantly enhanced preference for ethanol after a lifetime of ethanol exposure. The cat-2 and tph-1 mutant animals have defects in the synthetic enzymes for dopamine and serotonin, respectively. These mutants are deficient in the development of ethanol preference, indicating that dopamine and serotonin are required for this form of behavioral plasticity. [source] Atrial fibrillation and bisphosphonate therapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2010Michael Pazianas Abstract Bisphosphonates are the most commonly used treatment for osteoporosis and have proven efficacy in the reduction of vertebral and nonvertebral fractures. Recently, concerns have been raised about a possible association between bisphosphonate therapy and atrial fibrillation (AF) following the report of a significant increase in risk of serious AF in women treated with zoledronic acid in the HORIZON study. Subsequent studies have produced conflicting results but have not excluded the possibility of such an association. Currently there is no direct evidence that bisphosphonates exert either acute or chronic effects on cardiac electrophysiology. Nevertheless, altered intracellular electrolyte homeostasis and proinflammatory, profibrotic, and antiangiogenic effects provide potential mechanisms by which atrial conduction could be affected in patients treated with bisphosphonates. In studies in which an increase in risk of AF has been identified, there is no evidence that this translates into increased mortality or increased risk of stroke, and the risk-benefit balance of bisphosphonate therapy in patients with osteoporosis and other forms of metabolic bone disease remains strongly positive. © 2010 American Society for Bone and Mineral Research [source] Acute and Chronic Ethanol Modulate Dopamine D2-Subtype Receptor Responses in Ventral Tegmental Area GABA NeuronsALCOHOLISM, Issue 5 2009Kimberly H. Ludlow Background:, Ventral tegmental area (VTA) ,-aminobutyric acid (GABA) neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in drug reward. VTA GABA neuron firing rate is reduced by acute ethanol and enhanced by DA via D2 receptor activation. The objective of this study was to evaluate the role of D2 receptors in acute ethanol inhibition of VTA GABA neuron activity, as well as the adaptation of D2 receptors by chronic ethanol consumption. Methods:, Using electrophysiological methods, we evaluated the effects of intraperitoneal ethanol on DA activation of VTA GABA neurons, the effects of DA antagonists on ethanol inhibition of their firing rate, as well as adaptations in firing rate following chronic ethanol consumption. Using single cell quantitative RT-polymerase chain reaction (PCR), we evaluated the expression of VTA GABA neuron D2 receptors in rats consuming ethanol versus pair-fed controls. Results:, In acute ethanol studies, microelectrophoretic activation of VTA GABA neurons by DA was inhibited by acute intraperitoneal ethanol, and intravenous administration of the D2 antagonist eticlopride blocked ethanol suppression of VTA GABA neuron firing rate. In chronic ethanol studies, while there were no signs of withdrawal at 24 hours, or significant adaptation in firing rate or response to acute ethanol, there was a significant down-regulation in the expression of D2 receptors in ethanol-consuming rats versus pair-fed controls. Conclusions:, Inhibition of DA activation of VTA GABA neuron firing rate by ethanol, as well as eticlopride block of ethanol inhibition of VTA GABA neuron firing rate, suggests an interaction between ethanol and DA neurotransmission via D2 receptors, perhaps via enhanced DA release in the VTA subsequent to ethanol inhibition of GABA neurons. Down-regulation of VTA GABA neuron D2 receptors by chronic ethanol might result from persistent DA release onto GABA neurons. [source] Genetic Correlations Between Initial Sensitivity to Ethanol and Brain cAMP Signaling in Inbred and Selectively Bred MiceALCOHOLISM, Issue 6 2001Shelli L. Kirstein Background: Several lines of evidence have suggested a role for cAMP (adenosine 3,,5,-cyclic monophosphate) signaling in the acute and chronic effects of ethanol. This study investigated whether there is a genetic correlation between cAMP synthesis in the brain and the acute effects of ethanol [alcohol sensitivity or acute functional tolerance (AFT)]. Methods: By using nine inbred strains of mice, we measured initial sensitivity and AFT to ethanol with a test of balance on a dowel. Initial sensitivity was defined by the blood ethanol concentration (BEC0) at the loss of balance on a dowel after an ethanol injection [1.75 g/kg intraperitoneally (ip)]. When mice were able to regain balance on the dowel, BEC1 was determined, and a second ethanol injection was given (2 g/kg ip). Upon final regaining of balance, BEC2 was determined. AFT was defined by the difference between BEC1 and BEC2 (AFT =,BEC = BEC2, BEC1). Cyclic AMP synthesis was measured in whole-cell preparations in the cerebellum and other brain areas of mice of the nine inbred strains. Results: Significant differences in BEC0 and AFT were seen among the mice of the nine inbred strains. Cerebellar basal and forskolin- and isoproterenol-stimulated cAMP production differed significantly between the strains, and BEC0 was found to correlate significantly with forskolin- and isoproterenol-stimulated cAMP accumulation in the cerebellum (r= 0.70 and 0.94, respectively). When we measured cAMP production in mesencephalic and telencephalic tissue in three strains of mice that differed significantly in isoproterenol-stimulated cAMP accumulation in the cerebellum, significant differences between strains were found only in telencephalic tissue. The relative relationship between the rank order of the three strains for cAMP accumulation in the telencephalon and initial sensitivity to ethanol was identical to that seen with the cerebellum. However, AFT did not correlate with cAMP accumulation in the cerebellum or any other brain area tested. Conclusions: These results suggest that cAMP-generating systems of the cerebellum and possibly the brain areas contained in telencephalic tissues (e.g., basal ganglia) may have an important relationship to an animal's initial sensitivity to the incoordinating effects of ethanol. [source] Ethanol Dependence Has Limited Effects on GABA or Glutamate Transporters in Rat BrainALCOHOLISM, Issue 4 2001Leslie L. Devaud Background: Neuroadaptations of GABAergic and glutamatergic systems appear to play an important role in both the acute as well as chronic effects of ethanol. Chronic ethanol intake leads to the development of ethanol tolerance and dependence that is associated with a decrease in GABAergic and an increase in glutamatergic function. The present report assessed the involvement of GABA and glutamate transporters in the chronic ethanol-induced adaptations of these two neuronal systems. Methods: Male and female rats were made ethanol dependent by 2-week administration of ethanol in a liquid diet. Levels of GABA (GAT-1, GAT-3) and glutamate (GLT-1, EAAC-1) transporters were assayed by immunoblotting. Transporter function was assessed by [3H]GABA and [3H]glutamate uptake assays. Results: Ethanol dependence did not alter levels of GABA or glutamate transporters in cerebral cortex compared with pair-fed control values. There were increases in some, but not all, transporter levels in hippocampus and hypothalamus with the development of ethanol dependence. A decreased rate of uptake was observed for GABA in cerebral cortex. There was no change in maximal GABA uptake or in glutamate uptake (Vmax). Conclusions: These results suggest that alterations in GABA and glutamate transporters have only a limited role in neuroadaptations to chronic ethanol intake in rats. However, the observed alterations were region-specific, supporting the complex responses to chronic ethanol exposure and suggesting that neuroadaptations of GABAergic and glutamatergic systems vary across the brain. [source] Acute and Chronic Effects of Nitrite on White Shrimp, Litopenaeus vannamei, Cultured in Low-Salinity Brackish WaterJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2004Amit Gross The marine white shrimp Litopenaeus vannamei is widely cultured. Recently, farmers have begun to culture this shrimp in low-salinity brackish water (< 6 g/L). The intensification of shrimp culture often results in occurrences of elevated nitrite concentration during the growing season. Nitrite is toxic to shrimp and exposure to high concentrations may cause retarded growth and mortalities. The current study was aimed at investigating the acute and chronic toxicity of nitrite to L. vannamei grown in low-salinity (2 g/L) brackish water. Studies of the 96-h EC50 and LC50 values of nitrite were performed to determine the acute toxicity, and an aquarium growth study (2 d post exposure to elevated nitrite concentrations) was conducted to evaluate the chronic effects of nitrite on shrimp production. The 96-h EC50 and LC50 values for juvenile L. vannamei grown in water of 2 g/L salinity was about 9 mg/L NO2 -N, suggesting a safe concentration for shrimp production in ponds to be less than 0.45 mgIL NO2 -N. Exposing shrimp to nitrite concentration of 4 mg/L for 2 d reduced their growth but did not affect their survival. [source] Disagreement between acute and chronic haemodynamic effects of nadolol in cirrhosis: a pathophysiological interpretationALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2005C. MERKEL Summary Background :,The acute effects of , -blockers may be different from chronic; mechanisms underlying this difference are poorly elucidated. Aim :,To assess portal pressure and its pathophysiological determinants after acute and chronic administration of nadolol. Methods :,In 24 patients with cirrhosis and portal hypertension hepatic venous pressure gradient, portal blood flow and resistance to portal blood flow were measured before, 60,90 min after acute administration of nadolol, and after 1 month. Patients were good-responders if hepatic venous pressure gradient was ,12 mmHg, or decreased by at least 20%. Results :,Eleven and 13 patients were good- and poor-responders to acute administration, respectively. Acute poor-responders showed a lower decrease in portal blood flow (P = 0.04) and a less evident decrease in mean arterial pressure (P < 0.001). Eleven and 13 patients were good- and poor-responders to chronic administration, respectively. Chronic poor-responders showed a larger increase in resistance to portal blood flow compared with good-responders (P = 0.01). Disagreement between acute and chronic effects was seen in 12 patients: six were acute good-responders chronic poor-responders and six were acute poor-responders chronic good-responders. Acute good-responders chronic poor-responders patients had the smallest decreases in portal blood flow and in mean arterial pressure after acute administration, while acute poor-responders chronic good-responders showed the largest (P = 0.05 and 0.01). Conclusions :,Disagreement between acute and chronic effects of nadolol on hepatic venous pressure gradient is common. The mechanism responsible is complex, the acute effect being mainly modulated by arterial hypotension and the chronic effect by changes in portal resistance. [source] Recent advances in mycotoxin determination in food and feed by hyphenated chromatographic techniques/mass spectrometryMASS SPECTROMETRY REVIEWS, Issue 1 2006Stefano Sforza Abstract Mycotoxins are fungal toxins produced by molds, which occur universally in food and feed derivatives, and are produced under certain environmental conditions in the field before harvest, post-harvest, during storage, processing, and feeding. Mycotoxin contamination is one of the most relevant and worrisome problem concerning food and feed safety because it can cause a variety of toxic acute and chronic effects in human and animals. In this review we report the use of mass spectrometry in connection with chromatographic techniques for mycotoxin determination by considering separately the most diffuse class of mycotoxins: patulin, aflatoxins, ochratoxin A, zearalenone, trichothecenes, and fumonisins. Although the selectivity of mass spectrometry is unchallenged if compared to common GC and LC detection methods, accuracy, precision, and sensitivity may be extremely variable concerning the different mycotoxins, matrices, and instruments. The sensitivity issue may be a real problem in the case of LC/MS, where the response can be very different for the different ionization techniques (ESI, APCI, APPI). Therefore, when other detection methods (such as fluorescence or UV absorbance) can be used for the quantitative determination, LC/MS appears to be only an outstanding confirmatory technique. In contrast, when the toxins are not volatile and do not bear suitable chromophores or fluorophores, LC/MS appears to be the unique method to perform quantitative and qualitative analyses without requiring any derivatization procedure. The problem of exact quantitative determination in GC/MS and LC/MS methods is particularly important for mycotoxin determination in food, given the high variability of the matrices, and can be solved only by the use of isotopically labeled internal standards or by the use of ionization interfaces able to lower matrix effects and ion suppressions. When the problems linked to inconstant ionization and matrix effects will be solved, only MS detectors will allow to simplify more and more the sample preparation procedures and to avoid clean-up procedures, making feasible low-cost, high-throughput determination of mycotoxins in many different food matrices. © 2005 Wiley Periodicals, Inc. [source] Changes in Protein, Carbohydrate, and Fat Metabolism with Aging: Possible Role of InsulinNUTRITION REVIEWS, Issue 1 2000Paolo Tessari M.D. Age is associated with modifications of body composition, i.e., an increase in body fat mass and a decrease in protein mass. Because insulin controls substrate disposal and production, these changes could theoretically be related to changes in either insulin action or secretion on the various substrates. On the basis of available evidence, insulin action on whole-body amino acid and protein metabolism seems not to be impaired in the aged. Decreased synthesis of contractile and mitochondrial proteins in muscle, associated with decreased gene expression, was described in humans. Decreased physical activity apparently represents an important factor responsible for decreased muscle protein synthesis and mass in the elderly. Exercise in the elderly may acutely revert these changes, although its chronic effects are still uncertain. In addition, the possible interaction between insulin and exercise in the maintenance of muscle mass needs to be specifically investigated in aged people. Higher free fatty acid (FFA) absolute flux and oxidation rates were observed in healthy elderly subjects in both the fasting state and following hyperinsulinemia, but not when normalized over fat mass. This suggests that FFA kinetics reflect the established changes in fat mass. Insulin sensitivity on glucose metabolism is usually normal in the aged, despite subtle impairments in insulin secretion, hepatic uptake, and onset of action. Finally, data support the operation of the Randle cycle (i.e., inverse relationships between fat and glucose oxidation) in the elderly [source] Chronic Amiodarone Effects on Epicardial Conduction and Repolarization in the Isolated Porcine HeartPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7 2000DOMINIQUE LACROIX Amiodarone is a potent antiarrhythmic agent with complex chronic effects, notably on repolarization and conduction, that are not fully understood. Its low arrhythmogenic potential has been related to a lack of increase in repolarizution dispersion. Since its effects are not documented in pigs we conducted a mapping study of activation and repolarization in isolated perfused porcine hearts. Amio20 female pigs (n = 7) received amiodarone 20 mg/kg per day over 4 weeks while Amio 5O female pigs (n = 7) received 50 mg/kg per day over 4 weeks. Concentrations of the drug encompassed values found in clinical studies. Then, activation patterns and activation-to-recovery intervals (ARI) were mapped epicardially from 128 unipolar electrograms in isolated perfused hearts in corroboration of epicardial action potential recordings. Mean ARI was longer in Amio20 experiments compared to the seven control hearts (325 ±11 ms vs 288 ± 5 m.s at 1,000 ms), whereas ARI dispersion was not different, being comprised between 7 and 11 ms and generating smooth gradients. In Amio5O experiments, mean ARI was further prolonged (390 ±10 ms at 1,500 ms) with an exaggerated reverse rate dependence concomitant with a depressant effect on the plateau of the action potential. Again, ARI dispersion did not differ from controls. Finally, the drug depressed the maximal rate of depolarization (Vmax) and slowed conduction in a rate dependent and concentration dependent fashion. In conclusion, chronic amiodarone induces Class I and Class HI antiarrhythmic effects in ventricular porcine epicardium that are concentration dependent but does not affect dispersion of repolarization. This may partly explain its low arrhythmogenic potential. [source] Epigenetics and the embodiment of race: Developmental origins of US racial disparities in cardiovascular healthAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 1 2009Christopher W. Kuzawa The relative contribution of genetic and environmental influences to the US black-white disparity in cardiovascular disease (CVD) is hotly debated within the public health, anthropology, and medical communities. In this article, we review evidence for developmental and epigenetic pathways linking early life environments with CVD, and critically evaluate their possible role in the origins of these racial health disparities. African Americans not only suffer from a disproportionate burden of CVD relative to whites, but also have higher rates of the perinatal health disparities now known to be the antecedents of these conditions. There is extensive evidence for a social origin to prematurity and low birth weight in African Americans, reflecting pathways such as the effects of discrimination on maternal stress physiology. In light of the inverse relationship between birth weight and adult CVD, there is now a strong rationale to consider developmental and epigenetic mechanisms as links between early life environmental factors like maternal stress during pregnancy and adult race-based health disparities in diseases like hypertension, diabetes, stroke, and coronary heart disease. The model outlined here builds upon social constructivist perspectives to highlight an important set of mechanisms by which social influences can become embodied, having durable and even transgenerational influences on the most pressing US health disparities. We conclude that environmentally responsive phenotypic plasticity, in combination with the better-studied acute and chronic effects of social-environmental exposures, provides a more parsimonious explanation than genetics for the persistence of CVD disparities between members of socially imposed racial categories. Am. J. Hum. Biol., 2009. © 2008 Wiley-Liss, Inc. [source] Acute and chronic effects of vitamin C on endothelial fibrinolytic function in overweight and obese adult humansTHE JOURNAL OF PHYSIOLOGY, Issue 14 2008Gary P. Van Guilder We determined the effects of acute intra-arterial vitamin C administration and chronic oral vitamin C supplementation on the capacity of the endothelium to release t-PA in overweight and obese adults. Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside in 33 sedentary adults: 10 normal-weight (BMI: 23.4 ± 0.5 kg m,2; 7M/3F); and 23 overweight/obese (BMI: 31.2 ± 0.8 kg m,2; 15M/8F). In 10 normal weight and eight overweight/obese adults the dose,response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C (24 mg min,1). Seventeen of the 23 overweight/obese adults completed a 3 month chronic oral vitamin C (500 mg day,1) supplementation intervention. Intra-arterial administration of vitamin C significantly potentiated t-PA release in overweight/obese adults. Net release of t-PA was ,95% higher (P < 0.01) after (from ,0.9 ± 1.1 to 94.6 ± 16.2 ng (100 ml tissue),1 min,1) compared with before (from ,0.8 ± 0.8 to 49.9 ± 7.7 ng (100 ml tissue),1 min,1) vitamin C administration. Daily vitamin C supplementation significantly increased t-PA release in overweight/obese adults (from 0.2 ± 0.9 to 48.2 ± 6.5 ng (100 ml tissue),1 min,1) before supplementation versus (0.3 ± 0.5 to 66.3 ± 8.7 ng (100 ml tissue),1 min,1) after supplementation. These results indicate that the antioxidant vitamin C favourably affects the capacity of the endothelium to release t-PA in overweight/obese adults. Daily vitamin C supplementation represents an effective lifestyle intervention strategy for improving endothelial fibrinolytic regulation in this at-risk population. [source] Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disordersANNALS OF NEUROLOGY, Issue 3 2010Yeon-Joo Kang PhD Objective Prolonged human immunodeficiency virus-1 (HIV-1) infection leads to neurological debilitation, including motor dysfunction and frank dementia. Although pharmacological control of HIV infection is now possible, HIV-associated neurocognitive disorders (HAND) remain intractable. Here, we report that chronic treatment with erythropoietin (EPO) and insulin-like growth factor-I (IGF-I) protects against HIV/gp120-mediated neuronal damage in culture and in vivo. Methods Initially, we tested the neuroprotective effects of various concentrations of EPO, IGF-I, or EPO+IGF-I from gp120-induced damage in vitro. To assess the chronic effects of EPO+IGF-I administration in vivo, we treated HIV/gp120-transgenic or wild-type mice transnasally once a week for 4 months and subsequently conducted immunohistochemical analyses. Results Low concentrations of EPO+IGF-I provided neuroprotection from gp120 in vitro in a synergistic fashion. In vivo, EPO+IGF-I treatment prevented gp120-mediated neuronal loss, but did not alter microgliosis or astrocytosis. Strikingly, in the brains of both humans with HAND and gp120-transgenic mice, we found evidence for hyperphosphorylated tau protein (paired helical filament-I tau), which has been associated with neuronal damage and loss. In the mouse brain following transnasal treatment with EPO+IGF-I, in addition to neuroprotection we observed increased phosphorylation/activation of Akt (protein kinase B) and increased phosphorylation/inhibition of glycogen synthase kinase (GSK)-3,, dramatically decreasing downstream hyperphosphorylation of tau. These results indicate that the peptides affected their cognate signaling pathways within the brain parenchyma. Interpretation Our findings suggest that chronic combination therapy with EPO+IGF-I provides neuroprotection in a mouse model of HAND, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3, signaling. This combination peptide therapy should therefore be tested in humans with HAND. ANN NEUROL 2010;68:342,352 [source] Reversal Blood Flow Component as Determinant of the Arterial Functional Capability: Theoretical Implications in Physiological and Therapeutic ConditionsARTIFICIAL ORGANS, Issue 3 2009Daniel Bia Abstract In several physiological, pathological, and therapeutic circumstances, the arterial blood flow is acutely modified, increasing, in some vascular segments the reversal (SSR) and oscillatory (SSO) components of the shear stress. Recently, in an in vivo model we found a relationship between acute changes in SSR and SSO, and variations in the arterial viscoelasticity. As the arterial viscoelasticity and diameter are the main determinants of the arterial buffering (BF) and conduit (CF) functions, changes in those functions could be expected associated with variations in SSR and SSO. The aim was to analyze the association between acute increases in SSR and SSO, and changes in the aortic CF and BF. Aortic flow, pressure, and diameter were measured in 16 sheep under basal and high reversal and oscillatory flow conditions (high SSR and SSO). Aortic BF and CF were quantified, and their potential association with the SSR and SSO components were analyzed. During high reversal flow rate conditions, a smooth muscle contraction-pattern was evidenced, with an increase in BF and a decrease in CF. Changes in BF and CF were associated with the changes in SSR and SSO. The acute effects on the arterial wall biomechanics of variations in SSR and SSO could contribute to comprehend their chronic effects, and the meaning of the acute vascular effects of changes in SSR and SSO would depend on the situation. Increases in SSR and SSO could be associated with smooth muscle tone increase-dependent changes in arterial BF and CF. [source] Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus coeruleus neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2003Eduardo Ruiz-Durántez The aim of this study was to determine if 2-(2-benzofuranyl)-2-imidazoline (2-BFI) interacts with the opioid system in the rat locus coeruleus, using single-unit extracellular recordings. In morphine-dependent rats, acute administration of the selective imidazoline receptor ligands 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) or valldemossine (10 mg kg,1, i.p.) did not modify the naloxone-induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine-dependent control group. After chronic administration of 2-BFI (10 mg kg,1, i.p., three times daily, for 5 days) and morphine, naloxone-induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2-BFI (1 mg kg,1, i.p.) or valldemossine (10 mg kg,1, i.p.) were used. Acute administration of 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) but not valldemossine (40 mg kg,1, i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED50 values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met5 -enkephalin to inhibit locus coeruleus neurons was decreased when 2-BFI (100 ,M) was applied to rat brain slices (EC50 increased by 5.6; P<0.05). The present data demonstrate that there is an interaction between 2-BFI and the opioid system in the locus coeruleus. This interaction leads to an attenuation of both the hyperactivity of locus coeruleus neurons during opiate withdrawal and the development of tolerance to morphine when 2-BFI is chronically administered. These results suggest that imidazoline drugs may prove to be useful agents for the management of opioid dependence and tolerance. British Journal of Pharmacology (2003) 138, 494,500. doi:10.1038/sj.bjp.0705052 [source] Cardiovascular effects of endothelin-1 and endothelin antagonists in conscious, hypertensive ((mRen-2)27) ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2000S M Gardiner SB 209670 is a potent antagonist of the vasoconstrictor (ETA - and ETB -receptor-mediated) and vasodilator (ETB -receptor-mediated) effects of endothelin, whereas SB 234551 is relatively selective for the constrictor (ETA -receptor-mediated) effects. Since we had previously found SB 209670 exerted antihypertensive, vasodilator effects in conscious, heterozygous, transgenic ((mRen-2)27) (abbreviated to TG) rats, here we compared the two antagonists in that model, and assessed their chronic effects on responses to exogenous endothelin-1. We did this to test our global hypothesis, namely, that SB 209670, but not SB 234551, would cause inhibition of the depressor effects of exogenous endothelin-1 in vivo, and that this differential effect would be associated with a more marked antihypertensive action of SB 234551 in TG rats. SB 209670 and SB 234551 (infused for 50 h) exerted similar, sustained, antihypertensive effects in TG rats. The antihypertensive effects of the antagonists occurred at times when the pressor effects of exogenous endothelin-1 were not significantly inhibited. Furthermore, SB 234551 did not exert a greater antihypertensive effect than SB 209670 at a time (i.e., 2,4 h) when the depressor effects of endothelin-1 were abolished by the latter, but not by the former (although this differential action was lost after 24 h infusion). The results caused us to reject the hypothesis that selective antagonism of the vasoconstrictor effects of endothelin-1 would result in SB 234551 exerting a greater antihypertensive effect than SB 209670 in TG rats. British Journal of Pharmacology (2000) 131, 1732,1738; doi:10.1038/sj.bjp.0703767 [source] Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS-1 cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 3 2001J. Blumentrath Abstract Both 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (ATRA) are active metabolites of vitamin A (retinol). There exists an interaction between retinoid receptors and peroxisome proliferator-activated receptors (PPAR,). To define their functions in an insulin secreting system the effects of ATRA, 9cRA and the PPAR, agonist rosiglitazone on cell proliferation, insulin release and glucose transporter (GLUT) 2 of INS-1 cells were tested. Retinoic acid receptor (RAR-, and -,) and retinoid X receptor (RXR-, and -,) proteins are present (immunoblots). Both 9cRA and ATRA inhibit INS-1 cell proliferation ([3H]-thymidine assay) in a concentration dependent manner. Both 9cRA and ATRA increased insulin release, but only ATRA ralsed the GLUT 2 mRNA in a bell-shaped concentration response curve after 48,h. The insulinotropic effect of one compound is not significantly superimposed by the other indicating that the same binding sites are used by 9cRA and ATRA. The acute and chronic effects of the PPAR, agonist rosiglitazone on insulin release were additionally determined since glitazones act as transcription factors together with RXR agonists. At high concentrations (100,,m) rosiglitazone inhibited glucose (8.3,mm) stimulated insulin secretion (acute experiment over 60,min). Insulin secretion, however, was increased during a 24,h treatment at a concentration of 10,,m and again inhibited at 100,,m. Changes in preproinsulin mRNA expression were not observed. Rosiglitazone (100,,m) increased GLUT 2 mRNA paralleled by an increase of GLUT 2 protein, but only after 24,h of treatment. This data indicate that RAR and RXR mediate insulin release. The changes in GLUT 2 have no direct impact on insulin release; the inhibition seen at high concentrations of either compound is possibly the result of the observed inhibition of cell proliferation. Effects of rosiglitazone on preproinsulin mRNA and GLUT 2 (mRNA and protein) do not play a role in modulating insulin secretion. With the presence of an RXR receptor agonist the effect of rosiglitazone on insulin release becomes stimulatory. Thus the effects of RAR-, RXR agonists and rosiglitazone depend on their concentrations, the duration of their presence and are due to specific interactions. Copyright © 2001 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||