The analysis of scientific data including American and European scientific communities concerning use of ractopamine as a growth factor in food animal production and the argumentation of the maximum permitted levels of ractopamine and levels of ractopamine in meat and byproducts (offal) is carried out. The position of the Russian side stated at the Codex Alimentarius commission 35th session that acceptable ractopamine daily intake is insufficiently validated and cannot be used for the determination of maximum permitted levels of ractopamine in meat and byproducts (offal) is confirmed. It is represented that residual ractopamine intake together with food on the levels which are recommended by the Codex Alimentarius commission and by taking into account the levels of animal products consumption in Russian Federation will lead to unacceptable human health risk level that will promote increasing heart diseases and life expectancy reduction. In this connection Russia states against of acceptance of maximum permitted levels of ractopamine in food.
A human genome-wide linkage scan for obesity identified a linkage peak on chromosome 5q13-15. Positional cloning revealed an association of a rare haplotype to high body-mass index (BMI) in males but not females. The risk locus contains a single gene, "arrestin domain-containing 3" (ARRDC3), an uncharacterized a-arrestin. Inactivating Arrdc3 in mice led to a striking resistance to obesity, with greater impact on male mice. Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues. ARRDC3 interacted directly with ß-adrenergic receptors, and loss of ARRDC3 increased the response to ß-adrenergic stimulation in isolated adipose tissue. These results demonstrate that ARRDC3 is a gender-sensitive regulator of obesity and energy expenditure and reveal a surprising diversity for arrestin family protein functions.
Cites: N Engl J Med. 1999 Sep 16;341(12):879-8410486419
The aim of this study was to investigate the effects of beta-stimulation in deep (25 degrees C) hypothermia. Cardiac catheterization was performed on seven anesthetized beagle dogs. They were cooled between ice bags down to 25 degrees C and received isoproterenol administered intravenously three times: at the normal body temperature (37 degrees C) before cooling, after cooling at 25 degrees C, and after rewarming at 37 degrees C. Circulatory function was measured for every 1 degree C of temperature change. Isoproterenol infusion at 37 degrees C induced cardiac acceleration, including the increases of heart rate, cardiac output, and peak first derivative of the left ventricular pressure curve. Systemic vascular and mean outflow resistances and mean aortic pressure decreased. During cooling, shivering thermogenesis continued, even down to 25 degrees C. At 25 degrees C, cardiac acceleration after isoproterenol infusion did not exist but relaxation rate increased slightly. Systemic vascular and mean outflow resistances decreased, but left ventricular end-diastolic and filling pressures increased. beta-Stimulation at normal body temperature increases shivering thermogenesis during cooling. The venous return to the left ventricle at 25 degrees C increased after isoproterenol infusion while systemic vascular resistance decreased, indicating systemic vasodilatation. This increase in preload is probably due to vasoconstriction in pulmonary vessels, which may be mediated by prejunctional beta-adrenoceptors. For cardiac inotrophy, the isoproterenol had no physiologically significant effects at 25 degrees C. After rewarming at 37 degrees C, the effects of isoproterenol were physiologically similar to the effects at the same temperature before cooling.
OBJECTIVE: To determine whether the administration of clenbuterol, a beta2-adrenergic agonist, prevents loss of muscle mass during a period of imposed inactivity. DESIGN: Randomized trial. SETTING: Basic laboratory research. ANIMALS: Thirty Fischer 344 Brown Norway F1 Hybrid rats, 12 and 30 months of age. INTERVENTIONS: The rats were randomly assigned to a control group, or to 1 of 2 experimental groups: hindlimb unweighted for 2 weeks (HU-2), or hindlimb unweighted with daily injections of clenbuterol for 2 weeks (HU-2Cl). MAIN OUTCOME MEASURES: Muscle mass weighed in milligrams and single fiber cross-sectional area histochemically evaluated. RESULTS: In both age groups, the HU-2 animals had greater muscle atrophy (decrease in muscle mass) in the soleus muscle than the extensor digitorum longus (EDL) muscle. In the HU-2Cl groups, the decline in muscle mass of both the soleus and EDL muscles was attenuated by about 4% to 20%. In the HU-2 group, single fiber cross-sectional area decreased for both fiber types (type I, 20%-40%; type II, 37%-50%) in both age groups. Clenbuterol retarded the inactivity-induced decline in single fiber cross-sectional area by 12% to 50%. In the EDL muscles of the HU-2Cl group, we found hypertrophy in both fiber types in the 30-month-old animals and in type I fibers in the 12-month-old animals. CONCLUSIONS: Clenbuterol attenuated the decrease in muscle mass and single fiber cross-sectional area in both age groups. By preventing the loss of muscle mass, clenbuterol administered early in rehabilitation may benefit severely debilitated patients imposed by inactivity. The attenuated muscle atrophy found with clenbuterol in the present study provides cellular evidence for the reported change in muscle strength after its administration after knee surgery. Thus, the administration of clenbuterol may lead to a more rapid rate of rehabilitation.
Brown adipose tissue is a mammalian thermogenic tissue. Its ability to dissipate energy as heat is due to a unique mitochondrial protein, uncoupling protein (UCP). Activation and expression of UCP is under control of the sympathetic nervous system acting through beta -adrenergic receptors (AR). In this study we used Siberian hamster brown adipocytes differentiated in vitro to investigate the expression of the fat specific beta 3-AR. Binding studies using the new labelled beta 3 adrenergic ligand [3H]SB 206606 showed a density of beta 3-AR in brown adipocyte plasma membranes comparable to that measured in vivo. beta 3-AR mRNA expression was very high in mature brown adipocytes and was started to be expressed during differentiation before UCP mRNA. Its half-life was approximately 50 min. Treatment of cells with non-specific beta adrenergic agonists, specific beta 3-adrenergic agonists, and dibutyryl cyclic AMP resulted in a marked down regulation of beta 3-AR mRNA level within several hours.
The influence of weight reduction and female sex hormones on the regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 20 obese hyperandrogenic women with polycystic ovary syndrome (PCOS). Nine PCOS women were reinvestigated after 8-12 weeks of weight reduction therapy (WR) with a very low calorie diet, inducing a mean loss of 8 +/- 3 kg, and 8 PCOS women were reinvestigated after 12 weeks of treatment with combined oral contraceptives (OC), containing ethinyl estradiol and norethisterone; the remaining 3 subjects were drop-outs. Both WR and OC normalized hyperandrogenicity. WR caused a 50% reduction of basal lipolysis rate and a 5- to 7-fold increased noradrenaline and terbutaline sensitivity (P
Effect of ionizing radiation in ultralow dose (5 microGy) on responses of erythrocyte electrophoretic motility (EPM) as a result of adrenoreceptor ligands binding (0.01-100 microM) has been investigated. The opposite directional EPM responses to agonists (adrenaline, isoprenaline) and antagonist (propranolol) of beta-adrenoreceptors was shown. At that, EPM response to the radiation coincides both with the direction and value of acting the beta-adrenoreceptor agonists depressing EPM. The EPM response to a combined action of beta-adrenoreceptors antagonist, propranolol (10 microM), and ionizing radiation is additive. The above listed is capable to evidence about the essential role of adrenoreceptors at formation of erythrocyte membrane surface charge under action of ionizing radiation in ultralow doses.
The purpose of this study was to examine the influence of ageing on the alterations in binding characteristics of adrenoceptors and membrane phospholipid fatty acids in rat heart following repeated administration of epinephrine. The maximal number of binding sites (Bmax) and dissociation constant (Kd) of [3H]prazosin and [3H]dihydroalprenolol binding to alpha 1- and beta-adrenoceptors, respectively, changed significantly during ageing. The downregulation of alpha 1- and beta-adrenoceptors after repeated epinephrine administration for one week, did not differ with age, but the response of the affinity (1/Kd) of both alpha 1- and beta-adrenoceptors to epinephrine treatment was age dependent. In 3-month-old rats the affinity of alpha 1-adrenoceptors was decreased after epinephrine treatment but the affinity of beta-adrenoceptors was unchanged. In 10- and 23-month-old rats the affinity of beta-adrenoceptors decreased after epinephrine treatment but the affinity of alpha 1-adrenoceptors did not change. During ageing the linoleic acid (18:2(n-6)) level decreased in phosphatidylcholine and the arachidonic acid (20:4(n-6)) level increased in phosphatidylcholine and phosphatidylethanolamine. After epinephrine administration the 18:2(n-6) level decreased and the docosahexaenoic acid (22:6(n-3)) level increased in phosphatidylcholine and phosphatidylethanolamine and those changes were not age dependent. The 20:4(n-6) level increased in phosphatidylcholine after epinephrine administration, but that increase was smaller in old than in young rats. The results show that both ageing and epinephrine administration simultaneously modify the fatty acid composition of membrane phospholipids and the binding properties of alpha 1- and beta-adrenoceptors in rat heart.