Growth of long range forward-backward multiplicity correlations with centrality in Au + Au collisions at square root of sNN = 200 GeV.

Forward-backward multiplicity correlation strengths have been measured with the STAR detector for Au + Au and p + p collisions at square root of s(NN) = 200 GeV. Strong short- and long-range correlations (LRC) are seen in central Au + Au collisions. The magnitude of these correlations decrease with decreasing centrality until only short-range correlations are observed in peripheral Au + Au collisions. Both the dual parton model (DPM) and the color glass condensate (CGC) predict the existence of the long-range correlations. In the DPM, the fluctuation in the number of elementary (parton) inelastic collisions produces the LRC. In the CGC, longitudinal color flux tubes generate the LRC. The data are in qualitative agreement with the predictions of the DPM and indicate the presence of multiple parton interactions.

K/pi Fluctuations at relativistic energies.

We report K/pi fluctuations from Au + Au collisions at sqrt[s(NN)]= 19.6, 62.4, 130, and 200 GeV using the STAR detector at the Relativistic Heavy Ion Collider. K/pi fluctuations in central collisions show little dependence on incident energy and are on the same order as those from NA49 at the Super Proton Synchrotron in central Pb + Pb collisions at sqrt[s(NN)]=12.3 and 17.3 GeV. We report results for the collision centrality dependence of K/pi fluctuations and results for charge-separated fluctuations. We observe that the K/pi fluctuations scale with the charged particle multiplicity density.

Observation of two-source interference in the photoproduction reaction AuAu --> AuAurho0.

In ultraperipheral relativistic heavy-ion collisions, a photon from the electromagnetic field of one nucleus can fluctuate to a quark-antiquark pair and scatter from the other nucleus, emerging as a rho{0}. The rho{0} production occurs in two well-separated (median impact parameters of 20 and 40 F for the cases considered here) nuclei, so the system forms a two-source interferometer. At low transverse momenta, the two amplitudes interfere destructively, suppressing rho{0} production. Since the rho{0} decays before the production amplitudes from the two sources can overlap, the two-pion system can only be described with an entangled nonlocal wave function, and is thus an example of the Einstein-Podolsky-Rosen paradox. We observe this suppression in 200 GeV per nucleon-pair gold-gold collisions. The interference is 87%+/-5%(stat.)+/-8%(syst.) of the expected level. This translates into a limit on decoherence due to wave function collapse or other factors of 23% at the 90% confidence level.

Indications of conical emission of charged hadrons at the BNL relativistic heavy ion collider.

Three-particle azimuthal correlation measurements with a high transverse momentum trigger particle are reported for pp, d+Au, and Au+Au collisions at sqrt[s_{NN}]=200 GeV by the STAR experiment. Dijet structures are observed in pp, d+Au and peripheral Au+Au collisions. An additional structure is observed in central Au+Au data, signaling conical emission of correlated charged hadrons. The conical emission angle is found to be theta=1.37+/-0.02(stat)-0.07+0.06(syst), independent of p_{ perpendicular}.

Forward neutral-pion transverse single-spin asymmetries in p + p collisions at sqrt[s] = 200 GeV.

We report precision measurements of the Feynman x (xF) dependence, and first measurements of the transverse momentum (pT) dependence, of transverse single-spin asymmetries for the production of pi0 mesons from polarized proton collisions at sqrt[s] = 200 GeV. The xF dependence of the results is in fair agreement with perturbative QCD model calculations that identify orbital motion of quarks and gluons within the proton as the origin of the spin effects. Results for the pT dependence at fixed xF are not consistent with these same perturbative QCD-based calculations.

System-size independence of directed flow measured at the BNL relativistic heavy-ion collider.

We measure directed flow (v_{1}) for charged particles in Au+Au and Cu+Cu collisions at sqrt[s_{NN}]=200 and 62.4 GeV, as a function of pseudorapidity (eta), transverse momentum (p_{t}), and collision centrality, based on data from the STAR experiment. We find that the directed flow depends on the incident energy but, contrary to all available model implementations, not on the size of the colliding system at a given centrality. We extend the validity of the limiting fragmentation concept to v_{1} in different collision systems, and investigate possible explanations for the observed sign change in v_{1}(p_{t}).

Longitudinal double-spin asymmetry for inclusive jet production in p[over -->] + p[over -->] collisions at sqrt[s]=200 GeV.

We report a new STAR measurement of the longitudinal double-spin asymmetry A(LL) for inclusive jet production at midrapidity in polarized p + p collisions at a center-of-mass energy of sqrt[s]=200 GeV. The data, which cover jet transverse momenta 5

Partonic Flow and phi-Meson production in Au+Au collisions at sqrt radical sNN = 200 GeV.

We present first measurements of the phi-meson elliptic flow (v2(pT)) and high-statistics pT distributions for different centralities from radical sNN=200 GeV Au+Au collisions at RHIC. In minimum bias collisions the v2 of the phi meson is consistent with the trend observed for mesons. The ratio of the yields of the Omega to those of the phi as a function of transverse momentum is consistent with a model based on the recombination of thermal s quarks up to pT approximately 4 GeV/c, but disagrees at higher momenta. The nuclear modification factor (R CP) of phi follows the trend observed in the K S 0 mesons rather than in Lambda baryons, supporting baryon-meson scaling. These data are consistent with phi mesons in central Au+Au collisions being created via coalescence of thermalized s quarks and the formation of a hot and dense matter with partonic collectivity at RHIC.

Measurement of transverse single-spin asymmetries for Dijet production in proton-proton collisions at sqrt[s]=200 GeV.

We report the first measurement of the opening angle distribution between pairs of jets produced in high-energy collisions of transversely polarized protons. The measurement probes (Sivers) correlations between the transverse spin orientation of a proton and the transverse momentum directions of its partons. With both beams polarized, the wide pseudorapidity (-1< or = eta < or = +2) coverage for jets permits separation of Sivers functions for the valence and sea regions. The resulting asymmetries are all consistent with zero and considerably smaller than Sivers effects observed in semi-inclusive deep inelastic scattering. We discuss theoretical attempts to reconcile the new results with the sizable transverse spin effects seen in semi-inclusive deep inelastic scattering and forward hadron production in pp collisions.

Transverse momentum and centrality dependence of high-pT nonphotonic electron suppression in Au+Au collisions at sqrt[s NN]=200 GeV.

The STAR collaboration at the BNL Relativistic Heavy-Ion Collider (RHIC) reports measurements of the inclusive yield of nonphotonic electrons, which arise dominantly from semileptonic decays of heavy flavor mesons, over a broad range of transverse momenta (1.2

The antilipolytic agent 3,5-dimethylpyrazole inhibits insulin release in response to both nutrient secretagogues and cyclic adenosine monophosphate agonists in isolated rat islets.

This study intended to test the hypothesis that intracellular lipolysis in the pancreatic beta cells is implicated in the regulation of insulin secretion stimulated by nutrient secretagogues or cyclic adenosine monophosphate (cAMP) agonists. Indeed, although lipid signaling molecules were repeatedly reported to influence beta-cell function, the contribution of intracellular triglycerides to the generation of these molecules has remained elusive. Thus, we have studied insulin secretion of isolated rat pancreatic islets in response to various secretagogues in the presence or absence of 3,5-dimethylpyrazole (DMP), a water-soluble and highly effective antilipolytic agent, as previously shown in vivo. In vitro exposure of islets to DMP resulted in an inhibition (by approximately 50%) of the insulin release stimulated not only by high glucose, but also by another nutrient secretagogue, 2-ketoisocaproate, as well as the cAMP agonists 3-isobutyl-1-methylxanthine and glucagon. The inhibitory effect of DMP, which was not due to alteration of islet glucose oxidation, could be reversed upon addition of sn-1,2-dioctanoylglycerol, a synthetic diglyceride, which activates protein kinase C. The results provide direct pharmacologic evidence supporting the concept that endogenous beta-cell lipolysis plays an important role in the generation of lipid signaling molecules involved in the control of insulin secretion in response to both fuel stimuli and cAMP agonists.

Dexamethasone-induced insulin resistance and pancreatic adaptive response in aging rats are not modified by oral vanadyl sulfate treatment.

OBJECTIVE: To explore the adaptive response of the endocrine pancreas in vivo and in vitro and the possible beneficial effect of the insulino-mimetic agent vanadyl sulfate (VOSO(4)), using glucocorticoid treatment to increase insulin resistance, in aging rats. DESIGN AND METHODS: Dexamethasone (Dex) (0.13 mg/kg b.w.) was administered daily for 13 days to 3- and 18-month old Sprague-Dawley rats and oral VOSO(4) was given from the 5th day. Plasma glucose, insulin and free fatty acids (FFA) concentrations were measured during these treatments and the insulin secretory response of the isolated perfused pancreas was assessed at the end of the experiment. RESULTS AND CONCLUSIONS: In both young and aging rats, particularly in the latter, hyperinsulinemia and increased in vitro insulin responsiveness to glucose were observed in response to Dex treatment, concomitant with an increase in plasma FFA concentrations. Thus, in glucocorticoid-treated animals, the beta-cell adaptive response occurred in both age groups and could possibly be mediated by increased circulating FFA; however, it was insufficient to prevent hyperglycemia in 60% of aging animals. Oral VOSO(4) administration failed to correct Dex-induced alterations in glucose and lipid metabolism, although it influenced in vitro beta-cell responsiveness to stimuli in aging rats.

p38 kinase inhibitors for the treatment of arthritis and osteoporosis: thienyl, furyl, and pyrrolyl ureas.

Inhibitors of the MAP kinase p38 are potentially useful for the treatment for osteoporosis, arthritis, and other inflammatory diseases. A series of thienyl, furyl, and pyrrolyl ureas has been identified as potent p38 inhibitors, displaying in vitro activity in the nanomolar range.

Age-dependent reduction in GLUT-2 levels is correlated with the impairment of the insulin secretory response in isolated islets of Sprague-Dawley rats.

In this study we have investigated the insulin secretory response to glucose and other secretagogues (2-ketoisocaproate, 3-isobutyl-1-methyl-xanthine and arginine) of pancreatic islets isolated from Sprague-Dawley rats of various ages (from 2 to 28 months). Our results showed a significant decline in the glucose-stimulated insulin secretion, starting at 12 months of age. On the other hand, the response to non-glucose secretagogues (and mainly to 2-ketoisocaproate) was less impaired with advancing age than that to glucose. We also observed a progressive age-related decline of protein levels of the glucose transporter GLUT-2 in pancreatic islets, which was temporally concomitant and quantitatively comparable with the beta-cell alteration in glucose responsiveness (-40/50%). Finally, we observed a significant increase of the islets insulin content in older rats with respect to younger animals. We conclude that in the islet of older rats the impaired capability to respond to glucose could be dependent, at least in part, on the age-dependent reduction in GLUT-2 and could be compensated by mechanisms including a preserved responsiveness to non-glucose secretagogues and/or the development of islet hypertrophy.

Effects of low-dose VOSO(4) on age-related changes in glucose homeostasis in rats.

The effects of low doses of vanadyl sulfate (0.2 mg/ml in the drinking water) on the age-related impairment of glucose homeostasis in Sprague-Dawley rats were investigated. VOSO(4) administration was initiated in 5-month-old animals and lasted 3 months. Thus, in 8-month-old rats, we investigated glucose metabolism in vivo and insulin secretory function in vitro. Results showed that VOSO(4) allowed the disposal of an oral glucose load at lower insulin levels than in age-matched controls. No significant changes were found in muscle glucose transporter (GLUT-4) levels or in glycogen content upon VOSO(4) treatment. Islets isolated from VOSO(4)-treated rats released less insulin than control islets, but showed a better preserved sensitivity to secretagogues, in terms of incremental release over basal release, secretory efficiency, and maintenance of the priming effect of glucose. In conclusion, chronic low-dose VOSO(4) treatment facilitates insulin action by a mechanism independent of muscle GLUT-4 levels and helps preserve the appropriate sensitivity of beta cells to stimuli, thereby preventing age-dependent functional alterations.

Verapamil acute administration: a new dynamic test in hyperprolactinemic states.

We studied the effect of acute administration of the calcium-channel blocker verapamil (VER) in 27 patients with tumoral hyperprolactinemia ([THPRL] prolactinomas and pseudoprolactinomas). We also studied the effect of VER in seven patients with idiopathic hyperprolactinemia (IHPRL) and a small group of patients with normal prolactin (PRL) levels and minimal incidental anomalies shown by magnetic resonance imaging (MRI). The study was performed on 2 separate days: on the first day, all subjects received VER, and on the second they received placebo. Acute administration of VER evoked a remarkable increase in serum PRL in IHPRL (as in normal healthy subjects used as controls), but no response was shown in THPRL, with no overlap between the two conditions. Acute administration of VER stimulated PRL secretion in patients with minimal incidental lesions shown by MRI; however, this increase was smaller in patients whose PRL level consistently reached the upper-normal limit. Although the meaning of such minimal anomalies shown by MRI is unknown, this could suggest that the test is precociously altered. To further elucidate the action of VER on lactotropes, we investigated the effect of VER given intravenously (IV) and compared different oral formulations in healthy subjects. Our data show that the VER test is effective in distinguishing between THPRL and IHPRL, but unfortunately, like other tests, it is not able to individualize patients in whom THPRL is the result of diminished dopaminergic tone (pseudoprolactinoma). From a pathophysiological point of view, calcium influx would appear less important in PRL regulation in chronic disorders of PRL secretion. VER given IV did not stimulate PRL release in normal subjects. This suggests that IV administration could produce a peak with an inadequate duration or that oral formulations may act also by metabolites formed on first-pass metabolism in the liver.

Insufficient adaptive capability of pancreatic endocrine function in dexamethasone-treated ageing rats.

This study was aimed at exploring the capability of the pancreatic endocrine adaptive mechanisms of ageing Sprague-Dawley rats to counteract the metabolic challenge induced by the prolonged administration of dexamethasone (DEX) (0.13 mg/kg per day for 13 days). DEX treatment induced peripheral insulin resistance in 3-, 18- and 26-month-old rats, as indicated by the significant and persistent rise of plasma insulin levels in each age group (plasma insulin in 3-, 18- and 26-month-old rats from basal values of 4.3+/-0.8, 4.7+/-0.5 and 5.6+/-1.0 ng/ml (means+/-s.e.m.) respectively, rose to 11.9+/-1.7, 29.1+/-5.5 and 27.9+/-2.7 ng/ml respectively, after 9 days of administration). However, plasma glucose concentrations remained unchanged during the treatment in young rats, whereas they increased up to frankly diabetic levels in most 18-month-old and in all 26-month-old animals after a few days of DEX administration. Plasma free fatty acid concentrations increased 2-fold in 3- and 26-month-old rats and 4-fold in 18-month-old rats and could possibly be involved in the glucocorticoid-induced enhancement in insulin resistance, although they showed no significant correlation with glycaemic values. Incubation of pancreatic islets obtained from treated rats showed that DEX administration increased the insulin responsiveness of islets from not only younger but also older donors. However, in the islets of ageing rats, which already showed an age-dependent impairment of the sensitivity to glucose and other secretagogues, this enhancing effect was clearly attenuated with respect to the younger counterpart. Furthermore, DEX treatment depressed significantly the priming effect of glucose in islets isolated from all the three age groups. In conclusion, our results show that ageing rats are unable to counteract effectively a prolonged hyperglycaemic challenge as such induced by DEX administration. This homeostatic defect can be ascribed to the age-dependent failure of the endocrine pancreas to provide enough insulin to overcome the aggravation of an antecedent state of increased peripheral insulin resistance.

Glycated plasma proteins in experimentally induced acute toxic renal failure by dichromate injection: evidence for loss with urine and decreased plasma levels.

In the rat, a single subcutaneous injection of sodium dichromate (20 mg/kg) causes acute renal injury and significant polyuria, proteinuria, and glycosuria (peaking 2-3 days after treatment, and returning to normal by day 5) without any changes in the plasma levels of protein, glucose, and glycated haemoglobin. Surprisingly, the percentage levels of glycated plasma total proteins and albumin (assayed by boronate affinity chromatography) transiently and significantly decrease during recovery from proteinuria (days 4 and 10 after treatment) and were found in the normal range of values by day 18. These changes are concomitant with a significant increase in the percentage level of glycated albumin in urine. Constancy of total plasma protein and the temporal pattern of levels of glycation suggest that changes in the percentage values of glycated proteins are secondary to a transient selective loss of glycated plasma proteins in urine.

Protein glycation in the aging male Sprague-Dawley rat: effects of antiaging diet restrictions.

Protein glycation and accumulation of advanced glycosylated end-products (AGEs) are supposed to play an important role in the process of aging. Dietary restriction increases life span and delays the onset of most age-associated diseases. Age-dependent changes in glucose homeostasis and glycated plasma proteins and hemoglobin were determined, and AGEs formation was measured as fluorescence in skin and aortic collagens in male Sprague-Dawley rats fed ad libitum or subjected to every-other-day feeding or 40% food restriction. In aging control rats, skin and aortic collagen-linked fluorescence increased with a similar exponential curve (aortic value being always higher), whereas glycated plasma protein and hemoglobin decreased slightly. Dietary restrictions decreased glycated plasma proteins and fluorescent products in skin collagen of younger but not older rats, and did not affect glycated hemoglobin or aortic collagen fluorescence. In conclusion, our data indicate that age-related changes in glucose homeostasis do not play a substantial role in aging; and collagen-linked fluorescence increases significantly during aging, but it may not be sensitive to dietary intervention.