Inclusive Dijet Production at HERA: Direct Photon Cross Sections in Next-To-Leading Order QCD

We have calculated inclusive two-jet cross sections in next-to-leading order QCD for direct photoproduction in low $Q^2$ $ep$ collisions at HERA. Infrared and collinear singularities in real and virtual contributions are cancelled with the phase space slicing method. Analytical formulas for the different contributions giving the dependence on the slicing parameter are presented. Various one- and two-jet distributions have been computed demonstrating the flexibility of the method.Comment: 30 pages, latex, 11 figures appended as uuencoded fil

A Lattice Study of the Nucleon Excited States with Domain Wall Fermions

We present results of our numerical calculation of the mass spectrum for isospin one-half and spin one-half non-strange baryons, i.e. the ground and excited states of the nucleon, in quenched lattice QCD. We use a new lattice discretization scheme for fermions, domain wall fermions, which possess almost exact chiral symmetry at non-zero lattice spacing. We make a systematic investigation of the negative-parity $N^*$ spectrum by using two distinct interpolating operators at $\beta=6/g^2=6.0$ on a $16^3 \times 32 \times 16$ lattice. The mass estimates extracted from the two operators are consistent with each other. The observed large mass splitting between this state, $N^*(1535)$, and the positive-parity ground state, the nucleon N(939), is well reproduced by our calculations. We have also calculated the mass of the first positive-parity excited state and found that it is heavier than the negative-parity excited state for the quark masses studied.Comment: 46 pages, REVTeX, 11 figures included, revised version accepted for publication in Phys. Rev.

Modulation of cyclic nucleotides and cyclic nucleotide phosphodiesterases in pancreatic islet beta-cells and intestinal l-cells as targets for treating diabetes mellitus

Cyclic 3'5'-AMP (cAMP) is an important physiological amplifier of glucose-induced insulin secretion by the pancreatic islet beta-cell. In the beta-cell, cAMP is formed by the activity of adenylyl cyclase, especially in response to the incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic peptide. cAMP may also play a similar role in regulating GLP-1 secretion from intestinal L-cells. cAMP influences many steps involved in glucose-induced insulin secretion and may be important in regulating pancreatic islet beta-cell differentiation, growth and survival. cAMP itself is rapidly degraded in the pancreatic islet beta-cell by cyclic nucleotide phosphodiesterase enzymes. This review will discuss the possibility of targeting cAMP mechanisms in the treatment of type 2 diabetes mellitus, in which insulin release in response to glucose is impaired

The effects of lignocaine on actions of the venom from the yellow scorpion "leiurus quinquestriatus" in vivo and in vitro

Fatani, A.J., Harvey, A.L., Furman, B.L., and Rowan, E.G. The effects of lignocaine on actions of the venom from the yellow scorpion, Leiurus quinquestriatus, in vivo and in vitro. Toxicon, 19. Many toxins from scorpion venoms activate sodium channels, thereby enhancing neurotransmitter release. The aim of the present work was to determine if the in vivo and in vitro effects of Leiurus quinquestriatus venom (LQQ) could be ameliorated by lignocaine, a sodium channel blocker. In urethane anaesthetised rabbits, LQQ venom (0.5 mg kg−1, i.v.) caused initial hypotension and bradycardia followed by hypertension, pulmonary oedema, electrocardiographic changes indicating conduction defects, ischaemia, infarction, and then hypotension and death. Lignocaine (1 mg kg−1 i.v. bolus initially, followed by i.v. infusion of 50 μg kg−1 min−1) significantly attenuated the majority of the venom-evoked effects and reduced mortality. Addition of LQQ venom (1, 3 and 10 μg ml−1) to chick biventer cervicis, guinea pig ileum, and rat vas deferens preparations, increased the height of electrically-induced twitches, elevated resting tension, and caused autorhythmic oscillations. Lignocaine (3 × 10−4-1.2 × 10−3 M) greatly attenuated these venom-evoked actions in the three preparations. Antagonists of appropriate neurotransmitters were also tested to determine the contribution of released transmitters to LQQ effects. Atropine significantly decreased the venom-elicited effects on guinea pig ileum preparations, while prazosin and guanethidine significantly reduced the venom's actions on rat vas deferens. In chick biventer cervicis preparations, tubocurarine and hexamethonium significantly attenuated the venom-induced effects. This study supports the hypothesis that many effects of LQQ venom involve the release of neurotransmitters and may be ameliorated by treatment with lignocaine

The effect of nCX4016 [2-acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester] on the consequences of ischemia and reperfusion the streptozotocin diabetic rat

The aim of this study was to assess the effect of chronic administration of NCX4016 [2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester], a nitric oxide-releasing aspirin derivative on the consequences of coronary artery occlusion in streptozotocin-diabetic rats. Rats were made diabetic by injection of streptozotocin (60 mg kg–1) and received insulin (2.5 U kg–1 s.c.) daily for 4 weeks. Animals received vehicle (1 ml kg–1 polyethylene glycol), aspirin (65.2 mg kg–1), NCX4016 (60 mg kg–1), or (iv) NCX4016 (120 mg kg–1) orally, once daily for the last 5 days before coronary artery occlusion (CAO). One hour after the last dose, pentobarbital-anesthetized rats were subjected to CAO for 30 min followed by 120-min reperfusion. Neither drug significantly modified initial hemodynamics or plasma glucose levels compared with vehicle treatment in either nondiabetic or diabetic rats. Neither drug modified the total ventricular premature beat (VPB) count in normal animals, although NCX4016, but not aspirin, reduced the total VPB count and the incidence of ventricular tachycardia in diabetic rats. In nondiabetic animals, both aspirin and NCX4016 reduced infarct size. However, in diabetic rats, infarct size was reduced only by the larger dose of NCX4016 (120 mg kg–1) but not by aspirin or the lower dose of NCX4016. These results demonstrate that the cardioprotective effects of NCX4016 are reduced in the presence of diabetes compared with the effects seen in nondiabetic animals. In summary, the present study confirms the protective effect of NCX4016 against ischemia-reperfusion injury in the normal rat heart and demonstrates for the first time its protective effect in the heart of streptozotocin-diabetic rats

Streptozotocin diabetes protects against arrhythmias in rat isolated hearts: role of hypothyroidism

We examined the contribution of hypothyroidism to streptozotocin diabetes-induced alterations in the arrhythmia susceptibility of ex vivo hearts to regional zero-flow ischaemia. Diabetic rats received either protamine zinc insulin (10 IU/kg/day, s.c.) or triiodothyronine (10 microg/kg/day, s.c.) for 8 weeks commencing 72 h after injection of streptozotocin (60 mg/kg, i.p.). Arrhythmias were determined in ex vivo Langendorff-perfused hearts, subjected to a 30-min main left coronary artery occlusion, followed by 30-min reperfusion. Serum free thyroxine concentrations, rectal temperature and ex vivo heart rate were significantly decreased in the 8-week diabetic group

Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion

The ryanodine (RY) receptors in β-cells amplify signals by Ca2+-induced Ca 2+ release (CICR). The role of CICR in insulin secretion remains unclear in spite of the fact that caffeine is known to stimulate secretion. This effect of caffeine is attributed solely to the inhibition of cAMPphosphodiesterases (cAMP-PDEs). We demonstrate that stimulation of insulin secretion by caffeine is due to a sensitization of the RY receptors. The dose-response relationship of caffeineinduced inhibition of cAMP-PDEs was not correlated with the stimulation of insulin secretion. Sensitization of the RY receptors stimulated insulin secretion in a context-dependent manner, that is, only in the presence of a high concentration of glucose. This effect of caffeine depended on an increase in [Ca2+]i. Confocal images of β-cells demonstrated an increase in [Ca2+]iinduced by caffeine but not by forskolin. 9-Methyl-7-bromoeudistomin D (MBED), which sensitizes RY receptors, did not inhibit cAMP-PDEs, but it stimulated secretion in a glucose-dependent manner. The stimulation of secretion by caffeine and MBED involved both the first and the second phases of secretion. We conclude that the RY receptors of β-cells mediate a distinct glucose-dependent signal for insulin secretion and may be a target for developing drugs that will stimulate insulin secretion only in a glucose-dependent manner