The effects of a sustained-release L-arginine formulation on blood pressure and vascular compliance in 29 healthy individuals

Abstract Vascular endothelial function is crucial to cardiovascular function and thus to blood perfusion to the heart and throughout the body. A number of substances are produced and secreted by vascular endothelial cells, the most important of which is nitric oxide, a potent regulator of vascular function. Nitric oxide diffuses from endothelial cells into underlying smooth muscle, causing relaxation, which results in vasodilation. When this process is inhibited or inadequate the arteries cannot dilate as necessary, resulting in hypertonicity and reduced blood flow. Such endothelial dysfunction also causes increased platelet and monocyte adhesiveness and smooth muscle proliferation, processes thought to be at the genesis of atherosclerotic plaque formation. Since L-arginine is the body's only substrate for nitric oxide synthesis, adequate L-arginine must be present for proper nitric oxide production. In this open label trial, a group of 29 asymptomatic individuals were given L-arginine (1,050 mg, as Perfusia-SR®, a sustained-release preparation) twice daily (total 2.1 g daily) for one week. Systolic blood pressure was reduced in 62 percent of participants compared to baseline, with a nonsignificant mean decrease in all patients of 4 mmHg. Diastolic blood pressure was reduced in 69 percent of participants, with a mean reduction of 3.7 mmHg (p=0.005). In the 10 individuals who were borderline or hypertensive (systolic >130 or diastolic >85), there was a mean systolic reduction of 11 mmHg (p=0.05), while normotensives (n=19) had a mean systolic decrease of only 0.22 mmHg. Diastolic blood pressure was decreased a nonsignificant 4.9 mmHg in borderline or hypertensivesand4.5mmHg in normotensives(p=0.026). Vascular elasticity relates to endothelial function, and can be measured non-invasively. At baseline and follow-up, vascular compliance was assessed via digital pulse wave analysis (DPA; Meridian Medical). After one week, pulse wave analysis showed a significant increase in large artery compliance (mean 23% improvement; p=0.02) and a non-significant increase in small artery compliance (mean 23% improvement; p=0.15). This study demonstrates blood pressure reductions, especially in patients with borderline or frank hypertension, as well as improved vascular compliance -an indicator of improved endothelial function and perfusion -after a one-week trial of sustained-release L-arginine. Poor endothelial function due to inadequate endothelial nitric oxide production is present in hypertension, as well as in numerous other aspects of cardiovascular disease, including angina, erectile dysfunction, cerebrovascular disease, and peripheral vascular disease. This is the first study showing a moderate dose of sustained-release L-arginine can improve endothelial function and blood pressure

Biomechanical parameters of the golf swing associated with lower back pain: A systematic review.

Low back pain (LBP) is the most common injury in golfers of all abilities. The primary aim of this review was to improve understanding of human golf swing biomechanics associated with LBP. A systematic review using the PRISMA guidelines was performed. Nine studies satisfying inclusion criteria and dually reporting golf swing biomechanics and LBP were identified. Human golf swing biomechanics potentially associated with LBP include: reduced lumbar flexion velocity; reduced transition phase length; reduced lumbar torsional load; earlier onset of erector spinae contraction; increased lumbar lateral flexion velocity; reduced or greater erector spinae activity; and earlier onset of external oblique contraction. These potential associations were undermined by a very limited and conflicting quality of evidence, study designs which introduced a severe potential for bias and a lack of prospective study design. There is no conclusive evidence to support the commonly held belief that LBP is associated with "poor" golf swing technique. The potential associations identified should be further investigated by prospective studies of robust design, recruiting participants of both sexes and dexterities. Once firm associations have been identified, further research is required to establish how this knowledge can be best integrated into injury prevention and rehabilitation

A novel approach with "skeletonised MTR" measures tract-specific microstructural changes in early primary-progressive MS

We combined tract‐based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract‐specific short‐term changes in early primary‐progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty‐one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM “skeleton,” which represents the tracts that are “common” to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co‐registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a “skeletonised” MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow‐up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal‐appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract‐specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross‐subject and tract‐specific changes in MTR

Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record

Medvedev and Melott (2007) have suggested that periodicity in fossil biodiversity may be induced by cosmic rays which vary as the Solar System oscillates normal to the galactic disk. We re-examine the evidence for a 62 million year (Myr) periodicity in biodiversity throughout the Phanerozoic history of animal life reported by Rohde & Mueller (2005), as well as related questions of periodicity in origination and extinction. We find that the signal is robust against variations in methods of analysis, and is based on fluctuations in the Paleozoic and a substantial part of the Mesozoic. Examination of origination and extinction is somewhat ambiguous, with results depending upon procedure. Origination and extinction intensity as defined by RM may be affected by an artifact at 27 Myr in the duration of stratigraphic intervals. Nevertheless, when a procedure free of this artifact is implemented, the 27 Myr periodicity appears in origination, suggesting that the artifact may ultimately be based on a signal in the data. A 62 Myr feature appears in extinction, when this same procedure is used. We conclude that evidence for a periodicity at 62 Myr is robust, and evidence for periodicity at approximately 27 Myr is also present, albeit more ambiguous.Comment: Minor modifications to reflect final published versio

Removing exogenous information using pedigree data

Management of certain populations requires the preservation of its pure genetic background. When, for different reasons, undesired alleles are introduced, the original genetic conformation must be recovered. The present study tested, through computer simulations, the power of recovery (the ability for removing the foreign information) from genealogical data. Simulated scenarios comprised different numbers of exogenous individuals taking partofthe founder population anddifferent numbers of unmanaged generations before the removal program started. Strategies were based on variables arising from classical pedigree analyses such as founders? contribution and partial coancestry. The ef?ciency of the different strategies was measured as the proportion of native genetic information remaining in the population. Consequences on the inbreeding and coancestry levels of the population were also evaluated. Minimisation of the exogenous founders? contributions was the most powerful method, removing the largest amount of genetic information in just one generation.However, as a side effect, it led to the highest values of inbreeding. Scenarios with a large amount of initial exogenous alleles (i.e. high percentage of non native founders), or many generations of mixing became very dif?cult to recover, pointing out the importance of being careful about introgression events in populatio

Momentum asymmetries as CP violating observables

Three body decays can exhibit CP violation that arises from interfering diagrams with different orderings of the final state particles. We construct several momentum asymmetry observables that are accessible in a hadron collider environment where some of the final state particles are not reconstructed and not all the kinematic information can be extracted. We discuss the complications that arise from the different possible production mechanisms of the decaying particle. Examples involving heavy neutralino decays in supersymmetric theories and heavy Majorana neutrino decays in Type-I seesaw models are examined.Comment: 20 pages, 9 figures. Clarifying comments and one reference added, matches published versio

Superfluid behaviour of a two-dimensional Bose gas

Two-dimensional (2D) systems play a special role in many-body physics. Because of thermal fluctuations, they cannot undergo a conventional phase transition associated to the breaking of a continuous symmetry. Nevertheless they may exhibit a phase transition to a state with quasi-long range order via the Berezinskii-Kosterlitz-Thouless (BKT) mechanism. A paradigm example is the 2D Bose fluid, such as a liquid helium film, which cannot Bose-condense at non-zero temperature although it becomes superfluid above a critical phase space density. Ultracold atomic gases constitute versatile systems in which the 2D quasi-long range coherence and the microscopic nature of the BKT transition were recently explored. However, a direct observation of superfluidity in terms of frictionless flow is still missing for these systems. Here we probe the superfluidity of a 2D trapped Bose gas with a moving obstacle formed by a micron-sized laser beam. We find a dramatic variation of the response of the fluid, depending on its degree of degeneracy at the obstacle location. In particular we do not observe any significant heating in the central, highly degenerate region if the velocity of the obstacle is below a critical value.Comment: 5 pages, 3 figure

A Fast Track towards the `Higgs' Spin and Parity

The LHC experiments ATLAS and CMS have discovered a new boson that resembles the long-sought Higgs boson: it cannot have spin one, and has couplings to other particles that increase with their masses, but the spin and parity remain to be determined. We show here that the `Higgs' + gauge boson invariant-mass distribution in `Higgs'-strahlung events at the Tevatron or the LHC would be very different under the J^P = 0+, 0- and 2+ hypotheses, and could provide a fast-track indicator of the `Higgs' spin and parity. Our analysis is based on simulations of the experimental event selections and cuts using PYTHIA and Delphes, and incorporates statistical samples of `toy' experiments.Comment: 18 pages, 9 pdf figure

Characterisation of GLUT4 trafficking in HeLa cells: Comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)- containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA–GLUT4–GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA–GLUT4–GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells