Introgression of Brown Norway \u3cem\u3eCYP4A\u3c/em\u3e Genes onto the Dahl Salt-Sensitive Background Restores Vascular Function in SS-5\u3csup\u3eBN\u3c/sup\u3e Consomic Rats

The present study tested the hypothesis that the Dahl SS (salt-sensitive) rat has vascular dysfunction due, in part, to the up-regulation of the CYP4A/20-HETE (cytochrome P450 ω-hydroxylase 4A)/20-hydroxyeicosatetraenoic acid) system. To assess the role of vascular 20-HETE, SS rats were compared with SS-5BN consomic rats, carrying CYP4A alleles on chromosome 5 from the normotensive BN (Brown Norway) introgressed on to the SS genetic background. Cerebral arteries from SS-5BN rats had less CYP4A protein than arteries from SS rats fed either NS (normal-salt, 0.4% NaCl) or HS (high-salt, 4.0% NaCl) diet. ACh (acetylcholine)-induced dilation of MCAs (middle cerebral arteries) from SS and SS-5BN rats was present in SS-5BN rats fed on either an NS or HS diet, but absent in SS rats. In SS rats fed on either diet, ACh-induced dilation was restored by acute treatment with the CYP4A inhibitor DDMS (N-methyl-sulfonyl-12,12-dibromododec-11-enamide) or the 20-HETE antagonist 20-HEDE [20-hydroxyeicosa-6(Z),15(Z)-dienoic acid]. The restored response to ACh in DDMS-treated SS rats was inhibited by L-NAME (NGnitro-L-arginine methyl ester) and unaffected by indomethacin or MS-PPOH [N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide]. Vascular relaxation responses to the NO donor C5FeN6Na2O were intact in both SS and SS-5BN rats and unaffected by the acute addition of DDMS, indicating that the vascular dysfunction of the SS rat is due to a reduced bioavailability of NO instead of failure of the VSMCs (vascular smooth muscle cells) to respond to the vasodilator. Superoxide levels in cerebral arteries of SS-5BN rats [evaluated semi-quantitatively by DHE (dihydroethidium) fluorescence] were lower than those in the arteries of SS rats. These findings indicate that SS rats have an up-regulation of the CYP4A/20-HETE pathway resulting in elevated ROS (reactive oxygen species) and reduced NO bioavailability causing vascular dysfunction

Effect of Chronically Suppressed Plasma Angiotensin II on Regulation of the CYP4A/20-HETE Pathway in the Dahl Salt-Sensitive Rat

In Dahl salt-sensitive (SS) rats, impaired vascular relaxation can be restored by: (1) minipump infusion of a low (sub-pressor) dose of angiotensin II (ANG II) to restore physiological levels of plasma ANG II, (2) inhibition of 20-HETE production, and (3) introgression of a normally functioning renin allele from the Brown Norway rat (SS-13BN consomic rat). Unlike SS rats, SS-13BN rats have normal levels of ANG II on a normal-salt diet and suppressed ANG II on a high-salt (HS) diet. This study tested whether chronically low ANG II levels in SS rats upregulate cytochrome P450-4A (CYP4A) increasing the production of the vasoconstrictor 20-HETE. Although salt-induced suppression of ANG II levels increased reactive oxygen species (ROS) in basilar arteries from SS-13BN rats in previous studies, this study showed no change in vascular 20-HETE levels in response to ANGII suppression. CYP4A inhibition significantly reduced vascular ROS levels and restored endothelium-dependent relaxation in response to acetylcholine in the middle cerebral artery (MCA) of SS rats and HS-fed SS-13BN rats. These data demonstrate that both the renin–angiotensin system and the CYP4A/20-HETE pathway play a direct role in the vascular dysfunction of the Dahl SS rat but are independent of each other, even though they may both contribute to vascular dysfunction through ROS production

ANALISIS KEUNTUNGAN USAHA TANI BUDIDAYA IKAN NILA GIFT DI DESA LEMBONG URAM KECAMATAN LEBONG UTARA KABUPATEN LEBONG

Fishery cultIvation is one sub-sector which is really potential to be developed because it is to be renewed. Lebong Regency also have the potential to develop the fisheries sector especially in embong uram village north lebong sub- distrct lebong regency. The Fishery cultivation that developed in this place is nila gift fish. the purpose of the research is to know how io count the profits of cultivation of nila gift fish in embong uram village north lebong sub-district lebong regency with number of respondents are 20 persons. The results obtained by the nila gift fish stable price is in range of Rp.2O.OO0 with the production of nila gift fish 40 kg while the lowest to the highest level of production is 300 kg. For total fixed cost (TFC) in the range of Rp. 460.000 for the lowest and the highest total fixed cost Rp. 5.800.000. while tn Total variable cost (TVC) that incurred by farmers in average Rp 200.000. The, crop cultivation of nila gift fish in embong uram village north lebong sub-district lebong regency most benefit by the range is the lowest profit obtained Rp. 140.000 and tte nighest Rp. 2.425.000 but there is also the farmer who suffer losses of that is as much as 1 people with losses of Rp. 3.600.000 and a farmer has break even point which revenue as same as total cost. Key Words: price, production, cost and profi

Innate immunity and monocyte-macrophage activation in atherosclerosis

Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review

Hydrodynamic interaction in quasi-two-dimensional suspensions

Confinement between two parallel surfaces is found, theoretically and experimentally, to drastically affect the hydrodynamic interaction between colloid particles, changing the sign of the coupling, its decay with distance and its concentration dependence. In particular, we show that three-body effects do not modify the coupling at large distances as would be expected from hydrodynamic screening.Comment: 8 pages, 2 figure

Role of Vascular Reactive Oxygen Species in Regulating Cytochrome P450-4A Enzyme Expression in Dahl Salt-Sensitive Rats

Objective The potential contribution of CYP4A enzymes to endothelial dysfunction in Dahl salt-sensitive rats was determined by comparison to SS-5BN consomic rats having chromosome 5 carrying CYP4A alleles from the BN rat introgressed into the SS genetic background. Methods The following experiments were performed in cerebral arteries from HS-fed SS and SS-5BN rats ± the SOD inhibitor DETC and/or the superoxide scavenger Tempol: (i) endothelial function was determined via video microscopy ± acute addition of the CYP4A inhibitor DDMS or Tempol; (ii) vascular oxidative stress was assessed with DHE fluorescence ± acute addition of DDMS, l-NAME, or PEG-SOD; and (iii) CYP4A protein levels were compared by western blotting. Results In DETC-treated SS-5BN and HS-fed SS rats, (i) DDMS or Tempol ameliorated vascular dysfunction, (ii) DDMS reduced vascular oxidative stress to control levels, (iii) chronic Tempol treatment reduced vascular CYP4A protein expression, and (iv) combined treatment with Tempol and l-NAME prevented the reduction in CYP4A protein expression in MCA of HS-fed SS rats. Conclusion The CYP4A pathway plays a role in vascular dysfunction in SS rats and there appears to be a direct role of reduced NO availability due to salt-induced oxidant stress in upregulating CYP4A enzyme expression

Untersuchungen über die Ausscheidung des durch infusion in das Blut gebrachten phosphorsauren Natrons durch die Nieren

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Correlated particle dynamics in concentrated quasi-two-dimensional suspensions

We investigate theoretically and experimentally how the hydrodynamically correlated lateral motion of particles in a suspension confined between two surfaces is affected by the suspension concentration. Despite the long range of the correlations (decaying as 1/r^2 with the inter-particle distance r), the concentration effect is present only at short inter-particle distances for which the static pair correlation is nonuniform. This is in sharp contrast with the effect of hydrodynamic screening present in unconfined suspensions, where increasing the concentration changes the prefactor of the large-distance correlation.Comment: 13 page

Remarks on Screening in a Gauge-Invariant Formalism

In this paper we display a direct and physically attractive derivation of the screening contribution to the interaction potential in the Chiral Schwinger model and generalized Maxwell-Chern-Simons gauge theory. It is shown that these results emerge naturally when a correct separation between gauge-invariant and gauge degrees of freedom is made. Explicit expressions for gauge-invariant fields are found.Comment: 13 pages, 1 figure, to appear in PR

The Electron-Phonon Interaction in the Presence of Strong Correlations

We investigate the effect of strong electron-electron repulsion on the electron-phonon interaction from a Fermi-liquid point of view: the strong interaction is responsible for vertex corrections, which are strongly dependent on the $v_Fq/\omega$ ratio. These corrections generically lead to a strong suppression of the effective coupling between quasiparticles mediated by a single phonon exchange in the $v_Fq/\omega \gg 1$ limit. However, such effect is not present when $v_Fq/\omega \ll 1$. Analyzing the Landau stability criterion, we show that a sizable electron-phonon interaction can push the system towards a phase-separation instability. A detailed analysis is then carried out using a slave-boson approach for the infinite-U three-band Hubbard model. In the presence of a coupling between the local hole density and a dispersionless optical phonon, we explicitly confirm the strong dependence of the hole-phonon coupling on the transferred momentum versus frequency ratio. We also find that the exchange of phonons leads to an unstable phase with negative compressibility already at small values of the bare hole-phonon coupling. Close to the unstable region, we detect Cooper instabilities both in s- and d-wave channels supporting a possible connection between phase separation and superconductivity in strongly correlated systems.Comment: LateX 3.14, 04.11.1994 Preprint no.101