Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure

Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients. Based on results of whole-cell patch-clamp studies, we report that angiotensin II (Ang II) potentiated the activity of RVLM neurons, a sympathetic nervous center, whereas Ang II receptor blocker (ARB) reduced RVLM activities. Our optical imaging demonstrated that a longitudinal rostrocaudal column, including the RVLM and the caudal end of ventrolateral medulla, acts as a sympathetic center. By organizing and analyzing these data, we hope to develop therapies for reducing SNA in our patients. Recently, 2-year depressor effects were obtained by a single procedure of renal nerve ablation in patients with essential hypertension. The ablation injured not only the efferent renal sympathetic nerves but also the afferent renal nerves and led to reduced activities of the hypothalamus, RVLM neurons and efferent systemic sympathetic nerves. These clinical results stress the importance of the RVLM neurons in blood pressure regulation. We expect renal nerve ablation to be an effective treatment for congestive heart failure and chronic kidney disease, such as diabetic nephropathy

Endothelial dysfunction promotes the transition from compensatory renal hypertrophy to kidney injury after unilateral nephrectomy in mice.

Loss of functional nephrons associated with chronic kidney disease induces glomerular hyperfiltration and compensatory renal hypertrophy. We hypothesized that the endothelial nitric oxide synthase (eNOS) [soluble guanylate cyclase (sGC)] protein kinase G (PKG) pathway plays an important role in compensatory renal hypertrophy after unilateral nephrectomy. Analysis of mice subjected to unilateral nephrectomy showed increases in kidney weight-to-body weight and total protein-to-DNA ratios in wild-type but not eNOS knockout (eNOSKO) mice. Serum creatinine and blood urea nitrogen increased after nephrectomy in eNOSKO but not in wild-type mice. Furthermore, Bay 41-2272, an sGC stimulator, induced compensatory renal hypertrophy in eNOSKO mice and rescued renal function. The NO donor S-nitrosoglutathione (GSNO) and Bay 41-2272 stimulated PKG activity and induced phosphorylation of Akt protein in human proximal tubular cells. GSNO also induced phosphorylation of eukaryotic initiation factor 4E-binding protein and ribosomal protein S6. Our results highlight the importance of the eNOS-NO-PKG pathway in compensatory renal hypertrophy and suggest that reduced eNOS-NO bioavailability due to endothelial dysfunction is the underlying mechanism of failure of compensatory hypertrophy and acceleration of progressive renal dysfunction

Manufacturing of superconducting cable for the LHC-Key technology and statistical analysis

Manufacturing of superconducting cable for the LHC main dipole magnet is in progress at The Furukawa Electric Co., Ltd. (here after referred to as "FEC"). Fabrication technology of Rutherford type cable for accelerator magnets has made a remarkable advance through development of the LHC Cable2 Key technology includes many different things such as multi-filament billet design, assembly, control of copper to superconductor ratio, optimization of thermo-mechanical heat treatment, drawing process, Sn-Ag coating and cabling. The well- balanced Cable2 with high quality was developed, and all of the electrical and mechanical performances met the specification requirements. (7 refs)

Development of high-strength and high-RRR aluminum-stabilized superconductor for the ATLAS thin solenoid

The ATLAS central solenoid magnet is being constructed to provide a magnetic field of 2 Tesla in the central tracking part of the ATLAS detector at the LHC. Since the solenoid coil is placed in front of the liquid-argon electromagnetic calorimeter, the solenoid coil must be as thin (and transparent) as possible. The high-strength and high- RRR aluminum-stabilized superconductor is a key technology for the solenoid to be thinnest while keeping its stability. This has been developed with an alloy of 0.1 wt% nickel addition to 5N pure aluminum and with the subsequent mechanical cold working of 21% in area reduction. A yield strength of 110 MPa at 4.2 K has been realized keeping a residual resistivity ratio (RRR) of 590, after a heat treatment corresponding to coil curing at 130 degrees C for 15 hrs. This paper describes the optimization of the fabrication process and characteristics of the developed conductor. (8 refs)