Electrochemical Growth of Copper Hydroxy Double Salt Films and Their Conversion to Nanostructured p-Type CuO Photocathodes.

New electrochemical synthesis methods were developed to produce copper hydroxy double salt(Cu-HDS) films with four different intercalated anions (NO3-, SO42-, Cl-, and dodecyl sulfate (DS)) as pure crystalline films as deposited (Cu2NO3(OH)3, Cu4SO4(OH)6, Cu2Cl(OH)3, and Cu2DS(OH)3). These methods are based on p-benzoquinone reduction, which increases the local pH at the working electrode and triggers the precipitation of Cu2+ and appropriate anions as Cu-HDS films on the working electrode. The resulting Cu-HDS films could be converted to crystalline Cu(OH)2 and CuO films by immersing them in basic solutions. Because Cu-HDS films were composed of 2D crystals as a result of the atomic-level layered structure of HDS, the CuO films prepared from Cu-HDS films have unique low-dimensional nanostructures, creating high surface areas that cannot be obtained by direct deposition of CuO, which has a 3D atomic-level crystal structure. The resulting nanostructures allowed the CuO films to facilitate electron-hole separation and demonstrate great promise for photocurrent generation when investigated as a photocathode for a water-splitting photoelectrochemical cell. Electrochemical synthesis of Cu-HDS films and their facile conversion to CuO films will provide new routes to tune the morphologies and properties of the CuO electrodes that may not be possible by other synthesis means.

Progress in bismuth vanadate photoanodes for use in solar water oxidation.

Harvesting energy directly from sunlight as nature accomplishes through photosynthesis is a very attractive and desirable way to solve the energy challenge. Many efforts have been made to find appropriate materials and systems that can utilize solar energy to produce chemical fuels. One of the most viable options is the construction of a photoelectrochemical cell that can reduce water to H(2) or CO(2) to carbon-based molecules. Bismuth vanadate (BiVO(4)) has recently emerged as a promising material for use as a photoanode that oxidizes water to O(2) in these cells. Significant advancement in the understanding and construction of efficient BiVO(4)-based photoanode systems has been made within a short period of time owing to various newly developed ideas and approaches. In this review, the crystal and electronic structures that are closely related to the photoelectrochemical properties of BiVO(4) are described first, and the photoelectrochemical properties and limitations of BiVO(4) are examined. Subsequently, the latest efforts toward addressing these limitations in order to improve the performances of BiVO(4)-based photoanodes are discussed. These efforts include morphology control, formation of composite structures, composition tuning, and coupling oxygen evolution catalysts. The discussions and insights provided in this review reflect the most recent approaches and directions for general photoelectrode developments and they will be directly applicable for the understanding and improvement of other photoelectrode systems.

Statins inhibit NK cell cytotoxicity by membrane raft depletion rather than inhibition of isoprenylation.

To investigate the potential determinants of the pleiotropic effects of statins, we measured NK cell cytotoxicity in samples from normal subjects and patients, including patients receiving statin therapy. In a multivariate analysis, NK cell cytotoxicity was related to total plasma cholesterol concentration rather than statin use. In vitro, we investigated the role of lipid modification, specifically the effects on membrane rafts and raft-dependent signal transduction. We demonstrate that statins reduce NK cell cytotoxicity and that membrane cholesterol depletion by cyclodextrins has a similar effect. In contrast, isoprenyl transferase inhibitors had little or no effect on NK cell function. We hypothesise that the pleiotropic effects of statins reflect changes in membrane cholesterol and, specifically, the density of membrane rafts. Moreover, there is likely to be a relationship between membrane cholesterol, membrane rafts and cell function that may be involved in the pathogenesis of cardiovascular and metabolic diseases.

Fluvastatin inhibits raft dependent Fcgamma receptor signalling in human monocytes.

Statins inhibit HMG-CoA reductase and thus block cholesterol and isoprenoid biosynthesis. Since statins also have anti-inflammatory effects, we investigated the effect of fluvastatin on monocyte Fcgamma receptor function. Fluvastatin (0.5-20 microM) inhibited Fcgamma receptor signal transduction at the level of tyrosine kinase activation, in a time and dose dependent manner. Initiation of tyrosine phosphorylation is not thought to involve prenylated proteins; thus, we hypothesised that fluvastatin might disrupt cholesterol and sphingolipid membrane rafts to impair signalling. Consistent with this hypothesis, fluvastatin decreased (and mevalonate rescued) signalling molecules within membrane rafts in parallel with effects on tyrosine phosphorylation events. Raft integrity was unaffected by prenyl transferase inhibitors. In addition, Fcgamma receptor mediated immune complex trafficking, activation of MAP kinases (ERK and p38), and downstream inflammatory mediator release (MMP-1 and IL-6) were blocked by fluvastatin. Thus, HMG-CoA reductase inhibition alters immune receptor signalling by disrupting membrane rafts essential for the initiation of signal transduction. Inhibition of Fcgamma receptor function may limit development and progression of atherosclerosis by decreasing monocyte/macrophage inflammatory mediator release. Since many receptors utilise cholesterol rich rafts this mechanism may have broader significance given the pleiotropic effects of statins.

Simvastatin inhibits lymphocyte function in normal subjects and patients with cardiovascular disease.

HMG-CoA reductase inhibitors (statins) block the mevalonate pathway, preventing biosynthesis of cholesterol and isoprenoids. We investigated the effect of simvastatin on lymphocytes from normal human subjects and cardiovascular disease patients in order to provide a model for the in vivo actions of statins. Thirteen healthy volunteers were treated with 40 mg per day of simvastatin following which mean total cholesterol was reduced by 23% (S.D.+/- 11.7%) and mean LDL-cholesterol by 36% (S.D.+/- 16.3%). Lymphocyte lipid raft levels, represented by Lyn and Fyn, were also reduced by simvastatin. Treatment with simvastatin did not alter ex vivo T-lymphocyte proliferation. However, the in vitro addition of 1 microM simvastatin reduced T-lymphocyte proliferation by 39% (S.D.+/- 18.1%) and a combination of prenyl transferase inhibitors reduced proliferation by 19% (S.D.+/- 22.7%). We also assessed the cytotoxicity of natural killer (NK) cells-a T-lymphocyte subset. NK cell cytotoxicity ex vivo was reduced by 30% (S.D.+/- 33.6%) following oral simvastatin treatment and by 56% (S.D.+/- 24.68%) after the in vitro addition of 1 microM simvastatin. Significant ex vivo reductions in T-cell proliferation and NK cell cytotoxicity were observed in patients with cardiovascular disease on treatment with statins. NK cells have been implicated in the pathogenesis of atherosclerosis, so the effect of statin therapy on NK cell cytotoxicity may contribute to the benefits of statins in cardiovascular disease.

Differentiation of the human monocyte cell line, U937, with dibutyryl cyclicAMP induces the expression of the inhibitory Fc receptor, FcgammaRIIb.

FC receptor for IgG receptor (Fcgamma) mediated activation of macrophages is essential for the clearance of immune complexes and control of inflammation. However, activated macrophages play an integral role in tissue destruction associated with autoimmune and inflammatory disease processes. Understanding the mechanisms which balance activating and inhibitory signals generated by immune complexes are therefore of critical importance to human disease. Here, we demonstrate that differentiation of the human monocytic U937 cell line to a macrophage phenotype with dibutyryl cyclicAMP induces both mRNA and protein expression of the inhibitory IgG receptor, FcgammaRIIb1. We further demonstrate that, following receptor aggregation, FcgammaRII transiently recruits the 5'-inositol phosphatase, SHIP. These data define a role for FcgammaRIIb in the modulation of immune complex mediated macrophage activation in a human model system.

The use of fluvastatin in cardiovascular risk management.

BACKGROUND: Fluvastatin was the first synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) to be developed and is used in the management of dyslipidaemia in primary and secondary prevention of cardiovascular disease. OBJECTIVE: This article reviews the properties of fluvastatin and experience accrued through its use in clinical practice and clinical trials. METHODS: Relevant publications were identified through the PubMed database and product information held by the US Federal Drug Administration was also reviewed. RESULTS/CONCLUSIONS: In the authors' opinion, fluvastatin exhibits a favourable safety profile in comparison to other statins, with a low incidence of adverse effects and a reduced propensity for interactions with other drugs. However, fluvastatin is a less potent cholesterol-lowering agent than newer statins on the market and its future predominant use is likely to be in niche patient groups at risk of side effects or drug interactions with other agents.

Expression of Fc alpha/mu receptor by human mesangial cells: a candidate receptor for immune complex deposition in IgA nephropathy.

IgA nephropathy is characterized by the deposition of IgA immune complexes in the glomerular mesangium, but the mechanisms responsible for this are not well understood. Human mesangial cells (HMCs) can bind IgA but do not express known IgA receptors. We show here that primary HMCs express mRNA for a novel receptor, the Fc alpha/mu receptor (Fcalpha/muR), and that receptor expression is upregulated by IL-1. We also detected mRNA for a novel receptor variant in HMCs that may encode a soluble form of the receptor. Fcalpha/muR was expressed in a heterologous system which showed that the receptor was approximately 58 kDa in weight and was only minimally N-glycosylated. As predicted from the characteristics of the murine homologue, the expressed human Fcalpha/muR was able to bind IgA and IgM, but not IgG. These results suggest that Fcalpha/muR may be the receptor responsible for mesangial IgA deposition in IgA nephropathy.

Persistent dipstick haematuria following renal transplantation.

Despite widespread testing for dipstick haematuria following renal transplantation, there are no published series describing the prevalence and possible causes of this complication in an adult population. A cross-sectional study of 640 renal transplant recipients under review at our follow-up clinic was performed. Persistent haematuria was defined as a minimum of 1+ of blood on urinalysis stick testing detected at not fewer than 75% of clinic visits since its onset, or since the start of routine testing, present over a period of at least 4 weeks. The prevalence of persistent dipstick haematuria was 13.3%. Median serum creatinine was higher in patients with persistent haematuria but age, gender and length of time since transplantation were not significantly different. Potential explanations for persistent haematuria in 21 of 85 affected patients were chronic infection, ureteric stent without chronic infection, regular or intermittent self-catheterization, persistent menstrual bleeding, anticoagulant therapy, graft calculus, and allograft renal cell carcinoma. Recurrent or de novo glomerular disease was confirmed by graft biopsy in 10 of 85 patients. Among the 41 recipients whose original cause of renal failure was IgA nephropathy (IgAN), the prevalence of persistent haematuria was 31.7% compared with 12% in the remaining patients (relative risk 2.6, 95% CI: 1.6-4.3). Persistent haematuria in IgAN patients was not associated with gender, age or time since transplantation. After 29 months of follow-up, 20% of patients with haematuria had progressed to graft failure or death compared with 11.6% of the unaffected group (p = 0.029). However, despite the association with earlier graft failure, haematuria did not predict this endpoint independently of renal function.