Overview of organic memory devices.

The demand for more efficient and faster memory structures is greater today than ever before. The efficiency of memory structures is measured in terms of storage capacity and the speed of functioning. However, the production cost of such configurations is the natural constraint on how much can be achieved. Organic memory devices (OMDs) provide an ideal solution, in being inexpensive, and at the same time promising high performance. However, all OMDs reported so far suffer from multiple drawbacks that render their industrial implementation premature. This article introduces the different types of OMDs, discusses the progress in this field over the last 9 years and invokes conundrums that scholars of this field are currently faced with, such as questions about the charging mechanism and stability of devices, contradictions in the published work and some future directions.

Gold nanoparticle charge trapping and relation to organic polymer memory devices.

Nanoparticle-based polymer memory devices (PMDs) are a promising technology that could replace conventional silicon-based electronic memory, offering fast operating speeds, simple device structures and low costs. Here we report on the current state of nanoparticle PMDs and review some of the problems that are still present in the field. We also present new data regarding the charging of gold nanoparticles in metal-insulator-semiconductor capacitors, showing that charging is possible under the application of an electric field with a trapped charge density due to the nanoparticles of 3.3 x 10(12) cm(-2).

Effects of hormone therapy on blood pressure and the renin-angiotensin system in postmenopausal women.

Observational studies have documented an association between lower rates of cardiovascular disease and hormone therapy (HT). Meanwhile, randomized clinical trials have documented increased rates of myocardial infarction and stroke in women receiving hormone therapy. These seemingly discordant findings have stimulated new research to examine estrogen's effects on the cardiovascular system, including its effects on blood pressure, regulation of the renin-angiotensin system (RAS), and the clinical consequences of hypertension. In the last 6 years several studies have better defined the mechanisms by which HT affect the RAS, blood pressure, and the clinical effects of hypertension. Recent studies documented increases in angiotensinogen synthesis and the suppression of active renin with estrogen replacement. Genotype may be a factor in determining the degree of suppression of angiotensin converting enzyme levels that occurs with estrogen therapy. Estrogen supplementation in postmenopausal women increases systemic angiotensin II, a potent vasoconstrictor. This vasopressor effect is attenuated by an estrogen-induced reduction of angiotensin II type 1 receptor expression. Renal blood flow reduction, in the absence of blood pressure changes, have been reported after estrogen replacement, and an increased risk of total stroke has been demonstrated in hypertensive women on HT compared to normotensive women on this therapy. Estrogen replacement affects many components of the RAS, but its effect on this system has little effect on blood pressure. Further studies are needed to describe the effects of estrogen replacement on abnormal vasculature and how these effects relate to myocardial infarction and stroke.

Transient spatial attention modulates distinct components of the auditory ERP.

We recorded ERPs to pairs of externally presented tones, T1 and T2, in the absence of attentional cues to determine whether attention is momentarily sustained at the location of a behaviourally relevant sound, and what effect this focusing of attention might have on the neural response to target stimuli. ERPs to T2 were more negative when the preceding T1 was presented on the same side of fixation than when T1 was presented on the opposite side of fixation. This negative difference consisted of an early, parietal phase and a later, frontocentral phase. These results confirm and extend previously reported effects of transient spatial attention on auditory ERPs, and they demonstrate that transient spatial attention has a distinct and robust effect on the early stages of stimulus processing in the auditory system.

Effect of Variable Inspiratory Flow Rate on the Performance of the Budesonide Rhinocort Turbuhaler™.

OBJECTIVE: To investigate the effect of variable nasal inspiratory flow rates in vitro on total drug delivery and deposition patterns of budesonide delivered from the Rhinocort Turbuhaler™. METHODS: The total dose of budesonide delivered at flow rates of 15, 30 and 60 L/min and the particle size distribution of the delivered drug at flow rates of 28 and 60 L/min were determined at regular intervals throughout the life of six Rhinocort Turbuhalers™, each containing 200 × 100µ,g doses of budesonide. The delivered dose was determined by drawing individual doses of budesonide through separate G0120 Filtrete electrostatic filters. Acascade impactor was used to determine the particle size distribution of the delivered drug. RESULTS: The amount of budesonide delivered from each Turbuhaler™ device was variable throughout the life of the devices and was dependent on the inspiratory flow rate. Variability was greatest at the lower flow rates and decreased slightly with increasing inspiratory flow rate. Similarly, the particle size distribution of budesonide throughout the cascade impactor was variable and dependent on the flow rate. CONCLUSION: This study suggested that the efficiency of the Rhinocort Turbuhaler™ device in the management of allergic rhinitis may be influenced by the severity of nasal symptoms, particularly rhinorrhoea and nasal blockage, which determine the peak nasal inspiratory flow rates in symptomatic individuals.

Latest advances in the development of dry powder inhalers.

The current market for dry powder inhalers (DPIs) has over 20 devices in present use and at least another 30 under development. Clinicians recognize that DPIs are a suitable alternative to pressurized metered dose inhalers (pMDIs) for some patients but the relative performance of devices is often unclear. The problem is compounded by the need to reformulate pMDIs with new propellants, introducing further products to the market with associated variations in performance. This article reviews the DPIs currently available, the driving forces governing new designs, and the claimed advantages of DPIs in the development pipeline.

A critical comparison of the dose delivery characteristics of four alternative inhalation devices delivering salbutamol: pressurized metered dose inhaler, Diskus inhaler, Diskhaler inhaler, and Turbuhaler inhaler.

Salbutamol is a short-acting beta 2 agonist which is effective as a rescue therapy in the treatment of asthma. This study uses in vitro test methods to compare the capability of four alternative devices to deliver an accurate and precise dose of salbutamol. It is demonstrated that the conventional metered dose inhaler (MDI) achieves excellent accuracy and precision in dose delivery. Additionally, it is the most efficient inhaler in terms of generating in-vitro a fine particle fraction from the dose. A spacer device has been shown to further enhance the dosing characteristics. When tested over a wide range of inspiratory air flow rates, the Diskus (GlaxoWellcome, Hertfordshire, UK) has comparable accuracy and precision to the MDI tested at 60 L/min, and it offers an advantage over two alternative dry powder inhalers (DPIs), delivering a more consistent dose across the range of flow rates tested and being more efficient at generating a fine particle fraction than either Turbuhaler (Astra, Lund, Sweden) or Diskhaler (GlaxoWellcome) at both 28 and 60 L/min inspiratory flow rates. Diskus, Diskhaler, Ventolin, Volumatic, and Rotadisk are trademarks of the GlaxoWellcome Group of companies. The Accuhaler is the alternative to the Diskus in those countries where the Diskus trademark is not available. Inspiryl and Turbuhaler are trademarks of the Astra Group of companies.

Review of dry powder inhalers.

The search for alternatives to metered-dose inhalers has accelerated recently in a bid to find effective products that do not use chlorofluorocarbon (CFC) propellants. This paper reviews the factors to be considered in developing dry powder inhalers (DPIs), particularly the formulation, metering design and flow path in the device. The advantages and disadvantages of current DPIs are discussed and possible future approaches outlined.

Analysis of polycyclic aromatic hydrocarbons in metered dose inhaler drug formulations by isotope dilution gas chromatography/mass spectrometry.

Organic compounds extracted into metered dose inhalers (MDIs) from the rubber components of the metering valve are of increasing interest in the development of these formulations. Polycyclic aromatic hydrocarbons (PAHs) are a class of extractable organic compounds whose source is the carbon black commonly used as a reinforcing agent in rubber. The analytical method for PAHs described in this report employs "cold filtration" to remove the suspended drug substance and excipients, and gas chromatography/mass spectrometry (GC/MS) for separation and detection of individual PAHs. After filtration, stable isotope labelled analogues of target PAHs are spiked into the drug product to act as internal standards, correcting for recovery (termed "isotope dilution GC/MS"). Validation of the method was accomplished with respect to linearity, precision, limit of detection/quantitation, selectivity and ruggedness. Application to a variety of MDI drug product formulations revealed that certain PAHs are present at the ng/inhaler level.

Treatment of childhood prednisone-resistant nephrotic syndrome and focal segmental glomerulosclerosis with intravenous methylprednisolone and oral alkylating agents.

Patients with prednisone-resistant nephrotic syndrome and biopsy-proven focal segmental glomerulosclerosis were treated with intravenous methylprednisone. After the first 2 weeks of therapy, the average urine protein excretion decreased from 247 to 96 mg/m2/h (p less than 0.04). Two of the 7 patients have had long-term, nearly complete remissions. The other patients relapsed. One relapsing patient was retreated with methylprednisolone and is now in remission. Four relapsing patients were treated with alkylating agents, in combination with methylprednisolone. All of these patients entered complete or partial remissions. Methylprednisolone causes a significant decrease in the proteinuria of children with focal segmental glomerulosclerosis. In addition, although the follow-up period is relatively short, it would appear that methylprednisolone, often in conjunction with an alkylating agent, has significantly improved the clinical status of these patients.

Effects of ureteral obstruction on the toxicity of cephalosporins in the rabbit kidney.

The nephrotoxicity of the cephalosporin antibiotics is closely related to their secretory transport into the proximal tubular cell at the antiluminal (blood) site. The present report describes the effects of transient ureteral obstruction, which increases intracellular concentrations of secreted organic anions, on the cortical uptake and the proximal tubular toxicity of several cephalosporins given in mildly toxic doses. Unilateral obstruction for 1-2 hr increased the cytotoxicity of cephaloglycin and cefaclor, both of which are rapidly secreted across the tubular cell, but not of cephaloridine, which undergoes minimal secretion. Bilateral obstruction significantly increased the toxicity of cefaclor, which is rapidly secreted, but not of cefazolin, which is slowly secreted. Finally, there was a further augmentation of the effects of obstruction on the toxicity of cefaclor by a minimally toxic pretreatment regimen of neomycin. Studies of cortical antibiotic concentrations support the conclusion that the effects on toxicity are largely the result of the increased intracellular accumulation that results from obstruction.

The formation and nature of the mixed valence copper-D-penicillamine-chloride cluster in aqueous solution and its relevance to the treatment of Wilson's disease.

Complex formation between D-penicillamine (Pen) and copper(II) ions has been studied under simulated physiological conditions in both the presence and absence of the blood plasma constituents albumin, alanine, histidine, and zinc(II). Chromatographic and uv/vis and electron spin resonance (esr) spectroscopic methods were used. The major species formed, at neutral pH and 0.15 mol dm-3 NaCl, is the violet species which is shown to have the same stoichiometry as the recently reported solid-state complex, i.e., [Cu8I Cu6II (Pen)12 Cl] 5-. The rate of formation of this species (MVC) is shown to be dependent on the Cu concentration, Cu:Pen ratio, relative Cl- ion concentration, pH, and temperature. Formation is inhibited by the presence of O2 and biological chelates. At the concentration levels found in blood plasma it is unlikely that the MVC ion has any significance in the therapeutic action of penicillamine in the treatment of Wilson's disease. Reexamination of the aqueous Cu-albumin-pen system reinforces earlier findings that pen is unable to mobilize Cu that is bound to albumin. Significant binding of pen to the protein is observed is not related to any protein-bound copper ions. Evidence that ternary complexes of the type amino acid-Cu-Pen can form in blood plasma is presented. These are unlikely, however, to be physiologically significant and the copper depletion induced by Pen in Wilson's disease cases must be elsewhere than in the blood plasma compartment.

Analysis of isomeric impurities in a synthesis of the novel anti-inflammatory drug, benoxaprofen.

Gas-liquid chromatographic procedures are described for the determination of isomeric impurities in rho-chlorobenzoyl chloride and the intermediates, 2-(rho-nitrophenyl)-proprionitrile and 2-phenylpropionitrile, in a ten-stage synthesis of benoxaprofen, 2-(rho-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid.

Analysis of 1-(2-phenyladamant-1-yl)-2-methylaminopropane as its chlorodifluoroacetyl derivative.

The diastereoisomeric content of 1-(2-phenyladamant-1-yl)-2-methylaminopropane can be determined by gas chromatography following treatment with chlorodifluoroacetic anhydride. Racemisation occurs in the synthesis of 2-phenyladamantane from the corresponding 2-chloroadamantane in the Friedel-Crafts reaction with aluminium chloride, but fractionation of the diastereoisomers can occur in the purification steps. A method for determining 2-phenyladamantane in plasma and urine extracts at the nanogram level using an electron-capture detector is described and compared with a previously described radio-assay procedure.