p-ERK1/2 is a predictive factor of response to erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes

Serum erythropoietin level less than 100U/L and a transfusion requirement of less than 2 units per month are the best predictive factors for response to treatment by erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes. To investigate the factors influencing the response to erythropoiesis-stimulating agents, we enrolled 127 low/int-1 myelodysplastic syndrome patients at diagnosis in a biological study of erythropoiesis. The 54 non-responders had a significantly lower number of burst-forming unit-erythroid and colony-forming unit-erythroid than responders. Erythropoietin-dependent proliferation and survival, and phospho (p)-ERK1/2 expression in steady state and after erythropoietin stimulation were defective in cultured erythroblasts. By flow cytometry, p-ERK1/2 was significantly lower in bone marrow CD45⁻/CD71⁺/GPA⁻cells from non-responders compared to responders or controls. Receiver Operator Characteristic curve analysis showed that this flow cytometry test was a sensitive biomarker for predicting the response to erythropoiesis-stimulating agents.     

The Acoustic Scatter from Single biSphere Microbubbles

Single microbubble acoustic acquisitions provide information on the behaviour of microbubble populations by enabling the generation of large amounts of data. Acoustic signals from single polylactide-shelled and albumin coated biSphere™ microbubbles have been acquired. The responses observed from a range of incident frequencies and acoustic pressures varied in duration. Partial echoes shorter than the incident pulse duration have been observed for low frequency pulses of sufficient amplitude, suggesting release of gas from bubbles. The results presented suggest that the mechanism of scatter from hard shelled agents may be shell disruption and gas release, or partly from gas leaking from defected shell sites, which has previously not been observed optically. These results can provide the basis for improved imaging through optimization of incident pulse parameters, with potential benefits to both diagnostic and therapeutic techniques. (E-mail: d.h.thomas@ed.ac.uk)     

Is chronic ulcerative stomatitis a variant of lichen planus,or a distinct disease?

Chronic ulcerative stomatitis is an immune‐mediated mucocutaneous disorder characterized clinically by erosions or ulcers. Most cases are limited to the mouth. The histopathological features are non‐specific or mimic those of oral lichen planus, and studies by immunofluorescent microscopy are essential for definitive diagnosis. The defining immunopathogenic mechanism is the binding of IgG to the nuclear protein deltaNp63alpha of keratinocytes in the basal and parabasal cell layers of the oral stratified epithelium. DeltaNp63alpha functions as a regulator of epithelial stem cell activity and as an antiapoptotic agent and regulates the expression of cell‐to‐cell and cell‐to‐basement membrane adhesion molecules. The autoimmune IgG‐deltaNp63alpha interaction is thought to result in damage to the structural attachment of keratinocytes to one another and to the epithelial basement membrane zone and in dysregulation of the cell cycle and apoptosis of basal keratinocytes with the development of erosions or ulcers. The aims of treatment are to suppress the pathogenic immunoinflammatory responses, to prevent local infection and to promote healing. The purpose of this article is to provide a succinct review of the diagnostic, clinical and etiopathogenic features of, and treatment guidelines for chronic ulcerative stomatitis, and to argue that this disease should be regarded as a variant of oral lichen planus, rather than as a distinct entity.     

Comparative cytotoxicity of five current dentin bonding agents: Role of cell cycle deregulation

To compare the cytotoxicity of three nano-dentin bonding agents (nano-DBAs) and two non-nano-DBAs using Chinese hamster ovary (CHO-K1) cells. We found that nano fillers were not the major contributing factor in DBA cytotoxicity, as analyzed by colony forming assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Exposure of CHO-K1 cells to all three tested total-etching DBAs led to G₀/G₁ cell cycle arrest, whereas exposure to higher concentrations of two tested nano-DBAs induced G₂/M arrest. All five DBAs further induced apoptosis at the highest concentration, as analyzed by propidium iodide staining flow cytometry. The toxicity of all DBAs (1:4000 v/v or higher) is related to increased reactive oxygen species (ROS) production, as analyzed by single cell DCF fluorescence flow cytometry. These results indicate that clinical application of DBAs may be potentially toxic to dental pulp tissues. Cytotoxicity of DBAs is associated with ROS production, cell cycle deregulation and apoptosis. Presence of methacrylate monomers such as PENTA and UDMA is possibly the major cytotoxic factor for DBAs. Further studies on other toxicological endpoints of nano-DBAs are necessary to highlight their safe use.     

Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127

Magnetic nanoparticles are promising molecular imaging agents due to their relatively high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co‐polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell‐culture model were quantified using concurrent assaying: a lactate dehydrogenase assay to determine cytotoxicity and a 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium, inner salt assay to determine viability for a 24 h incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents needs to be carefully constructed to avoid interference and erroneous results. Copyright © 2010 John Wiley & Sons, Ltd.     

An assessment of S-carboxymethylcysteine in the treatment of chronic bronchitis

Summary

A single-blind study is reported of S-carboxymethylcysteine, administered as a 5% w/v syrup at a dosage of 3×5 ml. three times daily, compared with placebo therapy in the treatment of 30 patients with chronic bronchitis.

The great majority of patients reported greater ease of expectoration, decrease in severity and frequency of coughing, and an increase in the volumes of sputum expectorated, A statistically significant increase in PEFR, accompanied by an improvement in the severity of dyspnoea and functional grade was recorded; these indices deteriorated following the withdrawal of S-carboxymethylcysteine.

Overall clinical assessment at the end of a period of 8 weeks (bweeks baseline therapy on placebo followed by 6-weeks treatment with S-carboxymethylcysteine syrup) indicated that 23 patients had improved and none had deteriorated. Deterioration in all parameters occurred after withdrawal of the drug.     

Section 3 Algodystrophies in the upper and lower limbs treated with ibuprofen

Summary

Fifty patients suffering from painful conditions in the upper and lower limbs arising from a variety of different causes were treated with 1000?mg. to 1200?mg. ibuprofen daily for periods up to 6 months. Treatment was found to be effective in terms of pain relief and the drug was well tolerated, only 2 patients developing side-effects.