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.     

Mycobacterium tuberculosis infection in cancer patients at a tertiary care cancer center in Japan

The characteristics of active tuberculosis in cancer patients in Japan and the effects of this infection on cancer treatment have not yet been clarified. The records of all consecutive patients with microbiologically documented Mycobacterium tuberculosis infection diagnosed between September 2002 and March 2008 at Shizuoka cancer center (a 557-bed tertiary care cancer center in Japan) were reviewed. There were 24 cancer patients with active tuberculosis during the study period. Of these, 23 had solid-organ tumors, and the most common site of the underlying malignancy was the lung. Most of the patients had pulmonary tuberculosis. Among 15 patients followed up for more than 2 months prior to the diagnosis of pulmonary tuberculosis, 12 had healed scars suggestive of old tuberculosis lesions, as shown by chest imaging obtained at the time of the initial evaluation. Discontinuation of cancer therapy or more than a month's delay in surgery occurred in 10 patients with pulmonary tuberculosis. Development of active tuberculosis can delay cancer treatment in Japanese centers. Cancer patients with scars suggestive of old tuberculosis disease lesions as shown by chest imaging should be screened for active tuberculosis and carefully followed up. In some cases, prophylactic treatment should be considered.     

IL-1β at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two birds with one stone?

Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1β in the pathogenesis of both the diseases, the efficacy of IL-1 blocking molecules in controlling these diseases, and will provide information suggesting that targeting IL-1β, in patients affected by both RA and T2D, may be a promising therapeutic choice.     

The Influence of Beta-Blocking Agents on Plasma Volume and Extracellular Volume in Ischaemic Heart Disease

Plasma volume and extracellular volume (sodium space) were found to be unchanged during treatment with propranolol (nine patients) and practolol (four patients) for well-compensated ischaemic heart disease. The volumes were determined before treatment and 2 days and 3 months after optimal dose for each patient was reached.     

New approaches to the treatment of nephropathy in diabetes

Introduction: In individuals with diabetes, the presence and severity of kidney disease adversely affects their well-being, significantly contributes to burden of morbidity and increases their risk of a premature death. The efficiency of current management strategies for the treatment of diabetic nephropathy, even in optimal combination, is partial, at best. There remains an unmet need for additional renoprotective interventions in patients with diabetes.

Areas covered: This review presents a comprehensive summary of some of the ‘new contenders’ for the treatment of diabetic nephropathy that have been tested or are being tested in randomised clinical trials in patients with diabetes with a predefined renal endpoint, but are not currently indicated for renoprotective therapy. Many of these drugs have been in clinical use for other indications, or initially developed for other purposes.

Expert opinion: Although substantial progress has been made towards understanding the pathogenesis of diabetic nephropathy, at present there are no new drugs that provide the solutions we want for our patients. Even when used in combination with standard medical care, current data indicate that renal complications are at best only modestly reduced, at the expense of additional pill burden and exposure to off-target effects. Given the ever-growing burden of diabetic kidney disease, there is a substantial opportunity for better and more targeted (‘smarter’) therapeutic interventions in this context.     

促血管生成因子在银屑病发病机制中的作用

微血管异常是银屑病组织病理学的显著特征,在银屑病发病机制中起着至关重要的作用.血管因子从作用机制上分为促血管生成因子和血管新生抑制因子,二者的平衡是维持血管稳定状态的关键.研究表明,银屑病皮损处角质形成细胞是血管生成因子的主要来源,血管生成因子有诱导血管增生的能力,而新生血管又为增生的角质形成细胞提供细胞和组织所需营养,并能促进炎症细胞迁移.探讨血管生成因子在银屑病中的作用将为临床治疗银屑病提供新思路.     

Tumour targeting by microtubule-depolymerising vascular disrupting agents

Low molecular weight vascular disrupting agents of the microtubule depolymerising family cause marked and selective disruption of the established tumour blood vessel network, resulting in tumour cell necrosis. The combretastatins are members of this family and these, together with several other related compounds, have undergone extensive preclinical testing and are now in clinical trials for cancer. Potentially, vascular disrupting agents can also interfere with angiogenesis and constitute a very promising group of novel cancer drugs. In vitro analysis of their signalling activities points to the endothelial cytoskeleton as being their major target and a key player in the events that culminate in vascular collapse. As more of these agents progress into the clinical setting, more research in this area is warranted in order to decipher exact mechanisms responsible for vascular disruption and to understand the reasons for drug selectivity for the tumour vasculature. This information is essential in order to identify new targets within the tumour vasculature and to improve present therapies.     

Atypical antipsychotics in the elderly: a review of therapeutic trends and clinical outcomes

Recent emerging data regarding the safety and tolerability of atypical antipsychotics in elderly patients with dementia have called into question common prescribing practices. Although the lifetime risk of developing significant psychopathology in dementia patients approaches nearly 100%, treatment options remain scant and controversial. Millions of people are suffering the consequences of these debilitating dementias. Yet the lack of regulatory approval or even recognition of the problem creates a dilemma for clinicians in practice who are trying to care for severely ill patients. There are data indicating that certain behavioral features can be treated successfully with atypical antipsychotics, offset by a high rate of adversity. This does not lead to the simple conclusion that they should never be used, since the alternatives are either fraught with the same shortcomings or actually lack evidence of benefit altogether. Further, it is not realistic to assume that nonpharmacological approaches, although preferred, will always carry the day. Since we do not have the evidence to define best practice for treating psychopathology, we are forced to make the most of the data we have and exercise best judgment about risk and benefit on a case-by-case basis.