Isobornyl acrylate: an impurity in alkyl glucosides

Context: Alkyl glucosides and alkyl poly-glucosides are widely used as wetting agents, surfactants and emulsifiers in several industrial and cosmetic products. They are known as well-tolerated and are usually added to the primary surfactants in order to reduce the irritating potential of the main foaming agents.

Objective: Recently, some authors suggested that allergic contact dermatitis to alkyl glucosides might be more frequent than suspected. On the other hand, the chemical structures of glucosides do not show potentially allergenic chemical groups or strongly polarized structures. The aim of our study is to investigate alkyl glucosides carrying out a detailed chemical analysis on samples of raw materials to identify potentially allergenic impurities or by-products contained in commercial samples of alkyl glucosides.

Materials and methods: We chemically analyzed samples of cocoyl glucoside, decyl glucoside and lauryl glucoside by three different analytical methods, in order to identify any undesired or polluting substances.

Result: In each of the three samples, we detected the presence of isobornyl acrylate. Its approximate content in the tested samples is 500?ng/g of the product.

Discussion: Isobornyl acrylate is not used in the synthesis of alkyl glucosides, but as a plasticizer in many plastic materials. It can be easily released to materials flowing over these surfaces when they have high extraction power, as glucosides.

Conclusion: Isobornyl acrylate may play a role as hidden allergen, in the form of an impurity collected during the industrial process, explaining some cases of allergic reaction to alkyl glucosides.     

Once-daily tramadol in rheumatological pain

New once-daily formulations of tramadol have been recently marketed in various countries. This review focuses on the matrix systems used in sustained-release formulations to control drug delivery, the pharmacokinetics and pharmacodynamic profile and the available clinical trials on once-daily tramadol. Four controlled clinical studies with a limited number of patients have shown that once-daily tramadol is safe and effective for up to 12 weeks in rheumatological pain treatment, with a favourable side effects profile. Once-daily tramadol has established efficacy superior to that of placebo for pain management and functional improvement in patients with osteoarthritis. Two randomised clinical trials demonstrated similar rates of efficacy between immediate-release and once-daily sustained-release formulation, without significant differences in the use of escape medications and the number of nights woken. Once-daily tramadol offers the advantage of a reduced dosing regimen that improves patient compliance.     

Avian metapneumoviruses expressing Infectious Bronchitis virus genes are stable and induce protection

The study investigates the ability of subtype A Avian metapneumovirus (AMPV) to accept foreign genes and be used as a vector for delivery of Infectious bronchitis virus (IBV) QX genes to chickens. Initially the GFP gene was added to AMPV at all gene junctions in conjunction with the development of cassetted full length DNA AMPV copies. After recombinant virus had been recovered by reverse genetics, GFP positions supporting gene expression while maintaining virus viability in vitro, were determined. Subsequently, either S1 or nucleocapsid (N) genes of IBV were positioned between AMPV M and F genes, while later a bivalent recombinant was prepared by inserting S1 and N at AMPV MF and GL junctions respectively. Immunofluorescent antibody staining showed that all recombinants expressed the inserted IBV genes in vitro and furthermore, all recombinant viruses were found to be highly stable during serial passage. Eyedrop inoculation of chickens with some AMPV-IBV recombinants at one-day-old induced protection against virulent IBV QX challenge 3 weeks later, as assessed by greater motility of tracheal cilia from chickens receiving the recombinants. Nonetheless evidence of AMPV/IBV seroconversion, or major recombinant tracheal replication, were largely absent.     

Exploring Oxidovanadium(IV) Complexes as YopH Inhibitors: Mechanism of Action and Modeling Studies

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Multicomponent Synthesis and Biological Evaluation of a Piperazine-Based Dopamine Receptor Ligand Library

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Prognostic value of p53 expression in early-stage breast-carcinoma compared with tumor angiogenesis, epidermal growth-factor receptor, C-erbb-2, cathepsin-d, DNA-ploidy, parameters of cell-kinetics and conventional features

p53 expression detected by immunocytochemistry is emerging as a novel potentially useful prognostic indicator in breast carcinoma. However, additional research is warranted because a consensus has not yet been achieved on: i) methodology and quality control issues; ii) its association with other new biological prognostic indicators; iii) its prognostic value in multivariate analysis including conventional and new pathobiological features and; iv) its clinical usefulness either as a prognostic and predictive factor. This study was undertaken in a series of 165 early-stage breast cancer patients (median follow-up of 5 years) to compare the prognostic role of p53 expression with that of several other markers that have been found to be of value, using a multivariate statistical analysis. These factors are: tumour angiogenesis, epidermal growth factor receptor (EGFR), c-erbB-2 expression, cathepsin D, growth fraction by Ki-67 antibody, DNA ploidy and S-phase fraction. The main results observed were: i) 47 of 165 (28.5%) carcinomas had pAb 1801 staining and were considered as p53-positive; ii) p53 expression was weakly associated with S-phase fraction by flow cytometry (OR=1.86; p=0.085); iii) p53 expression was significantly associated with recurrence (p53 negative [-] versus weak positive [+] tumours: p=0.07 and odds ratio of 2.21; p53 negative [-] versus high positive [++] tumours: p=0.01 and odds ratio of 2.86) and death (p53-versus +: p=0.53 and odds ratio of 1.35; p53- versus ++: p=0.05 and odds ratio of 2.53); iv) the determination of p53 is able to identify a subset of high risk patients in c-erbB-2 negative tumours, this group being generally considered at good prognosis; v) In multivariate analysis on relapse-free survival including all the above markers only tumour angiogenesis, cathepsin D, EGFR and S-phase fraction and nodal status retained significance, and for overall survival only tumour angiogenesis was significant and independent. This new information on p53 expression could be useful to the clinician for a more rationale approach in defining prognosis of breast cancer patients. The prognostic value of p53 depends on which other markers are additionally analyzed and previous studies have not always assayed tumour angiogenesis, which is the most important factor in this series. p53 still need to be assessed as a potential predictor of response to chemo or radiotherapy, because of its role in monitoring DNA damage.     

Pharmacotherapy of iron overload in thalassaemic patients

The recommended treatment for thalassaemia major is regular blood transfusions, although these lead to the harmful accumulation of iron in the body. If untreated, iron overload is responsible for heart, liver and endocrine diseases. The only two iron chelating agents available for the treatment of iron overload are deferoxamine and deferiprone. The standard iron chelation therapy is based on the use of deferoxamine. Although this drug was introduced in the 1970s, it still remains the treatment of choice. Recently, another iron chelator, deferiprone, became available for clinical use in the European Community. Deferiprone is indicated as second-line treatment in patients with thalassaemia major, for whom deferoxamine therapy is contraindicated or in patients who present with serious toxicity to deferoxamine therapy. This paper examines this chelating agent and compares it with deferoxamine in order to ascertain the current and potential contribution of deferiprone to the treatment of thalassaemic patients.     

Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation

Hematopoietic progenitor/stem cells (HPCs/HSCs) purified from human adult peripheral blood (PB) were triggered into cycling, retrovirally transduced with HOXB7 and then functionally assayed in vitro. HPCs were assayed in multi- and unilineage differentiation cultures in either liquid phase or semisolid medium, primitive HPCs in the high proliferative potential colony-forming cell (HPP-CFC) evaluation system and putative HSCs in Dexter type long-term culture (LTC) as LTC initiating cells (LTC-ICs). Control experiments ensured that the exogenous HOXB7 gene was constantly expressed, while the endogenous one was barely or not transcribed. Enforced expression of the gene markedly modulated the proliferation/differentiation program of the entire HSC/HPC population. Enforced HOXB7 expression exerted a potent stimulatory effect on the proliferation of the primitive HPC and putative HSC subsets, assayed as HPP-CFCs and LTC-ICs respectively. While not modifying the total number of HPCs, exogenous HOXB7 induced an increase of the number of granulo-monocytic (GM) HPCs [colony-forming unit GM (CFU-GM) CFU-GM, CFU-G and CFU-M, as evaluated by clonogenic assays] and markedly amplified the progeny of both CFU-G and CFU-M, which showed a sustained proliferation through at least 1-2 months (as evaluated in liquid suspension culture). The prolonged proliferative stimulus induced by HOXB7 transfer into LTC, primitive and GM oriented HPC culture was characterized by persistent proliferation of a discrete population of blast cells and a large pool of differentiated myeloid precursors. Altogether, these results suggest the hypothesis that the proliferative stimulus exerted by exogenous HOXB7 in primitive and GM-oriented HPCs may represent a preleukemic immortalization step. Consistent with the functional role of HOXB7 in the initial ontogenetic phase, these studies indicate that ectopic HOXB7 expression in early HPCs and HSCs from adult PB stimulates their self renewal, sustained proliferation and myeloid differentiation.