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Tumor tropism metastasis is a multi-step process that involves interactions between tumor cells and the microenvironment. Due to the limitations of experimental techniques, current studies are not able to gain insight into the dynamic process of such tropism migration. To overcome this issue, we developed a paper-supported co-culture system for dynamic investigations of the lung-tropic migration of breast cancer cells. This co-culture system contains a tumor layer, a recruitment layer, and several invasion layers between these two parts. The tumor and recruitment layers are impregnated with breast cancer cells and lung cells, respectively. Stacking these layers forms a co-culture device that comprises interactions between breast cancer and lung, destacking such a device represents cancer cells at different stages of the migration process. Thus, the paper-supported co-culture system offers the possibility of investigating migration from temporal and spatial aspects. Invasion assays using the co-culture system showed that breast cancer cells induced lung fibroblasts to convert to cancer-associated fibroblasts (CAFs), and the CAFs, in turn, recruited breast cancer cells. During migration, the local invasion of the cancer cells is a collective behavior, while the long-distance migration comes from individual cell behaviors. Breast cancer cells experienced repetitive processes of migration and propagation, accompanied by epithelial–mesenchymal and mesenchymal–epithelial transitions, and changes in stemness and drug resistance. Based on these results, the lung-tropic migration of breast cancer is interpreted as a process of bilateral interaction with the local and host-organ microenvironment. The developed paper-supported co-culture system offers the possibility of dynamically investigating tropism migration under the pre-metastatic niche, thus providing an advantageous tool for studying tumor metastasis.

WOS: 000313019700012, PubMed ID: 22271281, The purposes of this study were to investigate the biocompatibility of two different paper patches (carbon and cigarette papers) and compare the adhesion and proliferation features of L929 fibroblast cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT Test) test and scanning electron microscopy (SEM). In this study, time-dependent cytotoxic effects of cigarette and carbon papers used in repairing small traumatic TM perforations were investigated in vitro by using MTT test. And also adhesion and spreading of cells over disk surface were observed by SEM. Cytotoxicity test carried out by MTT analysis on leakage products collected from two types of paper patches at the end of 24 and 48 h revealed no cytotoxicity (P > 0.05). In SEM studies, it was observed that cells started to proliferate over disk surface as a result of 48-h incubation, and SEM revealed that the cell proliferation over cigarette paper was more compared to the one over carbon paper. We believe that this is the first study where biocompatibility and adhesion features of carbon and cigarette paper have been studied by using L929 fibroblast cell culture. As a result, biocompatibility of cigarette paper and also whether cigarette paper was superior to carbon paper in cell attachment and biocompatibility were studied. It was found, by MTT test and SEM test, that cigarette paper had a higher biocompatibility and cell attachment, and thus cigarette paper should be the patch to be preferred in cases where TM perforations are repaired by paper-patch method.

A novel and simple method to detect isothiazolinone-type biocides (2-methyl-3-isothiazolinone (MI), 5-chloro-2-methyl-3-isothiazolinone (CMI), 1,2-benzisothiazolinone (BIT) and 2-octyl-3-isothiazolinone (OIT)) in paper used for food packaging by ultrasonic extraction coupled with UPLC-MS/MS was developed. Parameters affecting process efficiency such as extraction solvents, UPLC mobile phase, gradient elution procedure and MS/MS conditions were studied to optimise the operating conditions. Using the optimised gradient elution procedure, the retention time was less than 6 min. The limits of detection (LODs) were found to be between 0.001 and 0.010 mg kg⁻¹, which was validated using actual concentrations. After diluting the standard solution with a blank matrix, the linear calibration curve ranges were 0.002-1.000 mg kg⁻¹ for BIT and OIT, 0.005-1.000 mg kg⁻¹ for MI, and 0.020-1.000 mg kg⁻¹ for CMI, with correlation coefficients higher than 0.9985 (n = 6). A good level of precision with a mean recovery greater than 81.3% and a relative standard deviation (RSD) less than 6.2% were also obtained. A methodology has been proposed for the analysis of isothiazolinones in paper.

Non-steroidal anti-inflammatory drugs (NSAIDs) account for more reports of drug related toxicity than any other class of drugs. Their most widely recognised adverse effects are on the gastrointestinal tract. They cause acute erosions and chronic ulcers that result in hospitalisation and death because of ulcer bleeding and perforation. Between them, aspirin and non-aspirin NSAIDs may account for more than half of all episodes of ulcer bleeding and perforation.

Background Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), a common preservative in some brands of moist toilet paper (baby wipes and moist towelettes), has been reported to be a cause of allergic contact dermatitis. However, few cases have been reported in the United States. Observations We report the cases of 4 adult patients with severe perianal and perineal allergic contact dermatitis seen at our institution during a 6-month period. With patch testing, we identified allergy to MCI/MI, and we determined that all 4 patients were using moist toilet paper. The dermatitis resolved after use of the moist toilet paper was discontinued. Conclusion This study highlights that the MCI/MI in moist toilet paper can be a cause of perianal and perineal allergic contact dermatitis.

Two cases of contact allergy to methylisothiazolinones from slimicides used in pulp and paper mills are described. The first patient worked as a batcher in a paper mill, and he was in charge of pumping slimicides containing methylisothiazolinones. During pumping, the liquid often overflowed, and his clothes were wet daily with slimicides. After 3 months of work, he began to suffer from dermatitis, which improved when he was away from work. A clinical investigation confirmed the dermatitis diagnosis and a positive skin patch test to Kathon® CG was found. The second patient worked as an agent for a firm marketing slimicides containing methylisothiazolinones. One of his tasks was to pump slimicides into the mills, and during such operations his clothes often got wet from slimicides. After some years of work, he began to suffer from erythema and dermatitis after contact with the slimicides. A skin patch test showed a strongly positive reaction to Katon® CG. These case reports draw the attention to the fact that employees in the pulp and paper industry handling slimicides are exposed to extraordinarily high concentrations of methylisothiazolinones and run a substantial risk of being sensitized. The report also stresses the need for improved handling routines of those strong sensitizers in the paper mills. Am. J. Ind. Med. 31:551–553, 1997. © 1997 Wiley-Liss, Inc.

9 pages, 4 figures, 3 tables.-- PMID: 14982380 [PubMed]., The risk associated with wood extractives, biocides, and other additives in pulp and paper mill effluents was evaluated by performing a characterization of process waters and effluents in terms of toxicity and chemical analysis. The individual toxicity of 10 resin acids, two unsaturated fatty acids, and three biocides was estimated by measuring the bioluminescence inhibition with a ToxAlert®100 system. Median effective concentration values (EC50) of 4.3 to 17.9, 1.2 to 1.5, and 0.022 to 0.50 mg/L were obtained, respectively. Mixtures of these three families of compounds showed antagonistic effects. Chemical analysis of process waters was performed by liquid chromatography–and gas chromatography–mass spectrometry. Biocides such as 2-(thiocyanomethylthio)-benzotiazole (TCMTB) (EC50 = 0.022 mg/L) and 2,2-dibromo-3-nitrilpropionamide (DBNPA) (EC50 = 0.50 mg/L) were the most toxic compounds tested and were detected at concentrations of 16 and 59 μg/L, respectively, in a closed-circuit recycling paper mill. Process waters from kraft pulp mills, printing paper mills, and packing board paper mills showed the highest concentration of resin acids (up to 400 μg/L) and accounted for inhibition percentages up to 100%. Detergent degradation products such as nonylphenol (NP) and octylphenol (OP) and the plasticizer bisphenol A (BPA) were also detected in the waters at levels of 0.6 to 10.6, 0.3 to 1.4, and 0.7 to 187 μg/L, respectively. However, once these waters were biologically treated, the concentration of detected organic compounds diminished and the toxicity decreased in most cases to values of inhibition lower than 20%., The European Union Energy, Environmental and Sustainable Development Program (CLOSEDCYCLE), Contract Number (EVK1-2000-00749), and the Ministerio de Ciencia y Tecnologia (PPQ2000-3007-CE) have supported this work.

OBJECTIVES: To examine the validity of [(123)I]beta-CIT SPECT for monitoring the progression of dopaminergic degeneration in Parkinson's disease; to investigate the influence of short term treatment with D(2)receptor agonists on striatal [(123)I]beta-CIT binding; and to determine the sample size and frequency of SPECT imaging required to demonstrate a significant effect of a putative neuroprotective agent. METHODS: A group of 50 early stage Parkinson's disease patients was examined. Two SPECT imaging series were obtained, 12 months apart. The mean annual change in the ratio of specific to non-specific [(123)I]beta-CIT binding to the striatum, putamen, and caudate nucleus was used as the outcome measure. RESULTS: A decrease in [(123)I]beta-CIT binding ratios between the two images was found in all regions of interest. The average decrease in [(123)I]beta-CIT binding ratios was about 8% in the whole striatum, 8% in the putaminal region, and 4% in the caudate region. Comparison of scans done in nine patients under two different conditions-in the off state and while on drug treatment-showed no significant alterations in the expression of striatal dopamine transporters as measured using [(123)I]beta-CIT SPECT. Power analysis indicated that to detect a significant (p < 0.05) effect of a neuroprotective agent with 0.80 power and 30% of predicted protection within two years, 216 patients are required in each group when the effects are measured in the whole putamen. CONCLUSIONS: [(123)I]beta-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in Parkinson's disease and may provide an objective method of measuring the effectiveness of neuroprotective treatments. Short term treatment with a D(2)agonist does not have a significant influence on [(123)I]beta-CIT binding to dopamine transporters. If the latter finding is replicated in larger groups of patients, it supports the suitability of [(123)I]beta-CIT SPECT for examining the progression of neurodegeneration in patients being treated with D(2)receptor agonists

Objective: To compare the tremorlytic properties of pramipexole, a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson's disease. Methods: Eighty four patients with early or advanced Parkinson's disease and marked, drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind, randomised, placebo controlled, multicentre study and assigned to add on treatment (7 week dose titration interval, 4 week maintenance period) with either pramipexole (n=44) or placebo (n=40) as adjunct. The primary end point was the absolute change in tremor score, defined as the sum of tremor related items (16, 20, 21) of the unified Parkinson's disease rating scale (UPDRS) in "on" periods. Secondary end points included the percentage change in tremor score, the absolute and percentage changes in long term EMG tremor registration, and the change in tremor self rating scales. Safety and tolerability were assessed on the basis of adverse events, laboratory tests, ECG, and vital signs. Results: Pramipexole was significantly superior to placebo with a difference between treatment groups in the mean absolute change in tremor score of -4.4 (95% confidence interval (95% CI) -6.2 to -2.5) (p

A controlled open trial was performed in 40 individuals suffering from chronic perianal eczema. Various toilet paper preparations representing the conventional type made of pure cellulose, the recycled and the moist type were investigated using the patch test as were allergens possibly related to toilet paper. In addition, a chronic use test and a repeated rubbing test were performed with a conventional and a recycled toilet paper preparation.A total of 20 patients could be evaluated in full. A variety of reactions were seen in the patch test, most of which were of the allergic type. Allergens included many different chemical entities, e.g. preservatives used in moist toilet paper such as Kathon CG and Euxyl K 400. In a volunteer allergic to Euxyl K 400, allergy to the moist toilet paper regularly used by him was established. After discontinuation of its application, perianal dermatitis disappeared. In the repeated rubbing test at the forearm, 10 volunteers showed a reaction with the recycled paper preparation while no such reaction was seen upon the application of the conventional type of toilet paper. The validity of these findings was corroborated by corresponding results in the use test.There is clearly a potential for allergic reactions to components of moist toilet paper and reactions to recycled toilet paper presumably irritant by nature. These irritant reactions are probably caused by the rough texture of current paper types and do not reflect the presence of potentially toxic ingredients such as metal salts.