Adenosine treatment attenuates cytokine interleukin-6 responses to endotoxin challenge in healthy volunteers

Anti-inflammatory effects of adenosine were evaluated in two randomized, double-blind, placebo-controlled studies. In one study healthy male volunteers received no endotoxin (adenosine study, n = 10), in the other intravenous endotoxin (4 ng/kg, endotoxin study n = 11) was given. All subjects were treated with adenosine infusion (40 microg/kg/min) and placebo (saline) infusion in a crossover design. Heart rate, body temperature, blood pressure and plasma cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, IL-10, and soluble TNF receptors I and II), nitric oxide oxidation products, nitrite and nitrate, as well as superoxide anions were determined. There were no significant changes of any measured parameter after adenosine treatment alone. Endotoxin elicited clinical signs of an inflammatory reaction, prominent release of all cytokines and O2- synthesis by neutrophils (N-formyl-methionin-leucyl-phenylalanin-stimulated cells measured by cytochrome C reduction). The plasma IL-6 response to endotoxin was attenuated by adenosine, as IL-6 increased from 0.9 (0.8-1.6) to 1345 (743-1906) pg/mL (median; 25-75th percentiles) with adenosine infusion, and from 0.8 (0.5-1) to 1,959 (1,344-2,505) pg/mL with placebo (P = 0.0065). There was no significant influence of adenosine infusion on the other variables examined. In conclusion, systemic adenosine infusion counteracts the release of IL-6 in healthy volunteers, indicating an anti-inflammatory effect of adenosine which should be further explored.     

Work performance and pain intensity during exercise. A before-and-after study of a cognitive-behavioural treatment in primary care of young immigrant patients

PURPOSE: To explore the efficacy of an exercise programme (EP) in primary care on work performance and pain intensity in young immigrants having pain. SUBJECTS: Patients on long-term sick leave, aged 20-45 years, categorized by sex and 'high education' (>/=8 years) or 'little education' (0-7 years). METHODS: The 4-week EP was combined to weekly, patient-doctor, dialogue sessions about pain. Two doctors established the clinical status, explored attitudes to exercise and stationary pain behaviour. The EP included daily sessions of an all-round training (15 exercises on five devices in three rounds) led by a physiotherapist, who neglected dysfunctional behaviours. The target for the training was a good work performance (1.5 points), consisting of endurance during a session (0=one round, 1=two rounds, 2=three rounds) and work behaviour (0=bad, 1=acceptable, 2=good), as well as reduced pain intensity measured on a visual analogue scale. Non-parametric statistics were used to detect significant differences between the before-and-after values. RESULTS: Forty-four men and 73 women, median education 7 years, participated. Nearly all were immigrants. All had muscular pain; 72% were anxious about the pain and 14% were depressed. At the start, nearly all were negative about exercise but participated anyway and significantly improved their work performance (p<0.001) from very low starting values (in median 0.0). Only the highly educated men reached the target levels. The highly educated persons reported less pain, while some men and women with little education reported more pain. The doctors also noted a significant decline in stationary pain behaviour in all sub-groups. CONCLUSIONS: A good efficacy regarding work performance and pain intensity was seen only in the highly educated group.     

Surfactant dependent toxicity of lipid nanocapsules in HaCaT cells

Lipid nanocapsules (LNC) have been suggested for a variety of pharmaceutical applications. Among them approaches for drug delivery to the skin appear particularly interesting. The current standard composition has been modified to better understand their properties by selecting a variety of different surfactants. LNC have been prepared using different non-ionic surfactants (Solutol(?) HS15: Polyoxyl 15 Hydroxystearate; Cremophor(?) EL: Polyoxyl 35 Castor Oil; Simulsol(?) 4000: Polyoxyl 40 Hydrogenated Castor Oil; Vitamin E TPGS(?): alpha-tocopheryl poly(ethylene glycol) succinate; Polysorbate 20 and 80) and analysed for their size, stability, drug release and toxicity on keratinocytes in cell culture. The feasibility of LNC using different surfactant was surprisingly easy and led to a variety of stable formulations that were selected for further investigations. Surfactants led to a variability of the release kinetics (t50% release varied from Polysorbate 20: 2.5h to Simulsol(?) 4000: 5.0h), however different formulations from the same surfactant did not differ significantly. In vitro toxicity of LNC was surfactant type dependent and a correlation between LNC and the pure respective surfactant was found. This toxicity was found to be mainly independent from the surface active properties. The surfactant type in LNC is easily interchangeable from formulation point of view. LNC appear to be appropriate as carrier for cutaneous delivery however toxicity can vary distinctly depending on the surfactant used for the preparation.     

Differential Effect of Imatinib and Synergism of Combination Treatment with Chemotherapeutic Agents in Malignant Glioma Cells

Abstract: Imatinib mesylate (STI571, Gleevec^®) is a signal transduction inhibitor and novel anti‐cancer agent. It selectively inhibits aberrantly activated tyrosine kinases in malignant cells, for example, bcr‐abl in leukaemia, platelet‐derived growth factor receptor and stem cell factor receptor (c‐Kit) in solid cancers including malignant glioma. However, recently published clinical studies with imatinib monotherapy in patients with malignant glioma demonstrated only very modest anti‐tumour activity. The aim of this study was to investigate the biological activity of imatinib, its cellular mechanisms of action and its synergism with other chemotherapeutic agents in human malignant glioma cells in culture. Expression of PDGF/R and c‐Kit was analyzed by RT‐PCR. Proliferation was measured by MTT assays and drug synergy was assessed by the Chou–Talalay method. Cell cycle and apoptosis were analyzed by flow cytometry and migration by monolayer migration assays. Multi‐immunoblot was performed on imatinib‐treated and control malignant glioma cells. Results indicate that imatinib is more effective in inhibiting cell colony formation and migration rather than proliferation. Imatinib treatment caused cell cycle arrest of glioma cells in G0–G1 or G2/M, with significant elevation of a few cyclin‐dependent kinases. Furthermore, imatinib acted synergistically with chemotherapy agents, such as the DNA alkylating agent, temozolomide, and riboneucleotide reductase inhibitors, for example, hydroxyurea at varied effective dose levels. In conclusion, imatinib exerts varied biological effects on malignant glioma cells in culture. Synergistic interaction of imatinib with chemotherapy agents may be related to cell cycle control mechanisms and could be potentially important in a clinical setting.     

Comparing longitudinal patient-reported outcome measures between Swedish patients with recent-onset systemic lupus erythematosus and early rheumatoid arthritis

Clinical Rheumatology - The onset of rheumatic disease affects each patient differently and may impact quality of life with progression. We investigated the relationship between patient-reported...