Objective:This prospective, randomized, double-blind, three-arm study was performed to investigate the efficacy of a medicated plaster containing the combination of diclofenac epolamine (DHEP) 180 mg and heparin 5600 IU in the treatment of unilateral blunt soft tissue injuries involving the upper or lower limb, complicated by severe local haematoma.Research design and methods:Patients with mild-to-moderate injuries complicated by local haematoma (<= 140 cm(2)) were included and randomly treated once daily with plasters containing DHEP/heparin, DHEP only, or placebo. Plasters were applied for at least 12 hours daily for 10 consecutive days.Main outcome measures:The time to complete haematoma dissolution was the primary efficacy endpoint; secondary endpoints were spontaneous pain reduction, pain on movement, muscle swelling and use of rescue analgesia.Results:A total of 185 patients (90 males and 95 females, aged 18-80 years) were evaluated for efficacy. Baseline clinical and demographic characteristics were similar across the treatment groups. The time to complete haematoma dissolution was significantly shorter with the DHEP/heparin plaster compared with both the DHEP and placebo plasters (p < 0.05). Patients in the DHEP/heparin group had a 60% probability of achieving complete haematoma dissolution within the 10-day treatment period compared with patients receiving either DHEP or placebo plasters. Patient-rated reductions in pain on movement were significantly (p < 0.05) greater in the two active treatment groups compared with placebo. Overall, the DHEP/heparin, DHEP and placebo plasters were well-tolerated. While a reliance on patient self-reporting had the potential to limit the usefulness of some data obtained in this study, the investigators accounted for this accordingly.Conclusions:The plaster formulation combining DHEP and heparin relieves pain and induces faster dissolution of superficial haematomas, and may therefore contribute to a more rapid and complete recovery.

Aryl hydrocarbon receptor (AhR) ligands and heavy metals are environmental co-contaminants and their molecular interaction may disrupt the coordinated regulation of AhR-dependent phase I and II drug metabolizing enzymes. To determine the effect of heavy metals on the AhR-regulated genes: cytochrome P4501A1 (Cyp1a1), NAD(P)H: quinone oxidoreductase (QOR) and glutathione S-transferase Ya (GST Ya), murine hepatoma Hepa 1c1c7 cells were treated with increasing concentrations of As3+ (1–10 μM), Cd2+ (1–25 μM) and Cr6+ (1–25 μM) with or without the AhR ligands: 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.1 nM), 3-methylcholanthrene (0.25 μM), β-naphthoflavone (10 uM), or benzo[a]pyrene (1 μM). Our results show that AhR ligands alone and As3+ or Cd2+ alone increased the catalytic activities and mRNA levels of all AhR-regulated genes. When metals were co-administered with an AhR ligand, all three metals inhibited the induction of Cyp1a1 activity by the AhR ligands but potentiated its mRNA and protein expression. In addition, all metals enhanced QOR and GST Ya at the activity and mRNA levels but modulated their induction by AhR ligands in a concentration, metal, and AhR ligand-dependent manner. Generally, Cr6+ inhibited while As3+ and Cd2+ potentiated the induction of QOR and GST Ya activities and mRNA levels. The three metals enhanced the expression of heme oxygenase-1, which coincided with the changes in the phase I and phase II enzyme activities. These results show that the ability of metals to alter the capacity of AhR ligands to induce the bioactivating phase I and the detoxifying phase II enzymes will influence the carcinogenicity and mutagenicity of the AhR ligands.

Diclofenac epolamine (2-hydroxyethyl-pyrrolidine) (DHEP) is a diclofenac salt endowed with enhanced cutaneous permeation. To optimize its absorption after topical application, a lecithin-enriched DHEP 1.3% gel has been developed (DHEP lecithin gel) and investigated in patients with shoulder periarthritis and lateral epicondylitis in a placebo-controlled, multicenter double-blind clinical trial. One hundred fifty-eight patients were randomized to a 10-day treatment with DHEP lecithin gel or placebo (5 g t.i.d. applied on the painful area). The efficacy criteria were pain measured by visual analog scale (VAS) while performing a specific standardized movement, intake of rescue medication (paracetamol), and the disabilities of the arm, shoulder and hand (DASH) questionnaire. VAS scores indicated a consistently higher analgesic activity of DHEP lecithin gel. At day 3, pain was reduced by -20.1 +/- 20.2 and -9.9 +/- 12.7 mm in the DHEP lecithin gel- and placebo-treated patients, respectively (p < 0.001); at day 6 of treatment, DHEP lecithin gel induced a pain reduction of -33.2 26.1 mm, while the reduction achieved with placebo was only -21.2 +/- 18.8 mm (p < 0.001). The mean changes in DASH questionnaire indicated that DHEP lecithin gel was more effective than placebo in improving patient well-being and reducing difficulties in performing the activities most severely impaired by rheumatism, while no difference was observed between the two treatments in consumption of rescue medication. In conclusion, these results indicate that DHEP lecithin gel is a topically effective analgesic product in patients with shoulder periarthritis or lateral epicondylitis and provide further evidence on the use of topical nonsteroidal anti-inflammatory drugs as an optimal approach to the treatment of localized musculoskeletal disorders.