Affinity chromatography and quantitation of soluble fibrin from plasma

By affinity chromatography on agarose-fixed fibrinogen (FG-ag) soluble fibrin can be isolated from plasma samples or aqueous solutions and quantified by radio-activity measurement or by the staphylococcal clumping test. Using radiolabelled fibrinogen for the insolubilization it could be shown that the FG-ag column is stable and is not degraded even after many runs of plasma samples over a long period of time. By addition of radioactive fibrinogen and fibrin to plasma samples standardized and reproducible conditions are established for clinical use of the method. The amount of soluble fibrin in normal donors was found to be about 0.6 - 0.7 mg%. An elevated fibrin concentration up to 6 mg% above the normal value was detected in plasma of patients after myocardial infarction, even when the coagulation parameters were still normal.     

Results of NC-6300 (Nanoparticle Epirubicin) in an Expansion Cohort of Patients with Angiosarcoma

BackgroundNC-6300 is a novel epirubicin (EPI) drug conjugated polymeric micelle developed using cutting-edge micellar nanoparticle technology. The nanoparticle epirubicin conjugates EPI to a polymer via a pH-sensitive linker which enables the selective EPI release into tumor. Tumor activity was observed in a monotherapy phase Ib trial, where two of two patients with angiosarcoma achieved a partial response. To further explore the activity of NC-6300 in angiosarcoma, an expansion cohort was undertaken.MethodsTen patients with angiosarcoma were enrolled in the expansion cohort. Patients were dosed using the recommended dose of 150 mg/m² intravenously (IV) once every 3 weeks. The primary endpoint was progression-free survival.ResultsThe most common adverse events (AEs) of any grade, regardless of the causal relationship with NC-6300, were neutropenia (90%), fatigue, and thrombocytopenia (60% each) and nausea (50%). The most common grades 3 and 4 AEs were neutropenia (80%), thrombocytopenia (40%), and anemia and leukopenia (20% each). The median progression-free survival (mPFS) for all subjects was 5.4 months. The mPFS was 3.8 months in subjects with prior anthracycline treatment and 8.2 months in subjects without prior anthracycline treatment.ConclusionNC-6300 was well tolerated, showing promising activity in angiosarcoma patients without prior anthracycline treatment. NC-6300 warrants further investigation (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03168061","term_id":"NCT03168061"}}NCT03168061).     

Immediate and delayed photocontact dermatitis from isopropyl dibenzoylmethane

Immediate and delayed photocontact dermatitis from the UVA absorber isopropyl dibenzoylmethane is described in 1 patient. In a dose response study in a 2nd patient with delayed photocontact dermatitis, the minimal dose of UVA needed to elicit a positive photopatch to isopropyl dibenzoylmethane 2% was determined to be 2 J/cm2.     

Sensitivity to sunscreens

The patients sensitised to sunscreen agents who attended our Contact Dermatitis Clinic between February 1985 to March 1987 have been reviewed. 15 (5%) of 280 patients tested with sunscreens had positive reactions; 3 of them were allergic to more than one agent. The most frequent contact allergens were hydroxy methoxy methyl benzophenone (Mexenone) [6], followed by isopropyl dibenzoylmethane (Eusolex 8020/8021) [5], octyl dimethyl para-aminobenzoate (Escalol 507) [2], and one reaction each to butyl methoxy dibenzoylmethane (Parsol 1789), amyl dimethyl para-aminobenzoate (Escalol 506), and ethoxy ethyl-p-methoxy cinnamate (Givtan F). Positive photopatch tests were seen with isopropyl dibenzoylmethane, butyl methoxy dibenzoylmethane, para-aminobenzoate (PABA) and ethoxy ethyl-p-methoxy cinnamate, one reaction each.     

Evaluation of customers'' complaints about sunscreen cosmetics sold by the Swedish pharmaceutical company

Sweden's pharmacies hold more than a 1/3 of the country's market for sunscreen cosmetics (sunscreens). Customers complaining of skin problems associated with the use of sunscreens obtained from the pharmacies were offered dermatological investigation and tests with standard allergens and sunscreens. 27 of 58 complaining customers were fully investigated, and another 8 partly tested. 2 disease entities, a burning sensation and erythema for one or a few days, and dermatitis with scaling lasting for up to 3 weeks, were about equally common. Contact or photocontact allergy to 2-hydroxy-4-methoxybenzophenone caused severe contact dermatitis in 3 individuals.     

Effect of combined treatment with the epirubicin‐incorporating micelles (NC‐6300) and 1,2‐diaminocyclohexane platinum (II)‐incorporating micelles (NC‐4016) on a human gastric cancer model

Anticancer agent‐incorporating polymeric micelles accumulate effectively in tumors via the enhanced permeability and retention effect to exert potent antitumor effects. However, combined use of such micelles has not been elucidated. We compared the effect of combining the epirubicin‐incorporating micelle NC‐6300 and 1,2‐diaminocyclohexane platinum (II) (oxaliplatin parent complex)‐incorporating micelle NC‐4016 (NCs) with that of epirubicin and oxaliplatin (E/O) in 44As3Luc cells using the combination index method. The in vivo antitumor activities of NCs and E/O were evaluated in mice bearing 44As3Luc xenografts. Pharmacokinetic analysis was performed by high‐performance liquid chromatography and mass spectrometry. Cardiotoxicity of NC‐6300 and epirubicin was assessed by echocardiography. Neurotoxicity of NC‐4016 and oxaliplatin was evaluated by examining the paw withdrawal response to noxious mechanical stimuli. NCs showed a highly synergistic activity equivalent to E/O. In vivo, NCs exhibited higher antitumor activity in the subcutaneous tumor model and longer overall survival in the orthotopic tumor model than E/O (p < 0.001, p = 0.015, respectively). The intratumor concentrations of epirubicin and platinum were significantly higher following NCs than following E/O administration. Moreover, the micelles showed lower cardiotoxicity and neurotoxicity than the corresponding conventional drugs. The combined use of the micelles was associated with remarkable efficacy and favorable toxicities in the human gastric cancer model, and warrants the conduct of clinical trials.