We report the results of a 2-week double-blind, parallel clinical trial comparing two superpotent topical glucocorticosteroid ointments, diflorasone diacetate 0.05% and betamethasone dipropionate 0.05%, in psoriatic adults. Both corticosteroid ointments were fast acting and highly efficacious. 40 of the 44 patients who initially enrolled completed the trial. There were no statistically significant differences between the two glucocorticoids with respect to erythema, scaling, induration or the investigator’s global evaluation after either 1 or 2 weeks of therapy. The level of patient satisfaction with the efficacy and cosmetic acceptability of these two category I glucocorticoids was similar. No systemic or local adverse reactions were noted.

Treatment with pro-inflammatory cytokine, IFNalpha was documented to result in neuropsychiatric complications including depression and treatment with antidepressant, paroxetine could improve the depressive symptoms. Therefore, the effects of IFNalpha on behaviour and cytokine changes in the whole blood culture and in the prefrontal cortex, hypothalamus and hippocampus areas of the brain in wistar rats were investigated with emphasis on the role of paroxetine in the prevention of depressive behaviour induced by pro-inflammatory cytokines. The group of rats treated with IFNalpha (s.c. 50,000 IU/kg for 3 days/week for 5 weeks) was compared with three other groups; 1) saline control group (s.c. normal saline 0.2 ml/kg/day for 7 weeks), 2) paroxetine control group (paroxetine suspension orally 10 mg/kg/day for 7 weeks) and 3) group treated with paroxetine for 2 weeks followed by IFNalpha for 5 weeks. In open filed, the IFNalpha treated rats showed anxiety behaviour compared to the rats from the other groups. There was no significant difference in home cage emergence test, Morris water maze and object recognition test. There is no significant difference in plasma corticosterone between groups. The pro-inflammatory cytokines (TNFalpha, IL1beta and IFNgamma), were significantly higher whereas the anti-inflammatory cytokine, IL10 was lower in the stimulated whole blood culture of IFNalpha treated rats. In the brain, both pro-inflammatory cytokine IL1beta and anti-inflammatory cytokine IL10 were higher in hypothalamus of the IFNalpha treated rats; by contrast the concentration of IL10 was lowest in hippocampus region of this group compared to the other groups. The paroxetine pretreated rats did not show these cytokine changes following IFNalpha treatment. Thus it appears that paroxetine pretreatment prevents the pro-inflammatory changes in blood and brain following IFNalpha treatment in turn prevents the anxiety behaviour.

The purification of human fibroblast interferon by chromatography on Blue Sepharose and high-performance liquid chromatography is described. The amino acid composition and a partial sequence of the homogeneous protein are reported. The NH2 terminus was determined to be NH2-Met- Ser-Tyr-Asn-Leu-Leu-Gly-Phe-Leu-Gln-Arg-Ser-Ser-Asn-PheGln-X-Gln-Lys.Other laboratories have reported on the purification and partial structural analysis of human fibroblast interferon (1, 2). We present a novel purification and some additional sequences of human fibroblast interferon. Interferon used in our studies was prepared in serum-free medium and was purified by a procedure based on the combination of affinity chromatography and high-performance liquid chromatography (HPLC).EXPERIMENTAL PROCEDURES Interferon Production and Assay. Crude fibroblast interferon was produced as described by Havell and Vilcek (3), except that serum was omitted from the overnight induction medium. Interferon titers were determined by a cytopathic effect inhibition assay that was modified so that the entire assay could be performed within 16 hr (4). All interferon titers were expressed in terms of reference units/ml, calibrated against the reference standard for human leukocyte interferon (G-023-901-527) provided by the Antiviral Substances Program of the National Institute of Allergy and Infectious Diseases, Bethesda, MD.Purification of Human Fibroblast Interferon on Blue Sepharose. Sodium chloride was added to medium containing interferon to a final concentration of 1 M, and the solution was then pumped onto a 25-ml Blue Sepharose CL-6B (Pharmacia) column (1, 5) at room temperature at a rate of 2.5 ml/min. The unfractionated interferon was maintained on ice during the loading process. The column was washed with 250 ml of sodium phosphate buffer (50 mM Na2HPO4 adjusted to pH 7.2 with HCI) containing 1 M NaCl and 30% (vol/vol) ethylene glycol. The interferon was eluted with the same solution containing 50% (vol/vol) ethylene glycol. Peak fractions of activity were pooled and stored at 40C until used (Fig. 1). Activity appeared to be stable for at least 3 mo at 4VC or in liquid nitrogen.In preparations having a low initial titer, a second passage through Blue Sepharose was required. In these instances, when a total of 25 liters of culture medium containing interferon had been chromatographed, the peak fractions from five columns were pooled and adjusted to 10% (vol/vol) ethylene glycol, 2 M NaCl, and 50 mM Na2HPO4 (pH 7.2). This material was then applied to another Blue Sepharose column. The column was then washed with 250 ml of the sodium phosphate buffer containing 2 M NaCl and 30% ethylene glycol. Some interferon was eluted at this step. The remaining interferon was eluted with the same solution containing 50% ethylene glycol. Interferon that eluted from the second Blue Sepharose column with both 30% and 50% ethylene glycol was satisfactory for use in the next step of the purification. The specific activity of the interferon that was deemed sati...

The recent in vivo appearance of acyclovir-resistant strains of herpes simplex virus stresses the need for new therapeutic agents to combat this common virus. Topical interferon preparations may help fill this void. In the present study dimethyl sulfoxide was combined with α-interferon in an ointment base to increase percutaneous penetration. In this double-blind, placebo-controlled trial, patients with recurrent genital herpes simplex using the topical α-interferon preparation had a more rapid cessation of viral shedding when compared to the placebo group (66% culture negative on day 1 vs. 25% of placebo patients; p < 0.02). In the 90-day post-treatment period, interferon-treated patients had fewer recurrences than their placebo-treated counterparts (1.18 vs. 2.25). This reduction while not statistically significant was encouraging (p < 0.10).