MtDNA mutagenesis impairs elimination of mitochondria during erythroid maturation leading to enhanced erythrocyte destruction.

Haematopoietic progenitor cells show special sensitivity to mitochondrial DNA (mtDNA) mutagenesis, which suggests that increased mtDNA mutagenesis could underlie anemias. Here we show that elevated mtDNA mutagenesis in mice with a proof-reading deficient mtDNA polymerase (PolG) leads to incomplete mitochondrial clearance, with asynchronized iron loading in erythroid precursors, and increased total and free cellular iron content. The resulting Fenton chemistry leads to oxidative damage and premature destruction of erythrocytes by splenic macrophages. Our data indicate that mitochondria actively contribute to their own elimination in reticulocytes and modulate iron loading. Asynchrony of this sequence of events causes severe mitochondrial anaemia by depleting the organism of red blood cells and the bone marrow of iron. Our findings account for the anaemia development in a progeroid mouse model and may have direct relevance to the anemias associated with human mitochondrial disease and ageing.

A double-blind study comparing oleum horwathiensis with placebo in the treatment of psoriasis.

The efficacy and tolerability of topically applied oleum horwathiensis were evaluated in a double-blind, placebo-controlled study of 42 patients with chronic stable psoriasis. Both groups of patients, 19 receiving oleum horwathiensis treatment and 23 receiving placebo treatment for 12 weeks, showed clinically significant effects of treatment. Oleum horwathiensis was more effective than placebo throughout the treatment period but the difference was not statistically significant at any time. No changes in laboratory values attributable to treatment were recorded. The symptoms of the oleum horwathiensis-treated group continued to be less severe than those of the placebo-treated group throughout the 12 weeks of follow-up. The follow-up period, however, occurred partly during the summer and since the clinical status of the patients may have been affected by climate the difference between the treatment groups was not analysed statistically. The tolerability and cosmetic acceptance of oleum horwathiensis were remarkably good, and good clinical efficacy in scalp lesions--which was not the subject of this study--was spontaneously reported by several patients.

Topical idoxuridine for treatment of genital warts in males. A double-blind comparative study of 0.25% and 0.5% cream.

Fifty heterosexual male patients with histologically verified genital warts of short duration (less than 3 months) were randomly allocated to treatment with either 0.25% or 0.5% idoxuridine cream. The application of the cream to the warts was performed twice daily for an initial period of 14 days, whereafter patients with partial improvement or no response were retreated in the same way for another period of 14 days. Patients not completely healed after 28 days were regarded as treatment failures and withdrawn from the study. After the initial treatment period of 14 days, 19 of 25 patients (76%) treated with 0.5% idoxuridine cream, and 9 of 25 patients (36%) treated with 0.25% idoxuridine cream were completely healed. This difference is significant (p less than 0.01). The corresponding figures at the second follow-up examination (28 days after start of the study) were 19 of 25 (76%) and 13 of 25 (52%), respectively. At the last follow-up examination three months after start of treatment, four patients treated with 0.5% idoxuridine cream and five patients treated with 0.25% idoxuridine cream had a relapse. Thus, the overall rate of complete healing was 15 of 25 (60%) for the patients treated with 0.5% idoxuridine cream and 8 of 25 (32%) for those treated with 0.25% idoxuridine cream. The difference is significant (p less than 0.01). No adverse reactions were observed or reported by the patients.

Combination of laser-therapy with 0.5% idoxuridine cream in the treatment of therapy-resistant genital warts in male patients: an open study.

Forty heterosexual male patients with therapy resistant penile warts of long duration (mean 12.9 months) were treated with carbon dioxide laser, immediately followed by topical application of 0.5% idoxuridine cream twice daily for 14 days. In case of incomplete or no response to the initial treatment, the treatment procedure was repeated once. All patients had previously been repeatedly treated with podophyllotoxin 0.5% solution and/or carbon dioxide laser surgery. After two weeks of treatment, 32 patients (80%) were completely healed. The remaining eight patients were retreated and four weeks after the start of the study 35 patients (87.5%) showed complete response. Three months after the study had been initiated 34 patients (85%) were still completely healed. No adverse reactions were observed. It was concluded that laser surgery followed by topical application of 0.5% idoxuridine cream for two to four weeks seems to be highly effective in the treatment of longstanding, therapy-resistant genital warts in men. Because of the uncontrolled nature of the present study and the relatively small number of patients treated, it would be important to carry out controlled studies in larger study populations and to carry out a follow-up examination of at least six months after treatment.

A dimethoxynaphthalene derivative (RS-43179 gel) compared with 0.025% fluocinolone acetonide gel in the treatment of psoriasis.

Thirty patients were entered into a double-blind trial comparing a dimethoxynaphthalene derivative (RS-43179 gel) and fluocinolone acetonide (Synalar gel) in the treatment of psoriasis. The two preparations were applied three times daily for 4 weeks, and the patients were assessed at weeks 1, 2, 3, 4, 7 and 9. No significant differences between the two preparations could be detected. By the end of the 4-week treatment period, the number of patients showing a 'Good, Excellent or Clear' therapeutic response was 25 out of 28 after RS-43179 treatment and 26 out of 28 after Synalar treatment. Four patients experienced irritation on the side treated with RS-43179. In two of these patients the reaction was severe and the treatment was discontinued, but in the other two patients, the local irritation was only moderate. No other adverse reactions were seen.

A new vaginal antifungal agent--butoconazole nitrate.

The continuously increasing incidence of vulvovaginal candidiasis necessitated a search for novel therapeutic modalities. Butoconazole nitrate (BN) a new imidazole, has been singled out for clinical studies since, in experimental vaginal candidiasis, it proved more effective than either miconazole nitrate (MN) or clotrimazole. One hundred and thirty volunteers with vaginal candidiasis, verified by wet mount and positive fungal culture, were randomly assigned to receive daily, for 6 days, either 1% BN (44 patients), or 2% BN (45 patients) vaginal cream or 2% MN (41 patients) vaginal cream. The patients were comparable regarding age (85% were 18-39 years of age), gravidity and parity. Twenty-five per cent had a recent history of unsuccessfully treated fungal vaginitis. Eight days after completion of treatment, negative fungal cultures were found in 98% of the patients using 2% BN, in 91% of patients using 1% BN and in 83% using 2% MN. The recurrence rate of the disease was low; about 80% of patients using 1% and 2% BN and 68% of those using 2% MN were culture-negative 30 days after conclusion of treatment. Rapid relief of clinical symptoms was experienced by patients in all three treatment groups. No significant side effects of the treatment were observed in any of the treatment groups.