An estrogen antagonist, cyclofenil, has anti-dengue-virus activity.

Dengue virus (DENV) infections are a major cause of morbidity and mortality in tropical and subtropical areas. Several compounds that act against DENV have been studied in clinical trials to date; however, there have been no compounds identified that are effective in reducing the severity of the clinical manifestations. To explore anti-DENV drugs, we examined small molecules that interact with DENV NS1 and inhibit DENV replication. Cyclofenil, which is a selective estrogen receptor modulator (SERM) and has been used clinically as an ovulation-inducing drug, showed an inhibitory effect on DENV replication in mammalian cells but not in mosquito cells. Other SERMs also inhibited DENV replication in mammalian cells, but cyclofenil showed the weakest cytotoxicity among these SERMs. Cyclofenil also inhibited the replication of Zika virus. A time-of-addition assay suggested that cyclofenil may interfere with two stages of the DENV life cycle: the translation-RNA synthesis and assembly-maturation stages. However, the level of intracellular infectious particles decreased more drastically after treatment with cyclofenil than the viral RNA level did, indicating that the assembly-maturation stage might be the main target of cyclofenil. In electron microscopy analysis, many aggregated particles were detected in DENV-infected cells in the presence of cyclofenil, supporting the possibility that cyclofenil impedes the process of assembly and maturation of DENV.

A new therapeutic method for climacteric disorders.

At the present time the administration of an exogeneous estrogen for the treatment of climacteric disorders is generally accepted both in Japan and foreign countries. However, there have been several reports to show that estrogen will promote carcinogenecity. With special attention to this point, the author performed the endocrinological treatment without estrogen for climacteric disorders. The author would like to propose the reactivation method on functionally declining ovary by the approach of induction of ovulation. In this paper the author describes a successful case treated by the new method of hormone therapy.

Treatment of progressive systemic sclerosis (scleroderma, PSS) with a new drug influencing connective tissue.

Cyclofenil is a new diphenyl ethylene derivative related to stilboestrol without oestrogenicity but with marked effects on connective tissue metabolism. The drug has been tested, in a daily dose of 200mg X3, in six patients with progressive systemic sclerosis (PSS) to analyze the expected beneficial effects on the PSS symptoms. The typical skin hardness, joint and muscle rigidity, and reduced breathing capacity were improved to varying dgrees. The only side-effect was a slight transient liver enzyme elevation in 1 out of 6 patients. A slight increase was found in urinary calcium and hydroxyproline excretion. In several cases serum calcium, cholesterol, triglyceride and in some cases the serum uric acid levels were decreased. The ANF titres diminished to varying degrees in 4 out of 6 patients. These results indicate that further detailed clinical and laboratory studies on the therapeutic potential of cyclofenil in PSS and other diseases affecting connective tissue seen to be justified.

A prospective, randomised, cross-over study comparing the effects of clomiphene citrate and cyclofenil on endometrial morphology in the luteal phase of normal, fertile women.

OBJECTIVE: To examine the effect of two anti-oestrogens, clomiphene citrate and cyclofenil, on endometrial morphology in the luteal phase. DESIGN: A prospective, randomised, cross-over study. SETTING: Jessop Hospital for Women, Sheffield, UK. SUBJECTS: 10 women who were previously fertile and regularly cycling. INTERVENTION: The administration of clomiphene citrate or cyclofenil in the treatment cycles. A LH timed endometrial biopsy was taken on day LH + 6. MAIN OUTCOME MEASURES: Histological dating and morphometric analysis of the endometrial sample. RESULTS: Only one out of 10 subjects had abnormal endometrium. There was no difference in the results between cycles treated with clomiphene citrate and cyclofenil. CONCLUSIONS: Clomiphene citrate or cyclofenil does not have a major adverse effect on endometrial morphology in the luteal phase of normal fertile subjects. The possible adverse effects of anti-oestrogens on endometrium may have been previously overestimated.

Chemical inducers of ovulation: comparative results.

Chemical inducers of ovulation are frequently used to reestablish a normal hypothalamic-ovarian function in the sterile woman. At present, several types are available and it is useful to evaluate comparatively their efficacy. In this paper we present our results in 396 cases treated with some of these drugs. Clomiphene citrate was administered to 307 patient. Ovulation was obtained in 85.99% and pregnancy in 35.50%. There were 16 abortions (14.68%) among the 109 pregnancies obtained. Cisclomiphene was used in 11 cases. The ovulation rate was 81.81%, with 54.5% of pregnancies. Thirty-eight patients were treated with Cyclophenil. Ovulation was obtained in 71.05% of the cases and pregnancy in 23.68%. In forty cases Tamoxifen was administered: the ovulation rate was 95% and the pregnancy rate was 35%, but the abortion rate was 35%. Tolerance was good with all medications. They had similar adverse side effects (mild and rare). None produced overstimulation. With Cyclophenil and specially with Tamoxifen the cycles were longer. The incidence of abortion in the 131 pregnancies obtained was 14.68% with Clomiphene; none with Cisclomiphene; 11.11% with Cyclophenil, and 35.10% with Tamoxifen. We conclude that Clomiphene is the drug which gives the best results at present.

Effect of cyclofenil treatment on arterial insufficiency demonstrated in a patient by colour thermography.

Cyclofenil, 200 mg t.i.d., was administered for four months to a 67-year-old woman, who suffered from a combination of scleroderma, Osler-Weber-Rendu disease and a severe atherosclerotic circulatory insufficiency. The effects on the severely impaired skin circulation in the face and hands were followed and recorded by colour isothermograms, using the AGA monitor system. The treatment resulted in a marked improvement of the arterial circulation with disappearance of the Raynaud phenomenon, complete arrest of gastrointestinal bleeding, disappearance of malabsorption, and relief of the joint stiffness.

Acute hepatitis induced by cyclofenil: a case report.

The case of a 47-year old woman suffering from acute hepatitis caused by cyclofenil, a drug proposed for the treatment of anovulation and scleroderma, is presented. Hepatitis developed seven weeks after the beginning of administration of the drug and its course was reversible after withdrawal. The case is documented on the basis of liver histology and the exclusion of other causes of acute hepatitis.