The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms.

Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I-control, II-rats with rapamycin (RA)-induced OAB, III-rats administered IMP at a dose of 10 mg/kg/day, and IV-rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB.

[Usefulness and necessity of unsynchronized photosolotherapy and bath-PUVA--two variants of balneophototherapy--in funded ambulatory health care]. / Nutzen und Notwendigkeit der nicht-synchronen Photosoletherapie und Bade-PUVA.--zweier Varianten der Balneophototherapie--in der ambulanten vertragsärztlichen Versorgung.

The Standing Committee of Statutory Health Insurance Physicians and Sickness Funds is the legal body that makes decisions on reimbursement for health care services in the German ambulatory health care sector. In 1994 the committee declined the reimbursement of balneophototherapy. Balneophototherapy comprises a bath in a saline solution followed by ("non-synchronous") or simultaneous ("synchronous") UVB-irradiation. Photochemotherapy with bath-water delivery of psoralens combined with UVA light is also covered by the term balneophotherapy. The main indication for both procedures is serious psoriasis. Bath PUVA was also recommended for atopic dermatitis, pityriasis lichenoides, lichen ruber and mycosis fungoides. An effectiveness study sponsored by the sickness funds with rather poor methodological design and conduct was not able to show an unbiased effect of balneophototherapy despite inclusion of thousands of patients. On the contrary, a poor adherence of patients and doctors was documented, since 63% of patients suffering from psoriasis and treated with saline bath followed by UVB-irradiation stopped early or used additional therapies like cortisone or vitamin D3 derivatives. Only 43% of patients suffering from psoriasis and treated by bath PUVA did not stop the initial therapy and did not receive additional therapy (UVB, cortisone). In addition, the committee also conducted a thorough review of the literature, guidelines and status in other health care systems. Finally the two modifications of balneophototherapy were again declined from reimbursement in the German ambulatory health care sector. There were no controlled clinical trials showing efficacy of saline bath followed by UVB irradiation. Up to now bath PUVA was only evaluated in small equivalence trials which despite the fact that a drug was tested did not apply basic ICH standards (international conference on harmonisation) for equivalence trials. Additionally, the long-term cancer risk inherent to the application of psoralenes must be considered. Since the definition of "severe psoriasis" is not trivial a wide use of bath PUVA in ambulatory health care has to be based on the results of rigorously conducted clinical trials showing the effectiveness, safety and appropriateness in comparison to other treatment modalities. In reaction to the decision of of the committee two randomised controlled trials for the evaluation of the efficacy of balneophototherapy are planned.

Modifications of PUVA.

The goal of photochemotherapy in psoriasis is to attempt to lower the number of exposures and the total cumulative doses while still maintaining good control of the disease. PUVA has been modified by using better psoralen preparations and more effective light sources, and it also has been combined with other treatment modalities. The objectives in modifying PUVA and combining PUVA with other treatment modalities are to increase efficacy, to reduce short- and long-term adverse effects, and to reduce the cost of treatment. Modalities that have been combined with PUVA include topical corticosteroids, anthralin, calcipotriene ointment, methotrexate, UVB, retinoids, and cyclosporine.