Simultaneous determination of multiple components in rat plasma and pharmacokinetic studies at a pharmacodynamic dose of Xian-Ling-Gu-Bao capsule by UPLC-MS/MS.

Xian-Ling-Gu-Bao capsule (XLGB) is an effective traditional Chinese medicine prescription (TCMP) that is used for the prevention and treatment of osteoporosis in China. A rapid, simple, efficient and stable method based on UPLC-MS/MS technology was developed for simultaneous determination of multiple components of XLGB in rat plasma. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). For twenty-one selected quantitative prototypes, all calibration curves showed favourable linearity (r>0.9932) in linear ranges. The lower limits of quantification (LLOQs) were 2 ng/mL for psoralen (PL), 2.5 ng/mL for asperosaponin VI (AS), 1 ng/mL for isopsoralen (IPS) and sweroside (SW), 0.5 ng/mL for magnoflorine (MA), bavachinin (BVN), tanshinone IIA (TA), timosaponin BII (TBII) and icaritin (ICT), 0.1 ng/mL for epimedin B (EB) and epimedin C (EC), 0.05 ng/mL for icariin (IC), isobavachalcone (IBC), psoralidin (PD), bavachin (BV), bavachalcone (BC), epimedin A (EA) and isobavachin (IBV), 0.02 ng/mL for neobavaisoflavone (NEO) and icariside I (ICI) and 0.01 ng/mL for icariside II (ICII). The intra-day and inter-day (low, medium, high) precision (relative standard deviation) for all analytes was less than 8.63%, and the accuracies (as relative error) were in the range of -12.45% to 8.91%. Extraction recoveries and matrix effects of analytes and IS were acceptable. All analytes were stable during the assay and storage in plasma samples. The validated method was successfully applied to the pharmacokinetics (PK) studies of the twenty-one prototypes at pharmacodynamic doses (0.3 and 1 g/kg/day). In addition, dynamic profiles of 28 metabolites (phase II conjugates: 23 glucuronide conjugates, 2 sulfate conjugates and 3 glucuronide or sulfate conjugates) were also monitored by their area/IS area-time curves. As a result, coumarins, prenylated flavonoids from Psoraleae Fructus, alkaloids and prenylated flavonol glycosides from Epimedii Herba, and iridoid glycosides, triterpenoid saponins from Dipsaci Asperoidis Radix were considered to be the key effective substances of XLGB due to their high exposure and appropriate pharmacokinetic features. This is the first report to reveal pharmacodynamic ingredients by a reversed pharmacodynamic (PD) - pharmacokinetics (PK) study.

The role of long-wavelength ultraviolet A1 (UVA1) in acral vitiligo.

INTRODUCTION: Acral vitiligo is a resistant subtype of vitiligo that does not respond easily to any treatment modality. Ultraviolet A1 (UVA1) (340-400 nm) therapy can penetrate the deep dermis of the skin and is relatively free of adverse effects associated with different phototherapeutic modalities. This study's objective was to evaluate the effect of medium-dose long-wavelength UVA1 (40-70 J) in acral vitiligo treatment and compare it with topical psoralen plus ultraviolet A (topical PUVA). METHODS: Patients in this randomized-controlled comparative clinical trial were divided into two groups, medium-dose UVA1 group and topical PUVA group (10 acral vitiligo patients each). Patients received 36 sessions of phototherapy over a period of 12 weeks. Every patient was clinically evaluated monthly as regards the appearance of new lesions or increase in diameter of the current lesion according to point counting and vitiligo area severity index. RESULTS: No statistically significant clinical difference was found between patients in UVA1 and topical PUVA groups regarding response and pattern of response (P > 0.05). CONCLUSION: Ultraviolet A1 seems to be of limited use as a monotherapy in acral vitiligo treatment. However, more studies combining it with other treatment modalities as systemic steroids and/or using higher UVA1 doses may prove beneficial.

Folliculotropic mycosis fungoides in a pediatric patient with response to psoralen-ultraviolet A phototherapy.

Mycosis Fungoides is the most common cutaneous T-cell lymphoma however, it is rare in children. We present the case of a Folliculotropic Mycosis Fungoides in a 13-year-old boy which initially presented as a plaque on his face and was treated with local PUVA therapy. Afterwards the lesions spread so the treatment was changed to systemic PUVA with good response. Although the experience in the treatment of Mycosis Fungoides in pediatric patients is limited, PUVA therapy seems to be an effective and safe option.

A non-inferiority randomized controlled clinical trial comparing Unani formulation & psoralen plus ultraviolet A sol in chronic plaque psoriasis.

BACKGROUND & OBJECTIVES: Though Unani medications have been used for centuries to treat psoriasis, there is paucity of published studies which have systematically evaluated their efficacy and safety. This study was conducted to establish non-inferiority of Unani medications (oral UNIM-401 and topical UNIM-403) vs psoralen plus ultraviolet A (PUVA) sol in treatment of moderate-severe chronic plaque psoriasis (CPP) in achieving psoriasis area severity index (PASI) 75 at 12 wk and to estimate proportion of patients who relapsed in follow up period of 12 weeks, after having achieved PASI 50. METHODS: In this randomized, controlled trial patients with CPP were block randomized to receive either Unani treatment (147 patients) or PUVA sol (140 patients) for 12 weeks. Percentage reduction in PASI was determined in each patient at 12 wk to calculate number of patients who achieved PASI 75 as also to estimate median of percentage reduction in PASI in each group. All patients who achieved PASI 50 at 12 weeks were followed up for another 12 wk to determine proportion of patients who relapsed. RESULTS: Of the 287 patients randomized, 84 of 147 in Unani group and 67 of 140 in PUVA sol group completed 12 weeks of treatment. On intention-to-treat (ITT) analysis, the response in patients on Unani medication was not inferior to those receiving PUVA sol, in attaining PASI 75 (16.3% in Unani group vs 15.7% in the PUVA sol group). Median of percentage reduction of PASI at 12 wk from baseline in Unani group (68.2%; -60, 100) and PUVA sol group (63%; -15.7, 100) was comparable. Proportion of patients who relapsed at 24 wk was comparable in both groups. However, frequency of clinical side effects was significantly higher (P =0.001) in PUVA sol group (16.4%) compared to Unani group (2%). INTERPRETATION & CONCLUSIONS: The findings of the present study indicated that oral UNIM-401 and topical UNIM-403 were effective and well tolerated therapeutic options in patients with moderate-severe CPP.

An observer-blinded randomized controlled pilot trial comparing localized immersion psoralen-ultraviolet A with localized narrowband ultraviolet B for the treatment of palmar hand eczema.

BACKGROUND: Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen-ultraviolet A (PUVA) with narrowband ultraviolet B (NB-UVB) have been small, nonrandomized and retrospective. OBJECTIVES: To conduct an observer-blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB-UVB for the treatment of chronic hand eczema unresponsive to topical steroids. METHODS: Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB-UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving 'clear' or 'almost clear' Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). RESULTS: In both treatment arms, 23 patients completed the 12-week assessment for the primary outcome measure. In the PUVA group, five patients achieved 'clear' and eight 'almost clear' [intention-to-treat (ITT) response rate 43%]. In the NB-UVB group, two achieved 'clear' and five 'almost clear' (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB-UVB 9) and at 12 weeks (PUVA 3, NB-UVB 4). Changes in DLQI were similar, with improvements in both groups. CONCLUSIONS: In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems - PGA, mTLSS and DLQI - as measures of treatment response, the trial demonstrated that both PUVA and NB-UVB reduced the severity of chronic palmar hand eczema.

Psoralen loaded liposomal nanocarriers for improved skin penetration and efficacy of topical PUVA in psoriasis.

Psoralen in combination with ultraviolet A radiation (PUVA) is an FDA recommended therapy for clinical application in the management of severe recalcitrant psoriasis. Psoralen acts by intercalation of DNA and upon exposure to UV-A, it forms monoadducts which in turn induce apoptosis. Poor skin deposition, weak percutaneous permeability of psoralen and adverse effects of severe burning, blisters, pigmentation associated with conventional topical psoralen vehicles hinders the therapeutic efficacy and safety of topical PUVA. The aim of the present study is to formulate psoralen loaded liposomal nanocarriers for enhanced skin penetration, safety and efficacy of topical PUVA in psoriasis. Two different liposomal compositions i.e., cationic liposomes composed of DC-Chol, cholesterol and anionic liposomes composed of egg lecithin, cholesterol, tetramyristoyl cardiolipin were prepared for the topical delivery of psoralen. Liposomal carriers were characterized with respect to size, zeta potential, entrapment efficiency, stability, in vitro drug release and in vivo studies. Both liposomes were prepared with particle size of nearly 100nm. Zeta potential and entrapment efficiency of cationic liposomes were +25.8mV, 75.12% and anionic liposomes were -28.5mV, 60.08% respectively. Liposomal dermal distribution demonstrated higher penetration of both liposomal carriers over solution. Similarly, skin permeation study indicated 5 fold increase in permeation of psoralen with liposomal carriers. Topical application of psoralen liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumor necrosis factor-α, IL-17 and IL-22. In conclusion, the developed liposomal carriers of psoralen were found to be promising and can find application for optimal safety and efficacy of topical PUVA in psoriasis.

Narrow-band UVB phototherapy and psoralen-ultraviolet A photochemotherapy in the treatment of cutaneous mastocytosis: a study in 20 patients.

BACKGROUND: In mastocytosis, the skin is almost invariably involved, and cutaneous symptoms deeply affect patients' quality of life. METHODS: A retrospective observational analysis of patients affected by cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM) treated with phototherapy/photochemotherapy (PUVA or NB-UVB) has been conducted. For each patient, total numbers of PUVA or NB-UVB exposures, the cumulative UV dose (J/cm2 ), serum tryptase profile, and pruritus, before and after treatment, according to the visual analogue scale (VAS) were considered. Skin lesions of each patient were assessed, before and after treatment, according to a cutaneous scale score. RESULTS: Twenty patients affected by CM and ISM were studied; in particular, 10 patients received NB-UVB therapy, and other 10 patients received PUVA. A statistically significant mean reduction of pruritus in both groups (P < 0.01) was observed. The number of treatments necessary to obtain symptom relief was significantly lower in the PUVA group, but the mean exposure dose was significantly higher, if compared to the NB-UVB group. Serum tryptase levels showed a downward trend. The cutaneous score improved in both groups. LIMITATIONS: This study was a retrospective study with a small sample size and without a control group. CONCLUSION: This work provides evidence that both NB-UVB and PUVA represent a safe and useful second-line therapy of the cutaneous symptoms in mastocytosis.

Phototherapy in the elderly.

BACKGROUND: Elderly patients present with a unique spectrum of dermatoses that pose particular management opportunities and challenges, which will be increasingly encountered in dermatological practice. The skin of elderly patients differs from that of younger patients not only in appearance but also in structure, physiology and response to ultraviolet (UV) radiation. However, little is known about the safety and efficacy of phototherapy in elderly patients and how phototherapy is currently being utilized to treat them. AIM: To investigate the safety, efficacy and utilization of phototherapy in elderly patients. METHODS: In January 2014, we analysed all patients recently referred for, currently receiving or recently having completed a course of phototherapy at a university teaching hospital in England (UK). RESULTS: In total, 249 patients were identified; 37 (15%) were over the age of 65 years (the WHO definition of an elderly or older person). The dermatoses being treated were psoriasis (51%), eczema (11%), nodular prurigo (11%), pruritus (11%), Grover disease (5%) and others (11%). One patient with dementia was deemed not safe to embark on phototherapy, and five patients were yet to start. The remaining 31 elderly patients received 739 individual phototherapy treatments: 88% narrowband (NB)-UVB and 12% systemic, bath and hand/foot psoralen UVA (PUVA). The acute adverse event (AE) rate was 1.89%, all occurring in those receiving NB-UVB. No severe acute AEs occurred. Of those who completed their course of phototherapy, 80% achieved a clear/near clear or moderate response, while just two patients (8%) had minimal response and two (8%) had worsening of the disease during treatment. Of those receiving NB-UVB for psoriasis, 91% achieved a clear or near-clear response. CONCLUSIONS: In this small survey, the first of its kind to focus on elderly patients, phototherapy appears to be well-tolerated, safe and efficacious in the short term. Further thought and investigation should be given to delivering phototherapy to an ageing population.

Systematic review of combination therapies for mycosis fungoides.

BACKGROUND: A variety of therapeutic options are available for mycosis fungoides, the most prevalent subtype of cutaneous T cell lymphomas, but thus far, no regimen has been proven to be curative. A combination of treatments is a well-established strategy to increase the therapeutic efficacy. However, data from clinical trials analyzing such combinations for the treatment of mycosis fungoides are scarce. OBJECTIVE: To analyze the available evidence on combination therapies with emphasis on the combination of psoralen with UVA phototherapy (PUVA), interferon-alpha and bexarotene with another treatment. METHODS: Systematic literature review of the databases Embase, Cochrane, Medline, and Medline in Process. RESULTS: Combination of PUVA with interferon-alpha or retinoids did not result in an increased overall response rate. Addition of methotrexate but not retinoids to interferon-alpha may increase the overall response rate. Bexarotene was investigated in one trial each with vorinostat, methotrexate or gemcitabine, whereby only methotrexate possibly enhanced the effect of bexarotene. CONCLUSION: For mycosis fungoides, no combination treatment has been demonstrated to be superior to monotherapy. Based on our analysis, we conclude that in certain clinical situations, patients may benefit from a combination of PUVA with interferon-alpha or a retinoid or a combination of the latter two. Furthermore, patients in advanced stages may benefit from the combination of methotrexate and interferon-alpha or bexarotene. Finally, the combination of bexarotene with either vorinostat or gemcitabine did not increase the overall response rate but resulted in more pronounced side effects and cannot be recommended.

Comparison of ethosomes and liposomes for skin delivery of psoralen for psoriasis therapy.

Recent reports have indicated that psoriasis may be caused by malfunctioning dermal immune cells, and psoralen ultraviolet A (PUVA) is an effective treatment for this chronic disease. However, conventional topical formulations achieve poor drug delivery across patches of psoriasis to their target sites. The present study describes the development of a novel psoralen transdermal delivery system employing ethosomes, flexible vesicles that can penetrate the stratum corneum and target deep skin layers. An in vitro skin permeation study showed that the permeability of psoralen-loaded ethosomes was superior to that of liposomes. Using ethosomes, psoralen transdermal flux and skin deposition were 38.89±0.32 µg/cm(2)/h and 3.87±1.74 µg/cm(2), respectively, 3.50 and 2.15 times those achieved using liposomes, respectively. The ethosomes and liposomes were found to be safe following daily application to rat skin in vivo, for 7 days. The ethosomes showed better biocompatibility with human embryonic skin fibroblasts than did an equivalent ethanol solution, indicating that the phosphatidylcholine present in ethosome vesicles improved their biocompatibility. These findings indicated that ethosomes could potentially improve the dermal and transdermal delivery of psoralen and possibly of other drugs requiring deep skin delivery.

Role of bath psoralen plus ultraviolet A in early-stage mycosis fungoides.

BACKGROUND: Psoralen plus ultraviolet (UV) A (PUVA) radiation is the preferred treatment for folliculotropic mycosis fungoides (MF) and MF refractory to narrowband (NB) UVB radiation. However, systemic PUVA has many unfavorable side effects and contraindications. Bath PUVA has been found to be a suitable alternative in patients with psoriasis, but data on MF are sparse. OBJECTIVE: The purpose of the study was to evaluate the effectiveness of bath PUVA in the treatment of folliculotropic MF and NB-UVB-refractory early-stage MF. METHODS: The study group included 26 patients of average age 44 years attending a tertiary medical center in 2004 through 2012, 14 with folliculotropic type and 12 with NB-UVB-refractory early-stage MF who were not amenable for oral PUVA. Treatment consisted of 0.2 mg/L 8-methoxypsoralen bath 3 times weekly followed by UVA irradiation at 0.3 J/cm(2) with fixed increments every second session. RESULTS: A complete clinical response was achieved in 62% of patients after an average of 33 weeks and a cumulative radiation dose of 158 J/cm(2). LIMITATIONS: This was a relatively small series. CONCLUSION: Bath PUVA is a good treatment option for superficial folliculotropic MF and NB-UVB-refractory early-stage MF.

Psoralen-narrowband UVB phototherapy for the treatment of vitiligo in comparison to narrowband UVB alone.

BACKGROUND: The potential of psoralen-narrowband ultraviolet B (NBUVB) photochemotherapy has been investigated in vitiligo. The present study aims to evaluate the efficacy of psoralen-NBUVB (P-NBUVB) vs. NBUVB in vitiligo. METHODS: In a randomized study, 45 Indian patients (age above 13 years) with vitiligo involving more than 5% body surface area were randomly allocated to receive either NBUVB or P-NBUVB treatment. Both groups received NBUVB exposure thrice weekly, with a total of 60 sessions. The extent of repigmentation achieved was calculated on the basis of Vitiligo Area Severity Index (VASI) scoring. RESULTS: Forty patients were available for analysis at the end of the study. The extent of repigmentation in the P-NBUVB group was statistically significantly greater in face and neck (P = 0.006, t-test) and hands (P = 0.007, t-test) in comparison with the NBUVB group (t-test). Percentage reduction in VASI scores was statistically significantly greater in the P-NBUVB group (29.2% vs. 21.7%, P = 0.043, t-test). The response to P-NBUVB therapy started earlier than the response to NBUVB. After excluding sunlight as a confounding factor, treatment response was also significantly better in the P-NBUVB group (P = 0.005). CONCLUSION: Addition of psoralen increased the extent of repigmentation due to NBUVB therapy in vitiligo. Further studies are required to determine the long-term efficacy and safety of P-NBUVB.

Factors associated with the length of remission of psoriasis vulgaris.

BACKGROUND: Cardiovascular risk factors are found with significantly high frequency in psoriatic patients. Periods of remission and reactivation of lesions are common in psoriasis. OBJECTIVE: Considering the association of chronic inflammation with the atherogenic process, we aimed to search for a possible relationship between the lipid profile, adipokine levels and body mass index (BMI) at the end of a successful treatment for psoriasis, and the length of remission of psoriasis. METHODS: Forty-three patients were clinically and analytically studied after a successful treatment [as shown by Psoriasis Area and Severity Index (PASI)]--nine treated with topical agents, 17 with narrow-band UV light B (NB-UVB) and 17 with psoralen plus UVA-and were followed to record the length of remission. RESULTS: The length of psoriasis remission correlated negatively and significantly with cholesterol levels, which correlated significantly and positively with C-reactive protein (CRP). In multiple linear regression analysis, cholesterol, CRP, PASI and BMI were associated with the length of remission. Patients with cholesterol levels <200 mg/dL (n = 13) presented a significantly longer remission, lower BMI and triglycerides values, and a trend towards lower PASI and CRP values than those with high cholesterol (n = 30). Considering patients according to the treatment used, cholesterol was also associated with length of remission, especially for patients treated with NB-UVB and topical therapy. CONCLUSION: Psoriasis patients with the highest cholesterol levels presented higher BMIs, triglycerides levels and shorter remission periods. Our data suggest that the identification of potentially treatable conditions, such as dyslipidaemia and obesity, and their adequate treatment may benefit psoriasis patients by increasing the length of remission of the disease.

Case experience of 308-nm excimer laser therapy compatibility with PUVA and oral bexarotene for the treatment of cutaneous lesions in mycosis fungoides.

Little is known about the safety and effectiveness of excimer laser therapy when used in conjunction with other therapies in the treatment of mycosis fungoides (MF) lesions. We describe the use of adjunctive excimer laser therapy in combination with psoralen plus ultraviolet A (PUVA) and oral bexarotene for the treatment of recalcitrant and sanctuary plaques in a patient with MF. In our patient, this regimen successfully induced clinical and histologic resolution in MF plaques with minimal side effects limited to mild, short-lived tenderness and, rarely, local erythema. Our experience suggests that adjunctive excimer laser therapy with PUVA and oral bexarotene has the potential to be a safe, well-tolerated, and effective focal treatment regimen for cutaneous MF lesions.

Randomized controlled observer-blinded treatment of chronic foot eczema with iontophoresis and bath-PUVA.

The aim of this study was to investigate the effect of iontophoresis combined with local psoralen plus ultraviolet A (PUVA) therapy in chronic foot eczema. A randomized, observer-blinded, multi-centre study was conducted in 48 patients with chronic moderate-to-severe foot eczema randomized to one of 3 groups: In the iontophoresis group local bath-PUVA was preceded by iontophoresis. In the PUVA group only local PUVA was given. The corticosteroid group was treated with fluticasone. All treatments were given for 8 weeks, with an 8-week follow-up period. The primary efficacy parameter was eczema score described by Rosén et al. Secondary efficacy parameters were a global impression by the patient, and the Dermatology Life Quality Index (DLQI). The eczema score and the DLQI decreased significantly over time. There were no significant differences in the decrease in eczema score (p=0.053) and DLQI values (p=0.563) between the 3 treatments. The DLQI values in our chronic foot eczema patients were high. There was no obvious advantage of local bath-PUVA with or with-out iontophoresis over local steroid therapy.

Comparative study of systemic psoralen and ultraviolet A and narrowband ultraviolet B in treatment of chronic urticaria.

BACKGROUND: Previous success rates of psoralen and ultraviolet A (PUVA) and narrowband UVB (NB-UVB) in the treatment of chronic urticaria are reported in few studies with no previous reports on the comparable efficacy of both modalities in the disease. AIM: We aimed to compare the efficacy of PUVA versus NB-UVB in the treatment of chronic urticaria. METHODS: Twenty-four patients with chronic urticaria were included and divided into two groups: 12 patients subjected to PUVA and 12 subjected to NB-UVB. They were compared according to the urticaria Total Severity Score (TSS) before and after treatment, cumulative dose, and side effects. RESULTS: There was a statistically significant decrease in urticaria TSS in both the NB-UVB- and PUVA-treated groups after than before treatment (P < 0.05), with no significant difference between both groups regarding the percentage of improved patients and the mean decrease of urticaria TSS (P > 0.05). Gastrointestinal upset was reported at a significantly higher percentage in the PUVA-treated group than in the NB-UVB-treated group. CONCLUSION: Both NB-UVB and PUVA show comparable efficacy in the treatment of chronic urticaria with minimal reversible side effects.

Comparison of pegylated interferon α-2b plus psoralen PUVA versus standard interferon α-2a plus PUVA in patients with cutaneous T-cell lymphoma.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy profile of pegylated interferon α-2b (PEG-IFN α-2b) in combination with photochemotherapy (PUVA) in the treatment of cutaneous T-cell lymphoma (CTCL) in comparison with standard IFN α plus PUVA. DESIGN: Retrospective cohort study over a period of 7 years. PATIENTS AND INTERVENTIONS: A total of 17 consecutive CTCL patients (stage IA-IV) were retrospectively analysed for toxicity and response rates associated with PEG-IFN α-2b (1.5 µg/kg weekly) plus PUVA (n = 9) or standard IFN α-2a (9 MIU 3×/week) plus PUVA (n = 8). MAIN OUTCOME MEASURES: Differences of response rates (complete/partial remission), progression-free survival, discontinuation of therapy, safety and toxicity profiles according to World Health Organization - Common Terminology Criteria of Adverse Events (WHO-CTCAE). RESULTS: Myelosuppression and liver toxicity occured more frequently during PEG-IFN α-2b plus PUVA treatment than during standard IFN α-2a plus PUVA therapy [77.8 vs. 50% (odds ratio 1.477) and 77.8 vs. 50% (odds ratio 1.692), respectively]. By contrast, the occurence of constitutional side-effects (mainly fatigue) [100 vs.77.8% (odds ratio 0.889)] and more adverse events leading to study discontinuation was considerably higher in the standard IFN α-2a plus PUVA group. The overall response rate in the PEG-IFN α-2b plus PUVA group (89%) was significantly superior. CONCLUSIONS: In patients with cutaneous T-cell lymphoma PEG-IFN α-2b plus PUVA might become a promising treatment alternative as its higher rate of myelosuppression and liver toxicity is outweighed by its lower percentage of constitutional side-effects, and its significantly higher overall response. Due to the small number of participants at this retrospective study, a larger prospective study is essential to verify our results.

[Inhibitory acting mechanism of psoralen-osthole on bone metastasis of breast cancer--an expatiation viewing from OPG/RANKL/RANK system].

OBJECTIVE: To find the optimal proportion of Composite Fructus Psoralea and Fructus Cnidii (CFPC) for inhibiting the bone metastasis of breast cancer by way of exploring its acting mechanism viewing from OPG/RANKL/RANK system. METHODS: The human bone metastasis of breast cancer model was established by injecting tumor cells of MDA-MB-231BO cell line into the left cardiac ventricle of nude mice. The modeled mice were randomly divided into seven groups: the blank group administered with normal saline by gastrogavage, the positive control group with zoledronic acid via peritoneal injection, and the 5 tested group with CFPC in different proportions of Fructus Psoralea and Fructus Cnidii, i.e., (A, 4:0; B, 3:1; C, 1:1; D, 1:3, and E 0:4), given by gastric infusion. The treatment started from 1 week after modeling and lasted for six weeks. By the end of the experiment, the metastatic foci in bone were imaged by radionuclide tracing method and X-ray photograph, and separated for detecting gene and protein expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), interleukin-8 (IL-8), parathyroid hormone-related protein (PTHrP), macrophage colony stimulating factor (MCSF) by Real-time PCR and Western blot respectively. RESULTS: Inhibition of bone metastasis gene was displayed to some extent in all the tested groups treated with CFPC, showing an increased level of OPG mRNA expression (It was 60.343 +/- 6.274 in the tested group C), and decreased mRNA expressions of IL-8, PTHrP, MCSF, RANKL (218.010 +/- 12.802, 232.399 +/- 14.354, 319.831 +/- 5.322, and 195.701 +/- 4. 862, respectively in the tested group C). The optimal effect was shown in the tested group C, showing significant difference to that in the blank group (P < 0.01). Meanwhile, the OPG in the bone metastatic foci could be up-regulated and protein expressions of RANKL/IL-8/PTHrP/MCSF down-regulated in all the tested groups. The optimal effect was shown in the tested group C, with significant difference from those of the normal saline group. CONCLUSION: CFPC could inhibit the bone metastasis of breast cancer through activating OPG/RANKL/RANK pathway. Among different proportions of Fructus Psoralea and Fructus Cnidii, 1:1 was the best one.