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Selected AbstractsGene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposomeTHE JOURNAL OF GENE MEDICINE, Issue 6 2010Jiong Li Abstract Background Topical transdermal gene delivery to the skin shows great potential for painless, non-invasive administration of vaccines and therapeutic agents. Interleukin (IL)-4 strategies have shown a good antipsoriatic effect in clinic trials. To date, no information has been acquired on the effectiveness of gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal penetration of murine IL-4 (mIL-4) using ultradeformable cationic liposome (UCL). Methods In the present study, we synthesized an UCL and determined a suitable formula for transdermally delivering plasmid DNA to mouse skin. We then tested the antipsoriatic efficacy in the K14-VEGF transgenic mouse model by transdermal delivery of mIL-4 using UCL. Results We found that plasmid DNA was transdermally delivered to vicinal sites of epidermis and hair follicles using this optimized formula. Plasmid DNA expression was detected in ear skin. Twenty-four hours after topical application, plasmid DNA was not detected in blood serum and liver, which may decrease the risk of insertion of promoter from plasmid to genomic DNA. Mice treated with UCL/mIL-4 displayed a mild psoriasis phenotype. Histological analysis of pathological score using the Baker scoring system revealed an antipsoriatic effect. Immunohistochemical analysis revealed that hyperplastic and inflamed vessels were suppressed. Conclusions These observations provide evidence of antipsoriatic efficacy by topical transdermal delivery of mIL-4. Therefore, topical transdermal gene transfer is attractive and offers future potential for application in human patients with other dermatogic diseases. Copyright © 2010 John Wiley & Sons, Ltd. [source] The Impairment of Sexual Function Is Less Distressing for Menopausal than for Premenopausal WomenTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2010Marta Berra MD ABSTRACT Introduction., Menopause requires psychological and physical adjustments because of the occurring significant hormonal changes. Sexuality is one of the aspects that undergoes the most profound modifications. Preliminary data suggest that sometimes women do not regard sexual changes as problematic and often readjust their life and relationship according to their new physical status. Aim., The aim of our study was to evaluate sexual function and the way women feel by comparing healthy postmenopausal and premenopausal women. Methods., One hundred menopausal (M) and 100 premenopausal (pM) healthy women were asked to complete anonymous questionnaires to assess sexual function and stress related to sexual activity. Main Outcome Measures., Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS) were completed by M and pM women. Results., Medium FSFI score was 20.5 ± 9.6 and 26.4 ± 7.7 (P < 0.0005) and medium FSDS score was 12.1 ± 11.7 (95% CI 9.7,14.4) and 11.3 ± 10.2 (P = 0.917) for M and pM women, respectively. Twenty-five of the 69 M women and 20 of the 31 pM women with a pathological score in the FSFI questionnaire scored higher than 15 in the FSDS (P < 0.0005). The overall prevalence of sexual dysfunction was 20% and 25% (P = 0.5) in the M and pM women. Conclusions., Our data confirm that menopause is associated with changes in sexual function that may be compatible with sexual dysfunction. However, personal distress caused by these changes in sexual life appears to be lower among menopausal women (36.2%) as compared with premenopausal women (64.5%). These data suggest that medical treatment for sexual health in menopause must be highly personalized and carefully prescribed. Berra M, De Musso F, Matteucci C, Martelli V, Perrone AM, Pelusi C, Pelusi G, and Meriggiola MC. The impairment of sexual function is less distressing for menopausal than for premenopausal women. J Sex Med 2010;7:1209,1215. [source] Evaluation by scanning acoustic microscopy (SAM) on glomerular lesion of IgA nephropathyNEPHROLOGY, Issue 2001H Kiyomoto IgA nephropathy (IgAN) is known to commonly cause of end-stage renal failure in Japan. The glomerular lesions of IgAN have histological variations. The determination of prognosis and therapeutic strategy should be carefully done by experts because morphological information from renal biopsies using ordinary optical microscopy is usually qualitative and subjective. Moreover, the histological items for the evaluation of glomerular lesions seems to be unsatisfactory for expression of the disease condition of IgAN. The beneficial properties of scanning acoustic microscopy (SAM) include not only observation of microstructure but also quantitative measurement of acoustic propagation speed (APS), indicating the tissue elasticity. In the present study we compared the APS of glomeruli with the pathological scores that were determined by ordinary light microscopy. We used stocked human renal biopsy specimens diagnosed as IgAN (n = 12) and normal/minimal changes (n = 5). All samples were taken by renal biopsy in Kagawa Medical University Hospital during 1997,2000 under informed consent of the patients. The obtained renal tissue were immersed in 10% formalin and embedded in paraffin. A fixed specimen was consecutively cut into 4 ,m slices. One of the deparaffinized 4 ,m-specimens was directly utilized for SAM without any staining, and the others were stained with haematoxylin-eosin and Masson Trichrome for counting cell number and evaluation of collagen accumulation. For the measurement of glomerular APS, the sample line was set on the equator of the glomerulus and then scanning of the X,Z axis was carried out to obtain the interference fringes that were analysed with a computer imaging software in order to calculate the APS. In light microscopic study, pathological scores were evaluated semiquantitatively by two independent investigators who were unaware of the sample number. Glomerular lesions were scored into five grades and glomerular cell number was also counted in individual glomerulus. The computer-assisted imaging analyser Win ROOF (Mitani, Fukui, Japan) was also used for the determination of glomerular collagen content in specimens stained by Masson Trichrome. A two-dimensional image (C-mode scanning) of SAM enabled imaging of glomerulus in renal biopsy specimen compatible with findings of ordinary light microscopy without staining dye. The glomerular APS in IgAN was significantly higher than in normal/minimal changes. This alteration of glomerular APS in IgAN was positively correlated to both semiquantitative pathological scores and glomerular collagen content determined by light microscopy. However, the cell number of glomelurus did not change between IgAN and normal/minimal change. As a result, we conclude that the glomerular lesion, especially matrix expansion in IgAN, was comparable with the absolute value among specimens. Therefore, it is suggested that SAM method is a novel and useful technique for quantitative evaluation of glomerular lesion in IgAN. [source] Long-term psychological consequences of pregnancy termination for fetal abnormality: a cross-sectional studyPRENATAL DIAGNOSIS, Issue 3 2005M. J. Korenromp Abstract Objective We examined women's long-term psychological well-being after termination of pregnancy (TOP) for fetal anomaly in order to identify risk factors for psychological morbidity. Methods A cross-sectional study was performed in 254 women, 2 to 7 years after TOP for fetal anomaly before 24 weeks of gestation. We used standardised questionnaires to investigate grief, posttraumatic symptoms, and psychological and somatic complaints. Results Women generally adapted well to grief. However, a substantial number of the participants (17.3%) showed pathological scores for posttraumatic stress. Low-educated women and women who had experienced little support from their partners had the most unfavourable psychological outcome. Advanced gestational age at TOP was associated with higher levels of grief, and posttraumatic stress symptoms and long-term psychological morbidity was rare in TOP before 14 completed weeks of gestation. Higher levels of grief and doubt were found if the fetal anomaly was presumably compatible with life. Conclusion Termination of pregnancy for fetal anomaly is associated with long-lasting consequences for a substantial number of women. Clinically relevant determinants are gestational age, perceived partner support, and educational level. Copyright © 2005 John Wiley & Sons, Ltd. [source] |