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1.The Biological Effects Of IFN-α 2b On Fibroblast Of Urethral Scars 2.Change Of Sexual Function In Patients With LUTS Before And After Ho:YAG Laser Enucleation Of The Prostate

Posted on:2008-01-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:F W MengFull Text:PDF
GTID:1104360212494852Subject:Surgery
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BACKGROUND: Urethral stricture is an increasingly common disease in the Urology, which arises from biopsy, instrumentation, catheterization, external trauma or urethritis. In the pathogenesis of urethral stricture, fibrosis is associated with an excessive collagen accumulate. Interferon-α2b(IFN-α2b) has been reported to be a possible therapeutic agent which is effective in decreasing collagen formation by dermal fibroblasts, hypertrophic scar fibroblasts and fibroblasts derived from sclerodermal lesions. IFN-α stimulates immediate-response genes, which have a significant effect on decreasing collagen synthesis by an indirect mechanism.The aim of the present study is to observe the impact of low doses of IFN-α2b on fibroblasts derived from urethral scar.TGF-β1 is one of the three isoforms of TGF-beta. The TGF-β family is a multifunctional regulator of cell growth, differentiation and extracellular matrix deposition including type I collagen. It was found to be expressed in many cells such as fibroblasts, macrophages, and epithelial and endothelial cells. Several studies found that TGF-β1 can enhance collagen synthesis and inhibit MMP-1 -induced collagen modification. Increased TGF-β1 production has been observed in several human fibrosis diseases. TGF-β1 stimulation has been shown to upregulate the production of collagen types I, III, VII, and fibronectin. The cellular effects of TGF-β1 are mediated via Smad and mitogen-activated protein kinase (MAPK) signaling pathways. Upon binding TGF-β to cell surface receptor, Receptor-activated Smad2 or Smad3 is phosphorylated and then form a heterodimer complex with Smad4. Subsequently, Smads complex translocates to nuclei, binds gene promoters, and regulates gene expression. Smad7, in contrast, is an inhibitory Smad, which represses nuclear translocation of Smad2(3)/4 complex.In the present study, we examined how IFN-α2b may affect collagen synthesis and TGF-β1 production on human urethral scar fibroblasts, explored the feasibility of IFN-α2b treatment on urethral stricture.Objective The purpose of this study was to investigate the effect of IFN-α2b on the growth and proliferation, the function of synthesis and secretion collagen and some cytofactors of fibroblast derived from urethral scar.Methods In vitro cultivation of fibroblasts derived from urethral scar was developed. 72 hours after IFN-α2b(0 IU/ml, 100 IU/ml, 500 IU/ml,1000 IU/ml) was added to the fibroblasts under culture, the shape structure were analyzed with photic microscope and transmission electronic microscope.The fluid cytometer is used to determine the percent of cell in G1,S,and G2+M periods;The OD value is taken with MTT technique and ~3H-proline marked technique is used to determine the collagen secreted by fibroblasts in the super-liquid of each group, and the last method of RT-PCR technique is used to determine the amount mRNA of TGF-β1,types I and III of collagen in fibroblasts.Results With the increasing of the concentration of IFN-α2b, the OD value of the fibroblasts derived from urethral scar are decreased obviously(p<0.01), there is a dose-effect relation between the concentration of IFN-α2b and the OD value of fibroblasts; all the cells show no prominent difference in shape; with the increasing of the concentration of IFN-α2b,in these samples, the percent of cell in G0+G1 period are increasing, that in S and G2+M period are decreasing(p<0.01); the amount of ~3H-proline mixing into collagen in 24 hour are decreasing(p<0.01); the expression of the amount of TGF-β1,types I and III collagen mRNA decreased(p<0.01). Conclusions The results show that IFN-α2b can inhibit the growth, proliferation, and function of fibroblasts derived from urethral scar. IFN-α2b as effective scar inhibitors may have application prospects in the treatment of urethral stricture. BACKGROUND: Recently, studies have indicated the correlation between lower urinary tract symptom caused by benign prostatic hyperplasia and some aspects of sexual problems. Baniel's study showed that 44.2% of the patients with severe urinary symptoms had unsuccessful coitus, compared to 13.1% of the patients with milder dysfunction. Burger's studies further identified the correlation between lower urinary tract symptoms and other sexual dysfunctions, including ejaculation disorders,a decreased sexual desire, and a diminished satisfaction.HorYAG laser enucleation of the prostate (HOLEP) is a new and promising technique for the resection of prostatic tissue. Ho:YAG laser technique possesses unique characteristics such as narrow range of hot injury (only 0.5 —1.0 mm) and good hematischesis.Ho:YAG laser technique enables the operating area to be kept clean and reduces the likelihood of breaking through the prostatic surgery membrane. The Ho:YAG laser rarely hurts the erectile nerves or penile blood vessels. HOLEP provides quick alleviation of symptoms and has been proven to be safe. It may, however, have some side effects, among which disturbances of sexual function were most often suspected. To evaluate the effect of HOLEP on sexual function, studies have been conducted, and the results are reported below.Objective: To analysis the correlation between LUTS and sexual function of old man, and to evaluate the effect of Ho:YAG laser on the sexual function of patients with BPH. METHODS: 108 patients with BPH were recruited and accepted the treatment with Ho:YAG laser. The effectiveness of treatment was evaluated by flow rate and the International Prostate Symptom Score (IPSS) before operation and 6 months afterwards. Meanwhile, international index of erectile function-5(IIEF-5), and Sexual Function Questionnaire were evaluated.Results: Our data indicate there is a positive correlation between patients age and LUTS, r=0.313, (P<0.01);and negative correlation between age and IIEF score, r= -0.478, (P<0.01); negative correlation between LUTS score and IIEF score, r= -0.669, (P<0.01). Before and 6 months after HOLEP treatment, the mean residual urine volume was reduced from 106.0± 51.7ml to 5.6±1.7ml (P<0.01). maximum flow rate(Qmax) was improved from 7.2±3.9 ml/s to 21.7±1.3ml/s(P<0.01), nocturia frequency was reduced from 5.5 to 1.5(P<0.01), the mean IPSS score was decreased from 19.4±5.6 to 7.4±2.6 (P<0.01).The proportion of patients satisfied with their libido were 55% before HOLEP and 57% 6 months afterwards, while 23.5% of the patients have no libido before and after operabbition.37% of the patients were satisfied with their erection before HOLEP and 40% were after 6 months.30% of the patients had completely satisfactory sex life before HOLEP, and 32% did 6 months later. The corresponding percentages of fully impotent patients increased from 33% before the procedure to 35% 6 months post operabbition. Early morning erections were reported by 45% of the patients before the procedure, and by 62% 6 months later(P<0.01). In 70% of the patients with normal sex life ejaculation was retrograde 6 months after HOLEP (P<0.01).Conclusion: There are correlation between age, LUTS and sexual function.Ho:YAG laser does not affect the sexual function of patients with BPH but does did improvethe ability of early morning erection, and caused retrograde ejaculation.
Keywords/Search Tags:IFN-α2b, fibroblast, urethral scar, collagen, HOLEP, BPH, LUTS, sexual function
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