Gene therapy: future therapy for erectile dysfunction

Advances in molecular biological techniques, completion of the Human Genome Project, and the ensuing age of molecular medicine, in conjuction with the sum of a decades-long accumulation of knowledge of the physiology of erection and the pathophysiology of erectile dysfunction have converged to make gene therapy for erectile dysfunc-tion a distinct possibility. In short, both the intrinsic complexities of mechanisms responsible for ensuring normal erection and the multifactorial nature of erectile dysfunction ensure that there is a relatively vast number of physiologically relevant molecular targets for gene therapy. As such, perhaps it is not surprising that virtually every preclinical gene therapy strategy/target examined thus far has been largely successful in ameliorating conditions associated with compromised erectile function in vivo and/or in vitro. This report highlights the goals and strategies of gene therapy for erectile dysfunction and reviews the strategies that initially have been employed. In short, the preclinical data, while still quite preliminary in many regards, are nonetheless quite impressive and encouraging. If similar success is obtained in clinical trials, gene therapy for erectile dysfunction may provide the first concrete “proof of concept” for using gene therapy in the treatment of human smooth muscle disorders.     

对慢性鼻窦炎药物治疗和手术治疗疗效比较

目的:探讨功能性鼻窦内镜手术(FESS)及药物治疗慢性鼻-鼻窦炎的疗效比较.方法:对2008年1月～2009年1月行功能性鼻窦内镜手术治疗慢性鼻-鼻窦炎患者78例(鼻窦炎症主要在上颌窦和前组筛窦.不伴有鼻息肉.鼻中隔明显偏曲者),患者术后6个月按时复查并有完整资料记录.及对2008年10月～2009年10月药物治疗有完整资料的慢性前组鼻窦炎患者(不伴有鼻息肉.鼻中隔明显偏曲者)82例,对疗效进行回顾性分析.(若患者有急性上呼吸道感染,就将评估时间推迟至症状完全消失2周以后进行).结果:慢性鼻-鼻窦炎患者药物治疗和手术治疗疗效相当.结论:对慢性鼻-鼻窦炎(前组鼻窦炎)应首选药物治疗.     

Physical therapy

Recently, pulmonary rehabilitation program is widely considered one of the most effective and evidence-based treatment for not only chronic obstructive pulmonary disease (COPD) but many clinical situations including neuro-muscular disease, post-operative status and weaning period from the ventilator, etc. The essential components of a pulmonary rehabilitation program are team assessment, patient training, psycho-social intervention, exercise, and follow-up. In 2003, Japanese medical societies (J. Thoracic Society, J. Pul. Rehabilitation Society and J. Physiotherapist Society) made a new guideline for pulmonary rehabilitation, especially how to aproach the execise training. As for the duration after surgical operation, airway cleaning is the important technique to prevent post-operative complications including pneumonia. Postural dranage technique is well known for such condition, at the same time, several instruments (flutter vulve, positive expiratory mask, high frequecy oscillation, etc) were also used for the patient to expectrate airway mucus easier. Lung transplantation is a new method of treatment for the critically-ill patients with chronic respiratoy failure. Several techniques of physical therapy are must be needed before and after lung transplantation to prevent both pulmonary infection and osteoporosis.     

Scrambler therapy

In neuropathies there are complex reactions that modify the homeostatic equilibrium of pain system. In such a context the Scrambler Therapy (ST5) interferes with pain signal transmission, by 'mixing' a 'non-pain' information into the nerve fibres. The aim of this study is to evaluate the effectiveness of ST5 in the treatment of neuropathic pain. The ST5 consists of a multiprocessor apparatus able to simulate 5 artificial neurons by the application of surface electrodes on skin pain areas. A total of 226 patients, all suffering from intense drug-resistant neuropathic pain, were recruited for this trial in 2004. Inclusion criteria: neuropathic pain, very high baseline visual analogue scale (VAS). Exclusion criteria: pacemaker users, neurolithic blocks or neurolesive pain control treatment. The treated neuropathic pain syndromes were: failed back surgery syndrome (FBSS), sciatic and lumbar painpost-herpetical (PHN), trigeminal neuralgia, post-surgery nerve lesion neuropathy, pudendal neuropathy, brachial plexus neuropathy, low back pain (LBP), others. The trial programme: 1 to 6 therapy sessions of 5 treatments, each one lasting 30 min. Pain intensity was evaluated using VAS before and after each treatment. The statistical significance of VAS was measured using the paired t-test. The total results show 80.09% of responders (pain relief>50%), 10.18% of partially responders (pain relief from 25% to 49%) and 9.73% of no responders (patients with pain relief<24% or VAS>3). The CONCLUSIONS: is draen that ST5 produced a statistically significant (P<0.0001) pain relief in all treated neuropathies.     

Gene therapy

We selected bone-metastatic prostate cancer as the target form of recurrent prostate cancer and developed a suicide-gene therapy based on an adenovirus vector with an organ-specific osteocalcin promoter. Related clinical studies have already been conducted in the United States at the University of Virginia, where results so far have established the safety of this therapy. In the present paper, in addition to presenting the results of these gene-therapy studies from the basic research to the clinical stage, we discuss the clinical studies begun by our group in August 2003. In the 21st century, therapeutic systems in use are undergoing major changes. Gene therapy is likely to become an important therapeutic option in recurrent prostate cancer. In terms of theory and technology however, this form of treatment is still at a very immature stage of development. We look forward to evolution in this field to provide an established treatment for recurrent prostate cancer and are committed to actively continuing with the development of gene therapy through translational research.     

Immunosuppressive therapy

Although several new immunosuppressive medications have been developed in the past decade, many possible avenues are yet to be explored. Although the newer agents have not reflected any clear benefit in patient or graft survival over CsA or tacrolimus, they have been useful in reducing the incidence and severity of rejection, reducing the concomitant use of steroids, and decreasing the doses of CsA or tacrolimus to minimize their toxicity profile. The appearance of these new agents has given more options to clinicians, who can select the one with the least toxicity and most efficacy for individual patients. In the future, combinations of these agents, in conjunction with a strategy to induce tolerance of the donor organ without drug toxicity, will be the goal.