ABSTRACT
Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.
Subject(s)
Erectile Dysfunction/therapy , Nerve Regeneration , Penis/innervation , Peripheral Nerve Injuries/therapy , Pudendal Nerve/injuries , Ultrasonic Therapy/methods , Animals , Cell Proliferation/radiation effects , Cell Survival/radiation effects , Erectile Dysfunction/etiology , Humans , Male , Mitosis/radiation effects , Nerve Growth Factors , Peripheral Nerve Injuries/complications , Schwann Cells/radiation effects , Signal Transduction , Ultrasonic WavesABSTRACT
PURPOSE: An unexplained increase in the incidence of hypospadias has been reported, and yet to our knowledge the molecular events and their regulation leading to hypospadias remain unknown, although environmental compounds capable of endocrine activity are suspected. We screened on a global scale abnormalities in gene expression in human hypospadiac tissue compared to those in nonhypospadiac tissue. Additionally, microarray analysis of tissue from a pair of fraternal twins, including 1 with and 1 without hypospadias, served as a control for genetic variability. We hypothesized that gene expression would differ between hypospadiac vs nonhypospadiac tissue and fraternal twin data would show patterns similar to those of group data on hypospadiac and nonhypospadiac tissue. MATERIALS AND METHODS: Microarray analysis was performed on tissue from patients with and without hypospadias, and from a pair of fraternal twins, including 1 with and 1 without hypospadias. Analysis incorporated the expression of 22,000 genes. RESULTS: We found significant differences in gene expression, specifically with a group of genes, including CYR61, CTGF, ATF3 and GADD45beta, known to be responsive to estrogen or to interact with estrogen receptor. CONCLUSIONS: Our findings provide support for the hypothesis that endocrine active environmental compounds may contribute to the development of hypospadias. Additionally, regulation of these genes may have a role in formation of the urethra.
Subject(s)
Activating Transcription Factor 3/genetics , Antigens, Differentiation/genetics , Hypospadias/genetics , Immediate-Early Proteins/genetics , Intercellular Signaling Peptides and Proteins/genetics , RNA/genetics , Up-Regulation , Activating Transcription Factor 3/metabolism , Antigens, Differentiation/metabolism , Cluster Analysis , Connective Tissue Growth Factor , Cysteine-Rich Protein 61 , Estrogens/metabolism , Foreskin/metabolism , Foreskin/pathology , Genetic Predisposition to Disease , Humans , Hypospadias/metabolism , Hypospadias/pathology , Immediate-Early Proteins/metabolism , Infant , Intercellular Signaling Peptides and Proteins/metabolism , Male , Microarray Analysis/methods , Receptors, Estrogen/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Neurogenic erectile dysfunction (NED) caused by pelvic floor surgeries/radiation therapies and associated with Parkinsons disease and diabetes remains a challenging healthcare issue. To facilitate NED research we have developed in vitro and in vivo experimental models. The in vitro model comprises the isolation, culture and treatment of rat major pelvic ganglia (MPG), which then produce outgrowing neurites whose length and molecular composition are indicative of the neurotrophic effect of the treatment agent. Through this approach we have confirmed that the brain-derived neurotrophic factor (BDNF) promotes nerve regeneration by activating the JAK/STAT signaling pathway. This has been further established by our in vivo model, which involves the transection or cruch of cavernous nerves and treatment with BDNF.
Subject(s)
Erectile Dysfunction/physiopathology , Ganglia/physiopathology , Nerve Regeneration , Animals , Disease Models, Animal , Humans , In Vitro Techniques , Male , Pelvis/innervation , Penis/innervation , Penis/physiopathologyABSTRACT
AIM: To identify proteins that are differentially expressed in cells derived from normal and diseased tunica albuginea (TA) as related to Peyronie's disease (PD). METHODS: Cells with characteristics of fibroblasts were isolated from two tissue sources. Those from the plaque of patients with PD were designated as PT cells, and those from the normally-appearing TA of the same patients were designated as NT cells. Messenger RNAs of these cells were analyzed by real-time polymerase chain reaction (RT-PCR) for the expression of monocyte chemoattractant protein 1 (MCP-1). Crude protein lysates were analyzed by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) with IMAC30-Cu, CM10, and H50 chips. Each lysate was then separated into six fractions, which were further analyzed by SELDI-MS. RESULTS: RT- PCR analysis showed that PT cells expressed higher levels of MCP-1 than their counterpart NT cells. SELDI-MS analysis showed that the crude protein lysates of all four cell strains produced similar and reproducible protein profiles on IMAC30-Cu and CM10 chips. Additional SELDI-MS analyses with the fractionated lysates detected three proteins of 11.6 kDa, 14.5 kDa, 22.6 kDa that were upregulated in PT cells and two proteins of 6.3 kDa and 46.9 kDa that were downregulated in PT cells. CONCLUSION: MCP-1, which is often involved in tissue fibrosis, was expressed at higher levels in PT than that in NT cells. Five potential biomarkers for PD were identified by SELDI-MS analysis.
Subject(s)
Biomarkers/analysis , Chemokine CCL2/metabolism , Penile Induration/metabolism , Base Sequence , Cells, Cultured , DNA Primers , Humans , Male , Mass Spectrometry/methods , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVE: To evaluate the relationship between the deformation of penile artery and the primary artery erectile dysfunction, and to improve the treatment and diagnosis of primary artery erectile dysfunction. METHODS: One case of primary artery erectile dysfunction was presented with its primary clinic data. RESULTS: The dorsal artery of the penis was thin and the bilateral penile arteries were lacking by arteriography. The implantation of a penile prosthesis significantly improved the patient's erectile function. CONCLUSION: The primary artery erectile dysfunction is a relatively rare disease. The possibility of primary artery erectile dysfunction should be kept in mind. Penile prosthesis implantation is an effective means for the treatment of primary artery erectile dysfunction.
Subject(s)
Impotence, Vasculogenic/physiopathology , Penile Implantation , Adult , Arteries/abnormalities , Humans , Impotence, Vasculogenic/diagnostic imaging , Impotence, Vasculogenic/surgery , Male , Penis/blood supply , Penis/diagnostic imaging , RadiographyABSTRACT
OBJECTIVE: To isolate embryonic stem cells that have differentiated along the neuronal cell line, and to assess whether injecting these neural stem cells into the corpus cavernosum influences cavernosal nerve regeneration and functional status. MATERIALS AND METHODS: Embryonic neural stem cells were obtained; 26 male Sprague-Dawley rats were divided into four groups: five had a sham operation; eight (controls) had a bilateral cavernosal nerve crush and injection of culture medium into the corpora cavernosa; four had an injection of neural embryonic stem (NES) cells into the major pelvic ganglion (MPG); and nine had bilateral cavernosal nerve crush and injection of NES cells into the corpora cavernosa. Erectile response was assessed by cavernosal nerve electrostimulation at 3 months, and penile tissue samples were evaluated histochemically for nitric oxide synthase (NOS)-containing fibres, tyrosine hydroxylase and neurofilament staining. RESULTS: The groups injected with NES cells into the MPG and corpora cavernosa had significantly higher intracavernosal pressures than the control group. Immunohistochemical staining also revealed differences in the quality of the NOS-containing nerve fibres. Neurofilament staining was significantly better in the experimental groups injected with NES cells. CONCLUSION: We were able to isolate embryonic stem cells that had differentiated along the neural cell line and, using these NES cells intracavernosally, showed improved erectile function in a rat model of neurogenic impotence.
Subject(s)
Penis/innervation , Stem Cell Transplantation , Trauma, Nervous System/therapy , Animals , Erectile Dysfunction/therapy , Immunohistochemistry , Male , Nerve Fibers/chemistry , Nitric Oxide Synthase/analysis , Penis/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To investigate the transduction of Wnt/Frizzled signaling pathway, especially the function of T cell factor 4 (TCF(4)), in renal carcinoma. METHODS: A renal carcinoma yeast two hybrid library and a human TCF(4) yeast two hybrid expression vector were constructed. Proteins interacting with the bait protein human TCF(4) were obtained from the renal carcinoma yeast two hybrid library by reverse yeast two hybrid system. RESULTS: 67 positive clones interacting with the bait protein TCF(4) were obtained by reverse yeast two hybrid system, including 18 beta-catenin clones, 24 TCF(4) clones and 25 unknown clones. CONCLUSION: Wnt/Frizzled signaling pathway exists in renal carcinoma. TCF(4), its important signal factor, interacts with beta-catenin and forms homodimer or homocopolymer by itself, thus displaying its constitutive transcriptional activity.
