Penile neurovascular structure revisited: immunohistochemical studies with three-dimensional reconstruction.

Penile erection is a neurovascular phenomenon that requires well coordinated and functional interaction between penile vascular and nervous systems. In order to provide a useful tool to examine pathologic changes in the erectile tissue, mainly focusing on penile neurovascular dysfunction, we established the technique to determine the differential distribution of endothelial cells, smooth muscle cells, pericytes, and nerve fibers in the mouse penis using immunohistochemical staining with three-dimensional reconstruction. Immunofluorescent staining of penile tissue was performed with antibodies against CD31 (an endothelial cell marker), smooth muscle α -actin (SMA, a smooth muscle cell marker), NG2 (a pericyte marker), or ßIII-tubulin (a neuronal marker). We reconstructed three-dimensional images of penile vascular or neurovascular system from stacks of two-dimensional images, which allows volume rendering and provides reliable anatomic information. CD31-positive endothelial cells, SMA-positive smooth muscle cells, and NG2-positive pericytes were evenly distributed and composed sinusoidal or venous wall. However, the endothelial layer of the cavernous artery or dorsal artery was mainly covered with smooth muscle cells and rarely associated with pericytes. The reconstructed three-dimensional images clearly visualized typical wavy appearance of nerve fibers that evenly innervate to cavernous sinusoids, cavernous artery, dorsal vein, and dorsal artery. We observed a significant decrease in CD31-positive endothelial cells, NG2-positive pericytes, and ßIII-tubulin-positive nerve fibers in the penis of diabetic mice compared with those in normal condition. Our protocol for immunofluorescent staining with three-dimensional reconstruction will allow a better understanding of the penile neurovascular anatomy and may constitute a standard technique to determine the efficacy of candidate therapeutics targeting therapeutic angiogenesis or neural regeneration.

Calorie restriction reverses age-related alteration of cavernous neurovascular structure in the rat.

Calorie restriction (CR) refers to a reduction of calorie intake without compromising essential nutrients to avoid malnutrition. CR has been established as a non-genetic method of altering longevity and attenuating biological changes associated with aging. Aging is also an important risk factor for erectile dysfunction. The aim of this study was to examine whether CR diet can reverse the age-related alterations of erectile tissue in the aged rat. Four groups of rats were used: young rats (7 months) + ad libitum, aged rats (22 months) + ad libitum, young rats + CR diet, and aged rats + CR diet. The ad libitum group had free access to both food and water, and CR groups were fed 60% of the food intake of their ad libitum littermates, starting from 6 weeks before sacrifice. The penis was harvested and stained with antibodies to von Willebrand factor, smooth muscle α-actin, platelet-derived growth factor receptor-ß, phospho-eNOS, nNOS, and neurofilament. We also performed Masson trichrome staining and TUNEL assay. The blood samples were collected for the measurement of serum total testosterone level. The contents of endothelial cells, smooth muscle cells, pericytes, and neuronal cells as well as serum testosterone levels were significantly lower in the penis of aged rats than in their young littermates. CR significantly restored cavernous endothelial cells, smooth muscle cells, pericytes, and neuronal cell contents and decreased cavernous endothelial cell apoptosis and fibrosis in both young and aged rats. CR also increased serum testosterone level in aged rats, but not in young rats. CR successfully improved age-related derangements in penile neurovascular structures and hormonal disturbance. Along with a variety of lifestyle modifications, our study gave us a scientific rationale for CR as a non-pharmaceutical strategy to reprogram damaged erectile tissue toward neurovascular repair in aged men.

Establishment of in vitro model of erectile dysfunction for the study of high-glucose-induced angiopathy and neuropathy.

Penile erection requires complex interaction between vascular endothelial cells, smooth muscle cells, pericytes, and autonomic nerves. Diabetes mellitus is one of the most common causes of erectile dysfunction (ED) and multiple pathogenic factors, such as cavernous angiopathy and autonomic neuropathy, are associated with diabetic ED. Although a variety of animal models of diabetic ED play an important role in understanding pathophysiologic mechanisms of diabetes-induced ED, these animal models have limitations for addressing the exact cellular or molecular mechanisms involved in ED. Therefore, we established an in vitro model of ED for the study of high-glucose-induced angiopathy and neuropathy. We successfully isolated and cultivated mouse cavernous endothelial cells (MCECs) and mouse cavernous pericytes (MCPs). The cells were exposed to the normal-glucose (5 mmoL) or high-glucose (30 mmoL) condition for 48 h. In vitro matrigel assay revealed impairments in tube formation in primary cultured MCECs or MCPs exposed to high-glucose condition. To study cellular interaction between MCECs and MCPs, co-culture systems including indirect contact, indirect non-contact, and direct mixed co-culture system, were established. We observed impaired tube formation and increased permeability in MCECs-MCPs co-culture exposed to high-glucose condition. To evaluate the effect of high-glucose on neurite sprouting, the mouse major pelvic ganglion (MPG) tissue was harvested and cultivated in matrigel. Neurite outgrowth and nNOS-positive nerve fibers were significantly lower in MPG tissues exposed to the high-glucose condition than in the tissues exposed to the normal-glucose condition. We believe that in vitro model of ED will aid us to understand the role of each cellular component in the pathogenesis of diabetic ED, and also be a useful tool for determining the efficacy of candidate therapeutics targeting vascular or neuronal function. This model would present a new avenue for drug discovery and development of novel therapeutic modalities for erectile dysfunction.

Gallbladder carcinoma: causes of misdiagnosis at CT.

Gallbladder carcinomas can present with varied imaging features on computed tomography. The three major imaging features include (1) focal or diffuse wall thickening with or without irregularity of the gallbladder; (2) polypoidal intraluminal mass; and (3) large mass obscuring and replacing the gallbladder, often extending to the liver. Patterns of wall thickening or polypoid growth are often confused with various benign gallbladder diseases due to overlap of imaging findings. Moreover, gallbladder carcinomas that coexist with benign gallbladder diseases make accurate preoperative diagnosis more difficult. Recently, high-resolution ultrasound (HRUS) has been regarded as a problem-solving tool for gallbladder diseases. In this article, we will illustrate various imaging presentations of gallbladder cancer, along with imaging pitfalls and recently updated HRUS findings.

Intracavernous delivery of clonal mesenchymal stem cells rescues erectile function in the streptozotocin-induced diabetic mouse.

The major hurdle for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes. The aim of this study was to examine the effectiveness of mouse clonal bone marrow-derived stem cells (BMSCs) obtained from a single colony by using subfractionation culturing method for erectile function in diabetic animals. Twelve-week-old C57BL/6J mice were divided into four groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of PBS (20 µL) or clonal BMSCs (3 × 10(5) cells/20 µL). Clonal BMSCs were isolated from 5-week-old C3H mice. Two weeks after treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was stained with antibodies to PECAM-1, smooth muscle α-actin, neuronal nitric oxide synthase (nNOS), neurofilament, and phosphorylated endothelial NOS (phospho-eNOS). We also performed Western blot for phospho-eNOS, and eNOS in the corpus cavernosum tissue. Local delivery of clonal BMSCs significantly restored cavernous endothelial and smooth muscle cell contents, and penile nNOS and neurofilament contents, and induced eNOS phosphorylation (Ser1177) in diabetic mice. Intracavernous injection of clonal BMSCs induced significant recovery of erectile function, which reached 80-90% of the control values. Clonal BMSCs successfully restored erectile function through dual angiogenic and neurotrophic effects in diabetic mice. The homogenous nature of clonal mesenchymal stem cells may allow their clinical applications and open a new avenue through which to treat diabetic erectile dysfunction.

Belching during gastroscopy and its association with gastroesophageal reflux disease.

Belching may result from transient lower esophageal sphincter relaxation; therefore, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). This study was conducted to investigate the frequency of belching during esophagogastroduodenoscopy (EGD) and its association with GERD. A retrospective review was performed on prospectively collected clinical and endoscopic data from 404 subjects who underwent EGD without sedation from December 2012 to May 2013 in a training hospital in Korea. All detectable belching events during endoscopy were counted. Frequency and severity of belching events were compared between the group with and without GERD using an ordinal logistic regression model. There were 145 GERD patients (26 erosive reflux disease and 119 nonerosive reflux disease [NERD]). In the multivariable analysis, GERD was significantly associated with a higher frequency of belching events (odds ratio = 6.59, P < 0.001). Central obesity, female, and younger age were also risk factors for frequent belching during EGD. Subgroup analyses were performed in subjects without erosive reflux disease (n = 378) and NERD (n = 293). NERD was also a predictive factor for frequent belching during EGD (odds ratio = 6.61, P < 0.001), and the frequency of belching was significantly correlated with GERD severity according to the Los Angeles classification (P < 0.05). Frequent belching during EGD was associated with GERD, including NERD. Future research should focus on its adjuvant role in the diagnosis of GERD/NERD and the necessity for applying differentiated endoscopy strategies for GERD patients, leading to less discomfort during EGD in patients at risk for intolerability.

Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner.

Aberrant expression of Wnt family contributes to the pathogenesis of diabetes-induced erectile dysfunction.

Diabetic erectile dysfunction (ED) has multiple causative factors, such as endothelial and smooth muscle dysfunction and cavernous fibrosis. Wnt signalling is essential for normal embryonic development and for tissue homeostasis in adults. Aberrant activation of Wnt family members has been implicated in tissue fibrosis and in angiogenesis. In this study, we investigated the differential expression of Wnts in the penises of mice with streptozotocin-induced diabetic ED. We also examined the effect of transforming growth factor-ß1 (TGF-ß1) on the expression of Wnts in primary cultured fibroblasts isolated from human tunica albuginea. Among the mouse and human Wnts tested, 16 mouse Wnts and 14 human Wnts were detected in the corpus cavernosum tissue of normal mice and in fibroblasts derived from human tunica albuginea respectively. We observed up-regulation of Wnt10b (known to be involved in tissue fibrosis) and down-regulation of Wnt16 (known to be involved in vasculogenesis and hematopoiesis), both in the diabetic condition in vivo and with treatment of fibroblasts with TGF-ß1 in vitro. Wnt10b was mainly expressed in fibroblasts and Wnt16 was colocalized with smooth muscle cells in the corpus cavernosum tissue. Cavernous TGF-ß1 protein expression and the degree of cavernous fibrosis determined by the ratio of collagen to smooth muscle content were significantly higher in diabetic mice than in controls. Cavernous endothelial content was significantly decreased by the diabetic condition. Overexpression of Wnt16 with plasmid vector accelerated tube formation in primary cultured mouse cavernous endothelial cells. However, down-regulation of Wnt10b with small interfering RNA did not decrease the production of extracellular matrix protein in human fibroblasts. This is the first report demonstrating the differential expression of Wnts in diabetic mouse penis. Aberrant Wnt expression might contribute to the pathogenesis of ED.

A guanidinylated bioreducible polymer as a novel gene carrier to the corpus cavernosum of mice with high-cholesterol diet-induced erectile dysfunction.

A prerequisite for the successful clinical application of gene therapy in erectile dysfunction (ED) is the availability of safe and efficient gene delivery systems. The aim of this study was to examine the effectiveness of guanidinylated bioreducible polymer (GBP) polyplexes for gene delivery systems, which take advantage of the biodegradability of reducible disulfide bonds and the cell-penetrating ability of guanidine groups. For in vitro transfection experiments, we used mouse cavernous endothelial cells and A7r5 rat vascular smooth muscle cells. For in vivo experiments, we used a mouse model of hypercholesterolaemic ED in which 2-month-old male C57BL/6 mice were fed a diet containing 4% cholesterol and 1% cholic acid for 3 months. Animals or cells were treated with pCMV-Luc, poly(ethyleneimine) (PEI)25k/pCMV-Luc polyplex (weight ratio: 1) and GBP/pCMV-Luc polyplexes (weight ratio: 20, 40, 60 and 80). Gene expression was evaluated by luciferase assay, and the gene expression area was evaluated by immunohistochemistry. GBP had greater transfection efficiency as the weight ratio increased. GBP had sevenfold higher gene delivery efficiency in A7r5 cells at a weight ratio of 80 than did PEI25k. Moreover, the gene expression was more profoundly induced by GBP/pCMV-Luc than by pCMV-Luc in both the corpus cavernosum tissue of hypercholesterolaemic mice and in mouse cavernous endothelial cells, although the expression levels induced by the GBP gene delivery system were lower than those induced by the PEI25k gene delivery system. GBP revealed no considerable cytotoxicity to A7r5 cells and mouse cavernous endothelial cells (relative cell viability: 95 and 88% respectively), whereas PEI25k resulted in high cytotoxicity. Interestingly, immunofluorescent double staining revealed that luciferase expression induced by the GBP polyplex mainly overlapped with cavernous endothelial cells, but rarely with smooth muscle cells. The GBP-based non-viral gene expression system may be useful for the development of gene therapy in vasculogenic ED.

Converging perturbed microvasculature and microglial clusters characterize Alzheimer disease brain.

We have investigated physical properties of microvasculature and vessel association with microglial clusters in cortical tissue from Alzheimer disease individuals, classified as severe (ADsev) or mild (ADmild), and nondemented controls (ND). Immunostaining with laminin or von Willerbrand factor demonstrated numbers of microvessels and microvascular density were significantly higher in ADsev cases compared with levels in ADmild or ND cases suggesting proangiogenic activity in ADsev brain. Evidence for extravascular laminin immunoreactivity was found in ADsev tissue and was largely absent in ADmild and ND cases suggesting vascular remodeling in ADsev brain included abnormalities in blood vessels. Microgliosis was progressively increased from ND to ADmild to ADsev with the latter demonstrating areas of clustered microglia (groupings of three or more cells) rarely observed in ADmild or ND cases. Microglial clusters in ADsev brain were in close proximity with extravascular laminin and also plasma protein, fibrinogen, implicating vascular perturbation as a component of inflammatory reactivity. ADsev brain also exhibited elevated levels of the pro-inflammatory/angiogenic factors tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in association, relative to non-association, with microglial clusters. The presence of extravascular laminin and fibrinogen and the vascular modifying factors, TNF-α and VEGF in localization with clusters of activated microglia, is consistent with microglial-induced vascular remodeling in ADsev brain. Microglial-vascular reciprocal interactions could serve a critical role in the amplification and perpetuation of inflammatory reactivity in AD brain.

Fibrinogen signal transduction in the nervous system.

Fibrinogen is a pleiotropic blood protein that regulates coagulation, inflammation and tissue repair. Fibrinogen extravasates in the nervous system after injury or disease associated with vascular damage or blood-brain barrier (BBB) disruption. Fibrinogen is not merely a marker of BBB disruption, but plays a causative role in neurologic disease as a potent inducer of inflammation and an inhibitor of neurite outgrowth. Fibrinogen mediates functions in the nervous system as a ligand for cell-specific receptors. In microglia, fibrinogen mediates activation of Akt and Rho via the CD11b/CD18 integrin receptor, while in neurons fibrinogen induces phosphorylation of epidermal growth factor (EGF) receptor via the alphavbeta3 integrin. Pharmacologic targeting of the interactions of fibrinogen with its nervous system receptors could provide novel strategies for therapeutic intervention in neuroinflammatory and neurodegenerative diseases.

Thalidomide inhibition of vascular remodeling and inflammatory reactivity in the quinolinic acid-injected rat striatum.

Effects of thalidomide administration on vascular remodeling, gliosis and neuronal viability have been studied in excitotoxin-injected rat striatum. Intrastriatal injection of quinolinic acid (QUIN) caused time-dependent changes (durations of 6 h, 1 and 7 d post-injection) in vascular remodeling. QUIN excitotoxic insult was associated with increased numbers of vessels (laminin or collagen IV markers) demonstrating considerable abnormalities in morphology, including short fragments and vascular loops. Non-lesioned striatum, with injection of phosphate buffer solution (PBS) as a vehicle, showed no evidence for vascular remodeling. A maximal extent of vascular remodeling was measured at 1 d post-QUIN and was correlated with marked increases in microgliosis (ED1 marker) and astrogliosis (glial fibrillary acidic protein [GFAP] marker) relative to control PBS injection. Double staining of laminin with ED1 and GFAP demonstrated areas of close association of glial cells with blood vessels. Treatment of QUIN-injected animals with the anti-inflammatory compound, thalidomide significantly inhibited vascular remodeling (by 43%) and reduced microgliosis (by 33%) but was ineffective in modifying extents of astrogliosis. Intrastriatal QUIN injection was associated with a marked loss of striatal neurons relative to non-lesioned control with thalidomide treatment exhibiting a significant degree of neuroprotection (24% recovery) against QUIN-induced neurotoxicity. These results suggest close links between microglial-mediated inflammatory responses and vascular remodeling, with inflammatory reactivity associated with, and contributing to, neuronal damage in excitotoxically-lesioned striatum.

Branch duct intraductal papillary mucinous neoplasms in a retrospective series of 190 patients.

BACKGROUND: A consensus conference has recommended close observation of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) smaller than 30 mm, without symptoms or mural nodules. This study investigated whether these recommendations could be validated in a single-centre experience of BD-IPMNs. METHODS: Some 190 patients with radiological imaging or histological findings consistent with BD-IPMN were enrolled between 1998 and 2005. Those with less than 6 months' follow-up and no histological confirmation were excluded. RESULTS: BD-IPMN was diagnosed by computed tomography and pancreatography in 105 patients and pathologically in 85. Eighteen patients had adenoma, 53 borderline malignancy, five carcinoma in situ and nine invasive carcinoma. Findings associated with malignancy were the presence of radiologically suspicious features (P < 0.001) and a cyst size of at least 30 mm (P = 0.001). Had consensus guidelines been applied, 54 patients would have undergone pancreatic resection, whereas only 28 of these patients actually had a resection; 12 of the latter patients had a malignancy compared with none of the 26 patients who were treated conservatively. CONCLUSION: A simple increase in cyst size is not a reliable predictor of malignancy. Observation is recommended for patients with a BD-IPMN smaller than 30 mm showing no suspicious features on imaging.

Relevance of abeta1-42 intrahippocampal injection as an animal model of inflamed Alzheimer's disease brain.

Injection of amyloid-beta peptide (Abeta1-42) into hippocampal and cortical regions of brain may have utility as an animal model of Alzheimer's disease (AD) emphasizing the inflammatory component of disease pathology. This review summarizes recent evidence supporting the relevance of the peptide injection model to describe inflammatory conditions in AD brain. A wide spectrum of responses are considered from effects of Abeta1-42 on animal behavior and cognitive performance to peptide actions at the cellular and molecular levels. In the latter case a particular focus is placed on inflammatory responses mediated by activated microglia. Specific pharmacological modulations of microglial signaling pathways and factors and how they shape patterns of inflammatory reactivity in peptide-injected brain are included. Overall, the considerations for the validity and limitations of Abeta1-42 injection as an animal model for AD pathology are also discussed.

Primary clear cell adenocarcinoma of the rectovaginal septum treated with concurrent chemoradiation therapy: a case report.

Primary clear cell adenocarcinoma of the rectovaginal septum is rare and typically emerges in the setting of endometriosis. We report a case of a 52-year-old woman with clear cell adenocarcinoma of the rectovaginal septum presenting with vaginal hemorrhage. Management with concurrent chemoradiation with cisplatin and paclitaxel is discussed. Six years following the completion of treatment, the patient is without evidence of disease or significant long-term toxicity.

Can we predict spontaneous capsule passage after retention? A nationwide study to evaluate the incidence and clinical outcomes of capsule retention.

BACKGROUND AND STUDY AIMS: Although capsule endoscopy has become a central diagnostic tool for small-bowel evaluation, retention of a capsule remains a major concern. This study attempted to investigate the incidence and clinical outcomes of capsule retention, and to determine the factors predictive of spontaneous capsule passage after retention. PATIENTS AND METHODS: Through a nationwide multicenter survey, we retrospectively reviewed the records of 1291 patients who had a capsule endoscopy between February 2002 and July 2006 in Korea. Clinical and procedural characteristics and postprocedural outcomes were analyzed for the cases with capsule retention. RESULTS: Capsule retention occurred in 2.5 % of total cases (32/1291). The major diseases accompanying capsule retention were Crohn's disease, malignant tumors, and tuberculous enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early surgical or endoscopic interventions were instituted for diagnosis or treatment of diseases before retention symptoms developed. The remaining 21 (65.6 %) patients initially received medical treatments. Of these, 10 (31.3 %) ultimately underwent surgical intervention due to the development of symptoms of intestinal obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed the capsule. The presence of a larger lumen diameter (greater than two-thirds of the capsule diameter) at the stricture site was associated with spontaneous passage. CONCLUSIONS: Our large-scale study suggests that retention occurs infrequently during capsule endoscopy. Moreover, a retained capsule might indicate the best intervention for the offending pathology, or it may spontaneously pass in the long run, particularly in patients with less small bowel stricture.

Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington's disease.

The combination effects of minocycline (MC), a second-generation tetracycline compound and pyruvate (PY), a glycolysis end metabolite with antioxidant activity were investigated in the rat striatum following an excitotoxic insult. Striatal injection of quinolinic acid (QUIN) resulted in marked inflammation characterized by microgliosis, astrogliosis and enhanced expressions of pro-inflammatory enzymes inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory responses were attenuated with administration of either MC or PY, however, the combination of both compounds was significantly more effective in reducing inflammation relative to MC or PY applied alone. Immunohistochemical analysis at 7 days post-intrastriatal QUIN injection showed extensive oxidative stress evident as lipid peroxidation, oxidative DNA damage and reactive oxygen species formation which was partially decreased by each agent applied separately but markedly inhibited with the combination of the two compounds. In addition, combination treatments significantly reduced neuronal loss in QUIN-injected striatum compared with the agents applied separately. Furthermore, long-term combination treatment decreased striatal lesions and inflammation after QUIN injection. These results demonstrate that MC and PY confer a considerably enhanced anti-inflammatory and neuroprotective efficacy when applied together and suggest this combinatorial procedure as a novel therapeutic strategy in neurodegenerative disorders such as Huntington's disease which exhibit excitotoxic insults.

Water-soluble lipopolymer as a gene carrier to corpus cavernosum.

Adenovirus or naked plasmid DNA (pDNA) has been used to deliver the therapeutic gene into corpus cavernosum. However, the potential risks of viral vector and inefficiency of naked pDNA have limited their clinical application. In this study, water-soluble lipopolymer (WSLP) was evaluated as a gene carrier to corpus cavernosum. The WSLP/pDNA complex was transfected to smooth muscle cells in vitro. WSLP had high transfection efficiency, which was comparable to poly(ethylenimine) (PEI). In addition, WSLP had much less cytotoxicity than PEI, suggesting that WSLP is a safer carrier than PEI. To evaluate the transfection efficiency to corpus cavernosum, the WSLP/pDNA complex was injected into the rat corpus cavernosum. As a result, the WSLP/pDNA complex showed higher transfection efficiency than naked pDNA. In addition, the gene expression was dependent upon the dose of the complex. The results suggest that WSLP may be useful for gene therapy of erectile dysfunction.

The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer.

The management of localized prostate cancer is based on stage, grade, PSA, and subjective assessment of comorbidity and life expectancy. Over the last 15 y, stage migration and the improved use of Gleason sum, PSA and TNM staging have led to many treatment options for patients with newly diagnosed localized prostate cancer. At the same time, advances in treatment techniques have helped decrease the long-term complications of surgery and radiotherapy. However, the importance of age and comorbidity, in survival outcomes and treatment decision-making has been largely overlooked. Currently, stage, grade, and PSA are the only quantifiable variables consistently used in research and treatment decision-making. Comorbidity and life expectancy have remained largely subjective variables. Increasing longevity and a rapidly aging population have made age and comorbidity increasingly important factors in clinical research and treatment decision-making. This article reviews the importance of age and comorbidity on treatment decisions and survival outcomes in prostate cancer, as well as their use as objectively quantifiable variables. Examples from the general oncology literature are given. The overview also examines validated comorbidity indices and advocates the use of the Charlson Comorbidity Index (CCI) in research outcomes and treatment decision-making in prostate cancer. Several clinical vignettes are provided to demonstrate the potential clinical utility of the CCI as applied to prostate cancer.