Effect of weight bearing exercise to improve bone mineral density in children with cerebral palsy: a meta-analysis.

BACKGROUND: Despite widespread clinical use of weight bearing exercises to manage low bone mineral density (BMD) in children and adolescents with cerebral palsy (CP), previous studies have reported heterogeneous results on the effect of weight bearing exercise on BMD. PURPOSE: We performed the current meta-analysis to assess the effects of weight bearing exercise on increasing BMD in children who have CP with low BMD. MATERIALS AND METHODS: We searched PubMed, Cochrane, and Embase from inception through to October 2016 for studies that aims to investigate the effect of weight bearing exercise on BMD in children with CP. Following the searching result, the 118 relevant studies were reviewed and undergone selection process. Standardized mean difference (SMD), 95% confidence intervals (CIs) and p-values were calculated for analysis. RESULTS: Three studies were ultimately included in the meta-analysis: one randomized-controlled study and two case-controlled studies. No significant difference was observed in the BMD of the lumbar spine between before treatment and after treatment (SMD,0.341; 95% CI,-0.647-1.330; p=0.449) but the BMD of the femur significantly improved after applying weight bearing exercise compared to pre-treatment values (SMD, 0.916; 95% CI, 0.382-1.114; p⟨0.001). CONCLUSIONS: Weight bearing exercise has a significant effect on improving BMD of the femur in children with CP.

Altered serotonin transporter binding potential in patients with obsessive-compulsive disorder under escitalopram treatment: [11C]DASB PET study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls. METHOD: Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory E max model we developed previously. RESULTS: The inhibitory E max model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), -5.67 (dorsal raphe nucleus)]. CONCLUSIONS: This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.

Semi-quantitative HPV viral load in patients with ASC-US cytology: viral load correlates strongly with the presence of CIN but only weakly with its severity.

OBJECTIVES: This study was performed to evaluate the prognostic significance of human papillomavirus (HPV) viral load, expressed in relative light units (RLUs), in patients with atypical squamous cells of undetermined significance (ASC-US) cytology. METHODS: A total of 349 ASC-US cases with HPV infection, detected using Hybrid Capture 2, were diagnosed histologically. A colposcopically directed punch biopsy was performed on acetowhite areas. Endocervical curettage biopsy and random cervical punch biopsy in four quadrants were performed in unsatisfactory colposcopy cases. In negative colposcopy cases, random cervical punch biopsy in four quadrants was performed. RESULTS: Case with no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2+ (CIN2/CIN3) accounted for 162, 135 and 52 cases, respectively. The mean age showed no difference among the three groups (P = 0.510). There was a significant correlation between RLU values and the presence of CIN (P < 0.001), but less so with its severity: the median RLU values for negative, CIN1 and CIN2+ cases were 42.68, 146.45 and 156.43, respectively, with widely overlapping confidence intervals. The cut-off values of RLU to detect CIN1+ and CIN2+ were 6.73 and 45.64, respectively. CONCLUSIONS: The HPV viral load in ASC-US cases showed a significant correlation with the presence of CIN and less so with its severity, and showed large overlap of viral loads between grades of CIN. In ASC-US cases, RLU was not an accurate predictor of immediate high-grade CIN.

The prognostic significance of pretreatment [18F]FDG-PET/CT imaging in patients with uterine cervical cancer: preliminary results.

PURPOSE OF INVESTIGATION: To evaluate the prognostic significance of positron emission tomography/computed tomography (PET/CT) in patients diagnosed with cervical cancer. MATERIALS AND METHODS: Patients with cervical cancer in FIGO Stages IB1 to IVB were imaged with PET/CT prior to treatment during one of the staging work-ups. The patients were observed for a median of 31.4 months (range, six to 89 months) after the initial treatment. The standardized uptake value (SUV) max of the primary cervical tumor mass was compared with the prognostic factors. RESULTs: A total of 81 patients who were primarily treated with radical hysterectomy (RH, n = 45) or concurrent chemoradiation (CCRT, n = 36) were analyzed. Multivariate analysis indicated that larger tumor size (> 4 cm, OR 8.694, 95% CI, 1.638-46.146), deep stromal invasion (≥ 1 cm, OR 7.249, 95% CI, 1.141-46.039) by the primary tumor, and pathologically confirmed pelvic lymph node involvement (positive, OR 14.586, 95% CI, 2.072-102.674) were significantly associated with recurrence after treatment. However, pretreatment SUVmax was not a significant independent predictor of disease recurrence (OR 1.058, 95% CI, 0.255-4.398). CONCLUSION: [18F]Fluorodeoxyglucose (FDG) uptake by the primary tumor showed a significant association with several risk factors that have been identified as treatment predictors. However, a high pretreatment SUVmax was not predictive of recurrence in uter- ine cervical cancer patients.

Characteristic features of ageing in Korean women's hair and scalp.

BACKGROUND: The effect of age on hair properties has previously been investigated in white and Japanese women; however, little is known of the age-related characteristic features of hair in Korean women. OBJECTIVES: To determine the ageing features of Korean women's hair by examining physical and biological factors in sufficient numbers of participants. METHODS: In total, 150 healthy Korean women (aged 23-69 years) living in Seoul were allocated to five age-graded groups. Age-related changes of various features of the scalp and hair shaft were measured, including hair density, diameter, tensile strength and lustre, and grey-hair ratio. The hair-shaft compositions of minerals, amino acids and steroid hormones were analysed by high-performance liquid chromatography. RESULTS: Hair-loss parameters (hair density, diameter and tensile strength) and hair lustre decreased significantly with age, beginning in the subjects' 40s. The hair-whiteness value increased significantly with age, beginning in their 60s, due to an increase in the ratio of grey hair. Calcium and magnesium levels greatly exceeded the reference ranges and declined in an age-dependent manner, while potassium and phosphorus levels increased with age. No age-related change of hair-shaft amino acid content was evident. The contents of sterols and their metabolites (cholesterol, desmosterol, lanosterol and pregnenolone) increased significantly with age, but there was no correlation between the examined sex steroids and age. CONCLUSIONS: These results show that intrinsic ageing produces diverse changes in the hair and scalp features of Korean women from their 40s, and the ageing features of Korean women's hair could be partially different from that of women in other countries.

Non-invasive prediction of intra-amniotic inflammation in women with preterm labor.

OBJECTIVE: To develop a model based on non-invasive variables to predict the probability of intra-amniotic inflammation in women with preterm labor and intact membranes. METHODS: Transvaginal ultrasonography and digital examination for the assessment of cervical length and cervical dilatation were performed, and maternal blood was collected for the determination of C-reactive protein and white blood cell (WBC) count immediately after amniocentesis in 153 consecutive women with preterm labor. Amniotic fluid obtained by amniocentesis was cultured for aerobic and anaerobic bacteria and mycoplasmas, and the WBC was determined. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 concentration (> 2.6 ng/mL). Receiver-operating characteristics (ROC) curves and logistic regression analysis were used for statistical analysis. RESULTS: The prevalence of a positive amniotic fluid culture was 7.2% (11/153) and the prevalence of intra-amniotic inflammation was 19.6% (30/153). The final logistic regression model was based on non-invasive clinical variables, including gestational age at assessment, cervical length and maternal blood WBC count, which were the best predictors of intra-amniotic inflammation. The model was shown to have an adequate goodness of fit (P = 0.754), and the area under the ROC curve was 0.724, indicating reasonably good discrimination. CONCLUSION: In women with preterm labor and intact membranes, the risk for intra-amniotic inflammation can be predicted non-invasively with a risk score based on gestational age, cervical length and maternal blood WBC count.

Comparison between sonographic cervical length and Bishop score in preinduction cervical assessment: a randomized trial.

OBJECTIVE: To compare sonographically measured cervical length with the Bishop score in determining the requirement for prostaglandin administration for preinduction cervical ripening in nulliparae at term. METHODS: One hundred and fifty-four women with singleton pregnancies at term who were scheduled for induction of labor were randomly assigned to receive prostaglandin for preinduction cervical ripening based on the Bishop score or sonographic cervical length. A cervix unfavorable for treatment with prostaglandin for preinduction cervical ripening was defined as having either a Bishop score of ≤ 4 or a cervical length of ≥ 28 mm. The primary outcome measures were induction success (defined as an ability to achieve the active phase of labor) and the percentage of patients treated with prostaglandin for preinduction cervical ripening. RESULTS: The two groups were similar with respect to maternal demographics, gestational age, cervical length, and Bishop score. The rates of induction success and Cesarean delivery, the interval to active phase of labor, and the interval to delivery were also similar in the two groups. However, in the transvaginal ultrasound group (n = 77), prostaglandin was administered to only 36% of the nulliparae compared with 75% of those in the Bishop score group (n = 77) (P < 0.0001). CONCLUSION: In comparison with the Bishop score, the use of sonographic cervical length for assessing the cervix prior to induction of labor can reduce the need for prostaglandin administration by approximately 50% without adversely affecting the outcome of induction in nulliparae at term if the cut-off values used are a Bishop score of ≤ 4 and a cervical length of ≥ 28 mm.

Coherent diffraction surface imaging in reflection geometry.

We present a reflection based coherent diffraction imaging method which can be used to reconstruct a non periodic surface image from a diffraction amplitude measured in reflection geometry. Using a He-Ne laser, we demonstrated that a surface image can be reconstructed solely from the reflected intensity from a surface without relying on any prior knowledge of the sample object or the object support. The reconstructed phase image of the exit wave is particularly interesting since it can be used to obtain quantitative information of the surface depth profile or the phase change during the reflection process. We believe that this work will broaden the application areas of coherent diffraction imaging techniques using light sources with limited penetration depth.

Degree of cervical shortening after initial induction of labor as a predictor of subsequent successful induction.

OBJECTIVE: To evaluate whether the degree of cervical length shortening is valuable in predicting the success of serial induction of labor on the second day in women in whom it failed on the first day, and to compare its performance with that of cervical length. METHODS: This was a prospective observational study. We enrolled 92 consecutive women with singleton gestations at > 34.0 weeks' gestation who failed labor induction on the first day of serial induction. Transvaginal sonographic measurement of cervical length and determination of the Bishop score were undertaken before performing each labor induction on the first and second days. RESULTS: The overall success rate of labor induction performed on the second day was 65% (60/92). Multiple logistic regression analysis demonstrated that the degree of cervical length shortening and cervical length were significantly associated with the successful induction of labor after adjustment for body mass index, parity, use of prostaglandin and Bishop score. There were no significant differences between areas under the ROC curves for degree of cervical length shortening and cervical length. CONCLUSIONS: The degree of cervical length shortening is valuable in predicting the success of induction of labor on the second day in women in whom induction failed on the first day. However, compared with sonographic cervical length it is no better at predicting the success of subsequent induction of labor.

Clinical and sonographic parameters at 37 weeks' gestation for predicting the risk of primary Cesarean delivery in nulliparous women.

OBJECTIVES: To identify the clinical and sonographic parameters at 37 weeks' gestation that predict the risk of Cesarean delivery in labor for nulliparas. METHODS: This prospective observational study recruited nulliparas with singleton pregnancies at 37 weeks' gestation. Determination of the Bishop score, ultrasound measurement of the cervical length, and fetal biometry were performed. The clinical parameters studied were maternal age, height and weight and Bishop score. The sonographic parameters included fetal biparietal diameter, femur length, abdominal circumference (AC), estimated fetal weight (EFW), amniotic fluid index and cervical length. RESULTS: Four hundred and fifty-three women were examined; 57 women (12.6%) underwent an emergency Cesarean delivery in labor. Logistic regression analysis identified maternal age and height and fetal AC and EFW, but not cervical length or Bishop score, as the best predictors of Cesarean delivery. Of these predictors, maternal age and height and fetal AC at 37 weeks were included in a final model for risk scoring. The model was shown to have an adequate goodness of fit (P = 0.473), and the area under the receiver-operating characteristics curve was 0.758, indicating reasonably good discrimination. CONCLUSIONS: Maternal age and height and fetal AC and EFW at 37 weeks' gestation are the most important parameters in predicting the risk of Cesarean delivery in nulliparas; sonographic measurement of the cervical length and the Bishop score were not predictive of Cesarean delivery. A predictive model using these parameters at 37 weeks provides useful information in the decision-making process regarding the mode of delivery.

Spitz naevus is rare in Korea.

BACKGROUND: Spitz naevi have not been widely studied in Asians. AIM: To compare the epidemiology and clinicopathological features of Spitz naevi in Koreans with lesions in western countries. METHODS: In total, 80 Spitz naevi in 77 patients diagnosed over 10 years at 17 university hospitals in Korea were analysed. RESULTS: The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most patients (75%) the Spitz naevi had been present for > 6 months. The size of the lesion was relatively large. Histologically, most of the lesions (54%) were the dermal type and pigmentation was common (49% of lesions). Immunohistochemical study found that all of the 34 lesions were positive for S-100 protein but only 14 (47%) were positive for HMB-45. CONCLUSION: Spitz naevus is rare in Korea. The lesions were more commonly larger, pigmented, and of the dermal type than reported in western countries.

Understanding effects of molecular adsorption at a single-wall boron nitride nanotube interface from density functional theory calculations.

In this paper, we explored computationally the feasibility of modulating the bandgap in a single-wall BN nanotube (BNNT) upon noncovalent adsorption of organic molecules, combined with the application of a transverse electric field. Effects of analytes' physisorption on the surface of BNNTs regarding structural and electronic properties were delineated. Relatively large binding energies were calculated, however, with minimal perturbation of the structural framework. Electronic structure calculations indicated that the bandgap of BNNTs can be modified by weak adsorption due to the presence of adsorbate states in the gap of the host system. Furthermore, we have shown that the application of a transverse electric field can tune the bandgap by shifting adsorbate states, consistent with calculated current-voltage characteristics.

Laparoscopy-assisted distal gastrectomy with D2 lymph node dissection for gastric cancer: technical and oncologic aspects.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) with lymph node dissection for advanced gastric cancer is still controversial. To evaluate the technical and oncologic feasibility and advantage of LADG with D2 lymph node dissection, the authors compared the surgical outcomes of LADG with D2 dissection and those of conventional open distal gastrectomy (ODG) for patients with early gastric cancer (EGC). METHODS: Between September 2004 and August 2005, the study enrolled 75 patients with a preoperative diagnosis of EGC. Of these 75 patients, 44 underwent LADG, and remaining 31 underwent ODG. All the patients received D2 lymph node dissection. Their clinicopathologic characteristics, postoperative outcomes, and retrieved lymph nodes were compared at each station. RESULTS: Although the operative time was significantly longer for the LADG group than for the ODG group, the perioperative recovery was shorter and, consequently, the postoperative hospital stay was significantly shorter for the LADG group (7.7 vs 9.4 days, respectively; p = 0.003). No significant differences were found in the total number of retrieved lymph nodes (37.2 vs 42.4; p > 0.05) or node stations (p > 0.05) between the two groups. CONCLUSIONS: LADG with D2 lymph node dissection is a safe and feasible procedure, and it is oncologically compatible with open gastrectomy. A large-scaled prospective randomized trial with advanced gastric cancer patients should be conducted to confirm the benefit of LADG.

Activation of NF-kappaB by HDAC inhibitor apicidin through Sp1-dependent de novo protein synthesis: its implication for resistance to apoptosis.

Histone deacetylase (HDAC) inhibitors are promising anti-cancer drugs, but these exert differential responses depending on the cell types. Here, we demonstrate a new mechanism for activation of nuclear factor-kappaB (NF-kappaB) by HDAC inhibitor apicidin and the role of NF-kappaB signaling pathway for mediating differential cellular responses, especially, apoptosis. Treatment of HeLa cells with apicidin increases transcriptional activity of NF-kappaB and its target gene IL-8 and cIAP-1 induction, which involves the activation of IKK-IkappaBalpha signaling pathway through Sp1-dependent de novo protein synthesis. In parallel, apicidin treatment leads to histone hyperacetylation in the IL-8 promoter region independent of NF-kappaB signaling pathway, which is not sufficient for full transcription of IL-8 gene. This NF-kappaB activation contributes to resistance of HeLa cells to apoptotic potential of apicidin. Collectively, our results suggest that activation of NF-kappaB signaling cascade functions as a critical modulator to determine cell fate on apoptosis in response to HDAC inhibitors.

Abdominal aortic aneurysm repair in kidney transplant recipients.

Renal transplant recipients currently survive many years with a consequent increase in the risk of presentation with vascular diseases. So aortic reconstruction in transplant patients has been increasingly reported the most common procedures involving abdominal aorta aneurysms (AAAs). The most important problem during the operation is ischemic injury to the transplanted kidney during aortic clamping. Protection for the grafted kidney from ischemic or reperfusion injury may be achieved by permanent or temporary axillo-femoral, femoro-femoral, aorto-iliac bypass, cold perfusion, local cold preservation, or autotransplantation. Some authors have reported protection of the transplanted kidney function without any other procedures. We had experience with four AAA cases in kidney transplant patients, including two cases of direct reconstruction of the AAA without any other surgical protection, one autotransplantation, and one AAA excision with using temporary aortofemoral bypass with good results. Herein, we report two cases of successful AAA excision without a surgical procedure for graft protection.

Lymphoproliferative diseases of fowl: chromosome breaks caused in lymphocytes by JM-V herpesvirus.

Chromosome preparations were made of bone marrow cells and peripheral lymphocytes isolated from chicks that developed leukemia following infection with JM-V herpes-virus. Karyotypic analysis revealed a high frequency of chromosome breaks and aneuploidy, as well as some pulverization of chromosomes. The number of chromosome breaks began to increase at 2-3 days post infection, and by 5 days post infection it reached 12.7% of bone marrow cells and 17.2% of peripheral lymphocytes. Similarly, the number of aneuploid metaphase figures increased rapidly and reached 12% of bone marrow cells and 19% of peripheral lymphocytes at 5 days post infection. Some specificity was observed in the chromosomes that were affected.

Pharmacokinetic and toxicity scaling of the antitumor agents amsacrine and CI-921, a new analogue, in mice, rats, rabbits, dogs, and humans.

The aim was to investigate interspecies relationships between body weight (W) (kg) and various pharmacokinetic parameters for the anti-tumor agents amsacrine and its 4-methyl-5-(N-methylcarboxamide) analogue, CI-921, and examine which pharmacokinetic parameter, if any, might be used to predict the toxicity of these agents. Pharmacokinetic, plasma protein binding, and toxicity data were available for CI-921 in mice, rats, rabbits, dogs, and humans. For amsacrine, similar interspecies pharmacokinetic data were available but toxicity and protein-binding data were available for only 3 species. Significant linear relationships were obtained for CI-921 between log W and log Vss (liters) (r = 0.971, P = 0.006), and log W and log Cl (liters/h) (r = 0.911, P = 0.031) resulting in the allometric equations Vss = 1.22W0.68 and Cl = 0.91W0.51. For amsacrine these corresponding equations were Vss = 3.37W0.81 (r = 0.996, P less than 0.001), and Cl = 2.28W0.46 (r = 0.952, P = 0.012). When interspecies differences in plasma protein binding were taken into account, the allometric relationships improved and the exponents of the power equations increased. For CI-921 the allometric equations for the kinetic parameters calculated from plasma "free" concentrations were: Vssfu (liters) = 247W0.93 (r = 0.984, P = 0.002) and Clu (liters/h) = 186W0.76 (r = 0.961, P = 0.009). The dog was a noticeable outlier in the relationship between the log maximum tolerated dose (MTD) (mg/kg) of CI-921 and log W. Omission of the latter resulted in a highly significant allometric relationship, MTD = 23.6W-0.14 (r = -0.988, P = 0.012). For amsacrine there was no significant allometric relationship between MTD and W. CI-921s prolonged t1/2 in the dog and the dog's increased susceptibility to CI-921 toxicity suggested a relationship between MTD and t1/2 (h). A significant linear relationship was observed between in MTD and t1/2 (r = -0.994, P less than 0.001), from which the following equation was developed MTD = 47.5e-0.51t1/2 Combining the amsacrine toxicity data in the latter relationship yielded a similar equation MTD = 44.7e-0.51t1/2 (r = -0.933, P less than 0.0001). It was concluded that allometric equations may be developed for CI-921 and amsacrine from animal pharmacokinetic data which allow a reasonable prediction of Cl and Vss in patients, despite these agents being eliminated mainly by biotransformation. However, similar relationships between toxicity and body weight were susceptible to variation between individual species. Species differences in the toxicity of these agents were predictable from the t1/2. This study emphasized the importance of pharmacokinetic data in preclinical toxicity and efficacy testing of antitumor agents.

The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling.

Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15-lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by ß3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co-culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild-type mice. Finally, in vivo ß3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and ß3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling.

Polysaccharides from Korean Citrus hallabong peels inhibit angiogenesis and breast cancer cell migration.

Although the peel of the hallabong (Citrus sphaerocarpa) fruit is rich in polysaccharides, which are valuable dietary ingredients for human health, it is normally wasted. The present study aimed to utilize the peel waste and identify properties it may have against breast cancer metastasis. Hallabong peel extract containing crude polysaccharides was fractionated by gel permeation chromatography to produce four different polysaccharide fractions (HBE-I, -II, -III, and -IV). The HBE polysaccharides significantly blocked tube formation of human umbilical vein vascular endothelial cells (HUVECs), at a concentration of 12.5 or 25 µg/mL. Tube formation appeared to be more sensitive to HBE-II than to other HBE polysaccharides. HBE-II also inhibited breast cancer cell migration, through downregulation of matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 triple-negative breast cancer cells. Therefore, inhibition of tube formation and MMP-9-mediated migration observed in HUVEC and MDA-MB-231 cells, respectively, are likely to be important therapeutic targets in triple-negative breast cancer metastasis.

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.