Sirolimus-eluting Biodegradable Poly-l-Lactic Acid Stent to Suppress Granulation Tissue Formation in the Rat Urethra.

Purpose To investigate the use of sirolimus-eluting biodegradable stents (SEBSs) to suppress granulation tissue formation after stent placement in a rat urethral model. Materials and Methods All experiments were approved by the animal research committee. A total of 36 male Sprague-Dawley rats were randomized into three equal groups after biodegradable stent placement. Group A received control biodegradable stents. Groups B and C received stents coated with 90 µg/cm2 and 450 µg/cm2 sirolimus, respectively. Six rats in each group were sacrificed after 4 weeks; the remaining rats were sacrificed after 12 weeks. The therapeutic effectiveness of SEBSs was assessed by comparing the results of retrograde urethrography and histologic examination. Analysis of variance with post hoc comparisons was used to evaluate statistical differences. Results SEBS placement was technically successful in all rats. Urethrographic and histologic examinations revealed significantly less granulation tissue formation at both time points in the rats receiving SEBSs (groups B and C) compared with those that received control stents (group A) (P < .05 for all). There were no significant differences in urethrographic and histologic findings between groups B and C (P > .05 for all). However, the mean number of epithelial layers in group B was higher than that in group C at 4 weeks after stent placement (P < .001). Apoptosis increased in group C compared with groups A and B (P < .05 for all). Conclusion The use of SEBSs suppressed granulation tissue formation secondary to stent placement in a rat urethral model; local therapy with SEBSs may be used to decrease stent-related granulation tissue formation. © RSNA, 2017.

Fluoroscopic subtraction Eustachian tubography: initial feasibility test in a cadaver model.

OBJECTIVES: To evaluate the technical feasibility of direct Eustachian tube catheterisation and subtraction Eustachian tubography in a cadaver model. METHODS: A total of 12 separate sessions were performed on both sides of the Eustachian tube (ET) in six human cadavers. Cadavers were positioned for the submentovertical view on a fluoroscopy table. Endoscopy-guided ET selection was used in the first three cadavers, whereas fluoroscopy-guided ET selection was used in the remaining three. Eustachian tubography was performed by injecting 2 ml of contrast media through a 5-Fr catheter. We recorded the success of ET selection, number of attempts, procedure time, and tubography quality using native and subtraction images (range, 0-3). RESULTS: Both endoscopy- and fluoroscopy-guided selections were successfully performed in five of six sessions (83.3%). There were no statistically significant differences between the endoscopy- and fluoroscopy-guided procedures in terms of the number of attempts, procedure time, rate of immediate contrast leak to the middle ear cavity, and quality of tubography (p > 0.05). An excellent quality of tubography was obtained in 83.3% (10 of 12 sessions) of subtraction images and in 33.3% (4 of 12 sessions) of native images. The tubography quality score was significantly higher for the subtraction images than for the native images (p = 0.04). CONCLUSION: Subtraction Eustachian tubography using direct catheterisation seems to be technically feasible. The entire ET can be well visualised; thus, this technique can be used as a simple tool for assessment of ET function and anatomy. KEY POINTS: • Direct catheterisation of the Eustachian tube is technically feasible. • The entire Eustachian tube could be well visualised by direct Eustachian tubography. • Subtraction Eustachian tubography images have better image quality than native images. • Subtraction Eustachian tubography can provide objective assessment of ET function and anatomy.

Self-Expandable Metal Stent Use to Palliate Malignant Esophagorespiratory Fistulas in 88 Patients.

PURPOSE: To identify predictors associated with clinical outcomes (initial clinical failure, stent patency, and survival) after self-expandable metal stent (SEMS) placement for malignant esophagorespiratory fistulas (ERFs). MATERIALS AND METHODS: Using logistic and Cox regression analyses, this study reviewed 88 patients (mean age 59.4 y ± 8.4; 84 men [95.5%] and 4 women [4.5%]) who underwent fluoroscopic SEMS placement for palliating malignant ERF from January 2000 to December 2016. RESULTS: Technical success was achieved in all patients. Initial clinical success was achieved in 78.4% (69/88; 95% confidence interval [CI], 68.7%-85.7%). Among the 69 patients in whom initial clinical success was achieved, aspiration symptoms recurred in 37.7% (26/69; 95% CI, 27.2%-49.5%). Overall major complication rate was 25.0% (22/88; 95% CI, 17.1%-35.0%). Cumulative stent patency and cumulative survival rates at 1, 3, 6, and 12 months were 72.8%, 38.9%, 32.4%, and 21.6% and 81.4%, 51.9%, 30.5%, and 13.3%, respectively. Stricture of the upper esophagus was an independent predictor of initial clinical failure (odds ratio, 3.760; 95% CI, 1.207-11.811) and shorter stent patency (hazard ratio [HR], 2.036; 95% CI, 1.170-3.544). Initial clinical failure was an independent predictor of shorter survival (HR, 2.902; 95% CI, 1.587-5.305). CONCLUSIONS: SEMS placement offers sufficient short-term relief despite considerable major complications. Stricture of the upper esophagus is an independent predictor of initial clinical failure and shorter stent patency. Initial clinical failure is an independent predictor of shorter survival.

In Vivo Fluorescence Microendoscopic Monitoring of Stent-Induced Fibroblast Cell Proliferation in an Esophageal Mouse Model.

PURPOSE: To evaluate the feasibility of self-expanding metal stent (SEMS) placement and fluorescence microendoscopic monitoring for determination of fibroblast cell proliferation after stent placement in an esophageal mouse model. MATERIALS AND METHODS: Twenty fibroblast-specific protein (FSP)-1 green fluorescent protein (GFP) transgenic mice were analyzed. Ten mice (Group A) underwent SEMS placement, and fluoroscopic and fluorescence microendoscopic images were obtained biweekly until 8 weeks thereafter. Ten healthy mice (Group B) were used for control esophageal values. RESULTS: SEMS placement was technically successful in all mice. The relative average number of fibroblast GFP cells and the intensities of GFP signals in Group A were significantly higher than in Group B after stent placement. The proliferative cellular response, including granulation tissue, epithelial layer, submucosal fibrosis, and connective tissue, was increased in Group A. FSP-1-positive cells were more prominent in Group A than in Group B. CONCLUSIONS: SEMS placement was feasible and safe in an esophageal mouse model, and proliferative cellular response caused by fibroblast cell proliferation after stent placement was longitudinally monitored using a noninvasive fluorescence microendoscopic technique. The results have implications for the understanding of proliferative cellular response after stent placement in real-life patients and provide initial insights into new clinical therapeutic strategies for restenosis.

Transnasal Placement of a Balloon-Expandable Metallic Stent: Human Cadaver Study of the Eustachian Tube.

PURPOSE: To investigate the technical feasibility of stent placement in the cartilaginous portion of the Eustachian tube (ET). MATERIALS AND METHODS: Twelve ETs of 6 cadavers were used. Two different-sized stents were placed on either the right (2.5 mm in diameter) or left (3.5 mm in diameter) side of the ET. The procedural feasibility was assessed by subtraction Eustachian tubography, computed tomography before and after the procedure, and fluoroscopic and endoscopic images. The stent location, inner luminal diameter of the stented ET, radiation dose, procedural time, and fluoroscopy time were analyzed. RESULTS: Stent placement was successful in 11 of 12 cadaveric specimens without procedure-related complications. In the 1 specimen, the balloon catheter with crimped stent was passed into the bony canal of the ET without any resistance. The distal end of the stent was located in the middle ear cavity. Stents were located within the cartilaginous portion of the ET (n = 1), the proximal tip bridging the nasopharyngeal orifice of the ET (n = 5), or the proximal end of the stent protruded from the tubal orifice (n = 5). The mean luminal diameter in the outer segment was significantly smaller than in the middle (P < .001) and inner (P < .001) segments. The mean procedure time was 128 ± 37 seconds. The mean radiation dose and fluoroscopy time of each cadaver were 3235.4 ± 864.8 cGy/cm2 and 139 ± 49 seconds, respectively. CONCLUSIONS: Stent placement of the ET under endoscopic and fluoroscopic guidance is technically feasible in a human cadaver model.

Radiation-induced esophageal strictures treated with fluoroscopic balloon dilation: clinical outcomes and factors influencing recurrence in 62 patients.

Background Balloon dilation is safe and effective for the treatment of radiation-induced esophageal stricture (RIES), with favorable short-term and mid-term outcomes; however, few reports of long-term outcomes exist. Few studies have evaluated factors associated with recurrence after balloon dilation. Purpose To evaluate the long-term outcome of balloon dilation in patients with RIES and to identify factors associated with stricture recurrence. Material and Methods The medical records of 62 consecutive patients who had undergone fluoroscopic balloon dilation for RIES at our institution between December 1998 and June 2016 were reviewed. Results One hundred and twenty balloon dilation sessions were performed in 62 patients (mean = 1.9 sessions per patient). Clinical success was achieved in 53 (86%) patients after single (n = 37) or multiple (n = 16) dilation sessions. Complications occurred in 27% of the dilation sessions. The primary patency rates at one, two, three, and five years were 60%, 56%, 52%, and 52%, respectively. Secondary patency rates at one, two, three, and five years were 87%, 85%, 85%, and 80%, respectively. Multivariate logistic regression analysis identified an interval from radiation therapy (RT) to stricture of ≥6 months (hazard ratio [HR] = 0.205; P < 0.001), strictures located at the cervical esophagus (HR = 5.846; P < 0.001), and stricture length of ≥2 cm (HR = 2.923; P = 0.006) as significant predictors of recurrence. Conclusion Despite the high incidence of ruptures and recurrences, fluoroscopic balloon dilation is valuable as an initial therapeutic option for patients with RIES.

EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus.

BACKGROUND AND AIMS: Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-ß type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. METHODS: Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. RESULTS: SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-ß1 and increased the expression level of E-cadherin (all P < .01). CONCLUSIONS: EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.

Recurrent Benign Urethral Strictures Treated with Covered Retrievable Self-Expandable Metallic Stents: Long-Term Outcomes over an 18-Year Period.

PURPOSE: To assess the long-term outcomes of covered retrievable self-expandable metallic stent (REMS) placement for recurrent benign urethral stricture and to compare the outcomes associated with 3 types of covered REMSs. MATERIALS AND METHODS: A retrospective study was performed in 54 male patients in whom 114 REMSs were placed between November 1998 and December 2016. These included 26 polyurethane-covered REMSs in 13 patients (group A), 47 internally polytetrafluoroethylene (PTFE)-covered REMSs in 21 patients (group B), and 41 externally PTFE-covered REMSs in 20 patients (group C). The outcomes were analyzed and compared between the groups. RESULTS: Overall clinical success was achieved in 14 of the 54 patients (24%) at 5-year follow-up (group A, 12%; group B, 19%; group C, 40%). The overall complication rate was 60.5%, and the complication rate was significantly higher in group B than in groups A or C (group A vs B, P = .018; group B vs C, P = .002). The median stent indwelling time and maintained patency period were 3.1 months and 108 months, respectively. In multivariate analysis, stent indwelling time was the only significant factor associated with maintained patency. CONCLUSIONS: The long-term outcome of covered REMSs has not achieved the desired success rate for the standard treatment of recurrent urethral stricture. However, externally PTFE-covered REMSs showed a better long-term outcome than the other studied types.

Significance of Stent Abutment in Gastroduodenal Stent Placement for Gastric Outlet Obstructions.

PURPOSE: To evaluate the frequency, severity, and clinical significance of stent abutment (SA) after gastroduodenal stent placement in patients with gastric outlet obstruction caused by unresectable gastric cancer. MATERIALS AND METHODS: A retrospective study was conducted in a single tertiary referral university hospital to identify the incidence and clinical significance of SA in 318 patients who underwent self-expandable metallic stent placement. SA was defined as abutment of the distal end of the stent to the duodenal wall and/or superior duodenal flexure. The outcomes included technical and clinical success, complications, repeat intervention, stent patency, and survival. RESULTS: A total of 318 patients, 107 with SA (33.6%) and 211 without, were included. SA occurred partially (n = 64; 59.8%) and completely (n = 43; 40.2%). The technical and clinical outcomes and survival were similar in the groups with and without SA. Food impaction and resultant repeat intervention rates were higher in the SA group than in the non-SA group (P < .001 and P < .001, respectively), and were associated with complete SA (P = .007). Stent patency rate was lower in the SA group than in the non-SA group (P = .003). CONCLUSIONS: SA was associated with increased food impaction, resulting in a greater incidence of stent malfunction and shorter stent patency compared with a lack of SA. The concept of SA may be useful for the improvement of stent patency and avoidance of food impaction.

Fluoroscopic Balloon Dilation for Treating Postoperative Nonanastomotic Strictures in the Proximal Small Bowel: A 15-Year Single-Institution Experience.

PURPOSE: To evaluate safety and effectiveness of fluoroscopic balloon dilation (FBD) for treating postoperative nonanastomotic strictures in proximal small bowel. MATERIALS AND METHODS: Data of 44 patients (26 men and 18 women; mean age, 53.7 y ± 13.0) treated with FBD for postoperative nonanastomotic strictures in the proximal small bowel between January 2000 and February 2016 were retrospectively reviewed. Site of stricture was located in the first portion of duodenum in 8 (18.2%) patients, second portion of duodenum in 8 (18.2%) patients, third portion of duodenum in 1 (2.3%) patient, fourth portion of duodenum in 1 (2.3%) patient, and proximal jejunum in 26 (59.1%) patients. Mean distance between the most anal-side lesion and the oral cavity was 63.9 cm ± 15.0. RESULTS: Technical success was achieved in 39 (88.6%) patients. Mean stricture length was 3.0 cm ± 1.8. Technical failure because of inability to negotiate the guide wire through the stricture occurred in 5 (13.6%) patients. Complete resolution of obstructive symptoms and resumption of oral intake of soft or solid food within 3 days occurred in 34 patients after 1 (n = 32) or 2 (n = 2) FBD sessions, rendering a clinical success rate of 87.2%. There were no major complications directly related to FBD. Median follow-up period was 1,406 days (interquartile range, 594-2,236 d). Nine (26.5%) patients had recurrence within a median 47 days (interquartile range, 20-212 d). CONCLUSIONS: FBD may be safe and effective for treating postoperative nonanastomotic strictures in the proximal small bowel.

A novel semi-automatic snake robot for natural orifice transluminal endoscopic surgery: preclinical tests in animal and human cadaver models (with video).

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) is an emerging surgical technique. We aimed to design, create, and evaluate a new semi-automatic snake robot for NOTES. MATERIALS AND METHODS: The snake robot employs the characteristics of both a manual endoscope and a multi-segment snake robot. This robot is inserted and retracted manually, like a classical endoscope, while its shape is controlled using embedded robot technology. The feasibility of a prototype robot for NOTES was evaluated in animals and human cadavers. RESULTS: The transverse stiffness and maneuverability of the snake robot appeared satisfactory. It could be advanced through the anus as far as the peritoneal cavity without any injury to adjacent organs. Preclinical tests showed that the device could navigate the peritoneal cavity. CONCLUSIONS: The snake robot has advantages of high transverse force and intuitive control. This new robot may be clinically superior to conventional tools for transanal NOTES.

Blood levels related to the Z-score of bone mineral density in young males and females.

[Purpose] The purpose of this study was to investigate the blood levels related to the bone mineral density by using the dual energy X-ray absorption for females before menopause and males younger than 50 years old. [Subjects and Methods] Between August 1, and September 15, 2013, the Z-score was measured in females before menopause and males younger than 50 years old using a bone mineral density measuring instrument. After the measurement, the subjects were classified into two groups, that is, the below expectations and within expectations groups. Next, we analyzed and compared the differences in age, body mass index, and blood levels between the 2 groups. [Results] The results showed a correlation of 0.212 for total protein, -0.317 for alanine aminotransferase, -0.199 for gamma-glutamyl transferase, -0.358 for alkaline phosphatase, 0.266 for uric acid, -0.313 for lactate dehydrogenase, 0.244 for creatinine, -0.234 for the red blood cell count, and -0.230 for the red cell distribution width in patients with less than expected level for their age. [Conclusion] In conclusion, osteoporosis may occur in females before menopause and males younger than 50 years old, and aggressive attention is required for prevention and treatment.

Factor analysis of biochemical markers associated with bone mineral density in adults.

[Purpose] The aim of this study was to find biochemical markers related to low bone mineral density in Korean adults. [Subjects and Methods] From August 1 to September 15, 2013, subjects receiving medical checkups were classified as lumbar spine bone normal, osteopenic, or osteoporotic using a bone mineral densitometer. Next, age, body mass index, and biochemical parameter differences were compared among the three groups. [Results] The results revealed that, the relevant factors were maximum blood pressure, minimum blood pressure, bone mineral density, total bilirubin, alkaline phosphatase (ALP), fasting blood glucose, iron, neutrophils, monocytes, and eosinophils. The bone mineral density of patients with osteoporosis was 0.763 times lower than that of normal subjects. The total bilirubin level of patients with osteoporosis was 0.45 times lower than that of normal subjects. The alkaline phosphatase level of patients with osteopenia was 1.059 times higher than that of normal subjects, and that in patients with osteoporosis was 1.088 times higher than that in normal subjects. The fasting blood glucose level of patients with osteoporosis was 0.963 times lower than that of normal subjects. The iron level of patients with osteoporosis was 0.986 times lower than that of normal subjects. [Conclusion] In conclusion, osteoporosis is a representative disease in elderly women due to aging and menopause, and more active interest should be taken for prevention and treatment.

GPR41 and GPR43: From development to metabolic regulation.

G-protein-coupled receptors are a diverse class of cell surface receptors that orchestrate numerous physiological functions. The G-protein-coupled receptors, GPR41 and GPR43, sense short-chain fatty acids (SCFAs), which are metabolites of dietary fermentation by the host's intestinal bacteria. These receptors have gained attention as potential therapeutic targets against various diseases because of their SCFA-mediated beneficial effects on the host's intestinal health. Mounting evidence has associated the activity of these receptors with chronic metabolic diseases, including obesity, diabetes, inflammation, and cardiovascular disease. However, despite intensive research using various strategies, including gene knockout (KO) mouse models, evidence about the precise roles of GPR41 and GPR43 in disease treatment remains inconsistent. Here, we comprehensively review the latest findings from functional studies of the signaling mechanisms that underlie the activities of GPR41 and GPR43, as well as highlight their multifaceted roles in health and disease. We anticipate that this knowledge will guide future research priorities and the development of effective therapeutic interventions.

Correlation between voluntary cough and laryngeal cough reflex flows in patients with traumatic brain injury.

OBJECTIVE: To correlate voluntary cough and laryngeal cough reflex (LCR) flows in patients with traumatic brain injury (TBI). DESIGN: Cross-sectional study. SETTING: University rehabilitation hospital. PARTICIPANTS: Patients with TBI (n=25) and healthy controls (n=48). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak cough flows (PCFs) and LCR flows were measured using a peak flow meter at the oral-nasal interface. The largest value of 3 attempts was recorded for PCF and LCR, respectively. LCR was elicited by 20% solution of pharmaceutic-grade citric acid dissolved in sterile .15M NaCl solution that was inhaled from a nebulizer. RESULTS: PCF was 447.4 ± 99.0 L/min in the control group and 211.7 ± 58.2 L/min in the patient group. LCR was 209.2 ± 63.8L/min in the control group and 170.0 ± 59.7 L/min in the patient group. Both PCF (P=.000) and LCR (P=.013) were significantly reduced in patients with TBI compared to that of the control group. LCR was strongly related to the PCF in both control (R=.645; P=.000) and patient (R=.711; P=.000) groups. CONCLUSIONS: As LCR can be measured as a numerical value and significantly correlates with PCF, LCR can be used to estimate cough ability of patients with TBI who cannot cooperate with PCF measurement.

Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection and dry needling in rotator cuff disease: a randomized controlled trial.

OBJECTIVE: To compare the effects of platelet-rich plasma injection with those of dry needling on shoulder pain and function in patients with rotator cuff disease. DESIGN: A single-centre, prospective, randomized, double-blinded, controlled study. SETTING: University rehabilitation hospital. PARTICIPANTS: Thirty-nine patients with a supraspinatus tendon lesion (tendinosis or a partial tear less than 1.0 cm, but not a complete tear) who met the inclusion criteria recruited between June 2010 and February 2011. INTERVENTION: Two dry needling procedures in the control group and two platelet-rich plasma injections in the experimental group were applied to the affected shoulder at four-week intervals using ultrasound guidance. MEASUREMENTS: The Shoulder Pain and Disability Index, passive range of motion of the shoulder, a physician global rating scale at the six-month follow-up, adverse effects monitoring and an ultrasound measurement were used as outcome measures. RESULTS: The clinical effect of the platelet-rich plasma injection was superior to the dry needling from six weeks to six months after initial injection (P < 0.05). At six months the mean Shoulder Pain and Disability Index was 17.7 ± 3.7 in the platelet-rich plasma group versus 29.5 ± 3.8 in the dry needling group (P < 0.05). No severe adverse effects were observed in either group. CONCLUSIONS: Autologous platelet-rich plasma injections lead to a progressive reduction in the pain and disability when compared to dry needling. This benefit is certainly still present at six months after treatment. These findings suggest that treatment with platelet-rich plasma injections is safe and useful for rotator cuff disease.

Garcinia Cambogia Improves High-Fat Diet-Induced Glucose Imbalance by Enhancing Calcium/CaMKII/AMPK/GLUT4-Mediated Glucose Uptake in Skeletal Muscle.

SCOPE: Garcinia cambogia (G. cambogia) is known to have antiobesity effects. In this study, the therapeutic effects of G. cambogia on glucose homeostasis in obesity-induced diabetes are explored and the underlying mechanisms are investigated. METHODS AND RESULTS: C2C12 myotubes are treated with G. cambogia; glucose uptake, intracellular Ca2+ levels, and related alterations in signaling pathways are examined. High-fat diet (HFD)-fed mice are administered G. cambogia for 8 weeks; oral glucose tolerance is evaluated, and the regulation of identified targets of signaling pathways in quadriceps skeletal muscle are examined in vivo. G. cambogia increases glucose uptake in C2C12 myotubes and induces the upregulation of AMPK, ACC, and p38 MAPK phosphorylation. Notably, G. cambogia markedly elevates both intracellular Ca2+ levels, activating CaMKII, a Ca2+ -sensing protein, and TBC1D4-mediated GLUT4 translocation, to facilitate glucose uptake. Furthermore, high-glucose-induced inhibition of glucose uptake and signal transduction is reverted by G. cambogia. In an HFD-induced diabetes mouse model, G. cambogia administration results in significant blood glucose-lowering effects, which are attributed to the regulation of targets that have been identified in vitro, in quadricep skeletal muscle. CONCLUSION: These findings provide new insights into the mechanism by which G. cambogia regulates glucose homeostasis in obesity-induced diabetes.

Therapeutic effect of local photothermal heating of gold nanoparticle-coated self-expandable metallic stents for suppressing granulation tissue formation in the mouse colon.

PURPOSE: To investigate the therapeutic effect of local photothermal (PT) heating on suppression of stent-induced granulation tissue formation in mouse colon. MATERIALS AND METHODS: A gold nanoparticle (GNP)-coated self-expandable metallic stent (SEMS) was prepared using a two-step synthesis process for local PT heating under near-infrared laser irradiation. Twenty-four mice were randomly divided into two groups of 12 and subjected to SEMS placement in the colon. Group A received a GNP-coated SEMS without local heating and Group B received a GNP-coated SEMS and underwent local heating at 55°C after SEMS placement. The therapeutic effect of local heating was assessed by comparing the histopathological, immunohistochemical, and endoscopic results. RESULTS: Four mice were excluded because of stent migration (n = 3, group B) or death (n = 1, group A). Stent-induced granulation tissue-related variables were significantly lower in group B than in group A (p < 0.001). In vivo endoscopic images, 4 weeks after stent placement, showed granulation tissue formation over the wire mesh in group A and relatively good patency of the stented colon with no definite irregularities in group B. There was more vascular endothelial growth factor (VEGF) positivity in group A than in group B. CONCLUSION: Local PT heating suppresses granulation tissue formation after stent placement in mouse colon.

Treatment With Glycogen Synthase Kinase 3ß Inhibitor Decreases Apoptotic and Autophagic Reactions in Rat Rotator Cuff Tears.

BACKGROUND: Apoptosis and autophagy are known to be correlated with the extent of damage in torn rotator cuffs, and there is no biological evidence for self-recovery or healing of the rotator cuff tear. PURPOSE: To establish in a rat model of partial- and full-thickness rotator cuff tears how a glycogen synthase kinase 3ß (GSK-3ß) inhibitor affects the expression of apoptotic and autophagic markers. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve-week-old Sprague Dawley rats were divided into 3 groups (n = 16 per group). Group 1 acted as the control, with no treatment; group 2 received partial-thickness (right side) and full-thickness (left side) rotator cuff tears only; and group 3 received the same rotator cuff injuries, with GSK-3ß inhibitor injected afterward. The tendons from each group were harvested 42 days after surgery. Evaluation of gene expression, immunohistochemistry, and TUNEL staining (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) were performed for the following markers: caspases 3, 8, and 9 as well as Bcl-2 (B-cell lymphoma 2); BAX (Bcl-2-associated X protein); beclin 1; p53; and GSK-3ß; which represented apoptotic and autophagic reactions. Statistical analysis was performed using 1-way analysis of variance. RESULTS: In the group 2 rats with partial- and full-thickness tears, there were significant increases in the mRNA levels (fold changes) of all 8 markers as compared with group 1 (control). All these increased markers showed significant downregulation by the GSK-3ß inhibitor in partial-thickness tears. However, the response to the GSK-3ß inhibitor in full-thickness tears was not as prominent as in partial-thickness tears. The number of TUNEL-positive cells in group 2 (partial, 35.08% ± 1.625% [mean ± SE]; full, 46.92% ± 1.319%) was significantly higher than in group 1 (18.02% ± 1.036%; P < .01) and group 3 (partial, 28.04% ± 2.607% [P < .01]; full, 38.97% ± 2.772% [P < .01]), and immunohistochemistry revealed increased expression of all the markers in group 2 as compared with control. CONCLUSION: The apoptotic and autophagic activity induced in a rat model of an acute rotator cuff tear was downregulated after treatment with a GSK-3ß inhibitor, particularly with partial-thickness rotator cuff tears. CLINICAL RELEVANCE: A GSK-3ß inhibitor may be able to modulate deterioration in a torn rotator cuff.

Estrogen Replacement Reduces Hearing Threshold Shifts and Cochlear Hair Cell Loss After Acoustic Overexposure in Ovariectomized Rats.

OBJECTIVES: The relationship of estrogen (the primary female sex hormone) with hearing function has been studied in both humans and animals. However, whether estrogen levels affect hearing remains uncertain. Therefore, in this study, we investigated changes in the vulnerability of hearing to acoustic overexposure in ovariectomized female rats. METHODS: Eighteen 8-week-old female Sprague-Dawley rats were separated into four groups as follows: sham ovariectomy (OP), OP only, and OP treated with low (10 µg/kg) or high doses (100 µg/kg) of estrogen. Rats in the estrogen replacement groups were given two intraperitoneal injections. Hearing thresholds were measured before noise exposure, and at 1 day and 2 weeks after exposure. RESULTS: The hearing thresholds of the sham OP and OP-only groups were not significantly different. However, both estrogen groups showed a lower threshold shift than the OP-only group. Histological immunostaining analyses showed that hair cell loss in the 32 kHz region was more severe in the sham OP group than in the OP-only group. Furthermore, there was little or no hair cell loss in either estrogen replacement group and significantly more hair cell loss in the OP-only group. CONCLUSION: These results suggest that estrogen replacement may reduce the vulnerability of hearing to noise exposure in menopausal women.