Epidermal growth factor receptor phosphorylation contributes to levobupivacaine-induced contraction in isolated rat aorta.

Vasoconstriction induced by levobupivacaine, a local anesthetic, is mediated by increased levels of calcium, tyrosine kinase, c-Jun NH2-terminal kinase (JNK), and phospholipase D, which are associated with prolonged local anesthesia. Epidermal growth factor receptor (EGFR) phosphorylation is associated with vasoconstriction. However, its role in levobupivacaine-induced contractions remains unknown. We determined whether EGFR phosphorylation is associated with levobupivacaine-induced contractions in isolated rat thoracic aortas and identified the underlying cellular signaling pathways. The effects of various inhibitors and a calcium-free solution alone or in combination on levobupivacaine-induced contractions were then assessed. Furthermore, we examined the effects of various inhibitors on levobupivacaine-induced EGFR and JNK phosphorylation and calcium levels in vascular smooth muscle cells (VSMCs) of rat aortas. The EGFR tyrosine kinase inhibitor AG1478, matrix metalloproteinase (MMP) inhibitor GM6001, Src kinase inhibitors PP1 and PP2, and JNK inhibitor SP600125 attenuated levobupivacaine-induced contractions. Moreover, although the calcium-free solution abolished levobupivacaine-induced contractions, calcium reversed this inhibitory effect. The magnitude of the calcium-mediated reversal of abolished levobupivacaine-induced contractions was lower in the combination treatment with calcium-free solution and AG1478 than in the treatment with calcium-free solution alone. Levobupivacaine induced EGFR and JNK phosphorylation. However, AG1478, GM6001, and PP2 attenuated levobupivacaine-induced EGFR and JNK phosphorylation. Moreover, although levobupivacaine induced JNK phosphorylation in control siRNA-transfected VSMCs, EGFR siRNA inhibited levobupivacaine-induced JNK phosphorylation. Furthermore, AG1478 inhibited levobupivacaine-induced calcium increases in VSMCs. Collectively, these findings suggest that levobupivacaine-induced EGFR phosphorylation, which may occur via the Src kinase-MMP pathway, contributes to vasoconstriction via JNK phosphorylation and increased calcium levels.

Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.

Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o8G) can change RNA-RNA interactions via o8G•A base pairing, but its regulatory roles remain elusive. Here, on the basis of o8G-induced guanine-to-thymine (o8G > T) variations featured in sequencing, we discovered widespread position-specific o8Gs in tumour microRNAs, preferentially oxidized towards 5' end seed regions (positions 2-8) with clustered sequence patterns and clinically associated with patients in lower-grade gliomas and liver hepatocellular carcinoma. We validated that o8G at position 4 of miR-124 (4o8G-miR-124) and 4o8G-let-7 suppress lower-grade gliomas, whereas 3o8G-miR-122 and 4o8G-let-7 promote malignancy of liver hepatocellular carcinoma by redirecting the target transcriptome to oncogenic regulatory pathways. Stepwise oxidation from tumour-promoting 3o8G-miR-122 to tumour-suppressing 2,3o8G-miR-122 occurs and its specific modulation in mouse liver effectively attenuates diethylnitrosamine-induced hepatocarcinogenesis. These findings provide resources and insights into epitranscriptional o8G regulation of microRNA functions, reprogrammed by redox changes, implicating its control for cancer treatment.

Chloroquine inhibits vasodilation induced by ATP-sensitive potassium channels in isolated rat aorta.

This study examined the effect of chloroquine on vasodilation induced by levcromakalim in isolated endothelium-denuded rat aortas and clarified the underlying mechanisms. We examined the effects of chloroquine, hydroxychloroquine, lipid emulsion, reactive oxygen species (ROS) scavenger N-acetyl-ʟ-cysteine (NAC), and KATP channel inhibitor glibenclamide on levcromakaliminduced vasodilation. The effects of chloroquine, hydroxychloroquine, NAC, and levcromakalim on membrane hyperpolarization and ROS production were examined in aortic vascular smooth muscle cells (VSMCs). Chloroquine inhibited levcromakalim-induced vasodilation more than hydroxychloroquine. NAC attenuated chloroquine-mediated inhibition of levcromakalim-induced vasodilation, while lipid emulsion had no effect. Glibenclamide eliminated levcromakalim-induced vasodilation in aortas pretreated with chloroquine. Chloroquine and hydroxychloroquine inhibited levcromakalim-induced membrane hyperpolarization in VSMCs. Chloroquine and hydroxychloroquine both produced ROS, but chloroquine produced more. NAC inhibited chloroquine-induced ROS production in VSMCs. Collectively, these results suggest that, partially through ROS production, chloroquine inhibits levcromakalim-induced vasodilation. In addition, chloroquine-induced KATP channel-induced vasodilation impairment was not restored by lipid emulsion.

Lipid emulsion inhibits the cardiac toxicity caused by chloroquine via inhibition of reactive oxygen species production.

BACKGROUND: Lipid emulsion (LE) is effective in treating intractable cardiac depression induced by the toxicity of highly lipid-soluble drugs including local anesthetics. However, the effect of LE on chloroquine (CQ)-evoked cardiac toxicity remains unclear. This study aimed to examine the effect of Lipofundin MCT/LCT, an LE, on the cardiotoxicity caused by CQ in H9c2 rat cardiomyoblasts and elucidate the underlying cellular mechanism. METHODS: The effects of CQ (1 × 10-4 M), LE, and the reactive oxygen species (ROS) scavengers mitotempo and N-acetyl-L-cysteine (NAC), alone or combined, on cell viability and migration, apoptosis, ROS production, calcium levels, mitochondrial membrane potential, and adenosine triphosphate (ATP) were examined. Additionally, the effects of LE on the activities of catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) induced by CQ were assessed. RESULTS: Pretreatment with LE, mitotempo, or NAC reversed the reduction in cell migration and viability, mitochondrial membrane potential, and ATP levels evoked by CQ, and inhibited the increase in cleaved caspase-3, ROS, and calcium concentration induced by CQ. LE inhibited the increase in Bax expression, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, MDA activity, and late apoptosis, and reversed the reduction in SOD and CAT activity induced by CQ. CQ did not significantly affect cleaved caspase-8 expression, and LE did not significantly affect CQ concentration. CONCLUSIONS: Collectively, these results suggest that LE (Lipofundin MCT/LCT) inhibits the cardiotoxicity and late apoptosis induced by CQ toxicity via the intrinsic mitochondrial apoptotic pathway that is associated with direct inhibition of ROS production.

Lipid emulsion attenuates propranolol-induced early apoptosis in rat cardiomyoblasts.

OBJECTIVE: Propranolol is used to treat several cardiovascular diseases; however, toxic doses of propranolol cause severe myocardial depression and cardiac arrest. The aim of this study was to examine the effects of lipid emulsion (LE) on cardiotoxicity induced by toxic doses of propranolol in H9C2 rat cardiomyoblast cell line and to elucidate the underlying mechanism. METHODS: The experimental groups comprised control, propranolol alone, esmolol alone, or LE followed by propranolol or esmolol treatment, and reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine (NAC) followed by propranolol treatment. The effects of propranolol, esmolol, NAC, and LE, alone or in combination, on cell viability, apoptosis, and ROS production were examined. Additionally, we investigated the effect of LE on propranolol concentration. RESULTS: LE and NAC reversed the inhibition of cell viability induced by propranolol (p < .001). However, LE had no effect on the inhibition of cell viability caused by esmolol. The LE inhibited propranolol-induced expressions of cleaved caspase-3 (p < .001), caspase-9 (p < .001), and Bax (p < .01), but not caspase-8. NAC inhibited the propranolol-induced expression of cleaved caspase-3. LE inhibited propranolol-induced early apoptosis, but had no effect on late apoptosis. Additionally, LE inhibited the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells generated by propranolol. It attenuated propranolol-induced ROS production. However, it had no effect on propranolol concentration. CONCLUSION: LE inhibits early apoptosis caused by a toxic dose of propranolol by suppressing the intrinsic apoptotic pathway, via direct inhibition of ROS production.

Dexmedetomidine-Induced Aortic Contraction Involves Transactivation of the Epidermal Growth Factor Receptor in Rats.

In this study, we examined whether aortic contraction, induced by the alpha-2 adrenoceptor agonist dexmedetomidine, is involved in the transactivation of the epidermal growth factor receptor (EGFR) in isolated endothelium-denuded rat aortas. Additionally, we aimed to elucidate the associated underlying cellular mechanisms. The effects of the alpha-2 adrenoceptor inhibitor rauwolscine, EGFR tyrosine kinase inhibitor AG1478, Src kinase inhibitors PP1 and PP2, and matrix metalloproteinase inhibitor GM6001 on EGFR tyrosine phosphorylation and c-Jun NH2-terminal kinase (JNK) phosphorylation induced by dexmedetomidine in rat aortic smooth muscles were examined. In addition, the effects of these inhibitors on dexmedetomidine-induced contraction in isolated endothelium-denuded rat aorta were examined. Dexmedetomidine-induced contraction was inhibited by the alpha-1 adrenoceptor inhibitor prazosin, rauwolscine, AG1478, PP1, PP2, and GM6001 alone or by a combined treatment with prazosin and AG1478. AG1478 (3 × 10-6 M) inhibited dexmedetomidine-induced contraction in isolated endothelium-denuded rat aortas pretreated with rauwolscine. Dexmedetomidine-induced EGFR tyrosine and JNK phosphorylation were inhibited by rauwolscine, PP1, PP2, GM6001, and AG1478. Furthermore, dexmedetomidine-induced JNK phosphorylation reduced upon EGFR siRNA treatment. Therefore, these results suggested that the transactivation of EGFR associated with dexmedetomidine-induced contraction, mediated by the alpha-2 adrenoceptor, Src kinase, and matrix metalloproteinase, caused JNK phosphorylation and increased calcium levels.

Lipid emulsions attenuate the inhibition of carnitine acylcarnitine translocase induced by toxic doses of local anesthetics in rat cardiomyoblasts.

The aim of this study was to examine the effects of lipid emulsions on carnitine palmitoyltransferase I (CPT-I), carnitine acylcarnitine translocase (CACT), carnitine palmitoyltransferase II (CPT-II), and the mitochondrial dysfunctions induced by toxic doses of local anesthetics in H9c2 rat cardiomyoblasts. The effects of local anesthetics and lipid emulsions on the activities of CPT-I, CACT, and CPT-II, and concentrations of local anesthetics were examined. The effects of lipid emulsions, N-acetyl-L-cysteine (NAC), and mitotempo on the bupivacaine-induced changes in cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and intracellular calcium levels were examined. CACT, without significantly altering CPT-I and CPT-II, was inhibited by toxic concentration of local anesthetics. The levobupivacaine- and bupivacaine-induced inhibition of CACT was attenuated by all concentrations of lipid emulsion, whereas the ropivacaine-induced inhibition of CACT was attenuated by medium and high concentrations of lipid emulsion. The concentration of levobupivacaine was slightly attenuated by lipid emulsion. The bupivacaine-induced increase of ROS and calcium and the bupivacaine-induced decrease of MMP were attenuated by ROS scavengers NAC and mitotempo, and the lipid emulsion. Collectively, these results suggested that the lipid emulsion attenuated the levobupivacaine-induced inhibition of CACT, probably through the lipid emulsion-mediated sequestration of levobupivacaine.

AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.

Small interfering RNAs (siRNAs) therapeutically induce RNA interference (RNAi) of disease-causing genes, but they also silence hundreds of seed-matched off-targets as behaving similar to microRNAs (miRNAs). miRNAs control the pathophysiology of tumors, wherein their accessible binding sites can be sequenced by Argonaute crosslinking immunoprecipitation (AGO CLIP). Herein, based on AGO CLIP, we develop potent anticancer siRNAs utilizing miRNA-like activity (mi/siRNAs). The mi/siRNAs contain seed sequences (positions 2-7) of tumor-suppressive miRNAs while maintaining perfect sequence complementarity to the AGO-accessible tumor target sites. Initially, host miRNA interactions with human papillomavirus 18 (HPV18) were identified in cervical cancer by AGO CLIP, revealing tumor-suppressive activity of miR-1/206 and miR-218. Based on the AGO-miRNA binding sites, mi/siRNAs were designed to target E6 and E7 (E6/E7) transcript with seed sequences of miR-1/206 (206/E7) and miR-218 (218/E7). Synergistic anticancer activity of 206/E7 and 218/E7 was functionally validated and confirmed via RNA sequencing and in vivo xenograft models (206/E7). Other mi/siRNA sequences were additionally designed for cervical, ovarian, and breast cancer, and available as an online tool (http://ago.korea.ac.kr/misiRNA); some of the mi/siRNAs were validated for their augmented anticancer activity (206/EphA2 and 206/Her2). mi/siRNAs could coordinate miRNA-like activity with robust siRNA function, demonstrating the potential of AGO CLIP analysis for RNAi therapeutics.

The stem cell marker Prom1 promotes axon regeneration by down-regulating cholesterol synthesis via Smad signaling.

Axon regeneration is regulated by a neuron-intrinsic transcriptional program that is suppressed during development but that can be reactivated following peripheral nerve injury. Here we identify Prom1, which encodes the stem cell marker prominin-1, as a regulator of the axon regeneration program. Prom1 expression is developmentally down-regulated, and the genetic deletion of Prom1 in mice inhibits axon regeneration in dorsal root ganglion (DRG) cultures and in the sciatic nerve, revealing the neuronal role of Prom1 in injury-induced regeneration. Elevating prominin-1 levels in cultured DRG neurons or in mice via adeno-associated virus-mediated gene delivery enhances axon regeneration in vitro and in vivo, allowing outgrowth on an inhibitory substrate. Prom1 overexpression induces the consistent down-regulation of cholesterol metabolism-associated genes and a reduction in cellular cholesterol levels in a Smad pathway-dependent manner, which promotes axonal regrowth. We find that prominin-1 interacts with the type I TGF-ß receptor ALK4, and that they synergistically induce phosphorylation of Smad2. These results suggest that Prom1 and cholesterol metabolism pathways are possible therapeutic targets for the promotion of neural recovery after injury.

A Comparative Study of Percutaneous Aspiration with Sclerotherapy and Laparoscopic Marsupialization for Symptomatic Simple Renal Cysts.

Background: Percutaneous aspiration with sclerotherapy (PAS) and laparoscopic marsupialization (LM) are minimally invasive treatment modalities for renal cysts. We aimed to compare the efficacy and cost/effectiveness of LM and PAS for the treatment of simple symptomatic renal cysts. Methods: Data were prospectively collected from three health care institutions in which 80 patients with symptomatic simple renal cysts underwent a single session of PAS with 95% ethanol (PAS group, n = 40) or underwent LM under general anesthesia (LM group, n = 40) between March 2012 and May 2016. We compared the patient profile, duration of procedure, duration of hospital stay, radiological and symptomatic success rates, treatment costs, and incidence of complications between the two groups. Results: At the 6-month follow-up, the radiological success rate in the LM group was significantly greater than that in the PAS group (97.5% versus 60%; P < .001). The symptomatic success rate was comparable in the two groups (95% versus 90%; P = .675). The treatment failure rate did not significantly differ between the two groups (5.0% versus 17.5%, P = .154). The mean total cost in the PAS and LM groups was 1256 USD and 2343 USD, respectively (P = .001). No significant between-group difference was noted regarding the overall complication rate (P = .615). Conclusions: Both LM and PAS are effective and safe procedures for the treatment of symptomatic simple renal cysts. A single session of PAS seems to be a cost-effective method for the management of symptomatic simple renal cysts.

siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects.

Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6Ø), of which impaired base pairing destabilizes transitional nucleation (positions 2-6). However, siRNA-6Ø varied in its conservation of on-target activity (∼80-100%), demanding bioinformatics to discover the principles underlying its on-target efficiency. Analyses of miRNA-target interactions (Ago HITS-CLIP) showed that the stability of transitional nucleation correlated with the target affinity of RNA interference. Furthermore, interrogated analyses of siRNA screening efficiency, experimental data and broadly conserved miRNA sequences showed that the free energy of transitional nucleation (positions 2-5) in siRNA-6Ø required the range of stability for effective on-target activity (-6 ≤ ΔG[2:5] ≤ -3.5 kcal mol-1). Taking into consideration of these features together with locations, guanine-cytosine content (GC content), nucleotide stretches, single nucleotide polymorphisms and repetitive elements, we implemented a database named 'siAbasic' that provided the list of potent siRNA-6Ø sequences for most of human and mouse genes (≥ ∼95%), wherein we experimentally validated some of their therapeutic potency. siAbasic will aid to ensure potency of siRNA-6Ø sequences without concerning off-target effects for experimental and clinical purposes.

CLIPick: a sensitive peak caller for expression-based deconvolution of HITS-CLIP signals.

High-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP, also called CLIP-Seq) has been used to map global RNA-protein interactions. However, a critical caveat of HITS-CLIP results is that they contain non-linear background noise-different extent of non-specific interactions caused by individual transcript abundance-that has been inconsiderately normalized, resulting in sacrifice of sensitivity. To properly deconvolute RNA-protein interactions, we have implemented CLIPick, a flexible peak calling pipeline for analyzing HITS-CLIP data, which statistically determines the signal-to-noise ratio for each transcript based on the expression-dependent background simulation. Comprising of streamlined Python modules with an easy-to-use standalone graphical user interface, CLIPick robustly identifies significant peaks and quantitatively defines footprint regions within which RNA-protein interactions were occurred. CLIPick outperforms other peak callers in accuracy and sensitivity, selecting the largest number of peaks particularly in lowly expressed transcripts where such marginal signals are hard to discriminate. Specifically, the application of CLIPick to Argonaute (Ago) HITS-CLIP data were sensitive enough to uncover extended features of microRNA target sites, and these sites were experimentally validated. CLIPick enables to resolve critical interactions in a wide spectrum of transcript levels and extends the scope of HITS-CLIP analysis. CLIPick is available at: http://clip.korea.ac.kr/clipick/.

Frontal Changes in the Lower Face After Clockwise Rotation of the Maxillomandibular Complex Without Perisurgical Orthodontic Treatment in Angle Class I and Skeletal Class III Women.

BACKGROUND: Orthognathic surgery has become more popular to slenderize a wide lower face and to improve facial esthetics in Asian patients with normal occlusion. Clockwise rotation (CR) of the maxillomandibular complex (MMC) steepens the mandibular plane. This study performed a quantitative analysis on the influence of CR on slenderness of the lower face from the frontal view. PATIENTS AND METHODS: This retrospective study included 36 female patients with Angle Class I occlusion and skeletal Class III pattern. The subjects underwent CR of the MMC without perioperative orthodontic treatment and change in the occlusion only for the purpose of esthetic improvement. Linear and angular variables were measured on a cephalogram and three-dimensional computed tomography (3D CT) obtained before and at least 6 months after surgery. Data were analyzed using paired t tests and Spearman correlations. Univariate regression analysis was used to predict the postoperative change according to the amount of posterior impaction. RESULTS: The mean posterior impaction was 3.81 mm. All mandibular plane angle (MPA) measurements were increased (ranged from 5.69° to 13.12°, p < 0.001), exhibiting a significant correlation with the amount of posterior impaction. Bigonial width measurements were decreased after surgery (ranged from 4.97 to 5.51 mm, p < 0.001). Among the MPAs derived from the 3D CT, the coronal projection from the frontal view exhibited a discrepancy between right and left side. CONCLUSIONS: The changes in linear and angular measurements in this study indicate that the lower face becomes narrower and more slender as the MMC rotates in a clockwise direction. Orthognathic surgery with CR has the advantage of increasing the MPAs and obtaining natural soft tissue contouring while minimizing the amount of bone resection. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266c .

Antifibrotic effect of dexamethasone/alginate-coated silicone sheet in the abraded middle ear mucosa.

Silicone sheet is a material which is commonly used in middle ear surgery to prevent the formation of adhesions between the tympanic membrane and the medial bony wall of the middle ear cavity. However, silicone sheet can induce a tight and hard fibrous capsule in the region of the stapes, and this is particularly common in cases of eustachian tube dysfunction. As a result of the fibrous encapsulation around the silicone sheet, postoperative aeration of the stapes can be interrupted causing poor hearing gain. In this study, we performed an in vitro and in vivo evaluation of the antifibrotic effects of a dexamethasone and alginate (Dx/alginate) coating on silicone sheet. The Dx/alginate-coated silicone sheets were fabricated using a plasma-treatment and coating method. The Dx/alginate-coated silicone sheets effectively limited in vitro fibroblast attachment and proliferation due to the controlled release of Dx, which can be modified by manipulation of the alginate coating. For the in-vivo evaluation, guinea pigs (albino, male, weighing 250g) were divided into two groups, with the control group (n=5) implanted with silicone sheet and the test group (n=5) receiving Dx/alginate-coated silicone sheet. Animals were sacrificed 3 weeks after implantation, and histological analysis was performed using hematoxylin and eosin (H&E) and immunohistochemical staining techniques. Dx/alginate-coated silicone sheets showed marked inhibition of fibrosis in both the in vitro and in vivo studies. Silicone sheet that incorporates a Dx/alginate coating can release Dx and inhibit fibrosis in the middle ear. This material could be utilized in middle ear surgery as a means of preserving proper aeration and hearing gain following ossiculoplasty.

Transitional Zone Index as a Predictor of the Efficacy of α-Blocker and 5α-Reductase Inhibitor Combination Therapy in Korean Patients with Benign Prostatic Hyperplasia.

INTRODUCTION: We investigated the value of the transitional zone index (TZI) for predicting treatment response to combination therapy involving α-blockers and 5α-reductase inhibitors for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Symptomatic BPH patients (n = 118) were randomized to receive 0.2 mg tamsulosin alone or with 0.5 mg dutasteride daily for 12 months. The TZI, International Prostate Symptom Scores, maximum urinary flow rates (Qmax), postvoid residual urine volumes, and prostate-specific antigen (PSA) were evaluated at baseline and after 12 months. The groups were subdivided according to a cut-off TZI value of 0.5 to compare treatment-related changes. RESULTS: After 12 months, the combination therapy group had significantly greater decreases in prostate volume (p < 0.001), TZ volume (p < 0.001) and PSA (p < 0.001) than the monotherapy group, regardless of TZI. However, combination therapy resulted in significantly greater Qmax increases (p < 0.001) only in patients with a TZI ≥0.5. Multivariate analysis determined that TZI was the strongest independent predictor of the Qmax increase at 12 months in the combination therapy group (ß = 13.7, p < 0.001). CONCLUSIONS: Greater Qmax improvement is expected with combination therapy comprising α-blockers and 5α-reductase inhibitors for patients with a TZI ≥0.5. The TZI may be useful for predicting the Qmax response to combination treatment for BPH.

Secondary Genioplasties for the Treatment of Chin Deformities After Orthognathic Surgery in Asian Women: Defining the Aesthetic Importance of Managing the Chin Shape in Orthognathic Surgery.

BACKGROUND: Achieving aesthetically favorable results in orthognathic surgery is equally as important as good postoperative occlusion and jaw function. Orthognathic surgery that only changes profile or proportion in the vertical dimension can often lead to patient's dissatisfaction and additional surgical revision. To achieve maximal aesthetic improvement and postoperative patient's satisfaction, the chin shape should be considered as important a component of orthognathic surgery as dental occlusion or jaw function. METHODS: From April 2010 to January 2014, 82 female patients with aesthetic complaints after previous orthognathic surgery visited our clinic for reevaluation and management. Among those 82 patients, 54 patients who were dissatisfied with their lower facial shape from the frontal view underwent revision surgery with narrowing genioplasty and contouring of the lower border of the mandible. RESULTS: Facial shapes, when viewed from the front in all patients, became more slender and balanced postoperatively, and there was no need for additional surgical revisions in this series. There were no significant complications caused by our surgical revisions. CONCLUSIONS: Good aesthetic results were obtained after 54 secondary genioplasties for chin deformities after orthognathic surgery. These results suggest that surgeons should give more attention to managing chin shape when performing orthognathic surgery to meet the high aesthetic demands of patients and to avoid surgical revisions.

Evaluation of the levator veli palatini muscle thickness in patients with velocardiofacial syndrome using magnetic resonance imaging.

Velocardiofacial syndrome (VCFS) is associated with velopharyngeal insufficiency, which occurs in approximately 75% of VCFS patients. Surgical management of velopharyngeal insufficiency in VCFS patients is difficult with a high revision rate due to the anatomic and physiological abnormalities of the velopharynx. The aims of this study were to evaluate the thickness and symmetry of the levator veli palatini (LVP) muscle using magnetic resonance imaging (MRI), and to compare the findings in VCFS patients to those in patients with nonsyndromic submucous cleft palate. We conducted a prospective analysis of 17 VCFS patients (nine boys, eight girls; age range, 4-9 years) and nine patients with submucous cleft palate without VCFS (eight boys, one girl; age range, 4-13 years) who had undergone MRI between March 2009 and August 2013. The thickness of the LVP muscle was measured at six locations in both groups. The symmetry was determined by comparing the values between the average of the left three points and the right three points. The mean LVP muscle thickness was significantly thinner in VCFS patients (2.14 ± 0.73 mm) than in patients without VCFS (3.70 ± 1.08 mm) (p < 0.001). In addition, the difference between the left and right sides of muscle thickness in the VCFS group was larger than that in the nonsyndromic submucous cleft palate group (0.25 and 0.09 mm, respectively). The thinness and asymmetry of the LVP muscle should be considered when determining the surgical management of velopharyngeal insufficiency in VCFS patients.

Comparison of tamsulosin plus serenoa repens with tamsulosin in the treatment of benign prostatic hyperplasia in Korean men: 1-year randomized open label study.

INTRODUCTION: In Korea, increasing attention has recently been given to the use of phytotherapeutic agents to alleviate the symptoms of BPH. Serenoa repens has been shown to have an equivalent efficacy to Finasteride or Tamsulosin in the treatment of BPH in previous studies. The present study was designed to compare the efficacy and safety of Serenoa repens plus tamsulosin with tamsulosin only over 12 months in men with LUTS secondary to BPH. MATERIALS AND METHODS: One hundred forty men with symptomatic BPH (IPSS≥10) were recruited in our hospital for a 12-month, open-label, randomized trial. Patients were randomly assigned to either tamsulosin 0.2 mg/day plus Serenoa repens 320 mg/day (n=60) or tamsulosin 0.2 mg/day only (n=60). Prostate volume and PSA were measured at baseline and at end-point, whereas total IPSS, and its storage and voiding subscores, LUTS-related QoL, Qmax, and PVR were evaluated at baseline and later every 6 months. RESULTS: Total 103 patients were finally available: 50 in the TAM+SR group and 53 in the TAM group. At 12 months, total IPSS decreased by 5.8 with TAM+SR and 5.5 with TAM (p=0.693); the storage symptoms improved significantly more with TAM+SR (-1.7 vs. -0.8 with TAM, p=0.024). This benefit with regard to storage symptom in the TAM+SR group lasts at 12 months (-1.9 vs. -0.9, p=0.024). The changes of voiding subscore, LUTS-related QoL, Qmax, PVR, PSA, and prostate volume showed no significant differences between the TAM+SR and TAM groups. During the treatment period, 8 patients (16.9%) with TAM and 10 (20%) with TAM+SR had drug-related adverse reactions, which included ejaculatory disorders, postural hypotension, dizziness, headache, gastro-intestinal disorders, rhinitis, fatigue and asthenia. CONCLUSIONS: The combination treatment of Serenoa repens and tamsulosin was shown to be more effective than tamsulosin monotherapy in reducing storage symptoms in BPH patients after 6 months and up to 12 months of treatment.

Angloplasty revision: importance of genioplasty for narrowing of the lower face.

BACKGROUND: Angloplasty is the most common procedure in facial contouring surgery among Asians. However, to achieve satisfactory results during procedures aimed at altering the lower facial contour, the shape of the mandible and the chin area in particular is an important consideration. In cases of reoperation for further improvement after angloplasty, surgeons should consider performing a genioplasty to improve the shape of the chin. METHODS: From March of 2010 to August of 2012, 52 women who were dissatisfied with results of angloplasty and wanted a slimmer lower face underwent genioplasty and revision angloplasty. The procedures included narrowing genioplasty and contouring of the lower border of the mandible from the parasymphysis area to the previously resected area. RESULTS: All patients were satisfied with their facial appearance, which had become slender when viewed from the front. There were no notable complications. No patient experienced permanent sensory numbness of the lower lip. Two patients complained of submental bulges and were treated postoperatively using laser-assisted liposuction. CONCLUSION: When performing revision surgery to restore the contour of the mandible, the surgeon should consider the shape of the mandible as a whole to create a slender face, which is achievable by simultaneous narrowing genioplasty and contouring of the lower border of the mandible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.