Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen-activated protein kinase and protein kinase B pathways.

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

[Enoxaparin and tinzaparin in pediatrics: Impact of recommendation on prescription quality and anti-Xa levels]. / Énoxaparine et tinzaparine en pédiatrie : impact de recommandations sur la qualité des prescriptions et l'activité anti-Xa.

OBJECTIVES: A protocol has been written and distributed in May 2017 to all prescribers in a pediatric hospital to standardize and to secure the prescriptions of enoxaparin and tinzaparin considered as two high risk medications. The aim of this study is to evaluate the impact of the protocol on those prescriptions in a pediatric population. METHODS: This is a monocentric retrospective study comparing prescriptions of this two low-molecular-weight heparins for patients under 18 years old in 2016 and 2018, thus before and after the protocol redaction. RESULTS: In 2016, 2246 prescriptions of enoxaparin and tinzaparin were analyzed for 627 patients. Among them, 142 (22.6%) patients have had at least one anti-Xa level dosed. On the other hand, in 2018, 2061 prescriptions were written for 628 patients including 96 (15.3%) who have had at least one anti-Xa level dosed. The conformity rate of the first dose in IU/kg/administration of the first enoxaparin prescription goes from 36.3% before protocol to 52.1% after (P=0.03*). Concerning tinzaparin, the conformity rate goes from 69.2% to 83.3%. (P=0.19). The rate of first anti-Xa level in the range 0.4 to 1.2 IU/ml increase between 2016 and 2018 from 27.7% to 43.8% (P<0.001*). CONCLUSION: This protocol enabled to improve the quality of prescriptions in terms of: dosage written in IU/kg/administration, frequency of administration, dilution conformity, and result of the first anti-Xa level. Some efforts must be made in writing the dose in IU not in mg or ml.

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial.

Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660-1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P = 0.0051), and by IRC (0.735; 0.525-1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

Role of the histone deacetylase inhibitor valproic acid in high-fat diet-induced hypertension via inhibition of HDAC1/angiotensin II axis.

BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice. Furthermore, we examined the mechanism of VPA-induced prevention of hypertension. METHODS: Nine-week-old male C57BL/6 mice were fed either a normal diet (ND) or HFD. When the HFD group reached a pre-hypertensive phase (130-140 mm Hg systolic blood pressure), VPA was administered for 6 days (300 mg kg-1 per day). Body weights and blood pressure (BP), expression of renin-angiotensin system (RAS) components and HDAC1 were determined. The direct role of HDAC1 in the expression of RAS components was investigated using gene silencing. RESULTS: HFD accelerated the increase in body weight from 22.4±1.3 to 31.9±3.0 compared to in the ND group from 22.7±0.9 to 26.0±1.7 (P=0.0134 ND vs HFD), systolic BP from 118.5±5.7 to 145.0±3.0 (P<0.001), and diastolic BP from 91.0±13.6 to 121.0±5.0 (P=0.006); BP was not altered in the ND group. HFD increased RAS components and HDAC1 in the kidneys as well as leptin in the plasma. VPA administration prevented the progression of hypertension and inhibited the increase in expression of HDAC1 and RAS components. VPA did not affect plasma leptin level. Knockdown of HDAC1 in MDCK cells decreased the expression of angiotensinogen and type 1 angiotensin II receptor. CONCLUSIONS: VPA prevented HFD-induced hypertension by downregulating angiotensin II and its receptor via inhibition of HDAC1, offering a novel therapeutic option for HFD-induced hypertension.

Influence of rabbit notochordal cells on symptomatic intervertebral disc degeneration: anti-angiogenic capacity on human endothelial cell proliferation under hypoxia.

OBJECTIVES: Symptomatic degenerative disc disease (DDD) is associated with neovascularization and nerve ingrowth into intervertebral discs (IVDs). Notochordal cells (NCs) are key cells that may lead to regeneration of IVDs. However, their activities under conditions of hypoxia, the real environment of IVD, are not well known. We hypothesized that NCs may inhibit neovascularization by interacting with endothelial cells (ECs) under hypoxia. DESIGN: Human IVDs were isolated and cultured to produce nucleus pulposus (NP) cell conditioned medium (NPCM). Immortalized human microvascular ECs were cultured in NPCM with notochordal cell-rich rabbit nucleus pulposus cells (rNC) under hypoxia. Vascular endothelial growth factor (VEGF), vascular cell adhesion molecule (VCAM), and interleukin-8 (IL-8) were analyzed by ELISA. Focal adhesion kinase (FAK), filamentous actin (F-actin), and platelet-derived growth factor (PDGF) were evaluated to investigate EC activity. Wound-healing migration assays were performed to examine EC migration. RESULTS: The VEGF level of EC cells cultured in NPCM was significantly higher under hypoxia compared to normoxia. VEGF expression was significantly decreased, and FAK, F-actin, PDGF expression were inhibited when ECs were cocultured with rNCs under hypoxia. ECs cocultured with rNC in NPCM showed significantly decreased migratory activity compared to those without rNC under hypoxia. CONCLUSIONS: The angiogenic capacity of ECs was significantly inhibited by NCs under hypoxia via a VEGF-related pathway. Our results suggest that NCs may play a key role in the development of IVDs by inhibiting vascular growth within the disc, and this may be a promising novel therapeutic strategy for targeting vascular ingrowth in symptomatic DDD.

Non-invasive tumescent cryolipolysis using a new 4D handpiece: a comparative study with a porcine model.

BACKGROUND/PURPOSE: The growing demand for a youthful appearance, including a favorable body shape, has motivated recent developments in noninvasive body contouring techniques. Our aim was to investigate the efficacy and safety of a new version of a 4D handpiece-mounted cooling device for cryolipolysis with or without tumescent injections. METHODS: We conducted a side-by-side comparative study using two female porcine models. Two areas of each pig's left abdomen were treated using a conventional device and the new cooling device, and two areas of the right abdomen were also treated using the conventional and new cooling device, but both were combined with tumescent-solution injections. RESULTS: The conventional method alone yielded a 75.25% reduction in skin thickness, while the new cooling device alone yielded a 81.63% reduction. When paired with tumescent injections, the conventional device yielded a 86.3% reduction in skin thickness and the cooling device yielded a 85.9% reduction. Using histological analysis with H&E, oil red O, and toluidine blue stain, we confirmed that selective cryolipolysis was able to induce selective apoptosis of fat cells. CONCLUSION: This in vivo study presents a new 4D handpiece-assisted cooling device with tumescent anesthesia that is safe and effective for fat reduction.

Transcutaneous pneumatic injection of glucose solution: a morphometric evaluation of in vivo micropig skin and tissue-mimicking phantom.

BACKGROUND: Needle-free, transcutaneous pneumatic injection systems can be used to deliver therapeutic solutions to targeted layers of skin in a minimally invasive manner. METHODS: To evaluate jet infiltration patterns and tissue reactions, 5% isotonic and 20% hypertonic glucose solutions were pneumatically injected into in vivo micropig skin. Gelatin TM phantom was additionally prepared to analyze penetration and dispersion patterns for different experimental settings. RESULTS: As immediate tissue reactions in the in vivo micropig skin, distinct pneumatic injection injury zones (PIIZs) in the dermis, extending from the papillary dermis deep into the dermo-subcutaneous junction, were generated with the 5% and 20% glucose solutions and with pneumatic pressures of 4.64 and 5.7 bars, respectively. PIIZs markedly decreased in appearance at 1 day after treatment, accompanied by inflammatory cell infiltration, and disappeared at 7 days post-treatment with increased collagen and elastin production. In TM phantom study, the PIIZs created by 20% glucose mainly comprised a single, homogenous, round to oval zone, whereas those created by 5% glucose were irregular and multi-lobular. CONCLUSION: The present study suggests that transcutaneous pneumatic injection therapy may exert mechanical stimulatory effects, immediate tissue shrinkage via hypertonic solutions, and late tissue regeneration effects during wound healing.

Efficacy and safety of non-invasive body tightening with high-intensity focused ultrasound (HIFU).

BACKGROUND: Noninvasive skin-tightening devices have become increasingly popular in response to increasing demand for improvements in skin laxity and tightening with minimal risk and recovery time. OBJECTIVE: We evaluated the efficacy and safety of HIFU for skin tightening in the face and body. METHODS: A total of 32 Korean subjects enrolled in this prospective clinical trial. The subjects were treated with HIFU to both cheeks, lower abdomen, and thigh. Skin elasticity was measured before and after treatment using a Cutometer (CT575, Courage and Khazaka® , Cologne, Germany). Three blinded, experienced dermatologists evaluated paired pre- and post-treatment (week 4 and 12) photographs according to the Global Aesthetic Improvement Scale (GAIS). Participants also completed self-assessments using GAIS. Subjects rated their pain on a numeric rating scale (NRS) immediately, 7 days, 4 weeks, and 12 weeks after treatment. RESULTS: Skin elasticity measured via a Cutometer was significantly improved 12 weeks after treatment at all treated sites (P<.05). Both IGAIS and SGAIS showed significant improvements 12 weeks after treatment. Immediately after treatment the mean NRS score was 3.00±1.586, but no pain was reported at 4 and 12 weeks post-treatment. No serious adverse effects were observed during the follow-up period. CONCLUSION: HIFU safely and effectively improves skin elasticity and clinical contouring of the face and body.

Improved methods for evaluating pre-clinical and histological effects of subcutaneous fat reduction using high-intensity focused ultrasound in a porcine model.

BACKGROUND: Non-invasive body sculpting procedures are becoming increasingly popular. High-intensity focused ultrasound (HIFU) treatment is a non-surgical fat reduction procedure that permanently destroys unwanted abdominal fat. Despite its increasing popularity, evaluation methods for the procedure have not yet been fully developed. AIMS: The objective of this study was to develop evaluation methods for HIFU for non-surgical, permanent fat reduction in the anterior abdomen using a porcine model. METHODS: The abdomens of female pigs (Sus scrofa, n = 7) were treated with a HIFU device (SCIZER™ , Classys Inc, Seoul, Korea). We examined treatment effects using photography, ultrasound, gross and microscopic pathology, and serum lipid and liver function level analysis, carbon tracer test, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. RESULTS: HIFU treatment effectively reduced abdominal fat in a porcine model; it accurately treated the target subcutaneous fat layer and the subcutaneous fat was reduced effectively via ultrasonic measurement after HIFU treatment. On histological staining (H&E, toluidine blue, oil red O and immunohistochemistry), we found that subcutaneous fat reduction occurred effectively via accurate treatment of the targeted subcutaneous fat layer. On hematological assay, there were changes within normal range, and values remained stable after 48 h. Via carbon tracer test, the migration of activated macrophages was identified within the axillary lymph node (LN). PPAR-delta, a protein defined by immunohistochemistry staining, was overexpressed in the early stage on days 1 and 7, but a gradual decreasing pattern was confirmed. CONCLUSION: We successfully used a HIFU device for body contouring and fat reduction in a pre-clinical study. These results provide that the essential clues toward the effective evaluation, guiding selection of the appropriate diagnostic investigations.

Evaluation of the 3dMDface system as a tool for soft tissue analysis.

OBJECTIVES: To evaluate the accuracy of three-dimensional stereophotogrammetry by comparing values obtained from direct anthropometry and the 3dMDface system. To achieve a more comprehensive evaluation of the reliability of 3dMD, both linear and surface measurements were examined. SETTING AND SAMPLE POPULATION: UCLA Section of Orthodontics. Mannequin head as model for anthropometric measurements. MATERIAL AND METHODS: Image acquisition and analysis were carried out on a mannequin head using 16 anthropometric landmarks and 21 measured parameters for linear and surface distances. 3D images using 3dMDface system were made at 0, 1 and 24 hours; 1, 2, 3 and 4 weeks. Error magnitude statistics used include mean absolute difference, standard deviation of error, relative error magnitude and root mean square error. Intra-observer agreement for all measurements was attained. RESULTS: Overall mean errors were lower than 1.00 mm for both linear and surface parameter measurements, except in 5 of the 21 measurements. The three longest parameter distances showed increased variation compared to shorter distances. No systematic errors were observed for all performed paired t tests (P<.05). Agreement values between two observers ranged from 0.91 to 0.99. CONCLUSIONS: Measurements on a mannequin confirmed the accuracy of all landmarks and parameters analysed in this study using the 3dMDface system. Results indicated that 3dMDface system is an accurate tool for linear and surface measurements, with potentially broad-reaching applications in orthodontics, surgical treatment planning and treatment evaluation.

Hematological adverse effects and pharmacokinetics of ribavirin in pigs following intramuscular administration.

Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography-tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin-treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin-treated pigs until 5 days postinjection (dpi). The ribavirin-treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half-life of the RBV-DOE and RBV-Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (Cmax ) and area under the serum concentration-time curve from time zero to infinity (AUCinf ) of RBV-DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The Cmax and AUCinf of RBV-Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.

Impact of Shaggy Aorta in Patients with Abdominal Aortic Aneurysm Following Open or Endovascular Aneurysm Repair.

OBJECTIVE: To analyze the impact of the presence of shaggy aorta on 30 day morbidity and mortality and long-term survival in patients undergoing abdominal aortic aneurysm (AAA) repair. METHODS: This retrospective observational study included 447 consecutive patients who underwent AAA repair between January 2009 and December 2012. The study included 209 patients (47%) having open surgical repair (OSR) and 238 patients (53%) having endovascular aneurysm repair (EVAR). RESULTS: Of the 447 patients having elective AAA repair, 48 patients (11%) had shaggy aorta. Both the OSR (p = .005) and EVAR group (p = .007) demonstrated a higher 30 day morbidity and mortality in patients with shaggy aorta. On multivariate regression analysis, patients with shaggy aorta had 4.1 fold (95% CI = 1.7-9.7; p = .002) increase in 30 day morbidity and mortality. According to the Kaplan-Meier analysis, patients with shaggy aorta had significantly decreased long-term overall survival in comparison with the non-shaggy group (log-rank test; p = .005), and this resulted from comorbidities. CONCLUSIONS: Shaggy aorta is a prominent risk factor associated with 30 day morbidity and mortality. Poor long-term survival was expected in patients with shaggy aorta.

High intensity focused ultrasound as a potential new modality for the treatment of pigmentary skin disorder.

BACKGROUND/PURPOSE: The clinical skin tightening benefits of high intensity focused ultrasound (HIFU) have been established, but its mechanism of action in pigmented skin disorders remains unknown. We macroscopically and histopathologically investigated dermatological changes after HIFU at different exposure doses in a UVB-induced guinea pig model of hyperpigmentation. METHODS: We applied HIFU irradiation at 0.1 and 0.2 J/cm(2) to UVB-induced spotty hyperpigmentation in guinea pig skin. The therapeutic effects of HIFU were judged based on gross appearance using photography, dermoscopy, and chromametry during a period of 3 weeks after HIFU irradiation. Histological assessments were performed using Fontana-Masson staining 1 day before and 3 weeks after HIFU irradiation. RESULTS: Macroscopically, UVB-induced hyperpigmentation was significantly reduced 2 weeks after HIFU with 0.2 J/cm(2) , and 3 weeks after HIFU with 0.1 J/cm(2) . Histopathologically, the heavy deposition of melanin in the epidermis induced by UVB exposure was reduced 3 weeks after HIFU irradiation. CONCLUSION: We confirmed that HIFU has a positive effect on UVB-induced hyperpigmentation as well as mechanical destructive activity. We suggest that HIFU may be useful as an alternative modality for human patients suffering from skin pigmentary conditions.

Surgical treatment of central venous catheter related septic deep venous thrombosis.

OBJECTIVE/BACKGROUND: The aim of this study was to evaluate the clinical features and outcomes of catheter related central venous thrombosis and whether a surgical approach can be an effective treatment modality in selected cases that are refractory to conservative management. METHODS: This was a retrospective review of the 46 consecutive patients who were suspected of having central venous catheter related infected deep venous thrombosis and who met the eligibility criteria. RESULTS: Conservative management achieved clinical improvement in 26 (56.5%) patients and failed in 20 (43.5%), of whom surgical thrombectomy was performed in 13. The remaining seven patients died before surgery could be performed or their clinical condition was too poor. Apart from one case of wound hematoma (7.7%), post-operative complications that related to the surgical procedure were not observed. Patency of the involved vein was re-established in 12 of the 13 (92.3%) surgically treated patients, and clinical improvement was achieved in 11 (84.6%). In particular, the five patients whose blood cultures revealed Candida species exhibited prompt defervescence after surgical thrombectomy. CONCLUSION: Although conservative management is the first therapy of choice in patients with central venous catheter related infected thrombosis, surgical treatment that removes the septic material can be regarded as a last resort in critically ill patients with septic thrombophlebitis that is refractory to conservative management.

Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

BACKGROUND: Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). AIM: To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. METHODS: We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. RESULTS: We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE + MXD. CONCLUSIONS: From our data, we conclude that HPE increases ß-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans.

Improved methods for selective cryolipolysis results in subcutaneous fat layer reduction in a porcine model.

BACKGROUND/AIMS: Cryolipolysis is a noninvasive method for the selective reduction of localized fat tissues. It has demonstrated efficacy in both clinical and preclinical trials; however, despite its popularity, its mechanisms of action and evaluation methods are not yet fully defined. The purpose of this study was to improved methods for cryolipolysis using a porcine model. METHODS: The abdomens of female PWG micro-pigs were treated with a cooling device (CRYOLIPO II(™)), and we examined the treatment effects using photography, three-dimensional photography, ultrasound, gross, and microscopic pathology, and serum lipid level analyses in order to determine the mechanism of action, efficacy, and safety of CRYOLIPO II(™). RESULTS: CRYOLIPO II(™) successfully reduced abdominal fat in our porcine model. Gross and microscopic histological results confirmed the noninvasive cold-induced selective subcutaneous fat destruction, and showed increases in pre-adipocyte differentiation and in the activation of lipid catabolism. In particular, we found that CRYOLIPO II(™) may increase PPARδ (delta) levels in adipose tissue at 30-60 days post-treatment. CONCLUSION: Fat reduction by cryolipolysis was successfully achieved in our porcine model. Thus, our findings indicate that CRYOLIPO II(™) may be a promising fat reduction device for body contouring and fat reduction in humans, and that cryolipolysis exerts its effects, at least partly, by targeting the PPARδ signaling pathway. These results show that both investigative and diagnostic potentials capacity.

Pathologic findings in patients who underwent robot-assisted radical prostatectomy following active surveillance: a prospective study in a single center.

AIM: Active surveillance is the recommended treatment of option for men with very low-risk prostate cancer. In this study, the clinicopathological results of patients who were initially treated with active surveillance and subsequently underwent robot-assisted radical prostatectomy during follow-up are described. METHODS: A prospective cohort of 106 men enrolled in active surveillance was reviewed. Pathologic specimens for patients who ultimately underwent robot-assisted radical prostatectomy for progression or personal preference were analyzed. RESULTS: After exclusion of 14 patients who were lost to follow-up or with incomplete data collection, 92 men were included in the present analyses. Median follow-up was 27.6 months (range 3.3 to 193.1). Twenty-nine patients underwent robot-assisted radical prostatectomy. Progression occurred in 32 patients (34.8%), of which 23 men elected to undergo surgery. Robot-assisted radical prostatectomy was performed in 6 additional patients who chose definitive intervention due to anxiety. Pathologic analyses revealed organ-confined disease in 24 patients (82.8%), and Gleason score was ≥ 7 in nine (31%). Fourteen (48.3%) specimens were identified as having an advanced disease (Gleason score ≥ 7 and/or T3). In comparison to the patients with low-risk disease post-operatively (Gleason score <7 and T2), patients with advanced disease had significantly higher PSA density level and lower prostate volume. CONCLUSION: In this prospective active surveillance cohort, the progression rate was 34.8% over the follow-up period of 27.6 months. In specimens of patients who underwent robot-assisted radical prostatectomy, 48.3% displayed advanced pathologic features. Therefore we recommend that patients considering active surveillance should be counseled on risk of advanced disease as a possible hazard.

Evaluation of anatomic landmarks for axillary nerve block in the quadrilateral space.

BACKGROUND: Axillary nerve block (ANB) was recently introduced along with suprascapular nerve block as an alternative to inter-scalene brachial plexus block for post-operative pain control. However, the methods for performing ANB are variable. We studied the relationship between surface anatomy and the location of the axillary nerve in the quadrilateral space to ensure a technically safe and simple ANB. METHODS: Eighty-eight shoulders were included. All measurements were performed with the subjects seated and the shoulders in a neutral position. We located the posterior circumflex humeral artery (PCHA) using a vascular Doppler system and named this point 'AN'. We used this point to locate the axillary nerve, since this nerve is generally present with the PCHA in the quadrilateral space. We then examined the relationship between surface anatomic landmarks and AN. The depth of the medial side of the humerus at the AN (AN depth), which is at the lateral border of the quadrilateral space, was measured using ultrasonography. RESULTS: AN was located on the line between the posterolateral corner of the acromion (Ac) and the axillary fold (Axf) (Ac-Axf) in 77% of shoulders. The ratio of the distance from Ac to AN (Ac-AN) to Ac-Axf in all shoulders was 0.6 [standard deviation (SD), 0.1]. AN depth was 4.0 (SD, 0.5) cm in men and 3.6 (SD, 0.4) cm in women. CONCLUSION: Knowledge of the relationship between surface anatomy and AN, as well as estimated AN depth may aid in locating the axillary nerve in the quadrilateral space.

Eckols reduce dental pulp inflammation through the ERK1/2 pathway independent of COX-2 inhibition.

OBJECTIVES: The aim of this study was to elucidate the role of 6-6 bieckol (EB1) and pholorofucofuroeckol-A (EB5) from brown seaweed marine algae (Eisenia bicyclis) on lipopolysaccharide (LPS)-induced inflammation in human dental pulp cells (HDPCs). METHODS: The cytotoxicity of EB1 and EB5 was examined by MTT assay on LPS-induced human dental pulp cells. Their role on expression of inflammatory, odontogenic, and osteogenic molecules was determined by Western blot analysis. The dentin mineralization was checked by alkaline phosphatase activity. RESULTS: The five compounds from E. bicyclis have different structure with non-cytotoxic in HDPCs. EB1 and EB5 showed anti-inflammatory properties and inhibited phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) and phosphorylated-c-jun N-terminal kinases (p-JNK) without any cytotoxicity. In particular, EB1 inhibited cyclooxygenase-2 (COX-2) and p-ERK1/2 signaling, and EB5 inhibited only p-ERK1/2 signaling but not COX-2. Both compounds inhibited nuclear factor kappa-B (NF-κB) translocation. Furthermore, EB1 and EB5 increased dentinogenic and osteogenic molecules, and dentin mineralized via alkaline phosphatase activity (ALP) in LPS-induced HDPCs. CONCLUSIONS: This study elucidates that EB1 and EB5 have different types of anti-inflammatory property and help in dentin formation. Therefore, these compounds derived from marine algae of E. bicyclis may be used as selective therapeutic strategies for pulpitis and oral diseases.