Ketamine promotes breast tumor growth in a mouse breast tumor model involving with high expression of miR-27b-3p and EGFR.

Non-medical use of ketamine as an adulterant to ecstasy is more prevalent than amphetamine in Taiwan. Ketamine's effect on immunosuppression might play some functional role in tumor growth, while it is still controversial whether ketamine abuse could increase tumor growth or not. This study aimed to investigate the influence of ketamine addiction in breast tumors and related gene expressions. The effect of ketamine treatment on proliferation, colony formation, migration, and invasion of triple-negative breast cancer cell line EO771 was examined. In addition, a ketamine addiction mice model was established by intraperitoneal injection (IP) of ketamine in mice and used to investigate the effects of ketamine addiction on tumor growth and the possible mechanisms. In the in vitro studies, ketamine treatment at different concentrations did not affect EO771 cell proliferation and colony formation. But ketamine did enhance migration and invasion of EO771 cells. The in vivo experiments showed significantly increased breast tumor volume and weight in ketamine-addicted mice than in normal saline groups. miR-27b-3p level, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) significantly increased in tumors of ketamine addiction mice compared to control mice. In vivo evidence showed that Ketamine might increase tumor growth on the tumor microenvironment, and miR-27b-3p, HER2, and EGFR might play a role in the process.

Melatonin impedes prostate cancer metastasis by suppressing MMP-13 expression.

Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP-13) expression are higher in prostate cancer patients than in healthy cancer-free individuals. Mechanistic investigations revealed that melatonin inhibits MMP-13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c-Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP-13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.

Effect of phenylurea hydroxamic acids on histone deacetylase and VEGFR-2.

A series of phenylurea hydroxamic acids incorporating pharmacophores of inhibitors of HDAC inhibitors and VEGFR-2 has been designed. Most of the compounds show antiproliferative activity comparable to that of Vorinostat and Sorafenib, and better EPC inhibitory activity. Enzymatic assays and Western blotting results indicated that compound 14 not only inhibits HDAC but also has slight VEGFR-2 inhibitory activity. A docking study revealed that the polar hydroxamic acid retains the interaction with HDAC through a zinc ion and also interacts with some residues of the active site of VEGFR-2. Despite 14 displaying a weaker VEGFR-2 activity, a possible route to develop potent HDAC/VEGFR-2 inhibitors is suggested.

Synthesis and biological evaluation of 2-quinolineacrylamides.

A series of C6-substituted N-hydroxy-2-quinolineacrylamides (3-15), with four types of bridging groups have been synthesized. Most of these compounds exhibit antiproliferative activity against A549 and HCT116 cells and Western blot analysis revealed that they are able to inhibit HDAC. Measurement of the HDAC isoform activity of ether-containing compounds showed that compound 9 has distinct HDAC6 selectivity, more than 300-fold over other isoforms. This paper describes the development of 6-aryloxy-N-hydroxy-2-quinolineacrylamides as potential HDAC6 inhibitors.

Modified paramedian versus conventional paramedian technique in the residency training: an observational study.

BACKGROUND: Residency training includes positive and negative aspects. Well-trained doctors must be educated, but the process may bring additional risks to patients. Anesthesiologists' performance when conducting neuraxial anesthesia is related to their experience. We hypothesized that a modified neuraxial anesthesia method would improve both residency training and patient safety. METHODS: We recruited 518 patients who were scheduled for a cesarean section and used spinal anesthesia (n = 256), epidural anesthesia (n = 154), and combined spinal-epidural anesthesia (SEA; n = 108). We observed and evaluated the anesthesia performance of five second-year resident anesthesiologists in elective cesarean sections using the conventional and modified methods. The number of attempts, implant error rate, and the incidence of complications were recorded and analyzed. RESULTS: Better success puncture attempts occurred in all three groups when the modified method was applied. For the groups with an implant assessment, the complication rate and implant error rate were lower when using the modified method. We employed generalized estimating equation (GEE) analysis to correct for possible confounding factors. When using the conventional method, the resident anesthesiologists required more attempts, made more implant errors, and caused more complications in patients. CONCLUSIONS: We found that a modified method for neuraxial anesthesia could improve residency performance and patient safety. The modified method may be a suitable training process for resident anesthesiologists when practicing neuraxial anesthesia. TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of National Taiwan University (IRB:200812040R) Clinicaltrials register: NCT03389672 .

Phomaketide A Inhibits Lymphangiogenesis in Human Lymphatic Endothelial Cells.

Lymphangiogenesis is an important biological process associated with cancer metastasis. The development of new drugs that block lymphangiogenesis represents a promising therapeutic strategy. Marine fungus-derived compound phomaketide A, isolated from the fermented broth of Phoma sp. NTOU4195, has been reported to exhibit anti-angiogenic and anti-inflammatory effects. However, its anti-lymphangiogenic activity has not been clarified to date. In this study, we showed that phomaketide A inhibited cell growth, migration, and tube formation of lymphatic endothelial cells (LECs) without an evidence of cytotoxicity. Mechanistic investigations revealed that phomaketide A reduced LECs-induced lymphangiogenesis via vascular endothelial growth factor receptor-3 (VEGFR-3), protein kinase Cδ (PKCδ), and endothelial nitric oxide synthase (eNOS) signalings. Furthermore, human proteome array analysis indicated that phomaketide A significantly enhanced the protein levels of various protease inhibitors, including cystatin A, serpin B6, tissue factor pathway inhibitor (TFPI), and tissue inhibitor matrix metalloproteinase 1 (TIMP-1). Importantly, phomaketide A impeded tumor growth and lymphangiogenesis by decreasing the expression of LYVE-1, a specific marker for lymphatic vessels, in tumor xenograft animal model. These results suggest that phomaketide A may impair lymphangiogenesis by suppressing VEGFR-3, PKCδ, and eNOS signaling cascades, while simultaneously activating protease inhibitors in human LECs. We document for the first time that phomaketide A inhibits lymphangiogenesis both in vitro and in vivo, which suggests that this natural product could potentially treat cancer metastasis.

Butein inhibits metastatic behavior in mouse melanoma cells through VEGF expression and translation-dependent signaling pathway regulation.

BACKGROUND: Melanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated. METHODS: MTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL/6 mice. RESULTS: We first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations (1, 3, and 10 µM). In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR/p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model. CONCLUSION: The results of the present study indicate the potential utility of butein in the treatment of melanoma.

Comparison of extracorporeal shock wave lithotripsy running models between outsourcing cooperation and rental cooperation conducted in Taiwan.

BACKGROUND/PURPOSE: We conducted a retrospective study to compare the cost and effectiveness between two different running models for extracorporeal shock wave lithotripsy (SWL), including the outsourcing cooperation model (OC) and the rental cooperation model (RC). METHODS: Between January 1999 and December 2005, we implemented OC for the SWL, and from January 2006 to October 2011, RC was utilized. With OC, the cooperative company provided a machine and shared a variable payment with the hospital, according to treatment sessions. With RC, the cooperative company provided a machine and received a fixed rent from the hospital. We calculated the cost of each treatment session, and evaluated the break-even point to estimate the lowest number of treatment sessions to make the balance between revenue and cost every month. Effectiveness parameters, including the stone-free rate, the retreatment rate, the rate of additional procedures and complications, were evaluated. RESULTS: Compared with OC there were significantly less treatment sessions for RC every month (42.6±7.8 vs. 36.8±6.5, p=0.01). The cost of each treatment session was significantly higher for OC than for RC (751.6±20.0 USD vs. 684.7±16.7 USD, p=0.01). The break-even point for the hospital was 27.5 treatment sessions/month for OC, when the hospital obtained 40% of the payment, and it could be reduced if the hospital got a greater percentage. The break-even point for the hospital was 27.3 treatment sessions/month for RC. No significant differences were noticed for the stone-free rate, the retreatment rate, the rate of additional procedures and complications. CONCLUSION: Our study revealed that RC had a lower cost for every treatment session, and fewer treatment sessions of SWL/month than OC. The study might provide a managerial implication for healthcare organization managers, when they face a situation of high price equipment investment.

Asiatic acid exhibits antimetastatic activity in human prostate cancer cells by modulating the MZF-1/Elk-1/Snail signaling axis.

Prostate cancer metastasis is associated with poor prognosis and is difficult to treat clinically. Numerous studies have shown that Asiatic Acid (AA) has antibacterial, anti-inflammatory, and antioxidant effects. However, the effect of AA on prostate cancer metastasis is still unclear. This purpose of this study is to investigate the effect of AA on prostate cancer metastasis and to better understand its molecular mechanisms of action. Our results indicate that AA ≤ 30 µM did not influence cell viability and cell cycle distribution in PC3, 22Rv1 and DU145 cells. AA inhibited the migratory and invasive capabilities of three prostate cancer cells to be due to its effects on Snail, but did not have activity on Slug. We observed that AA inhibited the Myeloid zinc finger 1 (MZF-1) and ETS Like-1 (Elk-1) protein interaction and affected the complex's binding capacity to the Snail promoter region, ultimately blocking Snail transcription activity. Kinase cascade analysis revealed that phosphorylation of MEK3/6 and p38MAPK was inhibited by AA treatment. Moreover, knockdown of p38MAPK enhanced AA-suppressed protein levels of MZF-1, Elk-1, and Snail, suggesting that p38MAPK influences prostate cancer cell metastasis. These results provide promise for AA as a future candidate in the development of drug therapies to prevent or treat prostate cancer metastasis.

Ketamine Promoted Breast Cancer Invasion and Metastasis Through Up-regulating Wnt, BMP, and EGFR Signaling.

BACKGROUND/AIM: In this study, we used an orthotropic breast cancer model combined with ketamine addiction and next-generation sequencing (NGS) to comprehensively investigate molecular alterations in ketamine-mediated metastasis. Ketamine is widely used in anesthesia and drug abuse. Our previous study revealed that ketamine promotes the growth of breast cancer cells; however, the detailed molecular mechanism remains unknown. MATERIALS AND METHODS: An orthotropic breast cancer model was established by injecting EO771 breast cancer cells into the mammary fat pad of mice intraperitoneally administered ketamine (30 mg/kg, daily) for 68 days. Tumors collected at day 38 were frozen for future analysis, and their metastasis state was checked at day 68. RESULTS: Tumors were grouped and subjected to NGS analysis, followed by differential gene expression analysis (DEseq) and pathway identification. DEseq analysis showed that ketamine up-regulated metastasis-related signaling, and the key genes were BMP5, FZD6, MMP1B, EGFR, WNT5A, BMP7, and DCN. CONCLUSION: Ketamine addiction up-regulates the expression of genes involved in the Wnt, EGFR, and BMP signaling cascades, which may be associated with breast cancer progression and metastasis.

Ten-years outcome analysis in patients with clinically localized prostate cancer treated by radical prostatectomy or external beam radiation therapy.

Purpose: Since there was no consensus on treatment options for localized prostate cancer, we performed a retrospective study to compare the long-term survival benefit of radiotherapy (RT) versus laparoscopic radical prostatectomy (LRP) in Taiwan. Methods: 218 patients with clinically localized prostate cancer treated between 2008 and 2017 (64 with LRP and 154 with RT) were enrolled in this study. The outcomes of RT and LRP were assessed after patients were stratified according to Gleason score, stage, and risk group. Crude survival, prostate cancer-specific survival, and metastasis-free survival were evaluated using the log-rank test. Results: The 5-year crude survival rate was 93.3% in the LRP group and 59.3% in the RT group. A significant survival benefit was found in the LRP group compared with the RT group (p = 0.004). Furthermore, significant differences were found in disease-specific survival (93.3% vs. 64.7%, p = 0.022) and metastasis-free survival (48% vs. 40.2%, p = 0.045) between the LRP and RT groups. Conclusions: Men with localized prostate cancer treated initially with LRP had a lower risk of prostate cancer-specific death and metastases compared with those treated with RT.

Predictive factors of successful varicocelectomy in infertile patients.

AIM: To examine the predictive factors of successful varicocelectomy in infertile patients. METHODS: Thirty-five infertile male patients with varicocele and requiring varicocelectomy were recruited in this study. The patients were divided into 2 groups based on their recovery outcome after subinguinal microsurgical varicocelectomy. Patients who showed significant improvement on their sperm density, motility and morphology 6 months after varicocelectomy were designated as group 1, whereas those who showed no improvement 6 months after surgery were designated as group 2. The predictive factors that were examined included: age; preoperative semen quality (i.e. sperm density, motility and morphology); testicular volume; seminal volume; varicocele grade; the number of ligated veins; body mass index (BMI), and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, alkaline phosphatase (Alk-p), lactic dehydrogenase (LDH), cholesterol and triglyceride. RESULTS: Sperm density, motility and morphology improved significantly 6 months after varicocelectomy in group 1 patients (n = 35; 71.4%). Group 1 patients had significantly higher testicular volumes (mean ± SD: 29.6 ± 5.9 vs. 23.2 ± 6.1 ml), lower FSH (11.3 ± 2.9 vs. 16.1 ± 4.8 mIU/ml) and higher numbers of ligated veins (9.3 ± 0.8 vs. 7.9 ± 0.7) than group 2 patients. No significant association was observed between surgical outcome and age, preoperative sperm density, motility and morphology, seminal volume, varicocele grade, BMI and serum levels of LH, prolactin, testosterone, Alk-p, LDH, cholesterol and triglyceride. CONCLUSIONS: These findings suggest that the significant predictive factors of successful varicocelectomy in infertile patients were high testicular volume (>29.6 ml), low serum concentration of FSH (<11.3 mIU/ml) and high number of ligated veins (>9).

The difference in oxidative stress of the blood between using 5% glucose water and distilled water as the irrigant for BPH patients undergoing transurethral resection of the prostate.

INTRODUCTION: To evaluate the difference in oxidative stress in the blood between using 5% glucose water and using distilled water as the irrigant for BPH patients receiving transurethral resection of the prostate (TURP), we conducted this prospective study, on a total of 38 patients with symptomatic BPH. MATERIALS AND METHODS: All the patients were randomly divided into 2 groups. Distilled water in group A and 5% glucose water in group B were used as the irrigant. The oxidative stress and antioxidant capacity were evaluated by measuring malondialdehyde (MDA), mitochondrial DNA (mtDNA) copy number and total capacity of antioxidants (TOA) in the blood. The data were correlated with serum creatinine and sodium, which were measured before and immediately after TURP in all patients. RESULTS: Serum creatinine increased from 0.86 +/- 0.17 to 1.02 +/- 0.20 mg/dL while serum sodium decreased from 139.7 +/- 2.3 to 136.4 +/- 4.0 mEq/L immediately after surgery in patients of group A (p < 0.05). MDA was increased and TOA decreased in all the patients immediately after TURP. Patients in group A had significantly higher MDA, lower mtDNA copy number, higher degree of oxidative mtDNA damage and lower TOA than those in group B immediately after TURP. CONCLUSION: In conclusion, we observed an increase of MDA and decrease of TOA in blood in all the patients immediately after TURP, which might induce renal damage and decrease serum sodium. Moreover, the oxidative stress levels in blood of patients in group A were significantly higher than those in group B immediately after TURP.

Comparison of two different running models for the shock wave lithotripsy machine in Taipei City Hospital: self-support versus outsourcing cooperation.

To compare two different running models including self-support and outsourcing cooperation for the extracorporeal shock wave lithotripsy (SWL) machine in Taipei City Hospital, we made a retrospective study. Self-support means that the hospital has to buy an SWL machine and get all the payment from SWL. In outsourcing cooperation, the cooperative company provides an SWL machine and shares the payment with the hospital. Between January 2002 and December 2006, we used self-support for the SWL machine, and from January 2007 to December 2008, we used outsourcing cooperation. We used the method of full costing to calculate the cost of SWL, and the break-even point was the lowest number of treatment sessions of SWL to make balance of payments every month. Quality parameters including stone-free rate, retreatment rate, additional procedures and complication rate were evaluated. When outsourcing cooperation was used, there were significantly more treatment sessions of SWL every month than when utilizing self-support (36.3 +/- 5.1 vs. 48.1 +/- 8.4, P = 0.03). The cost of SWL for every treatment session was significantly higher using self-support than with outsourcing cooperation (25027.5 +/- 1789.8 NT$ vs. 21367.4 +/- 201.0 NT$). The break-even point was 28.3 (treatment sessions) for self-support, and 28.4 for outsourcing cooperation, when the hospital got 40% of the payment, which would decrease if the percentage increased. No significant differences were noticed for stone-free rate, retreatment rate, additional procedures and complication rate of SWL between the two running models. Besides, outsourcing cooperation had lower cost (every treatment session), but a greater number of treatment sessions of SWL every month than self-support.

Cost-effectiveness of treating ureteral stones in a Taipei City Hospital: shock wave lithotripsy versus ureteroscopy plus lithoclast.

AIM: To compare cost-effectiveness, success rates and sat isfaction score of ureteroscopic lithotripsy with lithoclast (URSL) and extracorporeal shock wave lithotripsy (ESWL) for ureteral stones in a Taipei City Hospital. METHODS: This is a retrospective study. From July 1998 to June 2000, 448 patients who underwent treatment for ureteral stones were included. The patients were divided into two treatment groups according to the initial method adopted for the management of their stone. Medical records and hospital financial records were collected for costs of implementing each treatment program. The satisfaction scores of patients (rating from 0 to 10) were collected by telephone interviews. Success was defined as complete clearance of the stone or fragmentation of stones smaller than 2 mm by plain abdominal film and complete relief of symptoms after initial treatment. RESULTS: A total of 360 patients were in the ESWL group (including 144 upper, 48 middle and 168 lower third stones) and 88 in the URSL group (including 28 upper, 24 middle and 36 lower third stones). The range of stone size was from 0.6 to 1.9 cm. The overall treatment cost was comparable in both groups with a trend for it to be higher in the ESWL group without reaching statistical significance (TWD 20,901.5 +/- 8,911.3 vs. 19,876.1 +/- 4,782.2). Stratified by the location of stone, the overall treatment cost was significantly higher in the ESWL group than in the URSL group for patients with upper third ureteral stones irrespective of stone size. The efficiency quotient for ESWL and URSL was 0.62 and 0.65, respectively. The success rate was significantly higher in the URSL group than in the ESWL group (89.8 vs. 71.7%). Satisfaction scores were similar for both groups with a trend to be higher in the ESWL group without reaching statistical significance (7.97 +/- 1.01 vs. 7.53 +/- 1.37). CONCLUSIONS: The overall treatment cost of patients with upper third ureteral stone was significantly higher in the ESWL group than in the URSL group, but the success rate was significantly higher in the URSL group than in the ESWL group.

Correlation between pretreatment serum biochemical markers and treatment outcome for prostatic cancer with bony metastasis.

BACKGROUND: This study was undertaken to evaluate whether or not pretreatment serum biochemical markers are prognostic factors for prostatic cancer with bony metastasis in patients on hormonal treatment. METHODS: Between 1983 and 1998, 127 patients with prostatic cancer and bony metastasis were included for evaluation. Serum prostate-specific antigen, alkaline phosphatase, calcium (Ca), lactic dehydrogenase, inorganic phosphate, gamma-glutamine transpeptidase, uric acid, albumin (Alb), iron, cholesterol (Cho), triglyceride, alanine aminotransferase, aspartate aminotransferase, and hemoglobin (Hb) were checked before treatment. The patients were divided into 2 groups according to their response (group 1, good response; group 2, poor response). RESULTS: There were 54 patients in group 1 and 73 patients in group 2. Pretreatment levels of serum Ca, Alb, Cho and Hb were higher in group 1 than in group 2, while the other parameters were lower in group 1 than in group 2; only pretreatment levels of serum Ca, Alb and Hb were significantly different between groups (p < 0.05). When stratified by tumor grading, patients in group 1 still had significantly higher pretreatment levels of Ca, Alb and Hb than those in group 2. CONCLUSION: Higher pretreatment serum levels of Ca, Alb and Hb are good prognostic factors for patients with metastatic prostatic cancer on hormonal treatment, irrespective of tumor grading.

Effects of systemic and neuraxial morphine on the immune system.

In the study, we tried to evaluate the effects of morphine injected through the systemic or neuraxial route on immune cell function and cytokine production in healthy women.In total, 29 paired samples of fresh peripheral blood were collected from healthy women who had been administered morphine for anesthetic analgesia through intravenous (IV), epidural, or spinal route postpartum. Their isolated peripheral blood mononuclear cells were mitogen-activated and stained with fluorochrome-conjugated anti-CD4, anti-CD8, anti-interleukin (IL)-2, and anti-interferon (IFN)-γ antibodies for flow cytometry, and the plasma levels of cytokines, including IL-6, IFN-α2, IL-10, IL-8, GM-CSF, and monocyte chemoattractant protein (MCP)-1, were measured through enzyme-linked immunosorbent assay.The results demonstrated that regardless of the administration route, morphine delivery slightly reduced IL-2 expression in CD4 cells after activation, and the same effect was not noted for CD8 cells. Intravenous or epidural morphine tended to reduce IFN-γ expression in CD8 cells. Spinal and IV morphine substantially increased IL-6 production, whereas epidural morphine hindered IL-10 and GM-CSF production. IV morphine injection reduced MCP-1 production in plasma. Compared with spinal morphine, IV or epidural morphine may more effectively inhibit the expression of various cytokines and thus affect immune response.All 3 routes of morphine injection tended to decrease IL-2 production by CD4 cells, whereas IV or epidural morphine injection showed lower IFN-γ production by CD8 cells. However, additional large-scale studies with longer follow-up durations are warranted.

Resistin facilitates VEGF-A-dependent angiogenesis by inhibiting miR-16-5p in human chondrosarcoma cells.

Resistin is an adipokine that is associated with obesity, inflammation, and various cancers. Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. VEGF-A is a critical angiogenic factor that is known to promote angiogenesis and metastasis in chondrosarcoma. It is unknown as to whether resistin affects human chondrosarcoma angiogenesis. In this study, we show how resistin promotes VEGF-A expression and subsequently induces angiogenesis of endothelial progenitor cells (EPCs). Resistin treatment activated the phosphatidylinositol-3-kinase (PI3K) and Akt signaling pathways, while PI3K and Akt inhibitors or siRNA diminished resistin-induced VEGF-A expression. In vitro and in vivo studies revealed the downregulation of micro RNA (miR)-16-5p in resistin-induced VEGF-A expression and EPCs angiogenesis. We also found a positive correlation between resistin and VEGF-A expression, and a negative correlation between resistin and VEGF-A with miR-16-5p in chondrosarcoma patients. These findings reveal that resistin facilitates VEGF-A expression and angiogenesis through the inhibition of miR-16-5p expression via PI3K/Akt signaling cascades. Resistin may be a promising target in chondrosarcoma angiogenesis.

Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele.

PURPOSE: We examined changes due to oxidative damage to spermatozoa and alterations in antioxidant capacity in subfertile patients with varicocele before and after varicocelectomy in a prospective study. MATERIALS AND METHODS: A total of 30 young subfertile male patients with varicocele were recruited in this study. Varicocele was diagnosed by physical examination and Doppler ultrasound. Semen analysis was performed in the 30 patients before and 6 months after varicocelectomy using a computer assisted semen analyzer. The parameters for evaluating oxidative stress changes were 4977 bp deletion of mitochondrial DNA in sperm, as detected by polymerase chain reaction, the 8-OHdG (8-hydroxy-2'-deoxyguanosine) content in spermatozoa DNA, as measured by a high performance liquid chromatography electrochemical method, and seminal plasma protein thiols and ascorbic acid, as measured by spectrophotometric methods. RESULTS: Semen quality, including motility, morphology and sperm density, was improved in 22 patients (73.3%) after varicocelectomy. The incidence of 4977 bp deletion of mitochondrial DNA in sperm was 40% (12 of 30 patients) and 13.3% (4 of 30) before and after surgery, respectively. Mean +/- SD 8-OHdG content in sperm DNA, and seminal plasma protein thiols and ascorbic acid were 10.27 +/- 2.24/10(5) 2'-deoxyguanosine, 0.77 +/- 0.75 nmole/ml and 1.87 +/- 0.40 mg/dl before operation, and 5.95 +/- 1.46/10(5) 2'-deoxyguanosine, 3.00 +/- 1.17 nmole/ml and 3.12 +/- 0.94 mg/dl after surgery, respectively. The incidence of 4977 bp deletion of mitochondrial DNA in sperm and the level of 8-OHdG in sperm DNA were decreased, and seminal plasma protein thiols and ascorbic acid were increased significantly in all 30 patients after varicocelectomy. Also, in the 8 patients in whom semen quality did not improve after surgery a significant decrease in 8-OHdG in sperm DNA, and a significant increase in seminal plasma protein thiols and ascorbic acid were observed. CONCLUSIONS: Subfertile patients with varicocele had a significant decrease in oxidative damage in sperm DNA and an increase in antioxidant capacity in seminal plasma after varicocelectomy, indicating that surgery is effective treatment in such patients.

Pharmacogenetic study of pruritus induced by epidural morphine for post cesarean section analgesia.

OBJECTIVE: The mechanism through which neuroaxial morphine causes pruritus has not been elucidated clearly and thoroughly. MATERIALS AND METHODS: a study in 129 female parturients was conducted to investigate the effect of 14 single nucleotide polymorphisms (SNPs) on phenotype (pruritus) induced by neuroaxial (including intrathecal or epidural) morphine for cesarean section. Clinical phenotype, subjective complaints and objective observations were recorded. DNA from blood samples was used to record the SNPs. Eleven SNPs were then analyzed further. RESULTS: no significant association with the presence of phenotype (pruritus) versus genotype was observed (all p-values > 0.05). No significant association with severity of phenotype versus genotype of the 11 SNPs was observed except for unadjusted data for rs2737703. There was no significant difference between severity or incidence of IVPCA morphine-induced nausea and vomiting and genotype (11 SNPs). CONCLUSION: our results showed no association between SNPs of any of the genes studied with neuroaxial morphine inducing pruritus.