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Sample records for reduced prostate size

  1. Red maca (Lepidium meyenii) reduced prostate size in rats

    PubMed Central

    Gonzales, Gustavo F; Miranda, Sara; Nieto, Jessica; Fernández, Gilma; Yucra, Sandra; Rubio, Julio; Yi, Pedro; Gasco, Manuel

    2005-01-01

    Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red) were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T) and estradiol (E2) levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE). Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1) region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl glucosinolate. Conclusions

  2. Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

    PubMed

    Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

    2011-07-01

    Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older

  3. Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia.

    PubMed

    Shin, In-Sik; Lee, Mee-Young; Jung, Da-Young; Seo, Chang-Seob; Ha, Hye-Kyung; Shin, Hyeun-Kyoo

    2012-03-01

    Benign prostatic hyperplasia (BPH) is characterized by hyperplasia of prostatic stromal and epithelial cells, which can lead to lower urinary tract symptoms. The prevalence of BPH increases in an age-dependent manner. We investigated the protective effect of ursolic acid in BPH development using a testosterone-induced BPH rat model. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP), for a period of four weeks. Ursolic acid was administrated daily by oral gavage at a dose level of 5mg/kg during the four weeks of TP injections. Animals were sacrificed on the scheduled termination, before prostates were weighed and subjected to histopathological examination. TP and dihydrotestosterone (DHT) levels in the serum and prostate were also measured. BPH-induced animals displayed an increase in prostate weight with increased testosterone and DHT levels in both the serum and prostate. However, ursolic acid treatment resulted in significant reductions in prostate weight and testosterone and DHT levels in both the serum and prostate, compared with BPH-induced animals. Histopathological examination also showed that ursolic acid treatment suppressed TP-induced prostatic hyperplasia. These findings indicate that ursolic acid may effectively inhibit the development of BPH and it may be a useful agent in BPH treatment.

  4. Does Prostate Size Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from the REDUCE Trial.

    PubMed

    Simon, Ross M; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Vidal, Adriana C; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2016-05-01

    It has been shown that increased prostate size is a risk factor for lower urinary tract symptom (LUTS) progression in men who currently have LUTS presumed due to benign prostatic hyperplasia (BPH). To determine if prostate size is a risk factor for incident LUTS in men with mild to no symptoms. We conducted a post hoc analysis of the REDUCE study, which contained a substantial number of men (n=3090) with mild to no LUTS (International Prostate Symptom Score [IPSS] <8). Our primary outcome was determination of the effect of prostate size on incident LUTS presumed due to BPH defined as two consecutive IPSS values >14, or receiving any medical (α-blockers) or surgical treatment for BPH throughout the study course. To determine the risk of developing incident LUTS, we used univariable and multivariable Cox models, as well as Kaplan-Meier curves and the log-rank test. Among men treated with placebo during the REDUCE study, those with a prostate size of 40.1-80ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23-2.26, p=0.001) of developing incident LUTS compared to men with a prostate size 40.0ml or smaller. There was no association between prostate size and risk of incident LUTS in men treated with 0.5mg of dutasteride. The post hoc nature of our study design is a potential limitation. Men with mild to no LUTS but increased prostate size are at higher risk of incident LUTS presumed due to BPH. This association was negated by dutasteride treatment. Benign prostatic hyperplasia (BPH) is a very common problem among older men, which often manifests as lower urinary tract symptoms (LUTS), and can lead to potentially serious side effects. In our study we determined that men with mild to no current LUTS but increased prostate size are much more likely to develop LUTS presumed due to BPH in the future. This association was not seen in men treated with dutasteride, a drug approved for treatment of BPH. Our study reveals that men with a prostate size of 40

  5. Obesity, serum prostate specific antigen and prostate size: implications for prostate cancer detection.

    PubMed

    Freedland, Stephen J; Platz, Elizabeth A; Presti, Joseph C; Aronson, William J; Amling, Christopher L; Kane, Christopher J; Terris, Martha K

    2006-02-01

    Obesity has been associated with lower serum testosterone, theoretically resulting in decreased PSA production. Obesity has also been associated with prostatic enlargement, making the detection of existent cancer more difficult. Together these findings would result in an apparent protective effect of obesity on prostate cancer risk due to technical detection issues unrelated to cancer biology. We examined the association between BMI, and PSA and prostate weight in a cohort of men undergoing RP. We evaluated the association of BMI with prostate weight and PSA using linear regression, adjusting for patient age at RP, year of RP, race, and pathological stage and grade in 1,414 men treated with RP between 1988 and 2004 at the 5 equal access medical centers that comprise the Shared Equal Access Regional Cancer Hospital Database. On multivariate analysis increasing BMI was associated with increasing prostate weight but only in men younger than 63 years and not in men 63 years or older (p-trend <0.001 and 0.44, respectively). In men younger than 63 years mean multivariate adjusted prostate weight +/- SE in those with a BMI of less than 25 vs 30 to 34.9 kg/m was 33.8 +/- 1.4 vs 41.4 +/- 1.6 gm. There was no significant association between BMI and preoperative PSA (p-trend = 0.70). In a cohort of men undergoing RP obesity was associated with larger prostate size but only in younger men. There was no association between BMI and PSA. Assuming equal PSA, the degree of prostatic enlargement observed in younger obese men in this study would be expected to result in a modest decrease in the odds of detecting prostate cancer in a contemporary series of PSA screened men due to the decreased sensitivity of cancer detection related to larger prostate size. Obesity may appear protective for prostate cancer in younger men due to technical issues unrelated to cancer biology.

  6. Plasmakinetic enucleation of the prostate vs plasmakinetic resection of the prostate for benign prostatic hyperplasia: comparison of outcomes according to prostate size in 310 patients.

    PubMed

    Luo, Yu-Hui; Shen, Ji-Hong; Guan, Run-Yun; Li, Hao; Wang, Jia

    2014-10-01

    To compare the safety and efficiency of plasmakinetic enucleation of the prostate (PKEP) with that of plasmakinetic resection of the prostate (PKRP) in the treatment of benign prostatic hyperplasia (BPH). Three hundred ten patients diagnosed to have BPH were randomized to undergo either PKEP or PKRP. The perioperative data and postoperative outcomes followed at 1, 3, 6, 12, 18, and 24 months after surgery were recorded and compared in the groups classified according to the baseline prostate volume: ≤ 60 mL and >60 mL. There were no significant differences in the preoperative data. Compared with PKRP, PKEP costs longer operative time (56.1 ± 14.6 vs 41.3 ± 9.6 min; P < .001) for prostate volume ≤ 60 mL, but reduced operative time (75.6 ± 12.3 vs 88.7 ± 14.3 minutes; P <.001) and caused less blood loss (167.6 ± 44.4 vs 225.7 ± 49.5 mL; P < .001) for prostate volume >60 mL. However, regardless of prostate size, the incidence of transient incontinence after PKEP was higher. The postoperative improvement among these groups in International Prostate Symptom Score, quality of life, and maximal flow rate was similar at 24-month follow-up. PKEP and PKRP are both safe and effective treatments for BPH independent of prostate size. Despite that the incidence of transient incontinence after PKEP was higher, PKEP was significantly superior to PKRP in operative time and blood loss for prostate volume >60 mL and may become the modern alternative to PKRP for large BPH. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Reducing infection rates after prostate biopsy.

    PubMed

    Wagenlehner, Florian M E; Pilatz, Adrian; Waliszewski, Przemyslaw; Weidner, Wolfgang; Johansen, Truls E Bjerklund

    2014-02-01

    Over the years, prostate biopsy has become the gold-standard technique for diagnosing prostate carcinoma. Worldwide, several million prostate biopsies are performed every year, most commonly using the transrectal approach. Preoperative antibiotic prophylaxis with fluoroquinolones has been shown to be effective for reducing infection rates. However, in recent years, an increase in febrile infection rates after transrectal prostate biopsy (from 1% to 4%) has been reported in retrospective and prospective studies. The predominant risk factor for infection seems to be the presence of fluoroquinolone-resistant bacteria in faeces. Patients at risk of fluoroquinolone resistance should receive carefully selected antibiotics at sufficient concentrations to be effective. Targeted prophylaxis after rectal flora swabbing has been shown to be efficacious compared with empirical antibiotic prophylaxis. Several forms of bowel preparations are under investigation, although none have yet been shown to significantly reduce infection rates. Perineal prostate biopsy is currently being evaluated as a strategy for preventing the inoculation of rectal flora, but limited data support this approach at present.

  8. Outcomes of transurethral resection of the prostate in benign prostatic hyperplasia comparing prostate size of more than 80 grams to prostate size less than 80 grams.

    PubMed

    Joshi, H N; De Jong, I J; Karmacharya, R M; Shrestha, B; Shrestha, R

    2014-01-01

    Benign prostatic hyperplasia is a condition occurring in elderly men in which the prostate gland is enlarged, hence the condition also known as benign enlargement of prostate. Benign hyperplasia can lead to both obstructive and irritative symptoms. Transurethral resection of prostate (TURP) still remains the gold standard modality of surgical treatment of obstructive lower urinary tract symptoms due to Benign hyperplasia. The objective of this study was to evaluate the outcomes of TURP in large prostate (>80 grams) in comparison to small prostate (<80 grams) in terms of efficacy, safety and complications. A total of 65 cases included in this prospective study, which were operated by a single surgeon with conventional monopolar TURP using standard technique. Intra -operative and post-operative complications, pre and post- operative quality of life (QoL) and international prostate symptom score (IPSS), operative time, time to removal of catheter and hospital stay were evaluated between small and large prostate gland volumes. Out of 65 cases, 30 were with large prostate size i.e. 80 grams or more (group 1), and 35 cases were with small prostate size than 80 grams size (group 2). Mean age was 71.8 SD ± 6.9 years in group 1 and 68.2 SD ± 12.7 years in group 2. The mean preoperative volume of prostate was 88.8 grams (range 80-115 grams) in group 1 and 40.3 (range 20-65 grams) in group 2. The mean preoperative post void residual volume of urine (PVRU) was 244 ml SD ± 190.8 ml in group 1 and 117 ml ± 70.3 ml in group 2. Mean resection time in group 1 was 110 (range 90-130) minutes and in group 2 it was 90 minutes (range 55-115) minutes. There were quite satisfactory improvements in IPSS and QoL. No significant complications were observed except TUR syndrome in 2 cases from group 2, which were managed well in postoperative period. With meticulous resection and intra-operative haemostasis using continuous out flow resectoscope, conventional monopolar TURP is equally safe

  9. Reference Works in Reduced Size

    ERIC Educational Resources Information Center

    Hennessey, David

    1977-01-01

    Lower cost and less shelf space requirements have made major reference works in miniaturized print editions attractive to small libraries. The major disadvantage is the necessity of a magnifying glass for reading entries. A bibliography of reduced-size editions is included. (JAB)

  10. Association of prostate size and perioperative morbidity in thulium:YAG vapoenucleation of the prostate.

    PubMed

    Netsch, Christopher; Tiburtius, Christian; Bach, Thorsten; Knipper, Sophie; Gross, Andreas J

    2014-01-01

    To evaluate the association between perioperative morbidity and prostate size in patients with benign prostatic obstruction treated with thulium:YAG vapoenucleation of the prostate (ThuVEP). 687 patients were prospectively analyzed. Prostate size was <40 ml in 196 (group A), 40-79 ml in 336 (group B) and ≥80 ml in 155 (group C) patients. The mean prostate sizes were 27.94 ± 6.77, 54.38 ± 10.54 and 109.8 ± 28.31 ml for groups A, B and C, respectively (p < 0.001). Hemoglobin loss (g/dl) differed significantly among group A (1.09 ± 1.02), group B (1.28 ± 1.27) and group C (1.62 ± 1.49) (p < 0.001). The correlation between hemoglobin loss and prostate size was very weak in all patients (r = 0.13, p ≤ 0.001). Peak urinary flow rates and post-voiding residual urine improved significantly (p < 0.001) without differences among the groups. The incidence of complications was low and not different among the groups (acute urinary retention 8%, urinary tract infection 4.66%, secondary apical resection 2.91%, transfusion rate 2.03%). Perioperative morbidity and micturition improvement are not associated with prostate size in ThuVEP. © 2014 S. Karger AG, Basel.

  11. The Effect of Two Weeks Preoperative Finasteride Therapy in Reducing Prostate Vascularity.

    PubMed

    Khwaja, Muhammad Athar; Nawaz, Gul; Muhammad, Shujah; Jamil, Muhammad Imran; Faisal, Muhammad; Akhter, Saeed

    2016-03-01

    To determine the effect of two weeks preoperative finasteride therapy in reducing prostate vascularity in terms of mean microvessel density (MVD) and expression of VEGF in prostate urothelium among patients of BPH by comparing with controls. Randomized controlled trial. Shifa International Hospital, Islamabad, from January 2013 to January 2014. A total of 80 patients of Benign Prostatic Hyperplasia (BPH) planned for Trans-Urethral Resection of Prostate (TURP) having prostate size of more than 40 grams on trans-abdominal ultrasonography was randomized into two groups, each group having 40 patients. The finasteride group (Group A) was prescribed oral 5 mg of finasteride daily for 2 weeks before surgery. The control group (Group B) did not receive any agent. After 2 weeks, TURP was performed and prostate samples were sent for histopathological determination of MVD and expression of VEGF. The mean age of patients was 66.21 ±10.08 years, ranging from 48 to 86 years. The mean prostate gland size was comparable in both groups (55 ±10.7 vs. 58.1 ±10.8 grams, p=0.21). Mean MVD in finasteride group (20.25 ±10.3) was significantly lower as compared to control group (48.9 ±22.6, p < 0.001). Similarly expression of VEGF was also significantly lower in finasteride group (30%) as compared to control group (65%) [p= 0.0017]. Mean MVD had a significant weak correlation with the size of prostate gland on Pearson correlation test (2-tailed) with r = 0.222. Finasteride reduces microvessel density and hence prostate vascularity with only 2-week therapy and the mean MVD is clearly correlated with size of prostate.

  12. The Influence of Androgen Deprivation Therapy on Prostate Size and Voiding Symptoms in Prostate Cancer Patients in Korea

    PubMed Central

    2016-01-01

    Purpose The goal of this study is to investigate the effects of androgen deprivation therapy (ADT) on total prostate volume and lower urinary tract symptoms (LUTS). Methods Between January 2007 and June 2014, 110 patients who received androgen deprivation treatment were enrolled in this retrospective study. Clinical parameters and urodynamic parameters along with changes at follow-up were analyzed. Factors such as reduction in prostate volume, changes in LUTS, and prostate volume tertiles were compared 1 year after ADT. Results After ADT, the total International Prostate Symptom Score (IPSS) score decreased from 17.45 to 12.21 and the IPSS voiding subscore decreased from 9.16 to 6.24. Maximal uroflow rate increased from 8.62 to 11.50 mL/sec and residual urine also reduced significantly by 29.34 mL. Change in prostate size was more prominent (–51.14%) in the patients with less than 1 year of ADT (n=21) than those who had more than 1 year of treatment (n=89, –44.12%). The decrease in the IPSS voiding subscore was greater within 1 year of ADT than after 1 year of treatment (–4.10 vs. –2.65). The differences were more significant in the 30–50 g group (n=59) and >50 g group (n=11) than the <30 g group (n=40) of the IPSS voiding subscore improvement (–3.76 , –4.91 vs. –2.10), and maximal uroflow rate improvement (2.78, 2.90 vs 1.49). Conclusion ADT resulted in statistically significant clinical improvement in terms of prostate volume, urodynamic parameters, and LUTS for patients with prostate cancer when analyzed by ADT duration and prostate volume. PMID:28043112

  13. Prostate cancer risk alleles are associated with prostate cancer volume and prostate size.

    PubMed

    Reinhardt, Daniel; Helfand, Brian T; Cooper, Phillip R; Roehl, Kimberly A; Catalona, William J; Loeb, Stacy

    2014-06-01

    Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms associated with prostate cancer risk. Some of these genetic variants are also associated with serum prostate specific antigen levels and lower urinary tract symptoms, raising the question of whether they are truly prostate cancer biomarkers or simply lead to detection bias. Therefore, we determined whether single nucleotide polymorphisms associated with prostate cancer risk are more strongly associated with tumor or prostate volume. The genotypes of 38 validated prostate cancer risk single nucleotide polymorphisms were determined in 1,321 white men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship of single nucleotide polymorphism frequency with total prostate and tumor volumes. On multivariate analysis 2 single nucleotide polymorphisms on chromosome 8q24, rs16901979 (A) and rs6983267 (G), were significantly associated with increased tumor volume (p=0.01 and 0.02, respectively). In contrast, rs17632542 (T) near the PSA gene on 19q13 was associated with significantly lower tumor volume and rs10788160 (A) on 10q26 was associated with significantly larger prostate volume (p=0.02 and 0.01, respectively). Analysis of 38 single nucleotide polymorphisms associated with prostate cancer risk revealed a significant association between several on chromosome 8q24 and increased tumor volume but not prostate volume. This suggests that they are bona fide markers of prostate cancer susceptibility and possibly more aggressive disease. Other prostate cancer risk alleles are associated with prostate specific antigen and increased prostate or decreased tumor volume, suggesting detection bias due to their phenotypic influence. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Baseline Prostate Atrophy is Associated with Reduced Risk of Prostate Cancer in Men Undergoing Repeat Prostate Biopsy.

    PubMed

    Moreira, Daniel M; Bostwick, David G; Andriole, Gerald L; Peterson, Bercedis L; Cohen, Harvey J; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2015-11-01

    We evaluated whether the presence and severity of baseline prostate atrophy in men with initial biopsy negative for prostate cancer was associated the risk of subsequent prostate cancer detection in a clinical trial with scheduled study mandated biopsies. We retrospectively analyzed the records of 3,084 men 50 to 75 years old with prostate specific antigen between 2.5 and 10 ng/ml, and a prior negative biopsy in the placebo arm of the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study who completed at least 1 per-protocol biopsy. Prostate cancer (defined as present or absent) and prostate atrophy (graded as absent, mild or moderate/marked) was assessed by central pathology review. The association of baseline atrophy with positive 2 and 4-year repeat biopsies was evaluated with logistic regression, controlling for baseline covariates. Baseline prostate atrophy was detected in 2,143 men (70%) and graded as mild and moderate/marked in 1,843 (60%) and 300 (10%) baseline biopsies, respectively. Patients with atrophy were older and had a larger prostate, and more acute and chronic prostate inflammation. At 2-year biopsy the prostate cancer incidence was 17% (508 cases). Baseline atrophy was significantly associated with lower prostate cancer risk (univariable and multivariable OR 0.60, 95% CI 0.50-0.74 and OR 0.67, 95% CI 0.54-0.83, p <0.001, respectively) at the 2-year biopsy. These results were similar at the 4-year biopsy (univariable and multivariable OR 0.70, 95% CI 0.53-0.93 and OR 0.72, 95% CI 0.53-0.97, p = 0.03, respectively). Relative to no atrophy the prostate cancer risk at the 2-year repeat biopsy was lower for mild atrophy (OR 0.69, 95% CI 0.55-0.86) and moderate/marked atrophy (OR 0.51, 95% CI 0.34-0.76, each p <0.001). Baseline prostate atrophy in men with a prostate biopsy negative for prostate cancer was independently associated with subsequent lower prostate cancer detection. Copyright © 2015 American Urological Association

  15. Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in the TRAMP Mouse Model

    PubMed Central

    Kazmierczak, Robert A.; Gentry, Bettina; Mumm, Tyler; Schatten, Heide; Eisenstark, Abraham

    2016-01-01

    Attenuated Salmonella typhimurium injected in the circulatory system of mammals selectively targets tumors. Using weekly intraperitoneal injections of attenuated Salmonella strain CRC2631, we tested for regression and/or inhibition of tumor development in the TRAMP prostate tumor mouse model, which utilizes SV40 early region expression for autochthonous formation of prostate tumors that progress into metastatic, poorly differentiated prostatic carcinomas in an immunocompetent murine model. Thirteen weekly intraperitoneal administrations of 105–107 CFU CRC2631 into 10 week old mice were well tolerated by the TRAMP model. Sacrifice and histological analysis of TRAMP prostates at 22 weeks indicated that Salmonella monotherapy at administrated levels decrease visible tumor size (>29%) but did not significantly inhibit previously described SV40 expression-driven TRAMP tumor progression to undifferentiated carcinomas when histologically examined. In conclusion, this work demonstrates baseline results for CRC2631 Salmonella monotherapy using the immunocompetent TRAMP prostate tumor model in preparation for study of combination therapies that resolve autochthonously generated TRAMP prostate tumors, further reduce tumor size, or inhibit prostate tumor progression. PMID:27504973

  16. Nano-sized titanium dioxide toxicity in rat prostate and testis: Possible ameliorative effect of morin.

    PubMed

    Shahin, Nancy N; Mohamed, Maha M

    2017-11-01

    This study investigated the effect of short-term oral exposure to nano-sized titanium dioxide (nTiO2) on Wistar rat prostate and testis, and the associating reproductive-related alterations. The study also evaluated the potential ameliorative effect of the natural flavonoid, morin, on nTiO2-induced aberrations. Intragastric administration of nTiO2 (50mg/kg/day for 1, 2 and 3weeks) increased testicular gamma-glutamyltransferase (γ-GT) activity and decreased testicular steroidogenic acute regulatory protein (StAR) and c-kit gene expression, serum testosterone level and sperm count. nTiO2-treated rats also exhibited prostatic and testicular altered glutathione levels, elevated TNF-α levels, up-regulated Fas, Bax and caspase-3 gene expression, down-regulated Bcl-2 gene expression and enhanced prostatic lipid peroxidation. Sperm malformation and elevated testicular acid phosphatase (ACP) activity and malondialdehyde level, serum prostatic acid phosphatase activity, prostate specific antigen (PSA), gonadotrophin and estradiol levels occurred after the 2 and 3week regimens. Morin (30mg/kg/day administered intragastrically for 5weeks) mitigated nTiO2-induced prostatic and testicular injury as evidenced by lowering serum PSA level, testicular γ-GT and ACP activities and TNF-α level, along with hampering both intrinsic and extrinsic apoptotic pathways. Moreover, morin alleviated prostatic lipid peroxidation, raised prostatic glutathione level, and relieved testicular reductive stress. Additionally, morin increased testicular StAR and c-kit mRNA expression, raised the sperm count, reduced sperm deformities and modified the altered hormone profile. Histopathological evaluation supported the biochemical findings. In conclusion, morin could ameliorate nTiO2-induced prostatic and testicular injury and the corresponding reproductive-related aberrations via redox regulatory, anti-inflammatory and anti-apoptotic mechanisms, promoting steroidogenesis and spermatogenesis, and

  17. Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study.

    PubMed

    Toren, Paul; Margel, David; Kulkarni, Girish; Finelli, Antonio; Zlotta, Alexandre; Fleshner, Neil

    2013-04-15

    To assess the role of dutasteride in preventing clinical progression of benign prostatic hyperplasia in asymptomatic men with larger prostates. Post hoc analysis of four year, double blind Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study 1617 men randomised to dutasteride or placebo with a prostate size >40 mL and baseline International Prostate Symptom Score (IPSS) <8. Subjects who took medications for benign prostatic hyperplasia were excluded at study entry. Placebo or dutasteride 0.5 mg daily. Comparison of risk of clinical progression of benign prostatic hyperplasia at four years (defined as a ≥ 4 point worsening on IPSS, acute urinary retention, urinary tract infection, or surgery related to benign prostatic hyperplasia). 825 participants took placebo, 792 took dutasteride. A total of 464 (29%) experienced clinical progression benign prostatic hyperplasia, 297(36%) taking placebo, 167 (21%) taking dutasteride (P<0.001). The relative risk reduction was 41% and the absolute risk reduction 15%, with a number needed to treat (NNT) of 7. Among men who had acute urinary retention and surgery related to benign prostatic hyperplasia, the absolute risk reduction for dutasteride was 6.0% and 3.8%, respectively. On multivariable regression analysis adjusting for covariates, dutasteride significantly reduced clinical progression of benign prostatic hyperplasia with an odds ratio of 0.47 (95% CI 0.37 to 0.59, P<0.001). Analysis of time to first event yielded a hazard ratio of 0.673 (P<0.001) for those taking dutasteride. Sexual adverse events were most common and similar to prior reports. Further prospective studies may be warranted to demonstrate generalisability of these results. This study is the first to explore the benefit of treating asymptomatic or mildly symptomatic men with an enlarged prostate. Dutasteride significantly decreased the incidence of benign prostatic hyperplasia clinical progression.

  18. Effect of dutasteride on clinical progression of benign prostatic hyperplasia in asymptomatic men with enlarged prostate: a post hoc analysis of the REDUCE study

    PubMed Central

    Toren, Paul; Margel, David; Kulkarni, Girish; Finelli, Antonio; Zlotta, Alexandre

    2013-01-01

    Objective To assess the role of dutasteride in preventing clinical progression of benign prostatic hyperplasia in asymptomatic men with larger prostates. Design Post hoc analysis of four year, double blind Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study Participants 1617 men randomised to dutasteride or placebo with a prostate size >40 mL and baseline International Prostate Symptom Score (IPSS) <8. Subjects who took medications for benign prostatic hyperplasia were excluded at study entry. Interventions Placebo or dutasteride 0.5 mg daily. Main outcome measures Comparison of risk of clinical progression of benign prostatic hyperplasia at four years (defined as a ≥4 point worsening on IPSS, acute urinary retention, urinary tract infection, or surgery related to benign prostatic hyperplasia). Results 825 participants took placebo, 792 took dutasteride. A total of 464 (29%) experienced clinical progression benign prostatic hyperplasia, 297(36%) taking placebo, 167 (21%) taking dutasteride (P<0.001). The relative risk reduction was 41% and the absolute risk reduction 15%, with a number needed to treat (NNT) of 7. Among men who had acute urinary retention and surgery related to benign prostatic hyperplasia, the absolute risk reduction for dutasteride was 6.0% and 3.8%, respectively. On multivariable regression analysis adjusting for covariates, dutasteride significantly reduced clinical progression of benign prostatic hyperplasia with an odds ratio of 0.47 (95% CI 0.37 to 0.59, P<0.001). Analysis of time to first event yielded a hazard ratio of 0.673 (P<0.001) for those taking dutasteride. Sexual adverse events were most common and similar to prior reports. Limitations Further prospective studies may be warranted to demonstrate generalisability of these results. Conclusions This study is the first to explore the benefit of treating asymptomatic or mildly symptomatic men with an enlarged prostate. Dutasteride significantly decreased the incidence of

  19. Finasteride Reduces the Risk of Low-Grade Prostate Cancer in Men 55 and Older

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Finasteride Reduces the Risk of Low-Grade Prostate Cancer ... PCPT) continue to show that regular use of finasteride (Proscar®) for up to 7 years decreased the ...

  20. Reducing Prostate Cancer Disparities through Behavioral and Biologic Epidemiologic Approaches

    DTIC Science & Technology

    2010-09-01

    Research Seminar Series, Boston, MA, 2006. Oral presentation. 3. Drake BF. Cancer Health Disparities. Young Woman’s Auxiliary of the South...Epidemiology. 18(7): 579-583, 2008. 7. Elder K, Drake BF, Wagner S, Hebert JR. Social and Clinical Influences of Prostate Cancer Treatment. Journal for...AD_________________ Award Number: W81XWH-09-1-0638 TITLE: Reducing Prostate Cancer

  1. Reducing Prostate Cancer Disparities Through Behavioral and Biologic Epidemiologic Approaches

    DTIC Science & Technology

    2010-09-01

    Research Seminar Series, Boston, MA, 2006. Oral presentation. 3. Drake BF. Cancer Health Disparities. Young Woman’s Auxiliary of the South...Epidemiology. 18(7): 579-583, 2008. 7. Elder K, Drake BF, Wagner S, Hebert JR. Social and Clinical Influences of Prostate Cancer Treatment. Journal for...AD_________________ Award Number: W81XWH-09-1-0638 TITLE: Reducing Prostate Cancer

  2. A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model

    USDA-ARS?s Scientific Manuscript database

    Dietary fat is linked to prostate cancer (PCa), the most commonly diagnosed male cancer, but the nature and strength of the relationships between total fat, n-6 and n-3 fatty acids and PCa remain incompletely understood. Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (N=10-12 per grou...

  3. Why are diabetics at reduced risk for prostate cancer? A review of the epidemiologic evidence.

    PubMed

    Pierce, Brandon L

    2012-09-01

    A large body of epidemiologic evidence provides strong support for the notion that type-2 diabetics are at decreased risk for prostate cancer. In this review article, we summarize the epidemiologic literature that explores the role of diabetes mellitus and related biomarkers in prostate cancer risk and detection, in order to create a better understanding of the potential mechanisms that underlie this inverse association. The bulk of the data supporting this association comes from the USA, as evidence for this association is less consistent in many other regions of the world. The relationship between diabetes and prostate cancer is suspected to be causal due to evidence of decreasing prostate cancer risk with increasing diabetes duration and lack of evidence for any confounding of this association. Hypothesized mechanisms for decreased prostate cancer risk among diabetics include (1) decreased levels of hormones and other cancer-related growth factors among diabetics, (2) the impact of diabetes on detection-related factors, such as prostate size, circulating prostate-specific antigen (PSA), and health-care seeking behaviors, (3) protective effects of diabetes medications, and (4) a protective effect of diabetes-induced vascular damage in the prostate. The evidence for screening-related factors is compelling, as diabetics appear to have reduced PSA and lower levels of health-care seeking behavior compared with nondiabetics. Furthermore, the inverse association between diabetes and prostate cancer is much less apparent in populations that do not perform biopsies based on PSA levels and in studies restricted to biopsied individuals. The inverse association appears to be stronger for low-grade disease, as compared with high-grade (Gleason >7), which is consistent with the observation that among patients receiving biopsy or prostate cancer treatment, diabetics are more likely to have high-grade disease as compared to nondiabetics, potentially resulting in worse outcomes

  4. External beam radiotherapy boosts to reduce the impact caused by edema in prostate permanent seed implants

    NASA Astrophysics Data System (ADS)

    Yue, Ning; Mori, Jonathan; Nath, Ravinder; Heron, Dwight E.; Saiful Huq, M.

    2006-05-01

    In prostate permanent seed implants, it has been shown that edema caused by the surgical procedure decreases dose coverage and hence may reduce treatment efficacy. This reduction in treatment efficacy has been characterized by an increase in tumour cell survival, and biomathematical models have been developed to calculate the tumour cell survival increases in seed implanted prostates of different edema magnitudes and durations. External beam boosts can be utilized to neutralize the negative impact of edema so that originally desired treatment efficacy can be achieved. In this study, a linear quadratic model is used to determine fractionation sizes of the external beam boosts for both 125I and 103Pd seed implants. Calculations were performed for prostates of different edema magnitudes and durations, and for tumour cells of different repair rates and repopulation rates.

  5. Reducing Class Size: Promises and Perils

    ERIC Educational Resources Information Center

    Bascia, Nina; Fredua-Kwarteng, Eric

    2008-01-01

    Reducing class size, especially in primary grades, can have tremendous academic and social benefits for children--benefits that endure well beyond those first years of school. But smaller class sizes are not a cure-all. Beyond the hoopla of enthusiasm for this seemingly simple change in educational practice lie serious consequences for students…

  6. Reducing Class Size: Promises and Perils

    ERIC Educational Resources Information Center

    Bascia, Nina; Fredua-Kwarteng, Eric

    2008-01-01

    Reducing class size, especially in primary grades, can have tremendous academic and social benefits for children--benefits that endure well beyond those first years of school. But smaller class sizes are not a cure-all. Beyond the hoopla of enthusiasm for this seemingly simple change in educational practice lie serious consequences for students…

  7. Prostate size correlates with fasting blood glucose in non-diabetic benign prostatic hyperplasia patients with normal testosterone levels.

    PubMed

    Kim, Won Tae; Yun, Seok Joong; Choi, Young Deuk; Kim, Gi-Young; Moon, Sung-Kwon; Choi, Yung Hyun; Kim, Isaac Yi; Kim, Wun-Jae

    2011-09-01

    We evaluated the correlations between BMI, fasting glucose, insulin, testosterone level, insulin resistance, and prostate size in non-diabetic benign prostatic hyperplasia (BPH) patients with normal testosterone levels. Data from 212 non-diabetic BPH patients with normal testosterone levels, who underwent transurethral resection of the prostate (TURP) due to medical treatment failure, were evaluated retrospectively. Patients with prostate specific antigen (PSA) levels of ≥ 3 ng/mL underwent multicore transrectal prostate biopsy before TURP to rule out prostate cancer. Patients with diabetes mellitus (DM) or serum testosterone levels of < 3.50 ng/mL were excluded from analysis. Correlations between clinical and laboratory parameters were determined. Prostate size correlated positively with age (r = 0.227, P < 0.001), PSA (r = 0.510, P < 0.001), and fasting glucose level (r = 0.186, P = 0.007), but not with BMI, testosterone, insulin level, or insulin resistance (each P > 0.05). Testosterone level inversely correlated with BMI (r = -0.327, P < 0.001), insulin level (r = -0.207, P = 0.003), and insulin resistance (r = -0.221, P = 0.001), but not with age, prostate size, PSA, or fasting glucose level (each P > 0.05). Upon multiple adjusted linear regression analysis, prostate size correlated with elevated PSA (P < 0.001) and increased fasting glucose levels (P = 0.023). In non-DM BPH patients with normal testosterone levels, fasting glucose level is an independent risk factor for prostate hyperplasia.

  8. Phenylthiourea specifically reduces zebrafish eye size.

    PubMed

    Li, Zeran; Ptak, Devon; Zhang, Liyun; Walls, Elwood K; Zhong, Wenxuan; Leung, Yuk Fai

    2012-01-01

    Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO) and sodium-iodide symporter (NIS), suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos.

  9. Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on Safety and Outcomes.

    PubMed

    Hueber, Pierre-Alain; Bienz, Marc Nicolas; Valdivieso, Roger; Lavigueur-Blouin, Hugo; Misrai, Vincent; Rutman, Matthew; Te, Alexis E; Chughtai, Bilal; Barber, Neil J; Emara, Amr M; Munver, Ravi; Trinh, Quoc-Dien; Zorn, Kevin C

    2015-08-01

    We evaluated photoselective vaporization of the prostate using the GreenLight™ XPS™ 180 W system for benign prostatic hyperplasia treatment in a large multi-institutional cohort at 2 years. We particularly examined safety, outcomes and the re-treatment rate in larger prostates, defined as a prostate volume of 80 cc or greater, to assess the potential of photoselective vaporization of the prostate as a size independent procedure. A total of 1,196 patients were treated at 6 international centers in Canada, the United States, France and England. All parameters were collected retrospectively, including complications, I-PSS, maximum urinary flow rate, post-void residual urine, prostate volume, prostate specific antigen and the endoscopic re-intervention rate. Subgroup stratified comparative analysis was performed according to preoperative prostate volume less than 80 vs 80 cc or greater on transrectal ultrasound. Median prostate size was 50 cc in 387 patients and 108 cc in 741 in the prostate volume groups less than 80 and 80 cc or greater, respectively. The rate of conversion to transurethral prostate resection was significantly higher in the 80 cc or greater group than in the less than 80 cc group (8.4% vs 0.6%, p <0.01). I-PSS, quality of life score, maximum urinary flow rate and post-void residual urine were significantly improved compared to baseline at 6, 12 and 24 months of followup without significant differences between the prostate size groups. The re-treatment rate at 2 years reported in 5 of 411 patients was associated with the delivery of decreased energy density (2.1 vs 4.4 kJ/cc) in the group without re-treatment. Photoselective vaporization of the prostate using the XPS 180 W system is safe and efficacious, providing durable improvement in functional outcomes at 2 years independent of prostate size when treated with sufficient energy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  10. Finasteride Reduces the Risk of Incident Clinical Benign Prostatic Hyperplasia

    PubMed Central

    Parsons, J. Kellogg; Schenk, Jeannette M.; Arnold, Kathryn B.; Messer, Karen; Till, Cathee; Thompson, Ian M.; Kristal, Alan R.

    2014-01-01

    Background Despite the high prevalence of clinical benign prostatic hyperplasia (BPH) among older men, there remains a notable absence of studies focused on BPH prevention. Objective To determine if finasteride prevents incident clinical BPH in healthy older men. Design, setting, and participants Data for this study are from the Prostate Cancer Prevention Trial. After excluding those with a history of BPH diagnosis or treatment, or an International Prostate Symptom Score (IPSS) ≥8 at study entry, 9253 men were available for analysis. Outcome measurements and statistical analysis The primary outcome was incident clinical BPH, defined as the initiation of medical treatment, surgery, or sustained, clinically significant urinary symptoms (IPSS >14). Finasteride efficacy was estimated using Cox proportional regression models to generate hazards ratios (HRs). Results and limitations Mean length of follow-up was 5.3 yr. The rate of clinical BPH was 19 per 1000 person-years in the placebo arm and 11 per 1000 person-years in the finasteride arm (p < 0.001). In a covariate-adjusted model, finasteride reduced the risk of incident clinical BPH by 40% (HR: 0.60; 95% confidence interval, 0.51–0.69; p < 0.001). The effect of finasteride on incident clinical BPH was attenuated in men with a body mass index ≥30 kg/m2 (pinteraction = 0.04) but otherwise did not differ significantly by physical activity, age, race, current diabetes, or current smoking. The post hoc nature of the analysis is a potential study limitation. Conclusions Finasteride substantially reduces the risk of incident clinical BPH in healthy older men. These results should be considered in formulating recommendations for the use of finasteride to prevent prostate diseases in asymptomatic older men. PMID:22459892

  11. Holmium laser enucleation of the prostate is effective in the treatment of symptomatic benign prostatic hyperplasia of any size including a small prostate.

    PubMed

    Lee, Min Ho; Yang, Hee Jo; Kim, Doo Sang; Lee, Chang Ho; Jeon, Youn Soo

    2014-11-01

    Although transurethral resection of the prostate (TURP) is considered the standard surgical treatment for benign prostatic hyperplasia (BPH), Holmium laser enucleation of the prostate (HoLEP) is replacing TURP. We compared TURP with HoLEP with matching for prostate size. We retrospectively reviewed the medical charts of patients who underwent TURP and HoLEP performed by one surgeon at our institute. All patients were categorized into 3 groups on the basis of prostate size (group 1, <40 g; group 2, 40-79 g; and group 3, >80 g), and 45 patients were selected for each method. No major intraoperative complications were encountered. The mean resected tissue weight was 6.3, 18.3, and 28.0 g for groups 1, 2, and 3, respectively, for TURP and 8.7, 25.0, and 39.8 g, respectively, for HoLEP. The mean operation time was 51.8, 89.3, and 101.9 minutes for TURP and 83.6, 122.8, and 131.2 minutes for HoLEP in groups 1, 2, and 3, respectively. HoLEP had better resection efficacy than TURP for any size prostate, but there was no statistical difference between the methods. Both methods resulted in an immediate and significant improvement of International Prostate Symptom Score, peak urinary flow rates, and postvoid residual urine volume. HoLEP is effective for BPH treatment, regardless of prostate size, even in a small prostate. The perioperative morbidity of HoLEP is also comparable to that of TURP.

  12. Statin Use, Serum Lipids, and Prostate Inflammation in Men with a Negative Prostate Biopsy: Results from the REDUCE Trial.

    PubMed

    Allott, Emma H; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2017-06-01

    Statin use is associated with lower advanced prostate cancer risk. In addition to cholesterol lowering, statins have systemic anti-inflammatory properties. However, their effect on histologic prostate inflammation is not well understood, particularly among men at increased prostate cancer risk but with a negative prostate biopsy. We examined associations between serum lipid levels, statin use, and histologic prostate inflammation using data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Statin use and lipid levels [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] were assessed at baseline. Inflammation was assessed by central review. Logistic regression was used to examine the effects of lipids and statin use on presence and extent of chronic and acute prostate inflammation [none, moderate (<20%), severe (≥20% biopsy cores)]. Chronic and acute inflammation affected 77% and 15% of men, respectively. Men with high HDL (≥60 vs. <40 mg/dL) had reduced presence of acute inflammation [OR, 0.79; 95% confidence interval (CI), 0.63-0.99] and were less likely to have severe acute inflammation (OR, 0.66; 95% CI, 0.45-0.97), but there were no other associations between lipids and inflammation. Statin users had reduced presence of chronic inflammation (OR, 0.81; 95% CI, 0.69-0.95) and were less likely to have severe chronic (OR, 0.80; 95% CI, 0.68-0.95) and severe acute inflammation (OR, 0.73; 95% CI, 0.53-1.00), relative to non-users. Given the possible role for inflammation in prostate cancer, the inverse association between statins and prostate inflammation suggests a mechanism linking statins with lower advanced prostate cancer risk. Cancer Prev Res; 10(6); 319-26. ©2017 AACR. ©2017 American Association for Cancer Research.

  13. 15-lipoxygenase-2 (15-LOX-2) is expressed in benign prostatic epithelium and reduced in prostate adenocarcinoma.

    PubMed

    Shappell, S B; Boeglin, W E; Olson, S J; Kasper, S; Brash, A R

    1999-07-01

    Human 15S-lipoxygenase-2 (15-LOX-2) is a recently identified lipoxygenase that has approximately 40% sequence identity to the known human 5S-, 12S-, and 15S-lipoxygenases. 15-LOX-2 has a limited tissue distribution, with mRNA detected in prostate, lung, skin, and cornea, but not in numerous other tissues, including peripheral blood leukocytes. In the current study, we have characterized the distribution of 15-LOX-2 in the human prostate by immunohistochemistry, demonstrated the ability of benign prostate tissue to form 15S-hydroxyeicosatetraenoic acid (15S-HETE) from exogenous arachidonic acid (AA), and begun characterizing possible alterations in 15-LOX-2 in prostate adenocarcinoma. Incubation of benign prostate tissue with [14C]AA resulted in formation of [14C]15-HETE, as determined by reverse- and straight-phase high-performance liquid chromatography. 15-HETE was the major AA metabolite formed. By immunohistochemistry, 15-LOX-2 is located in secretory cells of peripheral zone glands and large prostatic ducts and somewhat less uniformly in apical cells of transition and central zone glands. 15-LOX-2 was not detected in the basal cell layer, stroma, ejaculatory ducts, seminal vesicles, or transitional epithelium. Immunostaining of 18 radical prostatectomy specimens showed a loss of 15-LOX-2 in the majority of prostate adenocarcinomas; 14 of 18 cases showed loss of 15-LOX-2 in >25% of the tumor (mean, 74.9% negative for 15-LOX-2; range, 38.9% to 100%). Incubation of paired pure benign and pure malignant prostate tissue from the same radical prostatectomies showed that 15-HETE formation was markedly reduced (>90%) or undetectable in incubations of prostate adenocarcinoma. 15-LOX-2 is a novel human lipoxygenase with a limited tissue distribution that is strongly expressed in benign prostate glandular epithelium and lost to a variable degree in the majority of prostate adenocarcinomas.

  14. An Endorectal Balloon Reduces Intrafraction Prostate Motion During Radiotherapy

    SciTech Connect

    Smeenk, Robert Jan; Louwe, Robert J.W.; Langen, Katja M.; Shah, Amish P.; Kupelian, Patrick A.; Lin, Emile N.J.Th. van; Kaanders, Johannes H.A.M.

    2012-06-01

    Purpose: To investigate the effect of endorectal balloons (ERBs) on intrafraction and interfraction prostate motion during radiotherapy. Methods and Materials: Thirty patients were treated with intensity-modulated radiotherapy, to a total dose of 80 Gy in 40 fractions. In 15 patients, a daily-inserted air-filled ERB was applied. Prostate motion was tracked, in real-time, using an electromagnetic tracking system. Interfraction displacements, measured before each treatment, were quantified by calculating the systematic and random deviations of the center of mass of the implanted transponders. Intrafraction motion was analyzed in timeframes of 150 s, and displacements >1 mm, >3 mm, >5 mm, and >7 mm were determined in the anteroposterior, left-right, and superoinferior direction, and for the three-dimensional (3D) vector. Manual table corrections, made during treatment sessions, were retrospectively undone. Results: A total of 576 and 567 tracks have been analyzed in the no-ERB group and ERB group, respectively. Interfraction variation was not significantly different between both groups. After 600 s, 95% and 98% of the treatments were completed in the respective groups. Significantly fewer table corrections were performed during treatment fractions with ERB: 88 vs. 207 (p = 0.02). Intrafraction motion was significantly reduced with ERB. During the first 150 s, only negligible deviations were observed, but after 150 s, intrafraction deviations increased with time. This resulted in cumulative percentages of 3D-vector deviations >1 mm, >3 mm, >5 mm, and >7 mm that were 57.7%, 7.0%, 0.7%, and 0.3% in the ERB-group vs. 70.2%, 18.1%, 4.6%, and 1.4% in the no-ERB group after 600 s. The largest reductions in the ERB group were observed in the AP direction. These data suggest that a 5 mm CTV-to-PTV margin is sufficient to correct for intrafraction prostate movements when using an ERB. Conclusions: ERB significantly reduces intrafraction prostate motion, but not interfraction

  15. An observational Study of the Association between Androgenetic Alopecia and Size of the Prostate

    PubMed Central

    Ramsamy, Kanagaraj; Subramaniyan, Radhakrishnan; Patra, Anjan Kumar

    2016-01-01

    Introduction: Androgenetic alopecia (AGA) is characterized by miniaturization of the hair follicle, leading to vellus transformation of the terminal hair follicle. It is caused by interactions between androgens, several genes, and environmental factors with hair follicles. Benign prostatic hyperplasia (BPH) is highly prevalent among elderly men but infrequent in those younger than 40 years. Because both entities share a common pathogenesis and AGA manifests before the onset of BPH, there could be an association between AGA and BPH. Aim: To study the possible association between AGA and the size of prostate. Materials and Methods: Sixty-five consecutive male patients, 35–65 years of age with AGA of Hamilton–Norwood classification Grades 3–7, were included in the study. AGA of Grades 1 and 2 patients on treatment with minoxidil, finasteride, or other treatments for AGA with history of prostate cancer or prostate disease were excluded from the study. Prostate size was measured through transabdominal ultrasonography. Statistical analysis was done with SPSS software. Results: Of the 65 AGA patients, the mean age was 47.18 years. Grade 4 AGA was the most common grade seen in 19 patients (29.2%), out of which, most (47.4%) were in the 56–65 years age group. 52.3% patients had normal prostate volume, and 47.7% had an enlarged prostate. The percentage of patients with the normal and enlarged prostate in moderate Grade 3 AGA was 68.8% and 31.2%, and in severe Grade 6 AGA, it was 33.3% and 66.7%, respectively. Prostate enlargement was more likely to occur in severe AGA than in moderate AGA(odds ratio 3.311; P = 0.025, which is significant). Conclusion: This study revealed an increase in prostate size with increasing age, with higher prevalence of Grade 1 prostate enlargement in younger individuals, and with higher prevalence of Grade 3 prostate enlargement in elderly men. The study also found a positive correlation between AGA and prostate size, with higher grades of

  16. Reduced Boil-Off System Sizing

    NASA Technical Reports Server (NTRS)

    Guzik, Monica C.; Plachta, David W.; Feller, Jeffrey R.

    2015-01-01

    NASA is currently developing cryogenic propellant storage and transfer systems for future space exploration and scientific discovery missions by addressing the need to raise the technology readiness level of cryogenic fluid management technologies. Cryogenic propellants are baselined in many propulsion systems due to their inherently high specific impulse; however, their low boiling points can cause substantial boil-off losses over time. Recent efforts such as the Reduced Boil-off Testing and the Active Thermal Control Scaling Study provide important information on the benefit of an active cooling system applied to LH2 propellant storage. Findings show that zero-boil off technologies can reduce overall mass in LH2 storage systems when low Earth orbit loiter periods extend beyond two months. A significant part of this mass reduction is realized by integrating two stages of cooling: a 20 K stage to intercept heat at the tank surface, and a 90 K stage to reduce the heat entering the less efficient 20 K stage. A missing element in previous studies, which is addressed in this paper, is the development of a direct method for sizing the 90 K cooling stage. Such a method requires calculation of the heat entering both the 90 K and 20 K stages as compared to the overall system masses, and is reliant upon the temperature distribution, performance, and unique design characteristics of the system in question. By utilizing the known conductance of a system without active thermal control, the heat being intercepted by a 90 K stage can be calculated to find the resultant lift and mass of each active thermal control stage. Integral to this is the thermal conductance of the cooling straps and the broad area cooling shield, key parts of the 90 K stage. Additionally, a trade study is performed to show the ability of the 90 K cooling stage to reduce the lift on the 20 K cryocooler stage, which is considerably less developed and efficient than 90 K cryocoolers.

  17. Neutrophil stunning by metoprolol reduces infarct size

    PubMed Central

    García-Prieto, Jaime; Villena-Gutiérrez, Rocío; Gómez, Mónica; Bernardo, Esther; Pun-García, Andrés; García-Lunar, Inés; Crainiciuc, Georgiana; Fernández-Jiménez, Rodrigo; Sreeramkumar, Vinatha; Bourio-Martínez, Rafael; García-Ruiz, José M; del Valle, Alfonso Serrano; Sanz-Rosa, David; Pizarro, Gonzalo; Fernández-Ortiz, Antonio; Hidalgo, Andrés; Fuster, Valentín; Ibanez, Borja

    2017-01-01

    The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol acts during early phases of neutrophil recruitment by impairing structural and functional rearrangements needed for productive engagement of circulating platelets, resulting in erratic intravascular dynamics and blunted inflammation. Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade of PSGL-1, the receptor involved in neutrophil–platelet interactions, fully abrogated metoprolol's infarct-limiting effects. The association between neutrophil count and microvascular obstruction is abolished in metoprolol-treated AMI patients. Metoprolol inhibits neutrophil–platelet interactions in AMI patients by targeting neutrophils. Identification of the relevant role of ADRB1 in haematopoietic cells during acute injury and the protective role upon its modulation offers potential for developing new therapeutic strategies. PMID:28416795

  18. Reducing Prostate Cancer Disparities Through Behavioral and Biologic Epidemiologic Approaches

    DTIC Science & Technology

    2011-09-01

    PRESENTATIONS Oral 1. Drake BF. Prostate Cancer Walk – Prostate Cancer Education Session. Missouri Black Expo. St. Louis, MO. August 2011. Moderator. 2...Harvard Cancer Center Disparities Research Seminar Series, Boston, MA, 2006. Oral presentation. 8. Drake BF. Cancer Health Disparities. Young...MD, July 2011. Poster Presentation. 2. Wagner S, Drake BF, Elder K, Hebert JR. Social and clinical predictors of prostate cancer treatment

  19. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    USDA-ARS?s Scientific Manuscript database

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  20. A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice

    PubMed Central

    Tan, Dun-Xian; Manchester, Lucien C.; Korkmaz, Ahmet; Fuentes-Broto, Lorena; Hardman, W. Elaine; Rosales-Corral, Sergio A.; Qi, Wenbo

    2013-01-01

    It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet. PMID:23758186

  1. Developing a model for forecasting Gleason score ≥7 in potential prostate cancer patients to reduce unnecessary prostate biopsies.

    PubMed

    Li, Xiao; Pan, Yongsheng; Huang, Yuan; Wang, Jun; Zhang, Cheng; Wu, Jie; Cheng, Gong; Qin, Chao; Hua, Lixin; Wang, Zengjun

    2016-04-01

    The diagnosis of Gleason score (GS) ≥7 with distinction from GS < 7 remains a difficult problem instructing clinical decisions. Moreover, the present wide application of prostate biopsy to increase prostate cancer detection rate might cause unnecessary and excessive examination or treatment. Therefore, a risk assessment model for forecasting GS ≥ 7 in potential prostate cancer patients was established to reduce unnecessary prostate biopsies. Patients (n = 981; September 2009 to January 2013) who underwent trans-rectal ultrasound (TRUS)-guided core prostate biopsy were retrospectively evaluated in the first stage of the study. Age, prostate-specific antigen (PSA), free PSA (fPSA), the free/total PSA ratio (f/t), prostate volume (PV), PSA density (PSAD), digital rectal examination (DRE) findings (texture, nodules) and B-ultrasound detection results (normal or abnormal, presence of hypoechoic mass or microcalcification) were considered as potential predictive factors. After multiple logistic regression analysis, independent variables used to build a nomogram were selected using a backward elimination selection procedure. Then, a model to forecast GS ≥ 7 was designed for potential prostate cancer patients. In the second stage of the study, 410 cases (January 2013 to March 2015) were subsequently evaluated using our model for prostate biopsies, and the outcomes of biopsies were compared between the two stages. PSA, DRE texture, DRE nodules and B-ultrasound results were finally brought into our nomogram; a obviously greater area under the receiver operating characteristic (ROC) curve was obtained for the model than utilizing PSA, fPSA or PSAD alone (0.831 vs. 0.803, 0.770, 0.780 separately). We thereafter sought the best cutoff value in the ROC curve at 0.87, which provided sensitivity as high as 90%. Meanwhile, the specificity was 45.8%, which was much higher than the specificity of PSA, fPSA and PSAD at the same sensitivity level (37.7, 24.6 and 35

  2. The Paradox of Reducing Class Size and Improving Learning Outcomes

    ERIC Educational Resources Information Center

    Hattie, John

    2005-01-01

    This paper addresses four questions: What are the effects of reducing class size? How important are these effects? How can we explain these effects? and How can we improve the outcomes when class sizes are reduced? A major aim is to provide directions for resolving the paradox as to "Why reducing class size has not led to major improvements in…

  3. The Paradox of Reducing Class Size and Improving Learning Outcomes

    ERIC Educational Resources Information Center

    Hattie, John

    2005-01-01

    This paper addresses four questions: What are the effects of reducing class size? How important are these effects? How can we explain these effects? and How can we improve the outcomes when class sizes are reduced? A major aim is to provide directions for resolving the paradox as to "Why reducing class size has not led to major improvements in…

  4. Reducing Class Size: What Do We Know?

    ERIC Educational Resources Information Center

    Bascia, Nina

    2010-01-01

    This report provides an overview of findings from the research on primary class size reduction as a strategy to improve student learning. Its purpose is to provide a comprehensive and balanced picture of a very popular educational reform strategy that has often been seen as a "quick fix" for improving students' opportunities to learn in…

  5. Prostatitis

    PubMed Central

    Domingue, Gerald J.; Hellstrom, Wayne J. G.

    1998-01-01

    The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (controversial) leukocytes or bacteria in the expressed prostatic secretions. Despite these diagnostic criteria, the etiology of chronic idiopathic prostatitis is unknown. While this review covers the entire spectrum of microbially caused acute prostatitis (including common and uncommon bacteria, viruses, fungi, and parasites) and microbially associated chronic prostatitis, a special focus has been given to chronic idiopathic prostatitis. The idiopathic syndrome is commonly diagnosed in men but is poorly treated. Recent data convincingly suggests a possible bacterial etiology for the condition. Provocative molecular studies have been published reporting the presence of 16S rRNA bacterial sequences in prostate biopsy tissue that is negative for ordinary bacteria by routine culture in men with chronic idiopathic prostatitis. Additionally, special culture methods have indicated that difficult-to-culture coryneforms and coagulase-negative staphylococci are present in expressed prostatic secretions found to be negative by routine culture techniques. Treatment failures are not uncommon in chronic prostatitis. Literature reports suggest that antimicrobial treatment failures in chronic idiopathic prostatitis caused by organisms producing extracellular slime might result from the virulent properties of coagulase-negative staphylococci or other bacteria. While it is difficult to definitively extrapolate from animal models, antibiotic pharmokinetic studies with a murine model have

  6. Holmium laser enucleation of the prostate: a size-independent new "gold standard".

    PubMed

    Elzayat, Ehab A; Habib, Enmar I; Elhilali, Mostafa M

    2005-11-01

    We report our experience with holmium laser enucleation of the prostate (HoLEP) for treatment of 552 patients with symptomatic benign prostatic hyperplasia (BPH) and their long-term outcome. Between March 1998 and January 2005, a retrospective review was conducted at our institution of 552 cases in which patients underwent HoLEP. Patient characteristics, indications for surgery, preoperative and postoperative International Prostate Symptom Score (I-PSS), peak flow rate (Qmax), postvoid residual urine, operative data, catheterization time, hospital stay, and immediate and long-term complications were recorded. The mean age of patients was 73.7 +/- 7.9 years, and the mean follow-up time was 36 months. The mean preoperative prostate size was 83.7 +/- 49.7 cm3 (range, 20 to 351 cm3), the mean enucleation time was 86 minutes (range, 15 to 255 minutes), and the mean enucleated tissue weight was 52.1 +/- 43.7 g (range, 5 to 340 g). The voiding parameters were significantly improved, with a 200% increase in Qmax, as well as a 75% improvement in I-PSS at 1 year postoperatively, which continued to improve during subsequent follow-up. A total of 11 patients required blood transfusion; 8 of them were on anticoagulant therapy. Irritative symptoms were noted in 9.4% and transient stress incontinence in 4.2% of patients. Bladder neck contracture and urethral stricture each developed in 1.3% of patients. We conclude that HoLEP is a safe and effective procedure for treatment of symptomatic BPH, regardless of prostate size, with low morbidity and short hospital stay. HoLEP appears to be the modern alternative to transurethral resection of the prostate and open prostatectomy, and it may be considered a size-independent new "gold standard."

  7. Analysis of early morbidity and functional outcome of thulium: yttrium-aluminum-garnet laser enucleation for benign prostate enlargement: patient age and prostate size determine adverse surgical outcome.

    PubMed

    Rausch, Steffen; Heider, Thomas; Bedke, Jens; Kruck, Stephan; Schwentner, Christian; Fischer, Karsten; Stenzl, Arnulf; Kälble, Tilman

    2015-01-01

    To evaluate complications and functional outcome and to identify patient-associated risk factors, we analyzed consecutive patients undergoing thulium:yttrium-aluminum-garnet laser enucleation of the prostate (ThuLEP) in our department. A total of 234 patients were prospectively analyzed. Preoperative data, postoperative complications, and outcome at 6, 12, and 24 months were recorded. Individual risk factors for complications and treatment failure were assessed by univariate and multivariate analyses. Mean age at surgery was 72.88 ± 7.83 years. Mean preoperative prostate size was 84.8 ± 34.9 mL. Thirty-day complication rate was 19.7%. Functional treatment failure occurred in 9.0% of all patients. Decline of mean International Prostate Symptom Score was -75%, quality of life index -76%, and postvoid residual -86% at 24 months. Maximum urine flow at 24 months was improved at +231%. In univariate analysis, age >80 years and prostate size <50 mL were significant predictors of complications, which was confirmed by multivariate analysis (P = .0277 and .0409, respectively). Age >80 years, prostate size <80 mL or <50 mL, and American Society of Anesthesiologists classification were significant predictors of functional treatment failure in univariate analysis. Prostate size <80 mL or <50 mL was significantly associated with treatment failure (P < .001) in multivariate analysis. ThuLEP is a safe and efficient surgical procedure, even in a patient cohort with high prostate volumes, age, and comorbidities. However, high patient age and small prostate size were significant determinants of adverse outcomes after surgery. To address the question of optimal therapy selection for patients with prostates smaller than 80 mL, further prospective randomized evaluation of ThuLEP and alternative surgical interventions is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study.

    PubMed

    Vidal, Adriana C; Howard, Lauren E; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2014-12-01

    Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade prostate cancer in REDUCE, in which biopsies were largely independent of PSA. The REDUCE study tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI <25 kg/m(2) normal weight; 25-29.9 kg/m(2) overweight; and ≥30 kg/m(2) obese) and risk of high-grade (Gleason ≥7) or low-grade prostate cancer (Gleason <7) versus no prostate cancer was examined using multinomial logistic regression. Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of low-grade prostate cancer in both univariable (OR, 0.74; P = 0.001) and multivariable analyses (OR, 0.79; P = 0.01). In univariable analysis, obesity was not associated with high-grade prostate cancer (OR, 1.08; P = 0.50). However, in multivariable analysis, obesity was associated with increased risk of high-grade prostate cancer (OR, 1.28; P = 0.042). This analysis was not able to address how obesity may influence prostate cancer progression. Obesity is associated with decreased risk of low-grade and increased risk of high-grade prostate cancer. These data provide further support to the hypothesis that obesity is associated with aggressive prostate cancer. Obesity is linked with aggressive prostate cancer. Avoiding obesity may prevent the risk of developing high-grade prostate cancer. ©2014 American Association for Cancer Research.

  9. Correlation of Prostate Gland Size and Uroflowmetry in Patients with Lower Urinary Tract Symptoms.

    PubMed

    Sundaram, Deepak; Sankaran, Ponnusamy Kasirajan; Raghunath, Gunapriya; Vijayalakshmi, S; Vijayakumar, J; Yuvaraj, Maria Francis; Kumaresan, Munnusamy; Begum, Zareena

    2017-05-01

    Benign Prostatic Hyperplasia (BPH) is a common entity among men over 40 years of age with significant disability. It is a condition that occurs when the enlarged prostate gland compresses the urethra leading to Bladder Outlet Obstruction (BOO). To correlate the size of the prostate gland and uroflowmetry parameters in patients with Lower Urinary Tract Symptoms (LUTS). One hundred and twenty randomly selected male patients, from the ages of 41 to 70 years, with LUTS, and underwent trans abdominal sonogram and uroflowmetry were included in the study. The samples were divided into three groups according to the age; Group 1: 41 to 50 years, Group 2: 51 to 60 years, Group 3: 61 to 70 years. In Group 1 (41 to 50 years), there were totally 28 patients with LUTS, out of which seven patients had BPH, indicating that about 5% of patients with LUTS have BPH. In Group 2 (51-60 years) there were totally 31 patients with LUTS, out of which 10 patients had BPH, indicating that 8% of patients with LUTS have BPH. In Group 3 (61-70 years) there were totally 61 patients with LUTS, out of which 33 patients had BPH, indicating that 27% of patients with LUTS had BPH. The mean age of patients with LUTS was 60 years with mean prostate size of 45 cm(3). Enlarged prostate gland was present in 41% of patients with mean Q max of 14 ml/sec and post voidal volume of 48 ml. This study concludes that the LUTS in older patients are mostly due to BPH leading to BOO. Also, patients with BPH in early ages can lead to increased Post voidal Residual Volume (PVR) following uroflowmetry. Thus, screening male patients with LUTS, at 40 years and above, is an ideal way to detect prostatic problems at an early stage.

  10. Correlation of Prostate Gland Size and Uroflowmetry in Patients with Lower Urinary Tract Symptoms

    PubMed Central

    Sankaran, Ponnusamy Kasirajan; Raghunath, Gunapriya; Vijayalakshmi, S; Vijayakumar, J; Yuvaraj, Maria Francis; Kumaresan, Munnusamy; begum, Zareena

    2017-01-01

    Introduction Benign Prostatic Hyperplasia (BPH) is a common entity among men over 40 years of age with significant disability. It is a condition that occurs when the enlarged prostate gland compresses the urethra leading to Bladder Outlet Obstruction (BOO). Aim To correlate the size of the prostate gland and uroflowmetry parameters in patients with Lower Urinary Tract Symptoms (LUTS). Materials and Methods One hundred and twenty randomly selected male patients, from the ages of 41 to 70 years, with LUTS, and underwent trans abdominal sonogram and uroflowmetry were included in the study. The samples were divided into three groups according to the age; Group 1: 41 to 50 years, Group 2: 51 to 60 years, Group 3: 61 to 70 years. Results In Group 1 (41 to 50 years), there were totally 28 patients with LUTS, out of which seven patients had BPH, indicating that about 5% of patients with LUTS have BPH. In Group 2 (51-60 years) there were totally 31 patients with LUTS, out of which 10 patients had BPH, indicating that 8% of patients with LUTS have BPH. In Group 3 (61-70 years) there were totally 61 patients with LUTS, out of which 33 patients had BPH, indicating that 27% of patients with LUTS had BPH. The mean age of patients with LUTS was 60 years with mean prostate size of 45 cm3. Enlarged prostate gland was present in 41% of patients with mean Q max of 14 ml/sec and post voidal volume of 48 ml. Conclusion This study concludes that the LUTS in older patients are mostly due to BPH leading to BOO. Also, patients with BPH in early ages can lead to increased Post voidal Residual Volume (PVR) following uroflowmetry. Thus, screening male patients with LUTS, at 40 years and above, is an ideal way to detect prostatic problems at an early stage. PMID:28658743

  11. The Association between Phosphodiesterase Type 5 Inhibitors and Prostate Cancer: Results from the REDUCE Study.

    PubMed

    Jamnagerwalla, Juzar; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2016-09-01

    Despite routine use of phosphodiesterase type 5 inhibitor to treat erectile dysfunction the role in prostate cancer chemoprevention remains unclear. Only a few studies have explored the link between phosphodiesterase type 5 inhibitor use and prostate cancer. We tested the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial. REDUCE was a 4-year multicenter study testing the effect of daily dutasteride on prostate cancer risk in men with prostate specific antigen 2.5 to 10.0 ng/ml and negative biopsy who underwent study mandated biopsies at 2 and 4 years. The association of phosphodiesterase type 5 inhibitor with overall prostate cancer risk and disease grade (Gleason 2-6 and 7-10) was examined using adjusted logistic and multinomial regression analysis. Secondary analysis was performed to explore the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in North American men, given the significantly higher use of phosphodiesterase type 5 inhibitor in these subjects. Phosphodiesterase type 5 inhibitor was not associated with prostate cancer diagnosis (OR 0.90, 95% CI 0.68-1.20, p = 0.476), low grade disease (OR 0.93, 95% CI 0.67-1.27, p = 0.632) or high grade disease (OR 0.85, 95% CI 0.51-1.39, p = 0.508). An inverse trend was seen between phosphodiesterase type 5 inhibitor and prostate cancer diagnosis in North American men but this was not statistically significant (OR 0.67, 95% CI 0.42-1.07, p = 0.091). Phosphodiesterase type 5 inhibitor use was not associated with decreased prostate cancer diagnoses on post-hoc analysis of REDUCE. In North American men, who had much higher baseline use of phosphodiesterase type 5 inhibitor, this treatment was associated with an inverse trend of prostate cancer diagnosis that approached but did not reach statistical significance. Copyright © 2016 American Urological Association Education and

  12. Association between Biomarkers of Obesity and Risk of High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer - Evidence of Effect Modification by Prostate Size

    PubMed Central

    Fowke, Jay H.; Motley, Saundra; Dai, Qi; Concepcion, Raoul; Barocas, Daniel A.

    2012-01-01

    Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC. PMID:23079532

  13. Association between biomarkers of obesity and risk of high-grade prostatic intraepithelial neoplasia and prostate cancer--evidence of effect modification by prostate size.

    PubMed

    Fowke, Jay H; Motley, Saundra; Dai, Qi; Concepcion, Raoul; Barocas, Daniel A

    2013-01-28

    Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Metformin Use and Risk of Prostate Cancer: Results from the REDUCE Study

    PubMed Central

    Feng, Tom; Sun, Xizi; Howard, Lauren E.; Vidal, Adriana C.; Gaines, Alexis R.; Moreira, Daniel M.; Castro-Santamaria, Ramiro; Andriole, Gerald L.; Freedland, Stephen J.

    2015-01-01

    The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other anti-diabetic medications, vs. no anti-diabetic medication use and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4–6, high-grade Gleason 7–10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any anti-diabetic medications, 141 (26%) reported use of at least one anti-diabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR=1.19, p=0.50), low- (OR=1.01, p=0.96), or high-grade (OR=1.83, p=0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin anti-diabetic medications and prostate cancer risk in both crude (OR=1.02, p=0.95) and multivariable analysis (OR=0.85, p=0.56). Furthermore, the interactions between anti-diabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all p>0.05). Among diabetic men with a negative pre-study biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis. PMID:26353947

  15. Metformin use and risk of prostate cancer: results from the REDUCE study.

    PubMed

    Feng, Tom; Sun, Xizi; Howard, Lauren E; Vidal, Adriana C; Gaines, Alexis R; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2015-11-01

    The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6 and high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis.

  16. Reducing Toxicity of Radiation Treatment of Advanced Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    mice. The compound in question is an anti- inflammatory mediator that inhibits NF-κB activity and other key signaling events of relevance to prostate... pelvic lymph nodes. This is due, in large part, to ‘collateral damage’ by radiation, i.e. toxicity to the intestine and the bladder. Treatment...strategies to escalate the dose of radiation to the pelvic sentinel lymph nodes and/or the primary site, are limited by normal tissue dose constraints that

  17. Statin Use Reduces Prostate Cancer All-Cause Mortality: A Nationwide Population-Based Cohort Study.

    PubMed

    Sun, Li-Min; Lin, Ming-Chia; Lin, Cheng-Li; Chang, Shih-Ni; Liang, Ji-An; Lin, I-Ching; Kao, Chia-Hung

    2015-09-01

    Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60-0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose-response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose-response relationship may exist.

  18. A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

    PubMed Central

    Archibald, Monica; Pritchard, Tara; Nehoff, Hayley; Rosengren, Rhonda J; Greish, Khaled; Taurin, Sebastien

    2016-01-01

    Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. PMID:26811677

  19. Role of step size and max dwell time in anatomy based inverse optimization for prostate implants.

    PubMed

    Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R; Sresty, N V Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

    2013-07-01

    In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants.

  20. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

    PubMed Central

    Henke, Alex; Franco, Omar E.; Stewart, Grant D.; Riddick, Antony C.P.; Katz, Elad; Hayward, Simon W.; Thomson, Axel A.

    2016-01-01

    Background: Prostate cancer-associated fibroblasts (CAF) can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; Methods: We isolated CAF from prostate cancer patients of Gleason Score 6–10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90) inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; Results: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2) levels in CAF; Conclusions: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment. PMID:27563925

  1. Weight Management to Reduce Prostate Cancer Risk: A Survey of Men’s Needs and Interests

    PubMed Central

    Schleper, Amy; Sullivan, Debra K.; Thrasher, J. Brantley; Holzbeierlein, Jeffrey M.; Klemp, Jennifer; Befort, Christie; Hamilton-Reeves, Jill M.

    2016-01-01

    Obese men have a higher rate of prostate cancer-related death than non-obese men, and obesity increases the risk of prostate cancer progression and biochemical recurrence. The purpose of this study was to assess needs and interests of men for a technology-driven weight loss intervention to reduce prostate cancer risk. We distributed a survey collecting demographic characteristics, health history, exercise and eating habits (and perception of those habits), current and prior attempts of health behavior change, and technology use. Survey answers were summarized by count and percent of total respondents. Completed surveys (N = 109) described men with a family history of prostate cancer (25%), a history of elevated prostate specific antigen (26%), and prostate cancer survivors (22%). We compared body mass index (BMI) to perception of weight; overweight and obese men perceived their weight as more normal than their BMI category suggests. Most men reported their diet needed minor improvement (74%), and 65% of men reported they are either currently trying to lose weight or interested in weight loss. Most respondents access the internet (92%), while text messaging (60%) and smartphone application use (40%) are less frequent, especially in men over 60. Our results revealed a need and willingness for lifestyle modification and suggest a need for evidence-based weight loss strategies and for addressing the misperception of weight status. A male-tailored intervention that implements technology could improve energy balance, hold men accountable to healthy behavior change, and promote dietary patterns in order to reduce prostate cancer risk. PMID:27547287

  2. Does Obesity Modify the Ability of Prebiopsy Prostate Specific Antigen to Detect Prostate Cancer on Repeat Biopsy? Results from the REDUCE Study.

    PubMed

    Vidal, Adriana C; Howard, Lauren E; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2015-07-01

    Higher body mass index is linked to lower prostate specific antigen. This has given rise to concerns that prostate specific antigen may be less reliable for predicting prostate cancer among obese men. We tested the accuracy of prebiopsy prostate specific antigen for predicting prostate cancer across body mass index categories. We used the REDUCE study, which tested dutasteride for prostate cancer risk reduction in men with a prostate specific antigen of 2.5 to 10.0 ng/ml and a negative pre-study biopsy. All men were required to have a biopsy at 2 and 4 years independent of prostate specific antigen. We assessed the performance of prebiopsy prostate specific antigen to predict overall and high grade prostate cancer (Gleason sum 7 or greater) in each body mass index group using AUC. Of 6,103 men who had a 2-year biopsy 1,646 (27%) were normal weight, 3,209 (53%) were overweight and 1,248 (20%) were obese. Mean adjusted prostate specific antigen for normal weight, overweight and obese subjects on placebo was 7.73, 7.17 and 6.79 ng/ml (p-trend=0.192), and on dutasteride 3.16, 2.93 and 2.62 ng/ml (p=0.008). AUC analysis using raw prostate specific antigen data for predicting prostate cancer ranged from 0.60 to 0.64 in the placebo arm and 0.58 to 0.66 in the dutasteride arm with no difference across body mass index categories (p-interactions ≥0.212). Similar results were found for high grade prostate cancer with AUC ranging from 0.69 to 0.70 in the placebo arm and 0.65 to 0.75 in the dutasteride arm but no differences across body mass index categories (p-interactions ≥0.157). Among men with a previous negative biopsy the accuracy of prebiopsy prostate specific antigen to predict overall and high grade prostate cancer was independent of body mass index. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Evaluation of a patient education tool to reduce the incidence of incontinence post-prostate surgery.

    PubMed

    Ip, Virginia

    2004-10-01

    A pelvic floor muscle exercise program can reduce the incidence of incontinence post-prostate surgery. The purpose of this study was to validate a new education tool, a refrigerator magnet, in comparison to a paper copy with the same information, to determine if patient compliance with the exercises increased.

  4. Cholesterol and Benign Prostate Disease

    PubMed Central

    Freeman, Michael R.; Solomon, Keith R.

    2014-01-01

    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association bet ween BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemi, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept. PMID:21862201

  5. Cholesterol and benign prostate disease.

    PubMed

    Freeman, Michael R; Solomon, Keith R

    2011-01-01

    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept.

  6. Metabolic syndrome-like components and prostate cancer risk: results from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study

    PubMed Central

    Sourbeer, Katharine N.; Howard, Lauren E.; Andriole, Gerald L.; Moreira, Daniel M.; Castro-Santamaria, Ramiro; Freedland, Stephen J.; Vidal, Adriana C.

    2015-01-01

    Objective To evaluate the relationship between number of metabolic syndrome (MetS)-like components and prostate cancer diagnosis in a group of men where nearly all biopsies were taken independent of prostate-specific antigen (PSA) level, thus minimising any confounding from how the various MetS-like components may influence PSA levels. Subjects/Patients and Methods We analysed data from 6426 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study with at least one on-study biopsy. REDUCE compared dutasteride vs placebo on prostate cancer risk among men with an elevated PSA level and negative pre-study biopsy and included two on-study biopsies regardless of PSA level at 2 and 4 years. Available data for MetS-like components included data on diabetes, hypertension, hypercholesterolaemia, and body mass index. The association between number of these MetS-like components and prostate cancer risk and low-grade (Gleason sum <7) or high-grade (Gleason sum >7) vs no prostate cancer was evaluated using logistic regression. Results In all, 2171 men (34%) had one MetS-like component, 724 (11%) had two, and 163 (3%) had three or four. Men with more MetS-like components had lower PSA levels (P = 0.029). One vs no MetS-like components was protective for overall prostate cancer (P = 0.041) and low-grade prostate cancer (P = 0.010). Two (P = 0.69) or three to four (P = 0.15) MetS-like components were not significantly related to prostate cancer. While one MetS-like component was unrelated to high-grade prostate cancer (P = 0.97), two (P = 0.059) or three to four MetS-like components (P = 0.02) were associated with increased high-grade prostate cancer risk, although only the latter was significant. Conclusion When biopsies are largely PSA level independent, men with an initial elevated PSA level and a previous negative biopsy, and multiple MetS-like components were at an increased risk of high-grade prostate cancer, suggesting the link between Met

  7. Metabolic syndrome-like components and prostate cancer risk: results from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study.

    PubMed

    Sourbeer, Katharine N; Howard, Lauren E; Andriole, Gerald L; Moreira, Daniel M; Castro-Santamaria, Ramiro; Freedland, Stephen J; Vidal, Adriana C

    2015-05-01

    To evaluate the relationship between number of metabolic syndrome (MetS)-like components and prostate cancer diagnosis in a group of men where nearly all biopsies were taken independent of prostate-specific antigen (PSA) level, thus minimising any confounding from how the various MetS-like components may influence PSA levels. We analysed data from 6426 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study with at least one on-study biopsy. REDUCE compared dutasteride vs placebo on prostate cancer risk among men with an elevated PSA level and negative pre-study biopsy and included two on-study biopsies regardless of PSA level at 2 and 4 years. Available data for MetS-like components included data on diabetes, hypertension, hypercholesterolaemia, and body mass index. The association between number of these MetS-like components and prostate cancer risk and low-grade (Gleason sum <7) or high-grade (Gleason sum >7) vs no prostate cancer was evaluated using logistic regression. In all, 2171 men (34%) had one MetS-like component, 724 (11%) had two, and 163 (3%) had three or four. Men with more MetS-like components had lower PSA levels (P = 0.029). One vs no MetS-like components was protective for overall prostate cancer (P = 0.041) and low-grade prostate cancer (P = 0.010). Two (P = 0.69) or three to four (P = 0.15) MetS-like components were not significantly related to prostate cancer. While one MetS-like component was unrelated to high-grade prostate cancer (P = 0.97), two (P = 0.059) or three to four MetS-like components (P = 0.02) were associated with increased high-grade prostate cancer risk, although only the latter was significant. When biopsies are largely PSA level independent, men with an initial elevated PSA level and a previous negative biopsy, and multiple MetS-like components were at an increased risk of high-grade prostate cancer, suggesting the link between MetS-like components and high-grade prostate cancer is unrelated to a lowered

  8. Sunitinib reduces tumor hypoxia and angiogenesis, and radiosensitizes prostate cancer stem-like cells.

    PubMed

    Diaz, Roque; Nguewa, Paul A; Redrado, Miriam; Manrique, Irene; Calvo, Alfonso

    2015-08-01

    The need for new treatments for advanced prostate cancer has fostered the experimental use of targeted therapies. Sunitinib is a multi-tyrosine kinase inhibitor that mainly targets membrane-bound receptors of cells within the tumor microenvironment, such as endothelial cells and pericytes. However, recent studies suggest a direct effect on tumor cells. In the present study, we have evaluated both direct and indirect effects of Sunitinib in prostate cancer and how this drug regulates hypoxia, using in vitro and in vivo models. We have used both in vitro (PC-3, DU145, and LNCaP cells) and in vivo (PC-3 xenografts) models to study the effect of Sunitinib in prostate cancer. Analysis of hypoxia based on HIF-1α expression and FMISO uptake was conducted. ALDH activity was used to analyze cancer stem cells (CSC). Sunitinib strongly reduced proliferation of PC-3 and DU-145 cells in a dose dependent manner, and decreased levels of p-Akt, p-Erk1/2, and Id-1, compared to untreated cells. A 3-fold reduction in tumor growth was also observed (P < 0.001 with respect to controls). Depletion of Hif-1α levels in vitro and a decrease in FMISO uptake in vivo showed that Sunitinib inhibits tumor hypoxia. When combined with radiotherapy, this drug enhanced cell death in vitro and in vivo, and significantly decreased CD-31, PDGFRβ, Hif-1α, Id1, and PCNA protein levels (whereas apoptosis was increased) in tumors as compared to controls or single-therapy treated mice. Moreover, Sunitinib reduced the number of ALDH + cancer stem-like cells and sensitized these cells to radiation-mediated loss of clonogenicity. Our results support the use of Sunitinib in prostate cancer and shows that both hypoxia and cancer stem cells are involved in the effect elicited by this drug. Combination of Sunitinib with radiotherapy warrants further consideration to reduce prostate cancer burden. © 2015 Wiley Periodicals, Inc.

  9. Reducing the Size of the Federal Civilian Work Force

    DTIC Science & Technology

    1993-12-01

    33 Hiring Freezes 39 Early Retirement 48 vi REDUCING THE SIZE OF THE FEDERAL CIVILIAN WORK FORCE December 1993 FIVE USE OF SEPARATION INCENTIVES AT...Cash Costs and Savings of Early Retirement 22 11. Near-Term Costs and Savings of Offering Employees Cash Incentives to Separate 24 viii REDUCING THE...Changes in U.S. Postal Service Employment, 1992-1993 55 22. Effect of Incentives on Regular and Early Retirement at the U.S. Postal Service and

  10. Resveratrol Reduces Prostate Cancer Growth and Metastasis by Inhibiting the Akt/MicroRNA-21 Pathway

    PubMed Central

    Sheth, Sandeep; Jajoo, Sarvesh; Kaur, Tejbeer; Mukherjea, Debashree; Sheehan, Kelly; Rybak, Leonard P.; Ramkumar, Vickram

    2012-01-01

    The consumption of foods containing resveratrol produces significant health benefits. Resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis. These actions could be explained by its ability to inhibit (ERK-1/2), Akt and suppressing the levels of estrogen and insulin growth factor -1 (IGF-1) receptor. How these processes are manifested into the antitumor actions of resveratrol is not clear. Using microarray studies, we show that resveratrol reduced the expression of various prostate-tumor associated microRNAs (miRs) including miR-21 in androgen-receptor negative and highly aggressive human prostate cancer cells, PC-3M-MM2. This effect of resveratrol was associated with reduced cell viability, migration and invasiveness. Additionally, resveratrol increased the expression of tumor suppressors, PDCD4 and maspin, which are negatively regulated by miR-21. Short interfering (si) RNA against PDCD4 attenuated resveratrol’s effect on prostate cancer cells, and similar effects were observed following over expression of miR-21 with pre-miR-21 oligonucleotides. PC-3M-MM2 cells also exhibited high levels of phospho-Akt (pAkt), which were reduced by both resveratrol and LY294002 (a PI3-kinase inhibitor). MiR-21 expression in these cells appeared to be dependent on Akt, as LY294002 reduced the levels of miR-21 along with a concurrent increase in PDCD4 expression. These in vitro findings were further corroborated in a severe combined immunodeficient (SCID) mouse xenograft model of prostate cancer. Oral administration of resveratrol not only inhibited the tumor growth but also decreased the incidence and number of metastatic lung lesions. These tumor- and metastatic-suppressive effects of resveratrol were associated with reduced miR-21 and pAkt, and elevated PDCD4 levels. Similar anti-tumor effects of resveratrol were observed in DU145 and LNCaP prostate cancer cells which were associated with suppression of Akt and PDCD4, but

  11. Can serving-size labels reduce the portion-size effect? A pilot study.

    PubMed

    Spanos, Samantha; Kenda, Andree S; Vartanian, Lenny R

    2015-01-01

    Research has shown that the bigger the portion that people are served, the more food they eat; this phenomenon is referred to as the portion-size effect. Providing objective serving-size information on food products has been shown to reduce the influence of external food cues on people's eating behavior. The current study examined whether providing objective serving-size information would also reduce the portion-size effect. 100 female participants were served either a small or large portion of pizza in the context of a taste test. The large portion was either unlabeled, labeled as "Contains 2 servings," or labeled as "Contains 4 servings." Food intake was lower when the large portion was labeled "Contains 4 servings" compared to when it was labeled "Contains 2 servings." Moreover, participants' intake in the large portion/4 servings condition was statistically similar to the intake of participants in the small portion condition. Thus, the standard portion-size effect was observed when the large portion was unlabeled or was labeled as "Contains 2 servings," but not when the large portion was labeled as "Contains 4 servings". These findings suggest that providing serving-size information can reduce the portion-size effect, but that the specific content (and not just the presence) of serving-size information is important in determining food intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Risk of All-Cause and Prostate Cancer-Specific Mortality After Brachytherapy in Men With Small Prostate Size

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming H.; Choueiri, Toni K.; Hoffman, Karen E.; Hu, Jim C.; Martin, Neil E.; Beard, Clair J.; Dosoretz, Daniel E.; Moran, Brian J.; Katin, Michael J.; Braccioforte, Michelle H.; Ross, Rudi; Salenius, Sharon A.; Kantoff, Philip W.; D'Amico, Anthony V.

    2011-04-01

    Background: Brachytherapy for prostate cancer can be technically challenging in men with small prostates ({<=}20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates. Methods and Materials: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray's regression were used to determine whether volume {<=}20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer-specific mortality (PCSM), respectively, after adjustment for other known prognostic factors. Results: 443 patients (6.9%) had a prostate volume {<=}20 cc. After a median follow-up of 2.91 years (interquartile range, 1.06-4.79), volume {<=}20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08-1.65], p = 0.0085) with 3-year estimates of ACM for {<=}20 cc vs. >20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4). Conclusion: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume {<=}20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding.

  13. Prospective serum metabolomic profile of prostate cancer by size and extent of primary tumor.

    PubMed

    Huang, Jiaqi; Mondul, Alison M; Weinstein, Stephanie J; Karoly, Edward D; Sampson, Joshua N; Albanes, Demetrius

    2017-07-11

    Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1-20). LC/MS-GC/MS identified 625 known compounds, and logistic regression estimated odds ratios (ORs) associated with one-standard deviation differences in log-metabolites. N-acetyl-3-methylhistidine, 3-methylhistidine and 2'-deoxyuridine were elevated in men with T2 cancers compared to controls (ORs = 1.38-1.79; 0.0002 ≤ p ≤ 0.01). By contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl-linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and inositol 1-phosphate (ORs = 0.49-0.60; 0.000017 ≤ p ≤ 0.003). Secondary bile acid lipids, sex steroids and caffeine-related xanthine metabolites were elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit qualitatively different metabolite profiles years in advance of diagnosis that may represent etiologic factors, molecular patterns reflective of distinct primary tumors, or a combination of both.

  14. Prospective serum metabolomic profile of prostate cancer by size and extent of primary tumor

    PubMed Central

    Huang, Jiaqi; Mondul, Alison M.; Weinstein, Stephanie J.; Karoly, Edward D.; Sampson, Joshua N.; Albanes, Demetrius

    2017-01-01

    Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1–20). LC/MS-GC/MS identified 625 known compounds, and logistic regression estimated odds ratios (ORs) associated with one-standard deviation differences in log-metabolites. N-acetyl-3-methylhistidine, 3-methylhistidine and 2′-deoxyuridine were elevated in men with T2 cancers compared to controls (ORs = 1.38–1.79; 0.0002 ≤ p ≤ 0.01). By contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl-linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and inositol 1-phosphate (ORs = 0.49–0.60; 0.000017 ≤ p ≤ 0.003). Secondary bile acid lipids, sex steroids and caffeine-related xanthine metabolites were elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit qualitatively different metabolite profiles years in advance of diagnosis that may represent etiologic factors, molecular patterns reflective of distinct primary tumors, or a combination of both. PMID:28423352

  15. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  16. Reducing myocardial infarct size: challenges and future opportunities

    PubMed Central

    Bulluck, Heerajnarain; Yellon, Derek M; Hausenloy, Derek J

    2016-01-01

    Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is ‘myocardial reperfusion injury’, a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies—however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury. PMID:26674987

  17. Reducing myocardial infarct size: challenges and future opportunities.

    PubMed

    Bulluck, Heerajnarain; Yellon, Derek M; Hausenloy, Derek J

    2016-03-01

    Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is 'myocardial reperfusion injury', a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies-however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury.

  18. Optimization of collimator parameters to reduce rectal dose in intensity-modulated prostate treatment planning

    SciTech Connect

    Chapek, Julie . E-mail: Julie.chapek@hci.utah.edu; Tobler, Matt; Toy, Beau J.; Lee, Christopher M.; Leavitt, Dennis D.

    2005-01-01

    The inability to avoid rectal wall irradiation has been a limiting factor in prostate cancer treatment planning. Treatment planners must not only consider the maximum dose that the rectum receives throughout a course of treatment, but also the dose that any volume of the rectum receives. As treatment planning techniques have evolved and prescription doses have escalated, limitations of rectal dose have remained an area of focus. External pelvic immobilization devices have been incorporated to aid in daily reproducibility and lessen concern for daily patient motion. Internal immobilization devices (such as the intrarectal balloon) and visualization techniques (including daily ultrasound or placement of fiducial markers) have been utilized to reduce the uncertainty of intrafractional prostate positional variation, thus allowing for minimization of treatment volumes. Despite these efforts, prostate volumes continue to abut portions of the rectum, and the necessary volume expansions continue to include portions of the anterior rectal wall within high-dose regions. The addition of collimator parameter optimization (both collimator angle and primary jaw settings) to intensity-modulated radiotherapy (IMRT) allows greater rectal sparing compared to the use of IMRT alone. We use multiple patient examples to illustrate the positive effects seen when utilizing collimator parameter optimization in conjunction with IMRT to further reduce rectal doses.

  19. Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis.

    PubMed

    Mohsenzadegan, Monireh; Madjd, Zahra; Asgari, Mojgan; Abolhasani, Maryam; Shekarabi, Mehdi; Taeb, Jaleh; Shariftabrizi, Ahmad

    2013-10-01

    New gene expressed in prostate (NGEP) is a newly diagnosed prostate-specific gene that is expressed only in normal prostate and prostate cancer cells. Discovery of tissue-specific markers may promote the development of novel targets for immunotherapy of prostate cancer. In the present study, the staining pattern and clinical significance of NGEP were evaluated in a series of prostate tissues composed of 123 prostate cancer, 19 high-grade prostatic intraepithelial neoplasia and 44 samples of benign prostate tissue included in tissue microarrays using immunohistochemistry. Our study demonstrated that NGEP localized mainly in the apical and lateral membranes and was also partially distributed in the cytoplasm of epithelial cells of normal prostate tissue. All of the examined prostate tissues expressed NGEP with a variety of intensities; the level of expression was significantly more in the benign prostate tissues compared to malignant prostate samples (P value <0.001). Among prostate adenocarcinoma samples, a significant and inverse correlation was observed between the intensity of NGEP expression and increased Gleason score (P = 0.007). Taken together, we found that NGEP protein is widely expressed in low-grade to high-grade prostate adenocarcinomas as well as benign prostate tissues, and the intensity of expression is inversely proportional to the level of malignancy. NGEP could be an attractive target for immune-based therapy of prostate cancer patients as an alternative to the conventional therapies particularly in indolent patients.

  20. A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

    SciTech Connect

    Lips, Irene M.; Gils, Carla H. van; Kotte, Alexis N.T.J.; Leerdam, Monique E. van; Franken, Stefan P.G.; Heide, Uulke A. van der; Vulpen, Marco van

    2012-06-01

    Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

  1. Cannabidiol Reduces Leukemic Cell Size – But Is It Important?

    PubMed Central

    Kalenderoglou, Nikoletta; Macpherson, Tara; Wright, Karen L.

    2017-01-01

    The anti-cancer effect of the plant-derived cannabinoid, cannabidiol, has been widely demonstrated both in vivo and in vitro. However, this body of preclinical work has not been translated into clinical use. Key issues around this failure can be related to narrow dose effects, the cell model used and incomplete efficacy. A model of acute lymphoblastic disease, the Jurkat T cell line, has been used extensively to study the cannabinoid system in the immune system and cannabinoid-induced apoptosis. Using these cells, this study sought to investigate the outcome of those remaining viable cells post-treatment with cannabidiol, both in terms of cell size and tracking any subsequent recovery. The phosphorylation status of the mammalian Target of Rapamycin (mTOR) signaling pathway and the downstream target ribosomal protein S6, were measured. The ability of cannabidiol to exert its effect on cell viability was also evaluated in physiological oxygen conditions. Cannabidiol reduced cell viability incompletely, and slowed the cell cycle with fewer cells in the G2/M phase of the cell cycle. Cannabidiol reduced phosphorylation of mTOR, PKB and S6 pathways related to survival and cell size. The remaining population of viable cells that were cultured in nutrient rich conditions post-treatment were able to proliferate, but did not recover to control cell numbers. However, the proportion of viable cells that were gated as small, increased in response to cannabidiol and normally sized cells decreased. This proportion of small cells persisted in the recovery period and did not return to basal levels. Finally, cells grown in 12% oxygen (physiological normoxia) were more resistant to cannabidiol. In conclusion, these results indicate that cannabidiol causes a reduction in cell size, which persists post-treatment. However, resistance to cannabidiol under physiological normoxia for these cells would imply that cannabidiol may not be useful in the clinic as an anti-leukemic agent. PMID

  2. Body size across the life course and prostate cancer in the Health Professionals Follow-up Study

    PubMed Central

    Möller, Elisabeth; Wilson, Kathryn M.; Batista, Julie L.; Mucci, Lorelei A.; Bälter, Katarina; Giovannucci, Edward

    2016-01-01

    Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow-up Study. We assessed adult height, body mass index (BMI) in early and middle-to-late adulthood, adult waist circumference, and body shape at age 10. With follow-up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6183 incident cases. Tallness was associated with increased risk of advanced-stage tumors, particularly fatal disease (RR=1.66, 95% CI 1.23–2.23, highest versus lowest quintile, Ptrend<0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR=0.89, 95% CI 0.80–0.98, BMI ≥26 versus 20–21.9, Ptrend=0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (Pinteraction<0.001); high BMI was inversely associated with total prostate cancer (RR=0.64, 95% CI 0.51–0.78, BMI ≥30 versus 21–22.9, Ptrend<0.001) and with non-advanced and less aggressive tumors among men ≤65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. PMID:26355806

  3. Use of CT to reduce understaging in prostatic cancer: comparison with conventional staging techniques

    SciTech Connect

    Emory, T.H.; Reinke, D.B.; Hill, A.L.; Lange, P.H.

    1983-08-01

    Thirty prostatic cancer patients were evaluated for staging purposes with both CT (18-sec scan speed) and certain commonly used conventional diagnostic tests, namely: radionuclide bone scan with correlative plain films, the prostatic fraction of the serum acid phosphatase, excretory urogram, and chest radiograph. All patients included in the study had histopathologic proof of diagnosis. CT correctly identified extracapsular prostatic cancer spread locally or in pelvic lymph nodes in 14% of patients with completely negative conventional studies. Sensitivity of extracapsular tumor spread detection increased from 41% to 59% by adding CT to the conventional studies. CT confirmed the presence of tumor spread and localized it in 43% of patients with positive conventional studies. Conventional studies were positive when tumor spread was present in 32% of patients with negative CT. CT reduces understaging when conventional tests are negative, localizes and conforms tumor spread when conventional tests are positive, but cannot demonstrate tumor spread in some patients whose conventional tests are positive and who are subsequently shown to have tumor spread histopathologically.

  4. The association between prostate size and Gleason score upgrading depends on the number of biopsy cores obtained: results from the Shared Equal Access Regional Cancer Hospital Database

    PubMed Central

    Turley, Ryan S.; Terris, Martha K.; Kane, Christopher J.; Aronson, William J.; Presti, Joseph C.; Amling, Christopher L.; Freedland, Stephen J.

    2011-01-01

    OBJECTIVE To test the hypothesis that the association between prostate size and risk of Gleason grade upgrading varies as a function of sampling. PATIENTS AND METHODS We examined the association between pathological prostate weight, prostate biopsy scheme and Gleason upgrading (Gleason ≥7 at radical prostatectomy, RP) among 646 men with biopsy Gleason 2–6 disease treated with RP between 1995 and 2007 within the Shared Equal Access Regional Cancer Hospital Database using logistic regression. In all, 204 and 442 men had a sextant (six or seven cores) or extended-core biopsy (eight or more cores), respectively. Analyses were adjusted for centre, age, surgery, preoperative prostate-specific antigen level, clinical stage, body mass index, race, and percentage of cores positive for cancer. RESULTS In all, 281 men (44%) were upgraded; a smaller prostate was positively associated with the risk of upgrading in men who had an extended-core biopsy (P < 0.001), but not among men who had a sextant biopsy (P = 0.22). The interaction between biopsy scheme and prostate size was significant (P interaction = 0.01). CONCLUSIONS These data support the hypothesis that the risk of upgrading is a function of two opposing contributions: (i) a more aggressive phenotype in smaller prostates and thus increased risk of upgrading; and (ii) more thorough sampling in smaller prostates and thus decreased risk of upgrading. When sampled more thoroughly, the phenotype association dominates and smaller prostates are linked with an increased risk of upgrading. In less thoroughly sampled prostates, these opposing factors nullify, resulting in no association between prostate size and risk of upgrading. These findings help to explain previously published disparate results of the importance of prostate size as a predictor of Gleason upgrading. PMID:18778348

  5. Prostatic Arterial Embolization with Small Sized Particles for the Treatment of Lower Urinary Tract Symptoms Due to Large Benign Prostatic Hyperplasia: Preliminary Results

    PubMed Central

    Li, Qiang; Duan, Feng; Wang, Mao-Qiang; Zhang, Guo-Dong; Yuan, Kai

    2015-01-01

    Background: The clinical failure after prostatic artery embolization (PAE) with conventional particles was relatively high, in treatment for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). We reported the results of PAE with combined polyvinyl alcohol particles 50 μm and 100 μm in size as a primary treatment in 24 patients with severe LUTS secondary to large BPH. Methods: From July 2012 to June 2014, we performed PAE in 24 patients (65–85 years, mean 74.5 years) with severe LUTS due to large BPH (≥80 cm3) and refractory to medical therapy. Embolization was performed using combination of 50 μm and 100 μm in particles size. Clinical follow-up was performed using the International Prostate Symptom Score (IPSS), quality of life (QoL), peak urinary flow (Qmax), postvoid residual (PVR) volume, the International Index of Erectile Function (IIEF), prostatic specific antigen (PSA), and prostatic volume measured by magnetic resonance imaging at 1, 3, 6, and every 6-month thereafter. Technical success was defined when PAE was completed in at least one pelvic side. Clinical success was defined as the improvement of both symptoms and QoL. A Student's t-test for paired samples was used. Results: PAE was technically successful in 22 patients (92%). Bilateral PAE was performed in 19 (86%) patients and unilateral in 3 (14%) patients. Follow-up data were available for 22 patients observed for mean of 14 months. The clinical improvement at 1, 3, 6, and 12-month was 91%, 91%, 88%, and 83%, respectively. At 6-month follow-up, the mean IPSS, QoL, PVR, and Qmax were from 27 to 8 (P = 0.001), from 4.5 to 2.0 (P = 0.002), from 140.0 ml to 55.0 ml (P = 0.002), and from 6.0 ml/s to 13.0 ml/s (P = 0.001), respectively. The mean prostate volume decreased from 110 cm3 to 67.0 cm3 (mean reduction of 39.1%; P = 0.001). The PSA and IIEF improvements after PAE did not differ from pre-PAE significantly. No major adverse events were noted. Conclusions: The

  6. Prostate Diseases

    MedlinePlus

    The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine away from ... and out of the body. A young man's prostate is about the size of a walnut. It ...

  7. Selective detection of histologically aggressive prostate cancer: an Early Detection Research Network Prediction model to reduce unnecessary prostate biopsies with validation in the Prostate Cancer Prevention Trial.

    PubMed

    Williams, Stephen B; Salami, Simpa; Regan, Meredith M; Ankerst, Donna P; Wei, John T; Rubin, Mark A; Thompson, Ian M; Sanda, Martin G

    2012-05-15

    Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy. Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model. The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P < .001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P < .01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (<10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD >0.1 ng/mL/cc or abnormal DRE. When PSAD is <0.1 ng/mL/cc, family history or obesity can identify biopsy candidates. A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer. Copyright © 2011 American Cancer Society.

  8. The effectiveness of reducing the daily dose of finasteride in men with benign prostatic hyperplasia

    PubMed Central

    Sullivan, Michael J; Geller, Jack

    2002-01-01

    Background Finasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have show effectiveness with lower doses. The objective of the current study was to determine in men with benign prostatic hyperplasia, previously treated for at least one year with finasteride 5 mg daily, if they will maintain subjective and objective improvements in urinary obstruction when treated with 2.5 mg of finasteride daily for one year. Methods In an open label, prospective study, 40 men with benign prostatic hyperplasia, previously treated for at least one year with 5 mg of finasteride, took 2.5 mg of finasteride daily for one year. Measurements included AUA symptom score, maximum flow rate, voided volume and PSA. Results There were no significant changes in maximum flow rate, voided volume, or AUA symptom score after one year of finasteride 2.5 mg daily therapy. PSA increased significantly, p < .01, after one year of finasteride 2.5 mg daily, 2.0 +1.4 ng/ml, when compared to finasteride 5 mg daily, 1.4+ 1.0 ng/ml. Conclusions The daily dose of finasteride can be reduced to 2.5 mg daily without significant effect on subjective and objective measures of urinary obstruction. Although statistically significant increases in PSA are noted when reducing the daily finasteride dose from 5 mg to 2.5 mg, the clinical significance of a mean .6 ng/ml increase in PSA is questionable. PMID:11818031

  9. Diet, body size, physical activity and risk of prostate cancer: An umbrella review of the evidence.

    PubMed

    Markozannes, Georgios; Tzoulaki, Ioanna; Karli, Dimitra; Evangelou, Evangelos; Ntzani, Evangelia; Gunter, Marc J; Norat, Teresa; Ioannidis, John P; Tsilidis, Konstantinos K

    2016-12-01

    The existing literature on the relationship between diet, body size, physical activity and prostate cancer risk was summarised by the World Cancer Research Fund Continuous Update Project (CUP). An evaluation of the robustness of this evidence is required to help inform public health policy. The robustness of this evidence was evaluated using several criteria addressing evidence strength and validity, including the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, number of prostate cancer cases, between-study heterogeneity, 95% prediction intervals, small-study effects bias, excess significance bias and sensitivity analyses with credibility ceilings. A total of 248 meta-analyses were extracted from the CUP, which studied associations of 23 foods, 31 nutrients, eight indices of body size and three indices of physical activity with risk of total prostate cancer development, mortality or cancer development by stage and grade. Of the 176 meta-analyses using a continuous scale to measure the exposures, no association presented strong evidence by satisfying all the aforementioned criteria. Only the association of height with total prostate cancer incidence and mortality presented highly suggestive evidence with a 4% higher risk per 5 cm greater height (95% confidence interval, 1.03, 1.05). Associations for body mass index, weight, height, dietary calcium and spirits intake were supported by suggestive evidence. Overall, the association of diet, body size, physical activity and prostate cancer has been extensively studied, but no association was graded with strong evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Division of aperture to reduce the focus spot size

    NASA Astrophysics Data System (ADS)

    Li, Liangyu; Li, Changchun; Yang, Huajun; Li, Yinzhu; Dai, Yaping; Xie, Hu; Wang, Gongyu; Zhu, Jianqiang

    2000-10-01

    In the investigation of Inertial Confinement Fusion (ICF), the high power laser beam must be focused on the target (focus plane) given. In the ICF indirect drivers, the target fixed in a cavity is cylinderal, there are the Deuterium and the Tritium in the target, the experiment result relatives with the temperature radiated in the cavity, and the temperature relatives with the laser energy power incided. Thus, it is key that there must be enough of energy incided, and the energy runs out barely. So, to increase the laser energy incided, the focus spot should be very small. Base on the design of focus optical systems of the SHENGUANG serial facilities and the theory analyses, as the diffraction of the light, the laser beam passing through the optical systems gets a spot on the focus plane. In order to reduce the edge of the main spot or the focus spot size, we advance a method of dividing aperture of the focusing optical system, the diffraction theory of light shows that the diffraction main spot is reduced, it indicates that the method of dividing the aperture may be recommended.

  11. Chronic baseline prostate inflammation is associated with lower tumor volume in men with prostate cancer on repeat biopsy: Results from the REDUCE study.

    PubMed

    Moreira, Daniel M; Nickel, J Curtis; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2015-09-01

    To evaluate whether baseline acute and chronic prostate inflammation among men with initial negative biopsy for prostate cancer (PC) is associated with PC volume at the 2-year repeat prostate biopsy in a clinical trial with systematic biopsies. Retrospective analysis of 886 men with negative baseline prostate biopsy and positive 2-year repeat biopsy in the Reduction by Dutasteride of PC Events (REDUCE) study. Acute and chronic inflammation and tumor volume were determined by central pathology. The association of baseline inflammation with 2-year repeat biopsy cancer volume was evaluated with linear and Poisson regressions controlling for demographics and laboratory variables. Chronic, acute inflammation, and both were detected in 531 (60%), 12 (1%), and 84 (9%) baseline biopsies, respectively. Acute and chronic inflammation were significantly associated with each other (P < 0.001). Chronic inflammation was associated with larger prostate (P < 0.001) and lower pre-repeat biopsy PSA (P = 0.01). At 2-year biopsy, baseline chronic inflammation was associated with lower mean tumor volume (2.07 µl vs. 3.15 µl; P = 0.001), number of biopsy cores involved (1.78 vs. 2.19; P < 0.001), percent of cores involved (17.8% vs. 22.8%; P < 0.001), core involvement (0.21 µl vs. 0.31 µl; P < 0.001), and overall percent tumor involvement (1.40% vs. 2.01%; P < 0.001). Results were unchanged in multivariable analysis. Baseline acute inflammation was not associated with any tumor volume measurement. In a cohort of men with 2-year repeat prostate biopsy positive for PC after a negative baseline biopsy, baseline chronic inflammation was associated with lower PC volume. © 2015 Wiley Periodicals, Inc.

  12. [Administration of oral vitaprost for prevention of exacerbations of chronic abacterial prostatitis].

    PubMed

    Lopatkin, N A; Kamalov, A A; Mazo, E B; Dorofeev, S D; Efremov, E A; Kozdoba, A S; Popov, S V; Mel'nik, Ia I; Okhobotov, D A

    2009-01-01

    Active substance of vitaprost is a complex of water-soluble biologically active peptides isolated from bovine prostate. The prostatic extract has an organotropic action in relation to the prostate. As all peptide bioregulators, prostatic extract has antiaggregant and anticoagulant properties, enhances synthesis of antihistamine and antiserotonine antibodies, improves microcirculation in the prostatic gland. This accounts for its ability to reduce edema in prostatic inflammation. This clinical trial demonstrated that vitaprost tablets decreases twice probability of chronic prostatitis exacerbation, of development of secondary exacerbations. A prophylactic intake of vitaprost relieves symptoms of chronic prostatitis, first of all pain (discomfort), improvement of quality of life by NIH-CPSI, including exacerbation and significantly reduces size of the prostate. Vitaprost tablets can be effectively used prophylactively in chronic prostatitis for reducing probability of the disease exacerbations and their severity.

  13. HIV-1 enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma.

    PubMed

    Martellini, Julie A; Cole, Amy L; Svoboda, Pavel; Stuchlik, Olga; Chen, Li-Mei; Chai, Karl X; Gangrade, Bhushan K; Sørensen, Ole E; Pohl, Jan; Cole, Alexander M

    2011-01-20

    We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called "SEVI" and enhance HIV-1 infection in vitro. In order to understand the biological consequence of this proviral effect, we extended these studies in the presence of human SP. PAP-derived peptides were agitated to form SEVI and incubated in the presence or absence of SP. While PAP-derived peptides and SEVI alone were proviral, the presence of 1% SP ablated their proviral activity in several different anti-HIV-1 assays. The anti-HIV-1 activity of SP was concentration dependent and was reduced following filtration. Supraphysiological concentrations of PAP peptides and SEVI incubated with diluted SP were degraded within hours, with SP exhibiting proteolytic activity at dilutions as high as 1:200. Sub-physiological concentrations of two prominent proteases of SP, prostate-specific antigen (PSA) and matriptase, could degrade physiological and supraphysiological concentrations of PAP peptides and SEVI. While human SP is a complex biological fluid, containing both antiviral and proviral factors, our results suggest that PAP peptides and SEVI may be subject to naturally occurring proteolytic components capable of reducing their proviral activity.

  14. HIV-1 Enhancing Effect of Prostatic Acid Phosphatase Peptides Is Reduced in Human Seminal Plasma

    PubMed Central

    Martellini, Julie A.; Cole, Amy L.; Svoboda, Pavel; Stuchlik, Olga; Chen, Li-Mei; Chai, Karl X.; Gangrade, Bhushan K.; Sørensen, Ole E.; Pohl, Jan; Cole, Alexander M.

    2011-01-01

    We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called “SEVI” and enhance HIV-1 infection in vitro. In order to understand the biological consequence of this proviral effect, we extended these studies in the presence of human SP. PAP-derived peptides were agitated to form SEVI and incubated in the presence or absence of SP. While PAP-derived peptides and SEVI alone were proviral, the presence of 1% SP ablated their proviral activity in several different anti-HIV-1 assays. The anti-HIV-1 activity of SP was concentration dependent and was reduced following filtration. Supraphysiological concentrations of PAP peptides and SEVI incubated with diluted SP were degraded within hours, with SP exhibiting proteolytic activity at dilutions as high as 1∶200. Sub-physiological concentrations of two prominent proteases of SP, prostate-specific antigen (PSA) and matriptase, could degrade physiological and supraphysiological concentrations of PAP peptides and SEVI. While human SP is a complex biological fluid, containing both antiviral and proviral factors, our results suggest that PAP peptides and SEVI may be subject to naturally occurring proteolytic components capable of reducing their proviral activity. PMID:21283773

  15. Radiobiological Impact of Reduced Margins and Treatment Technique for Prostate Cancer in Terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)

    SciTech Connect

    Jensen, Ingelise; Carl, Jesper; Lund, Bente; Larsen, Erik H.; Nielsen, Jane

    2011-07-01

    Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on the Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications.

  16. Role of Intensity-Modulated Radiotherapy in Reducing Toxicity in Dose Escalation for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Heemsbergen, Wilma D.; Peeters, Stephanie T.H.; Lebesque, Joos V.

    2009-03-01

    Purpose: To compare the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated to a total dose of 78 Gy with either a three-conformal radiotherapy technique with a sequential boost (SEQ) or a simultaneous integrated boost using intensity-modulated radiotherapy (SIB-IMRT). Patients and Methods: A total of 78 prostate cancer patients participating in the randomized Dutch trial comparing 68 Gy and 78 Gy were the subject of this analysis. They were all treated at the same institution to a total dose of 78 Gy. The median follow-up was 76 and 56 months for the SEQ and SIB-IMRT groups, respectively. The primary endpoints were acute and late GI and GU toxicity. Results: A significantly lower incidence of acute Grade 2 or greater GI toxicity occurred in patients treated with SIB-IMRT compared with SEQ (20% vs. 61%, p = 0.001). For acute GU toxicity and late GI and GU toxicity, the incidence was lower after SIB-IMRT, but these differences were not statistically significant. No statistically significant difference were found in the 5-year freedom from biochemical failure rate (Phoenix definition) between the two groups (70% for the SIB-IMRT group vs. 61% for the SEQ group, p = 0.3). The same was true for the 5-year freedom from clinical failure rate (90% vs. 72%, p = 0.07). Conclusion: The results of our study have shown that SIB-IMRT reduced the toxicity without compromising the outcome in patients with localized prostate cancer treated to 78 Gy radiation.

  17. The Effect of a Pure Anti-inflammatory Therapy on Reducing Prostate-specific Antigen Levels in Patients Diagnosed With a Histologic Prostatitis.

    PubMed

    Gallo, Luigi

    2016-08-01

    To investigate the effectiveness and the tolerability of a combined pure anti-inflammatory therapy not associated with antibiotics on reducing PSA levels. Patients with a previous biopsy negative for prostate cancer and showing persisting level of prostate-specific antigen (PSA) greater than 4 ng/dl were recruited. The specimens of previous biopsy were classified as benign or showing inflammation. Eligible patients were divided into 2 equal groups. In group 1, men with histological findings of inflammation at the previous prostatic biopsy were selected, in group 2, patients without such findings were included. Men of both groups were treated for 3 months with the same pure anti-inflammatory scheme including nimesulide, Serenoa repens, bromelain, and quercetin. After treatment, PSA levels were determined again. Independently by the second PSA determinations, all patients underwent a second 16 core biopsy. A total of 140 patients were enrolled. No adverse reactions were reported. Total PSA lowered from 7.3 ng/mL at baseline to 4.6 ng/mL (P <.0001) after treatment in group 1, and from 7.2 ng/mL to 7 ng/mL (P = .0005) in group 2. Overall, we diagnosed a prostate cancer at the second biopsy in 27 men among 140 (19.2%). The percentage of cancer at re-biopsy was 20% (14 of 70) in group 1 and 18.5% (13 of 70) in group 2. We found no cancer at the second biopsy in cases of PSA reduction below 4 ng/mL in both groups. Our protocol was very effective and safe in reducing PSA levels. The second biopsy failed to show prostate cancer in all patients with PSA lower than 4 ng/mL. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Polyamine-reduced diet in metastatic hormone-refractory prostate cancer (HRPC) patients.

    PubMed

    Cipolla, B; Guillí, F; Moulinoux, J-P

    2003-04-01

    Polyamine (PA) deprivation is effective in prostate carcinoma models. We have assessed the observance by patients, tolerance and side effects of a PA-reduced diet (PRD) and intestinal decontamination (ID), in order to reduce PA dietary and intestinal bacterial pools, in metastatic, hormone-refractory prostate cancer (HRPC) patients. A total of 13 volunteers (mean age, 67+/-10 years) with metastatic HRPC were proposed for PRD and ID (0.75 g/day of oral neomycin every other week). The mean time from HRPC diagnosis to the start of the diet was 12+/-8 months. Of the total 13, seven patients had received prior chemotherapy or Estramustine phosphate. PRD was obtained after HPLC assessment of PA contents in current foods and given 5 days a week. Toxicity, performance and pain status were assessed according to the World Health Organisation and EORTC scales. Prostatic specific antigen (PSA), blood counts, ionograms, transaminases and erythrocyte PA spermidine (Spd) and spermine (Spm; assessed by HPLC) were evaluated regularly. Mean observance was 8+/-7 months (range, 2-26 months). One case of grade II toxicity to neomycin was observed. Cancer-specific survival (after the diet) was 14+/-7 months, and two patients are still alive. All the other patients have died of their cancer at 12+/-6 months (range, 4-20 months). Cancer-specific survival after hormonal escape was 27+/-11 months (range, 9-45 months). Performance status was improved during the regimen and deteriorated 3 months after stopping. Pain score was improved (1.3 versus 0.6; P =0.04) during the diet and increased (2.1 versus 0.3) 3 months after stopping. Erythrocyte Spd (11.6+/-7 versus 7.7+/-2 nmol/8 x 10(9) erythrocytes; P =0.036) and Spm (7+/-6 versus 3.9+/-1.6 nmol/8 x 10(9) erythrocytes; P =0.036) levels were significantly reduced at 3 months. One patient had a >50% reduction in PSA, three patients had PSA stabilization for 6 months. PSA progression was observed in all other patients. No significant

  19. The ability of winter grazing to reduce wildfire size, intensity ...

    EPA Pesticide Factsheets

    A recent study by Davies et al. sought to test whether winter grazing could reduce wildfire size, fire behavior metrics, and fire-induced plant mortality in shrub-grasslands. The authors concluded that ungrazed rangelands may experience more fire-induced mortality of native perennial bunchgrasses. The authors also presented several statements regarding the benefits of winter grazing on post-fire plant community responses. However, this commentary will show that the study by Davies et al. has underlying methodological flaws, lacks data necessary to support their conclusions, and does not provide an accurate discussion on the effect of grazing on rangeland ecosystems. Importantly, Davies et al. presented no data on the post-fire mortality of the perennial bunchgrasses or on the changes in plant community composition following their experimental fires. Rather, Davies et al. inferred these conclusions based off their observed fire behavior metrics of maximum temperature and a term described as the “heat load”. However, neither metric is appropriate for elucidating the heat flux impacts on plants. This lack of post-fire data, several methodological flaws, and the use of inadequate metrics describing heat cast doubts on the authors’ ability to support their stated conclusions. This article is a commentary highlights the scientific shortcomings in a forthcoming paper by Davies et al. in the International Journal of Wildland Fire. The study has methodological flaw

  20. Tunable Reduced Size Planar Folded Slot Antenna Utilizing Varactor Diodes

    NASA Technical Reports Server (NTRS)

    Scardelletti, Maximilian C.; Ponchak, George E.; Jordan, Jennifer L.; Jastram, Nathan; Mahaffey, Joshua V.

    2010-01-01

    A tunable folded slot antenna that utilizes varactor diodes is presented. The antenna is fabricated on Rogers 6006 Duriod with a dielectric constant and thickness of 6.15 and 635 m, respectively. A copper cladding layer of 17 m defines the antenna on the top side (no ground on backside). The antenna is fed with a CPW 50 (Omega) feed line, has a center frequency of 3 GHz, and incorporates Micrometrics microwave hyper-abrupt 500MHV varactors to tune the resonant frequency. The varactors have a capacitance range of 2.52 pF at 0 V to 0.4 pF at 20 V; they are placed across the radiating slot of the antenna. The tunable 10 dB bandwidth of the 3 GHz antenna is 150 MHz. The varactors also reduce the size of the antenna by 30% by capacitively loading the resonating slot line. At the center frequency, 3 GHz, the antenna has a measured return loss of 44 dB and a gain of 1.6 dBi. Full-wave electromagnetic simulations using HFSS are presented that validate the measured data. Index Terms capacitive loading, Duriod, folded slot antenna, varactor.

  1. The ability of winter grazing to reduce wildfire size, intensity ...

    EPA Pesticide Factsheets

    A recent study by Davies et al. sought to test whether winter grazing could reduce wildfire size, fire behavior metrics, and fire-induced plant mortality in shrub-grasslands. The authors concluded that ungrazed rangelands may experience more fire-induced mortality of native perennial bunchgrasses. The authors also presented several statements regarding the benefits of winter grazing on post-fire plant community responses. However, this commentary will show that the study by Davies et al. has underlying methodological flaws, lacks data necessary to support their conclusions, and does not provide an accurate discussion on the effect of grazing on rangeland ecosystems. Importantly, Davies et al. presented no data on the post-fire mortality of the perennial bunchgrasses or on the changes in plant community composition following their experimental fires. Rather, Davies et al. inferred these conclusions based off their observed fire behavior metrics of maximum temperature and a term described as the “heat load”. However, neither metric is appropriate for elucidating the heat flux impacts on plants. This lack of post-fire data, several methodological flaws, and the use of inadequate metrics describing heat cast doubts on the authors’ ability to support their stated conclusions. This article is a commentary highlights the scientific shortcomings in a forthcoming paper by Davies et al. in the International Journal of Wildland Fire. The study has methodological flaw

  2. Baseline subject characteristics predictive of compliance with study-mandated prostate biopsy in men at risk of prostate cancer: results from REDUCE.

    PubMed

    Fischer, S; Sun, S; Howard, L E; Moreira, D M; Castro-Santamaria, R; Andriole, G L; Vidal, A C; Freedland, S J

    2016-06-01

    Study compliance is crucial when the study outcome is determined by an invasive procedure, such as prostate biopsy. To investigate predictors of compliance in study-mandated prostate biopsies, we analyzed demographic, clinical and reported lifestyle data from the REDUCE trial. We retrospectively identified 8025 men from REDUCE with at least 2 years of follow-up, and used multivariable logistic regression to test the association between baseline demographic and clinical characteristics and undergoing the study-mandated prostate biopsy at 2 years. We then examined whether missing any of these data was associated with undergoing a biopsy. In REDUCE, 22% of men did not undergo a 2-year biopsy. On multivariable analysis, the non-North American region was predictive of 42-44% increased likelihood of undergoing a 2-year biopsy (P⩽0.001). Being enrolled at a center that enrolled >10 subjects (2nd and 3rd tertile) was associated with a 42-48% increased likelihood of undergoing a 2-year biopsy (P<0.001). In addition, black race predicted 44% lower rate of on-study 2-year biopsy (odds ratio (OR)=0.56; P=0.001). Finally, missing one or more baseline variables was associated with a 32% decreased likelihood of undergoing a 2-year biopsy (OR=0.68; P<0.001). In REDUCE, men outside North America, those at higher volume centers and those with complete baseline data were more likely to undergo study-mandated 2-year biopsies. Given prostate biopsy is becoming increasingly utilized as an endpoint in trials that are often multi-national, regional differences in compliance should be considered when designing future trials. Likewise, efforts are needed to ensure compliance in low-volume centers or among subjects missing baseline data.

  3. Baseline Subject Characteristics Predictive of Compliance with Study-Mandated Prostate Biopsy in Men at Risk of Prostate Cancer: Results from REDUCE

    PubMed Central

    Fischer, Sean; Sun, Stephanie; Howard, Lauren E.; Moreira, Daniel M.; Castro-Santamaria, Ramiro; Andriole, Gerald L.; Vidal, Adriana C.; Freedland, Stephen J.

    2015-01-01

    Introduction Study compliance is crucial when the study outcome is determined by an invasive procedure, such as prostate biopsy. To investigate predictors of compliance in study-mandated prostate biopsies, we analyzed demographic, clinical and reported lifestyle data from the REDUCE trial. Methods We retrospectively identified 8,025 men from REDUCE with at least 2-years of follow-up, and used multivariable logistic regression to test the association between baseline demographic and clinical characteristics and undergoing the study-mandated prostate biopsy at 2 years. We then examined whether missing any of these data was associated with undergoing a biopsy Results In REDUCE, 22% of men did not undergo a 2-year biopsy. On multivariable analysis, non-North American region was predictive of 42-44% increased likelihood of undergoing a 2-year biopsy (p≤0.001). Being enrolled at a center that enrolled >10 subjects (2nd and 3rd tertile) was associated with a 42-48% increased likelihood of undergoing a 2-year biopsy (p<0.001). Additionally, black race predicted 44% lower rate of on-study 2-year biopsy (OR=0.56; p=0.001). Finally, missing one or more baseline variables was associated with a 32% decreased likelihood of undergoing a 2-year biopsy (OR=0.68; p<0.001). Conclusions In REDUCE, men outside North America, those at higher volume centers, and those with complete baseline data were more likely to undergo study mandated 2-year biopsies. Given prostate biopsy is becoming increasingly utilized as an endpoint in trials that are often multi-national, regional differences in compliance should be considered when designing future trials. Likewise, efforts are needed to ensure compliance in low-volume centers or among subjects missing baseline data. PMID:26926927

  4. Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

    PubMed Central

    Yeung, Bonnie H. Y.; Shek, Felix H.; Lee, Nikki P.; Wong, Chris K. C.

    2015-01-01

    Growing evidence has revealed high expression levels of stanniocalcin-1 (STC1) in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC) an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL)-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal ≥ 2) were significantly smaller than the lower level (tumor/normal<2) samples (p = 0.008). A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 overexpression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients. PMID:26469082

  5. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production.

    PubMed Central

    Sharpe, R M; Fisher, J S; Millar, M M; Jobling, S; Sumpter, J P

    1995-01-01

    This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body, weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the

  6. Obesity Increases the Risk for High-grade Prostate Cancer: Results from the REDUCE study

    PubMed Central

    Vidal, Adriana C.; Howard, Lauren E.; Moreira, Daniel M.; Castro-Santamaria, Ramiro; Andriole, Gerald L.; Freedland, Stephen J.

    2014-01-01

    Background Studies suggest obesity is associated with lower risk of prostate cancer (PC) but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade PC in REDUCE, where biopsies were largely independent of PSA. Methods The REDUCE study tested dutasteride for PC risk reduction in men with a PSA of 2.5–10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI <25 kg/m2-normal weight; 25–29.9 kg/m2-overweight; ≥30 kg/m2-obese) and risk of high-grade (Gleason ≥7) or low-grade PC (Gleason <7) vs. no PC was examined using multinomial logistic regression. Results Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of low-grade PC in both univariable (OR 0.74, p=0.001) and multivariable analyses (OR 0.79, p=0.01). In univariable analysis, obesity was not associated with high-grade PC (OR 1.08, p=0.50). However, in multivariable analysis, obesity was associated with increased risk of high-grade PC (OR 1.28, p=0.042). The current analysis was not able to address how obesity may influence prostate cancer progression. Conclusions Obesity is associated with decreased risk of low-grade and increased risk of high-grade PC. These data provide further support to the hypothesis that obesity is associated with aggressive PC. Impact Obesity is linked with aggressive PC. Avoiding obesity may prevent the risk of developing high-grade PC. PMID:25261967

  7. [Treatment of prostatic adenoma with concomitant chronic bacterial prostatitis].

    PubMed

    Davidov, M I

    2011-01-01

    A randomized trial of efficacy and safety of vitaprost plus and vitaprost forte has been made in 70 patients with prostatic adenoma comorbid with chronic bacterial prostatitis. The patients were randomized into two groups: group 1 patients received vitaprost plus in rectal suppositoria for 1 months, then vitaprost forte for 2 months; group 2 patients (control) received gentos and lomefloxacin per os. Short- and long-term results were evaluated in 3 and 6 months. By all parameters group 1 achieved better treatment results than controls. Immediate positive response was observed in 97.1% patients, long-term positive effects were observed in 85.7%. Total points of prostatic adenoma symptoms reduced by 37%, chronic prostatitis--by 55%, residual urine diminished by 66%, Qmax increased, quality of life improved by 45%, sexual function enhanced. Size of the prostate decreased by 7.4 cm3, leukocyte count in prostatic secretion fell 6-fold, eradication of prostatitis causing agent was achieved in 3 months in 80% patients. Side effects and complications were not registered. Thus, vitaprost plus and vitaprost forte are highly effective and safe for treatment of patients with combination of prostatic adenoma with chronic bacterial prostatitis.

  8. Results of a comparative analysis of magnetic resonance imaging-targeted versus three-dimensional transrectal ultrasound prostate biopsies: Size does matter.

    PubMed

    Peltier, Alexandre; Aoun, Fouad; Albisinni, Simone; Marcelis, Quentin; Ledinh, Dam; Paesmans, Marianne; Lemort, Marc; van Velthoven, Roland

    2016-06-01

    The aim of this study was to compare the detection rate of clinically significant disease in magnetic resonance imaging (MRI)-targeted biopsies versus three-dimensional transrectal ultrasound (3D TRUS)-guided biopsies according to prostate size. The study compared 120 consecutive biopsy-naïve men who underwent 3D TRUS-guided systematic biopsy to 120 consecutive men who underwent MRI-targeted biopsy. Stratifications based on tertiles were used for assessing interactions between prostate volume and rates of detection of significant cancer. Older age, higher prostate-specific antigen level, lower prostate volume, increased number of cores and MRI-targeted biopsy were independent predictors of prostate cancer detection in the entire cohort on logistic regression. Clinically significant cancer detection rates were significantly higher in the MRI-targeted group than in the 3D TRUS-guided biopsy group (48.7% vs 29.4%, p = 0.002). When stratified according to prostate volume, these rates were significantly higher only in the third tertile group (volume > 50 cm(3)) for MRI-targeted biopsy compared to 3D TRUS-guided biopsy (56% vs 22%, p = 0.003). MRI-targeted biopsies increased the detection rate of clinically significant prostate cancer only in patients with enlarged prostates compared to the 3D TRUS.

  9. Resistance Exercise Reduces Body Fat and Insulin During Androgen-Deprivation Therapy for Prostate Cancer.

    PubMed

    Winters-Stone, Kerri M; Dieckmann, Nathan; Maddalozzo, Gianni F; Bennett, Jill A; Ryan, Christopher W; Beer, Tomasz M

    2015-07-01

    To determine whether exercise could reduce biomarkers of cancer progression in prostate cancer survivors (PCSs) on androgen-deprivation therapy (ADT). Randomized, controlled trial. Oregon Health and Science University School of Nursing. 51 PCSs randomized to one year of resistance and impact training or a stretching control group. The authors investigated changes in body composition and cancer-related biomarkers, and the influence of age and fat loss on changes in biomarkers. Body composition (total fat, trunk fat, and lean mass), insulin, insulin-like growth factor-1, and sex hormone-binding globulin. In the 36 PCSs with baseline and 12-month data, total fat (p = 0.02) and trunk fat (p = 0.06) mass decreased in the training group compared to gains in controls. Loss of total and trunk fat each mediated the relationship between groups and one-year change in insulin (p < 0.05). Age moderated the insulin response to exercise where insulin reductions were smaller with increasing age (p = 0.03). Resistance and impact exercise may reduce body fat among PCSs undergoing ADT, in turn exerting an insulin-lowering effect. Nurses should counsel PCSs to exercise to reduce the risk of obesity and associated conditions, including cancer progression.

  10. Synthesis And Characterization Of Reduced Size Ferrite Reinforced Polymer Composites

    SciTech Connect

    Borah, Subasit; Bhattacharyya, Nidhi S.

    2008-04-24

    Small sized Co{sub 1-x}Ni{sub x}Fe{sub 2}O{sub 4} ferrite particles are synthesized by chemical route. The precursor materials are annealed at 400, 600 and 800 C. The crystallographic structure and phases of the samples are characterized by X-ray diffraction (XRD). The annealed ferrite samples crystallized into cubic spinel structure. Transmission Electron Microscopy (TEM) micrographs show that the average particle size of the samples are <20 nm. Particulate magneto-polymer composite materials are fabricated by reinforcing low density polyethylene (LDPE) matrix with the ferrite samples. The B-H loop study conducted at 10 kHz on the toroid shaped composite samples shows reduction in magnetic losses with decrease in size of the filler sample. Magnetic losses are detrimental for applications of ferrite at high powers. The reduction in magnetic loss shows a possible application of Co-Ni ferrites at high microwave power levels.

  11. Reducing Router Forwarding Table Size Using Aggregation and Caching

    ERIC Educational Resources Information Center

    Liu, Yaoqing

    2013-01-01

    The fast growth of global routing table size has been causing concerns that the Forwarding Information Base (FIB) will not be able to fit in existing routers' expensive line-card memory, and upgrades will lead to a higher cost for network operators and customers. FIB Aggregation, a technique that merges multiple FIB entries into one, is probably…

  12. Reducing Router Forwarding Table Size Using Aggregation and Caching

    ERIC Educational Resources Information Center

    Liu, Yaoqing

    2013-01-01

    The fast growth of global routing table size has been causing concerns that the Forwarding Information Base (FIB) will not be able to fit in existing routers' expensive line-card memory, and upgrades will lead to a higher cost for network operators and customers. FIB Aggregation, a technique that merges multiple FIB entries into one, is probably…

  13. Reducing Class Size in New York City: Promise vs. Practice

    ERIC Educational Resources Information Center

    Farrie, Danielle; Johnson, Monete; Lecker, Wendy; Luhm, Theresa

    2016-01-01

    In the landmark school funding litigation, "Campaign for Fiscal Equity v. State" ("CFE"), the highest Court in New York recognized that reasonable class sizes are an essential element of a constitutional "sound basic education." In response to the rulings in the case, in 2007, the Legislature adopted a law mandating…

  14. Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO study.

    PubMed

    Shebl, F M; Sakoda, L C; Black, A; Koshiol, J; Andriole, G L; Grubb, R; Church, T R; Chia, D; Zhou, C; Chu, L W; Huang, W-Y; Peters, U; Kirsh, V A; Chatterjee, N; Leitzmann, M F; Hayes, R B; Hsing, A W

    2012-06-26

    Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear. We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55-74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified. After adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with <1 and ≥ 1 pill of aspirin daily were 0.98 (95% confidence interval (CI), 0.90-1.07) and 0.92 (95% CI: 0.85-0.99), respectively, compared with never use (P for trend 0.04). The effect of taking at least one aspirin daily was more pronounced when restricting the analyses to men older than age 65 or men who had a history of cardiovascular-related diseases or arthritis (HR (95% CI); 0.87 (0.78-0.97), 0.89 (0.80-0.99), and 0.88 (0.78-1.00), respectively). The data did not support an association between ibuprofen use and prostate cancer risk. Daily aspirin use, but not ibuprofen use, was associated with lower risk of prostate cancer risk.

  15. On being the right size: increased body size is associated with reduced telomere length under natural conditions.

    PubMed

    Ringsby, Thor Harald; Jensen, Henrik; Pärn, Henrik; Kvalnes, Thomas; Boner, Winnie; Gillespie, Robert; Holand, Håkon; Hagen, Ingerid Julie; Rønning, Bernt; Sæther, Bernt-Erik; Monaghan, Pat

    2015-12-07

    Evolution of body size is likely to involve trade-offs between body size, growth rate and longevity. Within species, larger body size is associated with faster growth and ageing, and reduced longevity, but the cellular processes driving these relationships are poorly understood. One mechanism that might play a key role in determining optimal body size is the relationship between body size and telomere dynamics. However, we know little about how telomere length is affected when selection for larger size is imposed in natural populations. We report here on the relationship between structural body size and telomere length in wild house sparrows at the beginning and end of a selection regime for larger parent size that was imposed for 4 years in an isolated population of house sparrows. A negative relationship between fledgling size and telomere length was present at the start of the selection; this was extended when fledgling size increased under the selection regime, demonstrating a persistent covariance between structural size and telomere length. Changes in telomere dynamics, either as a correlated trait or a consequence of larger size, could reduce potential longevity and the consequent trade-offs could thereby play an important role in the evolution of optimal body size. © 2015 The Author(s).

  16. Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria

    PubMed Central

    Di Sante, Gabriele; Pestell, Timothy G.; Casimiro, Mathew C.; Bisetto, Sara; Powell, Michael J.; Lisanti, Michael P.; Cordon-Cardo, Carlos; Castillo-Martin, Mireia; Bonal, Dennis M.; Debattisti, Valentina; Chen, Ke; Wang, Liping; He, Xiaohong; McBurney, Michael W.; Pestell, Richard G.

    2016-01-01

    Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD+-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1−/− cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD+-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival. PMID:25529796

  17. Smoking Is Associated with Acute and Chronic Prostatic Inflammation: Results from the REDUCE Study.

    PubMed

    Moreira, Daniel M; Nickel, J Curtis; Gerber, Leah; Muller, Roberto L; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2015-04-01

    Both anti- and proinflammatory effects of cigarette smoking have been described. As prostate inflammation is common, we hypothesized smoking could contribute to prostate inflammation. Thus, we evaluated the association of smoking status with acute and chronic inflammation within the prostate of men undergoing prostate biopsy. We retrospectively analyzed 8,190 men ages 50 to 75 years with PSA levels between 2.5 and 10 ng/mL enrolled in the Reduction by Dutasteride of Prostate Cancer Events study. Smoking status was self-defined as never, former, or current. Prostate inflammation was assessed by systematic central review blinded to smoking status. The association of smoking with inflammation in the baseline, 2-year, and 4-year biopsies was evaluated with univariable and multivariable logistic regressions. At study enrollment, 1,233 (15%), 3,203 (39%), and 3,754 (46%) men were current, former, and never smokers, respectively. Current smokers were significantly younger and had smaller prostates than former and never smokers (all P < 0.05). Former smokers were significantly heavier than current and never smokers (P < 0.001). Acute and chronic prostate inflammations were identified in 1,261 (15%) and 6,352 (78%) baseline biopsies, respectively. In univariable analysis, current smokers were more likely to have acute inflammation than former (OR, 1.35; P, 0.001) and never smokers (OR, 1.36; P, 0.001). The results were unchanged at 2- and 4-year biopsies. In contrast, current smoking was linked with chronic inflammation in the baseline biopsy, but not at 2- and 4-year biopsies. In conclusion, among men undergoing prostate biopsy, current smoking was independently associated with acute and possibly chronic prostate inflammations.

  18. Does Flattened Sky Dome Reduces Perceived Moon Size

    NASA Astrophysics Data System (ADS)

    Toskovic, O.

    2009-09-01

    The aim of this study was to examine the Flattened sky dome model as an explanation of the Moon illusion. Two experiments were done, in a dark room, in which distribution of depth cues is the same towards horizon as towards zenith. In the first experiment 14 participants had the task to equalize the perceived distances of three stimuli in three directions (horizontal, tilted 45 degrees and vertical). In the second experiment 16 participants had the task to estimate the perceived sizes of three stimuli in the same three directions. For distance estimates we found differences among three directions in a way, that as the head tilts upwards, the perceived space is being elongated, which is the opposite to flattened sky dome. For size estimates we found no difference among the three directions.

  19. Polyamine reduced diet (PRD) nutrition therapy in hormone refractory prostate cancer patients.

    PubMed

    Cipolla, Bernard G; Havouis, René; Moulinoux, Jacques-Philippe

    2010-05-01

    Reducing polyamine uptake by selecting low polyamine-containing foodstuffs and reducing bacterial gut production can improve performance status and pain control in hormone refractory prostate cancer (HRPC) patients. Long term PRD observance and tolerance were assessed. Cancer specific survival was studied in function of PRD and time of PRD initiation. Twenty-six volunteers, age: 68+/-10 years with metastatic HRPC accepted a polyamine reduced diet and partial gut decontamination with oral neomycin or nifuroxazide (750 mg daily, one week out of two). Time from HRPC to PRD initiation was 10+/-8 months. WHO performance status, EORTC pain scale, body weight, blood counts and serum proteins were regularly assessed. Sixteen other HRPC patients eating a normal diet served as "controls". Mean diet observance is 25+/-24 months. Tolerance is good. WHO performance status and EORTC pain scales were significantly improved respectively at 3 months (0.5+/-0.7 vs 0.7+/-0.9: p=0.03) and 6 months (0.5+/-0.8 vs 1+/-1.3, p=0.02) compared to initial values. Median cancer specific survival times after HRPC and PRD initiation are respectively 36 and 21 months. Eleven PRD patients started the diet before a 9 months cut-off period (after HRPC) and 15 patients after. Median cancer specific survival times for these two groups of patients are respectively 44 and 34 months, p=0.014. Median cancer specific survival times (after HRPC) for PRD patients compared to controls are 36 vs 17 months (p=0.004). Polyamine-reduced diet is well observed and tolerated. It seems to improve and/or maintain quality of life for HRPC patients. Early PRD initiation in HRPC is promising and may impact favorably cancer specific survival. These results open a rationale for PRD in HRPC management and warrant further investigation. 2010 Elsevier Masson SAS. All rights reserved.

  20. Reduced Connexin 43 expression is associated with tumor malignant behaviors and biochemical recurrence-free survival of prostate cancer

    PubMed Central

    Xu, Ning; Chen, Hui-Jun; Chen, Shao-Hao; Xue, Xue-Yi; Chen, Hong; Zheng, Qing-Shui; Wei, Yong; Li, Xiao-Dong; Huang, Jin-Bei; Cai, Hai; Sun, Xiong-Lin

    2016-01-01

    Connexin 43, a gap junction protein, coordinates cell-to-cell communication and adhesion. Altered Connexin 43 expression associated with cancer development and progression. In this study, we assessed Connexin 43 expression for association with clinicopathological features and biochemical recurrence of prostate cancer after radical prostatectomy. Pathological specimens were collected from 243 patients who underwent radical prostatectomy and from 60 benign prostatic hyperplasia (BPH) patients to construct tissue microarrays and immunohistochemical analysis of Connexin 43 expression. Kaplan-Meier curves and multivariable Cox proportion hazard model were performed to associate Connexin 43 expression with postoperative biochemical recurrence-free survival (BFS). Connexin 43 expression was significantly reduced or lost in tumor tissues compared to that of BPHs (39.1% vs. 96.7%, P<0.001). Reduced Connexin 43 expression was associated with high levels of preoperative PSA, high Gleason score, advanced pT stage, positive surgical margin, extracapsular extension, and seminal vesicle invasion (P < 0.05, for all). Kaplan–Meier curves showed that reduced Connexin 43 expression was associated with shortened postoperative BFS (P < 0.001). Multivariate analysis showed that reduced Connexin 43 expression, high Gleason score and advanced pT stage were independent predictors for BFS of patients (P < 0.05). Connexin 43 expression was significantly reduced or lost in prostate cancer tissues, which was associated with advanced clinicopathological features and poor BFS of patients after radical prostatectomy. PMID:27623212

  1. Knockout AR in Prostate

    DTIC Science & Technology

    2006-10-01

    enlarged ventral prostates, we evaluated fertility. We found that there were no significant differences in litter-size when either WT or pes-ARKO males...prostate (DLP), ventral prostate (VP) all lobes of prostate (Pr), testes (T), glans penis (Pe); *Pɘ.05, ***Pɘ.001. PI: Chang, Chawnshang 7

  2. [Changes in prostatic circulation in response to laser therapy and magnetic therapy in patients with benign prostatic hyperplasia].

    PubMed

    2005-01-01

    The results of preoperative preparation were analysed in 59 patients with prostatic benign hyperplasia (PBH) subjected to TUR. Treatment outcomes were assessed by transrectal ultrasound (color Doppler mapping) in two groups of patients. Group 1 received combined therapy including transrectal laser radiation of the prostate, group 2--transrectal magnetotherapy. The analysis showed that laser radiation reduced insignificantly the size of the prostate and adenomatous node, improved microcirculation and circulation in the prostate. This resulted in relief of inflammation and reduction of the number of postoperative inflammatory complications. Transrectal magnetotherapy has a positive effect on vascularization and hemodynamics of the prostate, local immunity, contamination of the tissues with pathogenic flora.

  3. High Speed Gear Sized and Configured to Reduce Windage Loss

    NASA Technical Reports Server (NTRS)

    Kunz, Robert F. (Inventor); Medvitz, Richard B. (Inventor); Hill, Matthew John (Inventor)

    2013-01-01

    A gear and drive system utilizing the gear include teeth. Each of the teeth has a first side and a second side opposite the first side that extends from a body of the gear. For each tooth of the gear, a first extended portion is attached to the first side of the tooth to divert flow of fluid adjacent to the body of the gear to reduce windage losses that occur when the gear rotates. The gear may be utilized in drive systems that may have high rotational speeds, such as speeds where the tip velocities are greater than or equal to about 68 m/s. Some embodiments of the gear may also utilize teeth that also have second extended portions attached to the second sides of the teeth to divert flow of fluid adjacent to the body of the gear to reduce windage losses that occur when the gear rotates.

  4. Reduced incidence of bone metastases in irradiated areas after external radiation therapy of prostatic carcinoma

    SciTech Connect

    Jacobsson, H.; Naeslund, I. )

    1991-06-01

    Fourteen males, out of 380 patients, treated with radiation to the central pelvis and lumbar spine for poorly differentiated prostatic carcinoma were analyzed in retrospect. The dose of radiation to the bones of the target area was 5,000 cGy. The patients showed no signs of metastases at bone scintigraphy performed in connection with the treatment. In an average of 34 months after finishing radiotherapy, the patients developed metastases at bone scintigraphy. The pattern was similar in all patients. The treated target area appeared as a cold zone surrounded by more or less homogenously and strongly increased activity of the axial skeleton, characteristic of bone metastases. Radiography, which was performed in 11 patients, confirmed widespread metastatic disease sparing the target area. This was interpretated as bone metastasis being precluded by the irradiation. The most probable explanation of this finding is eradication in situ of distant micrometastases already present in the bone marrow at the time of treatment. An alternate explanation is a reduced implantation of later seeded blood-born metastases as an effect of the irradiation. The characteristic pattern of this phenomenon must be recognized at bone scintigraphy.

  5. Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia.

    PubMed

    Gonzales, C; Leiva-Revilla, J; Rubio, J; Gasco, M; Gonzales, G F

    2012-05-01

    Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca.

  6. Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

    Cancer.gov

    The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a randomi

  7. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  8. Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO Study

    PubMed Central

    Shebl, F M; Sakoda, L C; Black, A; Koshiol, J; Andriole, G L; Grubb, R; Church, T R; Chia, D; Zhou, C; Chu, L W; Huang, W-Y; Peters, U; Kirsh, V A; Chatterjee, N; Leitzmann, M F; Hayes, R B; Hsing, A W

    2012-01-01

    Background: Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear. Methods: We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55–74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified. Results: After adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with <1 and ⩾1 pill of aspirin daily were 0.98 (95% confidence interval (CI), 0.90–1.07) and 0.92 (95% CI: 0.85–0.99), respectively, compared with never use (P for trend 0.04). The effect of taking at least one aspirin daily was more pronounced when restricting the analyses to men older than age 65 or men who had a history of cardiovascular-related diseases or arthritis (HR (95% CI); 0.87 (0.78–0.97), 0.89 (0.80–0.99), and 0.88 (0.78–1.00), respectively). The data did not support an association between ibuprofen use and prostate cancer risk. Conclusion: Daily aspirin use, but not ibuprofen use, was associated with lower risk of prostate cancer risk. PMID:22722313

  9. Testing new submersible pumps for proper sizing and reduced costs

    SciTech Connect

    O'Toole, W.P.; O'Brien, J.B.

    1986-01-01

    This paper describes an ongoing program to improve overall submersible pump performance by Thums Long Beach Company, acting as Contractor of the City of Long Beach, Operator of the Long Beach Unit. Thums Long Beach Company currently operates 700 submersible pump installations located on four man-made islands and one land fill pier location. The program began with spot testing of submersible pumps for Thums' use. It has evolved to 100 percent pump testing and the stipulation that only pumps with newly manufactured parts are acceptable. The primary goals of this program are to increase well production and lower lifting costs. Critical to these goals is increasing the average length of run by using accurate pump performance data to design equipment and by rejecting defective pumps before they are run. Increased production is realized from better designs. Lower lifting costs result from utilizing higher efficiency pumps and a reduced frequency of pulling submersible equipment.

  10. Testing new submersible pumps for proper sizing and reduced costs

    SciTech Connect

    O'Toole, W.P.; O'Brien, J.B.

    1989-02-01

    This paper describes an ongoing program to improve overall submersible pump performance by Thums Long Beach Co., acting as contractor for the City of Long Beach, operator of the Long Beach Unit. Thums Long Beach Co. currently operates 700 submersible pump installations located on four manmade islands and one landfill pier location. The program began with spot testing of submersible pumps for Thums' use. It has evolved to 100% pump testing and the stipulation that only pumps with newly manufactured parts are acceptable. The primary goals of this program are to increase well production and to lower lifting costs. Critical to these goals is increasing the average length of run by using accurate pump-performance data to design equipment and by rejecting defective pumps before they are run. Increased production is realized from better designs. Lower lifting costs result from using more efficient pumps and a reduced frequency of pulling submersible equipment.

  11. Encountering competitors reduces clutch size and increases offspring size in a parasitoid with female–female fighting

    PubMed Central

    Goubault, Marlène; Mack, Alexandra F.S; Hardy, Ian C.W

    2007-01-01

    Understanding the size of clutches produced by only one parent may require a game-theoretic approach: clutch size may affect offspring fitness in terms of future competitive ability. If larger clutches generate smaller offspring and larger adults are more successful in acquiring and retaining resources, clutch size optima should be reduced when the probability of future competitive encounters is higher. We test this using Goniozus nephantidis, a gregarious parasitoid wasp in which the assumption of size-dependent resource acquisition is met via female–female contests for hosts. As predicted, smaller clutches are produced by mothers experiencing competition, due to fewer eggs being matured and to a reduced proportion of matured eggs being laid. As assumed, smaller clutches generate fewer but larger offspring. We believe this is the first direct evidence for pre-ovipositional and game-theoretic clutch size adjustment in response to an intergenerational fitness effect when clutches are produced by a single individual. PMID:17698482

  12. A Cinematic Magnetic Resonance Imaging Study of Milk of Magnesia Laxative and an Antiflatulent Diet to Reduce Intrafraction Prostate Motion

    SciTech Connect

    Nichol, Alan M.; Warde, Padraig R.; Lockwood, Gina A.

    2010-07-15

    Purpose: To determine the reduction of prostate motion during a typical radiotherapy (RT) fraction from a bowel regimen comprising an antiflatulent diet and daily milk of magnesia. Methods and Materials: Forty-two patients with T1c-T2c prostate cancer voided the bladder and rectum before three cinematic magnetic resonance imaging scans obtained every 9 s for 9 min in a vacuum immobilization device. The MRIs were at baseline without bowel regimen (MRI-BL), before CT planning with bowel regimen (MRI-CT), and before a randomly assigned RT fraction (1-42) with bowel regimen (MRI-RT). A single observer tracked displacement of the posterior midpoint (PM) of the prostate. The primary endpoints were comparisons of the proportion of time that the PM was displaced >3 mm (PTPM3) from its initial position, and the secondary endpoints were comparisons of the reduction of initial rectal area, with and without the bowel regimen. Results: The mean rectal area was: 13.5 cm{sup 2} at MRI-BL, 12.7 cm{sup 2} at MRI-CT, and 12.3 cm{sup 2} at MRI-RT (MRI-BL vs. MRI-CT, p = 0.11; MRI-BL vs. MRI-CT, p = 0.07). Moving rectal gas alone (56%) and moving gas and stool (18%) caused 74% of intrafraction prostate motion. The PTPM3 was 11.3% at MRI-BL, 4.8% at MRI-CT, and 12.0% at MRI-RT (MRI-BL vs. MRI-CT, p = 0.12; MRI-BL vs. MRI-RT, p = 0.89). Conclusion: For subjects voiding their rectum before imaging, an antiflatulent diet and milk of magnesia laxative did not significantly reduce initial rectal area or intrafraction prostate motion.

  13. 43 CFR 4300.53 - Can BLM reduce the size of the land in my permit?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) GRAZING ADMINISTRATION; ALASKA; REINDEER; GENERAL Changes in the Size of the Permit Area § 4300.53 Can BLM reduce the size of the...

  14. 43 CFR 4300.53 - Can BLM reduce the size of the land in my permit?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) GRAZING ADMINISTRATION; ALASKA; REINDEER; GENERAL Changes in the Size of the Permit Area § 4300.53 Can BLM reduce the size of the...

  15. Can Images Obtained With High Field Strength Magnetic Resonance Imaging Reduce Contouring Variability of the Prostate?

    SciTech Connect

    Usmani, Nawaid; Sloboda, Ron; Kamal, Wafa; Ghosh, Sunita; Pervez, Nadeem; Pedersen, John; Yee, Don; Danielson, Brita; Murtha, Albert; Amanie, John; Monajemi, Tara

    2011-07-01

    Purpose: The objective of this study is to determine whether there is less contouring variability of the prostate using higher-strength magnetic resonance images (MRI) compared with standard MRI and computed tomography (CT). Methods and Materials: Forty patients treated with prostate brachytherapy were accrued to a prospective study that included the acquisition of 1.5-T MR and CT images at specified time points. A subset of 10 patients had additional 3.0-T MR images acquired at the same time as their 1.5-T MR scans. Images from each of these patients were contoured by 5 radiation oncologists, with a random subset of patients repeated to quantify intraobserver contouring variability. To minimize bias in contouring the prostate, the image sets were placed in folders in a random order with all identifiers removed from the images. Results: Although there was less interobserver contouring variability in the overall prostate volumes in 1.5-T MRI compared with 3.0-T MRI (p < 0.01), there was no significant differences in contouring variability in the different regions of the prostate between 1.5-T MRI and 3.0-T MRI. MRI demonstrated significantly less interobserver contouring variability in both 1.5-T and 3.0-T compared with CT in overall prostate volumes (p < 0.01, p = 0.01), with the greatest benefits being appreciated in the base of the prostate. Overall, there was less intraobserver contouring variability than interobserver contouring variability for all of the measurements analyzed. Conclusions: Use of 3.0-T MRI does not demonstrate a significant improvement in contouring variability compared with 1.5-T MRI, although both magnetic strengths demonstrated less contouring variability compared with CT.

  16. Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

    PubMed Central

    Newhauser, Wayne D.; Zhang, Rui; Jones, Timothy G.; Giebeler, Annelise; Taddei, Phillip J.; Stewart, Robert D.; Lee, Andrew; Vassiliev, Oleg

    2015-01-01

    Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality. PMID:25920039

  17. The Association Between Phosphodiesterase Type-5 Inhibitors and Prostate Cancer: Results from the REDUCE Study

    PubMed Central

    Jamnagerwalla, Juzar; Howard, Lauren E.; Vidal, Adriana C.; Moreira, Daniel M.; Castro-Santamaria, Ramiro; Andriole, Gerald L.; Freedland, Stephen J.

    2016-01-01

    Purpose Despite the routine use of phosphodiesterase type-5 inhibitors (PDE-5i) for treatment of erectile dysfunction, their role in prostate cancer (PC) chemoprevention remains unclear with only a few studies exploring the link between PDE-5i use and PC. We tested the association between PDE-5i use and PC risk in the REDUCE study. Materials & Methods REDUCE was a four-year multi-center study testing the effect of daily dutasteride on PC risk in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy, with men undergoing study-mandated biopsies at 2- and 4-years. The association between PDE-5i use and overall PC risk and disease grade (Gleason 2–6 and 7–10) was examined using adjusted logistic and multinomial regression analysis. Secondary analysis was performed exploring the association between PDE-5i use and PC risk in North American men given the significantly higher use of PDE-5i among these subjects. Results PDE-5i inhibitor use was not associated with PC diagnosis (OR=0.90, 95%CI 0.68–1.20, p=0.476) or low- (OR=0.93, 95%CI 0.67–1.27, p=0.632) or high-grade disease (OR=0.85, 95%CI 0.51–1.39, p=0.508). An inverse trend was seen between PDE-5i use and PC diagnosis in North American men, but was not statistically significant (OR=0.67, 95%CI 0.42–1.07, p=0.091). Conclusions PDE-5i use was not associated with decreased PC diagnosis in post-hoc analysis of the REDUCE study. In North American men, who had a much higher baseline use of PDE-5i, use was associated with an inverse trend of PC diagnosis that approached, but did not reach, statistical significance. PMID:27060053

  18. Inhibiting Vimentin or beta 1-integrin Reverts Prostate Tumor Cells in IrECM and Reduces Tumor Growth

    SciTech Connect

    Zhang, Xueping; Fournier, Marcia V.; Ware, Joy L.; Bissell, Mina J.; Zehner, Zendra E.

    2009-07-27

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphological changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional (3D) lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the parental prostate epithelial P69 cell line by selection in nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin or {alpha}6-, {beta}4- and {beta}1-integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via siRNA interference or {beta}1-integrin expression by the addition of the blocking antibody, AIIB2, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by subcutaneous injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in 3D lrECM gels. These studies suggest that the levels of vimentin and {beta}1-integrin play a key role in the homeostasis of the normal acini in prostate and that their dysregulation may lead to tumorigenesis.

  19. The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

    PubMed Central

    Capurso, Cristiano; Vendemiale, Gianluigi

    2017-01-01

    Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD) on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil, could exert a

  20. DNA Methyl Transferase 1 Reduces Expression of SRD5A2 in the Aging Adult Prostate

    PubMed Central

    Ge, Rongbin; Wang, Zongwei; Bechis, Seth K.; Otsetov, Alexander G.; Hua, Shengyu; Wu, Shulin; Wu, Chin-Lee; Tabatabaei, Shahin; Olumi, Aria F.

    2016-01-01

    5-α Reductase type 2 (SRD5A2) is a critical enzyme for prostatic development and growth. Inhibition of SRD5A2 by finasteride is used commonly for the management of urinary obstruction caused by benign prostatic hyperplasia. Contrary to common belief, we have found that expression of SRD5A2 is variable and absent in one third of benign adult prostates. In human samples, absent SRD5A2 expression is associated with hypermethylation of the SRD5A2 promoter, and in vitro SRD5A2 promoter activity is suppressed by methylation. We show that methylation of SRD5A2 is regulated by DNA methyltransferase 1, and inflammatory mediators such as tumor necrosis factor α, NF-κB, and IL-6 regulate DNA methyltransferase 1 expression and thereby affect SRD5A2 promoter methylation and gene expression. Furthermore, we show that increasing age in mice and humans is associated with increased methylation of the SRD5A2 promoter and concomitantly decreased protein expression. Artificial induction of inflammation in prostate primary epithelial cells leads to hypermethylation of the SRD5A2 promoter and silencing of SRD5A2, whereas inhibition with tumor necrosis factor α inhibitor reactivates SRD5A2 expression. Therefore, expression of SRD5A2 is not static and ubiquitous in benign adult prostate tissues. Methylation and expression of SRD5A2 may be used as a gene signature to tailor therapies for more effective treatment of prostatic diseases. PMID:25700986

  1. Female Employment and Reduced Family Size: Some Additional Insight on the Direction of the Relationship.

    ERIC Educational Resources Information Center

    Houseknecht, Sharon K.

    Results of a study of the relationship between female employment and reduced family size are reported. Specifically, the study sought to determine whether career involvement precedes the final family size decision or whether the family size decision precedes career involvement. Thirty-two voluntarily childless women constituted the sample. The…

  2. 13 CFR 121.802 - What size standards are applicable to reduced patent fees programs?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What size standards are applicable to reduced patent fees programs? 121.802 Section 121.802 Business Credit and Assistance SMALL... Eligibility Requirements for Paying Reduced Patent Fees § 121.802 What size standards are applicable to...

  3. 13 CFR 121.802 - What size standards are applicable to reduced patent fees programs?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false What size standards are applicable to reduced patent fees programs? 121.802 Section 121.802 Business Credit and Assistance SMALL... Eligibility Requirements for Paying Reduced Patent Fees § 121.802 What size standards are applicable to...

  4. CT, MR, and ultrasound image artifacts from prostate brachytherapy seed implants: The impact of seed size

    SciTech Connect

    Robertson, Andrew K. H.; Basran, Parminder S.; Thomas, Steven D.; Wells, Derek

    2012-04-15

    Purpose: To investigate the effects of brachytherapy seed size on the quality of x-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR) images and seed localization through comparison of the 6711 and 9011 {sup 125}I sources. Methods: For CT images, an acrylic phantom mimicking a clinical implantation plan and embedded with low contrast regions of interest (ROIs) was designed for both the 0.774 mm diameter 6711 (standard) and the 0.508 mm diameter 9011 (thin) seed models (Oncura, Inc., and GE Healthcare, Arlington Heights, IL). Image quality metrics were assessed using the standard deviation of ROIs between the seeds and the contrast to noise ratio (CNR) within the low contrast ROIs. For US images, water phantoms with both single and multiseed arrangements were constructed for both seed sizes. For MR images, both seeds were implanted into a porcine gel and imaged with pelvic imaging protocols. The standard deviation of ROIs and CNR values were used as metrics of artifact quantification. Seed localization within the CT images was assessed using the automated seed finder in a commercial brachytherapy treatment planning system. The number of erroneous seed placements and the average and maximum error in seed placements were recorded as metrics of the localization accuracy. Results: With the thin seeds, CT image noise was reduced from 48.5 {+-} 0.2 to 32.0 {+-} 0.2 HU and CNR improved by a median value of 74% when compared with the standard seeds. Ultrasound image noise was measured at 50.3 {+-} 17.1 dB for the thin seed images and 50.0 {+-} 19.8 dB for the standard seed images, and artifacts directly behind the seeds were smaller and less prominent with the thin seed model. For MR images, CNR of the standard seeds reduced on average 17% when using the thin seeds for all different imaging sequences and seed orientations, but these differences are not appreciable. Automated seed localization required an average ({+-}SD) of 7.0 {+-} 3.5 manual

  5. Prostate Diseases

    MedlinePlus

    ... The Most Common Types of Prostate Diseases Benign prostatic hyperplasia (BPH) Prostatitis Prostate cancer For men over the ... the prostate disease most often encountered is benign prostatic hyperplasia (BPH). If you have BPH, your prostate has ...

  6. Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression.

    PubMed

    Kim, Yesl; Lee, Seung Min; Kim, Jung-Hyun

    2014-01-01

    Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression.

  7. CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression.

    PubMed

    Deng, Chuangzhong; Chen, Jieping; Guo, Shengjie; Wang, Yanjun; Zhou, Qianghua; Li, Zaishang; Yang, Xingping; Yu, Xingsu; Zhang, Zhenfeng; Zhou, Fangjian; Han, Hui; Yao, Kai

    2017-08-01

    The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay. Protein and mRNA levels of full-length AR (AR-FL) and AR-V7 were determined by qPCR and western blot, respectively. The nuclear translocation of p50 and p65 was assessed to reflect the activity of the NF-κB pathway. CX4945 reduced the proliferation of CRPC cells in a dose-dependent and time-dependent manner. AR-V7 rather than AR-FL was downregulated by CX4945 in both the mRNA and protein level. Furthermore, CX4945 could restore the sensitivity of CRPC cells to bicalutamide. The analysis of possible mechanisms demonstrated that the inhibition of CK2 diminished the phosphorylation of p65 at ser529 and thus attenuated the activity of the NF-κB pathway. The inhibition of CK2 by CX4945 can repress the viability of CRPC cells and restore their sensitivity to anti-androgen therapy by suppressing AR-V7. This finding presents a potential option for the treatment of prostate cancer, especially CRPC.

  8. Association Between Travel Distance and Choice of Treatment for Prostate Cancer: Does Geography Reduce Patient Choice?

    PubMed

    Muralidhar, Vinayak; Rose, Brent S; Chen, Yu-Wei; Nezolosky, Michelle D; Nguyen, Paul L

    2016-10-01

    To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation. We identified 222,804 patients diagnosed with National Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted for geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage. Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living ≤5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (≤25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These trends were also present when each risk group was analyzed separately. Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for localized prostate cancer. Copyright © 2016 Elsevier Inc. All

  9. Examination of the relationship between symptoms of prostatitis and histological inflammation: baseline data from the REDUCE chemoprevention trial.

    PubMed

    Nickel, J Curtis; Roehrborn, Claus G; O'leary, Michael P; Bostwick, David G; Somerville, Matthew C; Rittmaster, Roger S

    2007-09-01

    Symptoms of abacterial chronic prostatitis/chronic pelvic pain syndrome are considered to be associated with prostate inflammation. The ongoing Reduction by Dutasteride of Prostate Cancer Events trial is a 4-year, phase III, placebo controlled study to determine whether 0.5 mg dutasteride daily decreases the risk of biopsy detectable prostate cancer. All men underwent biopsy before study entry, allowing review of the relationship between histological prostate inflammation and prostatitis symptoms. Eligible men were 50 to 75 years old with serum prostate specific antigen 2.5 ng/ml or greater and 10 ng/ml or less (ages 50 to 60 years), or 3.0 ng/ml or greater and 10 ng/ml or less (older than 60 years), and an International Prostate Symptom Score of less than 25 (or less than 20 if already on alpha-blocker therapy). Acute prostatitis was an exclusion criterion. The National Institutes of Health Chronic Prostatitis Symptom Index was used to assess prostatitis-like symptoms. Spearman rank correlations were used to assess the relationship between acute and chronic inflammation, and Chronic Prostatitis Symptom Index scores for the pain, urinary symptoms and quality of life domains as well as average pain, total score and prostatitis-like symptoms. Data were available on 5,597 patients. The distribution of inflammation status was similar for those with and without chronic prostatitis-like symptoms. Significant correlations were found between average chronic inflammation, and total Chronic Prostatitis Symptom Index score and subscores for urinary symptoms and quality of life but the magnitude of these correlations was small. A lack of clinically meaningful association was found between prostatitis-like pain symptoms and histological inflammation in the Reduction by Dutasteride of Prostate Cancer Events population, suggesting that the view that symptoms of chronic prostatitis/chronic pelvic pain syndrome and prostate inflammation are associated needs further scrutiny.

  10. Reduced growth and integrin expression of prostate cells cultured with lycopene, vitamin E and fish oil in vitro.

    PubMed

    Bureyko, T; Hurdle, H; Metcalfe, J B; Clandinin, M T; Mazurak, Vera C

    2009-04-01

    Integrins are transmembrane proteins that facilitate the interaction of cells with the extracellular environment. They have also been implicated in cancer progression. The effects of nutrients thought to be involved in the prevention of prostate cancer on integrin expression have not been determined. Prostate cancer cell lines representing a range of malignancy from normal (RWPE-1) to highly invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene (10 nM), vitamin E (5 microm) or fish oil (100 microm) for 48 h. Growth and integrin (alpha2beta1, alphavbeta3 and alphavbeta5) expression were assessed using Trypan Blue exclusion and monoclonal antibodies combined with flow cytometry. Vitamin E enhanced (P < 0.001) whereas fish oil reduced the growth of all the cell lines tested (P < 0.001). Lycopene had no effect on growth. All the malignant cell lines exhibited lower expression of alpha2beta1 with the addition of lycopene to culture media. Supplemental fish oil reduced alpha2beta1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins alphavbeta3 and alphavbeta5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.

  11. Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives

    PubMed Central

    Serrano, Nicholas A; Kalman, Noah S; Anscher, Mitchell S

    2017-01-01

    Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity. PMID:28814898

  12. Altering Beamline Components to Reduce the Cost of Prostate Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Jones, T.; Geibler, A.; Zhang, R.; Newhauser, W. D.

    2009-10-01

    Proton beam therapy is an advanced technique used for the control of localized cancers. Currently it is one of the most cutting edge treatment options for prostate cancer but is still scarce and expensive. The expense is due, in part, to the unique beam collimators and range compensators that are manufactured for each treatment beam. The purpose of this study is to determine whether the custom collimator could be replaced by a reusable multileaf collimator and by eliminating the range compensator. Treatment plans were retrospectively selected for 10 patients who were treated for prostate cancer with 69 Gy delivered by two proton treatment fields. The originals were altered to include the multileaf collimator and to eliminate the range compensators. The dose distributions for each plan were calculated using a treatment planning system, which uses an analytical dose algorithm. They were then verified with Monte Carlo simulations, which are able to take into account individual particle trajectories and calculate dose resulting from stray neutron exposure. The calculated dose distributions for the altered treatments were dosimetrically equal or superior to the original plans. Our findings suggest that the proton-beam treatment technique for prostate cancer could be substantially simplified, thus yielding substantial cost savings.

  13. Challenges for reducing the size of laser activated remote phosphor light engines for DLP projection

    NASA Astrophysics Data System (ADS)

    Hartwig, Ulrich; Bruemmer, Mathias

    2014-12-01

    Laser activated remote phosphor (LARP) is an upcoming technology for high luminance SSL light engines. This presentation outlines some of the challenges met reducing the engine's size, so it can be retrofitted into DLP-projectors.

  14. Petite mutation in yeast. II. Isolation of mutants containing mitochondrial deoxyribonucleic acid of reduced size.

    PubMed

    Goldring, E S; Grossman, L I; Marmur, J

    1971-07-01

    A series of petite mutants of Saccharomyces cerevisiae, generated after treatment for various times with ethidium bromide, was isolated, and the mitochondrial deoxyribonucleic acid size for each member was estimated. It was found that, as the treatment time with ethidium bromide was increased, the mitochondrial deoxyribonucleic acid isolated from the petite series was increasingly reduced in size.

  15. Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada.

    PubMed

    Whittemore, A S; Kolonel, L N; Wu, A H; John, E M; Gallagher, R P; Howe, G R; Burch, J D; Hankin, J; Dreon, D M; West, D W

    1995-05-03

    International and interethnic differences in prostate cancer incidence suggest an environmental, potentially modifiable etiology for the disease. We conducted a population-based case-control study of prostate cancer among blacks (very high risk), whites (high risk), and Asian-Americans (low risk) in Los Angeles, San Francisco, Hawaii, Vancouver, and Toronto. Our aim was to evaluate the roles of diet, physical activity patterns, body size, and migration characteristics on risk in these ethnic groups and to assess how much of the interethnic differences in risk might be attributed to interethnic differences in such lifestyle characteristics. We used a common protocol and questionnaire to administer personal interviews to 1655 black, white, Chinese-American, and Japanese-American case patients diagnosed during 1987-1991 with histologically confirmed prostate carcinoma and to 1645 population-based control subjects matched to case patients by age, ethnicity, and region of residence. Sera collected from 1127 control subjects were analyzed for levels of prostate-specific antigen (PSA) to permit comparison of case patients with control subjects lacking serological evidence of prostate disease. Odds ratios were estimated using conditional logistic regression. We estimated the proportion of prostate cancer attributable to certain risk factors and the proportion of interethnic risk differences attributable to interethnic differences in risk-factor prevalence. A positive statistically significant association of prostate cancer risk and total fat intake was found for all ethnic groups combined. This association was attributable to energy from saturated fats; after adjusting for saturated fat, risk was associated only weakly with monounsaturated fat and was unrelated to protein, carbohydrate, polyunsaturated fat, and total food energy. Saturated fat intake was associated with higher risks for Asian-Americans than for blacks and whites. In all ethnic groups combined, the risk

  16. Toremifene to Reduce Fracture Risk in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

    PubMed Central

    Smith, Matthew R.; Morton, Ronald A.; Barnette, K. Gary; Sieber, Paul R.; Malkowicz, S. Bruce; Rodriguez, Domingo; Hancock, Michael L.; Steiner, Mitchell S.

    2011-01-01

    Purpose Androgen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period. Materials and Methods In this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes. Results The 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI –1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p <0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p <0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups. Conclusions Toremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles. PMID:20723926

  17. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma

    PubMed Central

    Bonetta, Alberto; Di Pierro, Francesco

    2012-01-01

    Background Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition. Methods A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period. Results Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract. Conclusion Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa. PMID:22977312

  18. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma.

    PubMed

    Bonetta, Alberto; Di Pierro, Francesco

    2012-01-01

    Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition. A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6-7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period. Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract. Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa.

  19. Inflammation polymorphisms and prostate cancer risk in Jamaican men: Role of obesity/body size.

    PubMed

    Dubey, Bhawna; Jackson, Maria; Zeigler-Johnson, Charnita; Devarajan, Karthik; Flores-Obando, Rafael E; McFarlane-Anderson, Norma; Tulloch-Reid, Marshall; Aiken, William; Kimbro, Kevin; Jones, Dominique; Kidd, LaCreis R; Ragin, Camille

    2017-09-10

    African ancestry and obesity are associated with higher risk of prostate cancer (PC). In a pilot study, we explored interactions between obesity (as measured by waist to hip ratio (WHR)) and inflammatory SNPs in relation to PC risk among Jamaican men. This study evaluated 87 chemokine and cytokine associated SNPs in obese and normal weight cases (N=109) and controls (N=102) using a stepwise penalized logistic regression approach in multivariable analyses. Upon stratification by WHR (normal weight (WHR<0.90) or obese (WHR≥0.90)), inheritance of CCR6 rs2023305 AG+GG (OR=1.75, p=0.007), CCR9 rs7613548 AG+GG (OR=1.71, p=0.012) and IL10ra rs2229113 AG+GG (OR=1.45, p=0.01) genotypes was associated with increase in overall or low grade (Gleason score<7) PC risk among normal weight men. These odds were elevated among obese men who possessed the CCR5 rs1799987 AG+GG (OR=1.95, p=0.003) and RNASEL rs12135247 CT+TT genotypes (OR=1.59, p=0.05). CCR7 rs3136685 AG+GG (p=0.032) was associated with a 1.52-1.70 fold increase in the risk of high grade cancer (Gleason score≥7) among obese men. CCR7 variant emerged as an important factor associated with high grade PC risk among obese men in our analyses. Overall, genetic loci found significant in normal weight men were not significant in obese men and vice-versa, partially explaining the role of obesity on PC risk among black men. Also, older age was an important risk factor both in normal weight and obese men but only with regard to low grade PC. Associations of inflammatory SNPs with obesity are suggestive and require further validation in larger cohorts to help develop an understanding of PC risk among obese and non-obese men of African descent. Copyright © 2017. Published by Elsevier B.V.

  20. Ultrasonic processor reduces drill-cuttings size and eliminates subsea mounds

    SciTech Connect

    Gaddy, D.E.

    1997-10-06

    Drill cuttings size reduction using ultrasonics eliminated a subsea clean-up and significantly reduced the environmental impact in a North Sea drilling project. Reduction in cuttings size allows for a wider areal dispersion when released into the ocean because they are held in suspension longer than larger sizes. Thus, ocean currents carry the smaller cuttings farther away from the well template, leaving a much wider footprint than larger cuttings sizes. This eliminates the pile-up of cuttings that otherwise would contaminate and harm the marine habitat.

  1. Character-Size Optimization for Reducing the Number of EB Shots of MCC Lithographic Systems

    NASA Astrophysics Data System (ADS)

    Sugihara, Makoto

    We propose a character size optimization technique to reduce the number of EB shots of multi-column-cell (MCC) lithographic systems in which transistor patterns are projected with multiple column cells in parallel. Each and every column cell is capable of projecting patterns with character projection (CP) and variable shaped beam (VSB) methods. Seeking the optimal character size of characters contributes to minimizing the number of EB shots and reducing the fabrication cost for ICs. Experimental results show that the character size optimization achieved 70.6% less EB shots in the best case with an available electron beam (EB) size. Our technique also achieved 40.6% less EB shots in the best case than a conventional character sizing technique.

  2. Cancer–Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer

    PubMed Central

    Sebastian, Aimy; Hum, Nicholas R.; Hudson, Bryan D.; Loots, Gabriela G.

    2015-01-01

    Dynamic interaction between prostate cancer and the bone microenvironment is a major contributor to metastasis of prostate cancer to bone. In this study, we utilized an in vitro co-culture model of PC3 prostate cancer cells and osteoblasts followed by microarray based gene expression profiling to identify previously unrecognized prostate cancer–bone microenvironment interactions. Factors secreted by PC3 cells resulted in the up-regulation of many genes in osteoblasts associated with bone metabolism and cancer metastasis, including Mmp13, Il-6 and Tgfb2, and down-regulation of Wnt inhibitor Sost. To determine whether altered Sost expression in the bone microenvironment has an effect on prostate cancer metastasis, we co-cultured PC3 cells with Sost knockout (SostKO) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-SostKO osteoblast co-cultures and PC3-WT osteoblast co-cultures. Co-culturing PC3 cells with WT osteoblasts up-regulated cancer-associated long noncoding RNA (lncRNA) MALAT1 in PC3 cells. MALAT1 expression was further enhanced when PC3 cells were co-cultured with SostKO osteoblasts and treatment with recombinant Sost down-regulated MALAT1 expression in these cells. Our results suggest that reduced Sost expression in the tumor microenvironment may promote bone metastasis by up-regulating MALAT1 in prostate cancer. PMID:27600237

  3. Reduced body size and cub recruitment in polar bears associated with sea ice decline

    USGS Publications Warehouse

    Rode, K.D.; Amstrup, Steven C.; Regehr, E.V.

    2010-01-01

    Rates of reproduction and survival are dependent upon adequate body size and condition of individuals. Declines in size and condition have provided early indicators of population decline in polar bears (Ursus maritimus) near the southern extreme of their range. We tested whether patterns in body size, condition, and cub recruitment of polar bears in the southern Beaufort Sea of Alaska were related to the availability of preferred sea ice habitats and whether these measures and habitat availability exhibited trends over time, between 1982 and 2006. The mean skull size and body length of all polar bears over three years of age declined over time, corresponding with long-term declines in the spatial and temporal availability of sea ice habitat. Body size of young, growing bears declined over time and was smaller after years when sea ice availability was reduced. Reduced litter mass and numbers of yearlings per female following years with lower availability of optimal sea ice habitat, suggest reduced reproductive output and juvenile survival. These results, based on analysis of a longterm data set, suggest that declining sea ice is associated with nutritional limitations that reduced body size and reproduction in this population. ?? 2010 by the Ecological Society of America.

  4. Reduced body size and cub recruitment in polar bears associated with sea ice decline.

    PubMed

    Rode, Karyn D; Amstrup, Steven C; Regehr, Eric V

    2010-04-01

    Rates of reproduction and survival are dependent upon adequate body size and condition of individuals. Declines in size and condition have provided early indicators of population decline in polar bears (Ursus maritimus) near the southern extreme of their range. We tested whether patterns in body size, condition, and cub recruitment of polar bears in the southern Beaufort Sea of Alaska were related to the availability of preferred sea ice habitats and whether these measures and habitat availability exhibited trends over time, between 1982 and 2006. The mean skull size and body length of all polar bears over three years of age declined over time, corresponding with long-term declines in the spatial and temporal availability of sea ice habitat. Body size of young, growing bears declined over time and was smaller after years when sea ice availability was reduced. Reduced litter mass and numbers of yearlings per female following years with lower availability of optimal sea ice habitat, suggest reduced reproductive output and juvenile survival. These results, based on analysis of a long-term data set, suggest that declining sea ice is associated with nutritional limitations that reduced body size and reproduction in this population.

  5. Differential Responses of Nitrate Reducer Community Size, Structure, and Activity to Tillage Systems▿ †

    PubMed Central

    Chèneby, D.; Brauman, A.; Rabary, B.; Philippot, L.

    2009-01-01

    The main objective of this study was to determine how the size, structure, and activity of the nitrate reducer community were affected by adoption of a conservative tillage system as an alternative to conventional tillage. The experimental field, established in Madagascar in 1991, consists of plots subjected to conventional tillage or direct-seeding mulch-based cropping systems (DM), both amended with three different fertilization regimes. Comparisons of size, structure, and activity of the nitrate reducer community in samples collected from the top layer in 2005 and 2006 revealed that all characteristics of this functional community were affected by the tillage system, with increased nitrate reduction activity and numbers of nitrate reducers under DM. Nitrate reduction activity was also stimulated by combined organic and mineral fertilization but not by organic fertilization alone. In contrast, both negative and positive effects of combined organic and mineral fertilization on the size of the nitrate reducer community were observed. The size of the nitrate reducer community was a significant predictor of the nitrate reduction rates except in one treatment, which highlighted the inherent complexities in understanding the relationships the between size, diversity, and structure of functional microbial communities along environmental gradients. PMID:19304827

  6. Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG-fusion positive and PTEN deleted prostate cancers.

    PubMed

    Burdelski, Christoph; Kleinhans, Sandra; Kluth, Martina; Hube-Magg, Claudia; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Tsourlakis, Maria Christina; Wilczak, Waldemar; Marx, Andreas; Sauter, Guido; Wittmer, Corinna; Huland, Hartwig; Simon, Ronald; Schlomm, Thorsten; Steurer, Stefan

    2016-03-01

    Zinc-alpha 2-glycoprotein (AZGP1) is involved in lipid metabolism and was suggested as a candidate prognostic biomarker in prostate cancer. To evaluate the clinical impact and relationship with key genomic alterations in prostate cancer, AZGP1 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers. Data on ERG status and PTEN, 3p13, 5q21 and 6q15 deletions were available from earlier studies. AZGP1 expression was strong in benign prostatic glands but absent in 38.0% of 8,510 interpretable prostate cancers. Reduced AZGP1 expression was associated with TPMRSS2:ERG fusions, both by FISH and immunohistochemical analysis (p < 0.0001 each). For example, AZGP1 was absent in 54.6% of 2,029 ERG IHC positive but in only 28.1% of 2,398 ERG negative cancers. Irrespective of the ERG status, reduced AZGP1 expression was tightly linked to high Gleason score, advanced pathological tumor stage, positive nodal status and early PSA recurrence (p < 0.0001 each). Reduced AZGP1 expression was also strongly associated with PTEN deletions. AZGP1 immunostaining was lacking in 62.7% of 842 PTEN deleted but in only 37.3% of PTEN non-deleted cancers but retained strong prognostic influence in both subgroups (p < 0.0001 each). The prognostic role of AZGP1 expression was also independent of Gleason score, pT stage, pN stage, surgical margin status and preoperative PSA, irrespective of whether preoperative or postoperative variables were used for modeling. In conclusion, the results of our study demonstrate that reduced AZGP1 expression is strongly related to adverse prostate cancer prognosis, independently of established clinic-pathological variables and PTEN deletions. © 2015 UICC.

  7. Size-dependent mechanical properties of PVA nanofibers reduced via air plasma treatment

    NASA Astrophysics Data System (ADS)

    Fu, Qiang; Jin, Yu; Song, Xuefeng; Gao, Jingyun; Han, Xiaobing; Jiang, Xingyu; Zhao, Qing; Yu, Dapeng

    2010-03-01

    Organic nanowires/fibers have great potential in applications such as organic electronics and soft electronic techniques. Therefore investigation of their mechanical performance is of importance. The Young's modulus of poly(vinyl alcohol) (PVA) nanofibers was analyzed by scanning probe microscopy (SPM) methods. Air plasma treatment was used to reduce the nanofibers to different sizes. Size-dependent mechanical properties of PVA nanofibers were studied and revealed that the Young's modulus increased dramatically when the scales became very small (<80 nm).

  8. New mechanism to reduce the size of the monopivot magnetic suspension blood pump: direct drive mechanism.

    PubMed

    Yamane, T; Nishida, M; Kijima, T; Maekawa, J

    1997-07-01

    Size reduction of the monopivot magnetic suspension blood pump has been achieved by reducing the size of the magnetic suspension and employing a direct drive mechanism in place of a brushless DC motor and a magnetic coupling. The flow has also been improved using a closed hollow impeller to remove flow obstruction at the inlet and using radial straight vanes to reduce the impeller speed by 30%. Hemolysis testing was conducted for the new models. Results showed that model DD1 presented only a slightly higher level of hemolysis than a regular extracorporeal centrifugal pump.

  9. Reduced CD147 expression is linked to ERG fusion-positive prostate cancers but lacks substantial impact on PSA recurrence in patients treated by radical prostatectomy.

    PubMed

    Grupp, Katharina; Höhne, Thorsten Simon; Prien, Kristina; Hube-Magg, Claudia; Tsourlakis, Maria Christina; Sirma, Hüseyin; Pham, Taher; Heinzer, Hans; Graefen, Markus; Michl, Uwe; Simon, Ronald; Wilczak, Waldemar; Izbicki, Jakob; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Steurer, Stefan

    2013-10-01

    The extracellular matrix metalloproteinase inducer CD147 has been suggested as a prognostic marker in prostate cancer. CD147 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancer specimens. Results were compared to tumor phenotype, biochemical recurrence, ERG status and deletions on PTEN, 3p13, 6q15 and 5q21. CD147 expression was strong in benign prostatic glands and often reduced in prostate cancers. CD147 immunostaining was found in 71.7% of 7628 interpretable cases. CD147 staining was considered strong in 34.6%, moderate in 24.3% and weak in 12.8% of cancers while 28.3% did not show any CD147 reactivity. Reduced CD147 staining was strongly associated with both TMPRSS2-ERG-rearrangement and ERG expression (p<0.0001 each). Within the subgroups of ERG positive and negative cancers, deletions of PTEN, 3p13, 6q15 and 5q21 were unrelated to the CD147 expression status. Decreased CD147 expression was significantly linked to high preoperative PSA values, high Gleason grade, advanced tumor stage (p<0.0001 each), and positive lymph node involvement (p=0.0026) in all cancers. There was a marginal, but statistically significant, association of reduced CD147 expression with early biochemical recurrence (p=0.0296). The significant reduction of CD147 expression in ERG positive prostate cancer provides further evidence for marked biological differences between "fusion type" and "non-fusion type" prostate cancer. Despite a weak association with PSA recurrence, CD147 cannot be considered a relevant prognostic biomarker.

  10. Reducing sample size in experiments with animals: historical controls and related strategies.

    PubMed

    Kramer, Matthew; Font, Enrique

    2017-02-01

    Reducing the number of animal subjects used in biomedical experiments is desirable for ethical and practical reasons. Previous reviews of the benefits of reducing sample sizes have focused on improving experimental designs and methods of statistical analysis, but reducing the size of control groups has been considered rarely. We discuss how the number of current control animals can be reduced, without loss of statistical power, by incorporating information from historical controls, i.e. subjects used as controls in similar previous experiments. Using example data from published reports, we describe how to incorporate information from historical controls under a range of assumptions that might be made in biomedical experiments. Assuming more similarities between historical and current controls yields higher savings and allows the use of smaller current control groups. We conducted simulations, based on typical designs and sample sizes, to quantify how different assumptions about historical controls affect the power of statistical tests. We show that, under our simulation conditions, the number of current control subjects can be reduced by more than half by including historical controls in the analyses. In other experimental scenarios, control groups may be unnecessary. Paying attention to both the function and to the statistical requirements of control groups would result in reducing the total number of animals used in experiments, saving time, effort and money, and bringing research with animals within ethically acceptable bounds. © 2015 Cambridge Philosophical Society.

  11. Reduced sample sizes for atrophy outcomes in Alzheimer's disease trials: baseline adjustment

    PubMed Central

    Schott, J.M.; Bartlett, J.W.; Barnes, J.; Leung, K.K.; Ourselin, S.; Fox, N.C.

    2010-01-01

    Cerebral atrophy rate is increasingly used as an outcome measure for Alzheimer's disease (AD) trials. We used the Alzheimer's disease Neuroimaging initiative (ADNI) dataset to assess if adjusting for baseline characteristics can reduce sample sizes. Controls (n = 199), patients with mild cognitive impairment (MCI) (n = 334) and AD (n = 144) had two MRI scans, 1-year apart; ~ 55% had baseline CSF tau, p-tau, and Aβ1-42. Whole brain (KN–BSI) and hippocampal (HMAPS-HBSI) atrophy rate, and ventricular expansion (VBSI) were calculated for each group; numbers required to power a placebo-controlled trial were estimated. Sample sizes per arm (80% power, 25% absolute rate reduction) for AD were (95% CI): brain atrophy = 81 (64,109), hippocampal atrophy = 88 (68,119), ventricular expansion = 118 (92,157); and for MCI: brain atrophy = 149 (122,188), hippocampal atrophy = 201 (160,262), ventricular expansion = 234 (191,295). To detect a 25% reduction relative to normal aging required increased sample sizes ~ 3-fold (AD), and ~ 5-fold (MCI). Disease severity and Aβ1-42 contributed significantly to atrophy rate variability. Adjusting for 11 predefined covariates reduced sample sizes by up to 30%. Treatment trials in AD should consider the effects of normal aging; adjusting for baseline characteristics can significantly reduce required sample sizes. PMID:20620665

  12. Implantation of cocoa butter reduces egg and hatchling size in Salmo trutta.

    PubMed

    Hoogenboom, M O; Armstrong, J D; Miles, M S; Burton, T; Groothuis, T G G; Metcalfe, N B

    2011-09-01

    This study demonstrated that, irrespective of hormone type or dose, administering cocoa butter implants during egg development affected the growth of female brown trout Salmo trutta and reduced the size of their offspring. Cortisol treatment also increased adult mortality. Caution is urged in the use of implants for studies of maternal hormonal influences on adult fishes and their offspring.

  13. Polychlorinated biphenyls may alter marine trophic pathways by reducing phytoplankton size and production.

    PubMed

    O'Connors, H B; Wurster, C F; Powers, C D; Biggs, D C; Rowland, R G

    1978-08-25

    Polychlorinated biphenyls at concentrations of 1 to 10 micrograms per liter reduced phytoplankton biomass and size in natural estuarine phytoplankton communities grown within dialysis bags in situ in an estuarine marsh. In polychlorinated biphenyls-contaminated waters, these changes could increase the number of trophic levels and divert the flow of biomass from harvestable fish to jellyfish and other gelatinous predators.

  14. Reduced Sampling Size with Nanopipette for Tapping-Mode Scanning Probe Electrospray Ionization Mass Spectrometry Imaging

    PubMed Central

    Kohigashi, Tsuyoshi; Otsuka, Yoichi; Shimazu, Ryo; Matsumoto, Takuya; Iwata, Futoshi; Kawasaki, Hideya; Arakawa, Ryuichi

    2016-01-01

    Mass spectrometry imaging (MSI) with ambient sampling and ionization can rapidly and easily capture the distribution of chemical components in a solid sample. Because the spatial resolution of MSI is limited by the size of the sampling area, reducing sampling size is an important goal for high resolution MSI. Here, we report the first use of a nanopipette for sampling and ionization by tapping-mode scanning probe electrospray ionization (t-SPESI). The spot size of the sampling area of a dye molecular film on a glass substrate was decreased to 6 μm on average by using a nanopipette. On the other hand, ionization efficiency increased with decreasing solvent flow rate. Our results indicate the compatibility between a reduced sampling area and the ionization efficiency using a nanopipette. MSI of micropatterns of ink on a glass and a polymer substrate were also demonstrated. PMID:28101441

  15. Prostate biopsy

    MedlinePlus

    ... prostate biopsy; Fine needle biopsy of the prostate; Core biopsy of the prostate; Targeted prostate biopsy; Prostate ... to the principles of the Health on the Net Foundation (www.hon.ch). The information provided herein ...

  16. Reduced particle size wheat bran is butyrogenic and lowers Salmonella colonization, when added to poultry feed.

    PubMed

    Vermeulen, K; Verspreet, J; Courtin, C M; Haesebrouck, F; Ducatelle, R; Van Immerseel, F

    2017-01-01

    Feed additives, including prebiotics, are commonly used alternatives to antimicrobial growth promoters to improve gut health and performance in broilers. Wheat bran is a highly concentrated source of (in)soluble fiber which is partly degraded by the gut microbiota. The aim of the present study was to investigate the potential of wheat bran as such to reduce colonization of the cecum and shedding of Salmonella bacteria in vivo. Also, the effect of particle size was evaluated. Bran with an average reduced particle size of 280μm decreased levels of cecal Salmonella colonization and shedding shortly after infection when compared to control groups and groups receiving bran with larger particle sizes. In vitro fermentation experiments revealed that bran with smaller particle size was fermented more efficiently, with a significantly higher production of butyric and propionic acid, compared to the control fermentation and fermentation of a larger fraction. Fermentation products derived from bran with an average particle size of 280μm downregulated the expression of hilA, an important invasion-related gene of Salmonella. This downregulation was reflected in an actual lowered invasive potential when Salmonella bacteria were pretreated with the fermentation products derived from the smaller bran fraction. These data suggest that wheat bran with reduced particle size can be a suitable feed additive to help control Salmonella infections in broilers. The mechanism of action most probably relies on a more efficient fermentation of this bran fraction and the consequent increased production of short chain fatty acids (SCFA). Among these SCFA, butyric and propionic acid are known to reduce the invasion potential of Salmonella bacteria.

  17. Smaller food item sizes of snack foods influence reduced portions and caloric intake in young adults.

    PubMed

    Marchiori, David; Waroquier, Laurent; Klein, Olivier

    2011-05-01

    Studies considering the impact of food-size variations on consumption have predominantly focused on portion size, whereas very little research has investigated variations in food-item size, especially at snacking occasions, and results have been contradictory. This study evaluated the effect of altering the size of food items (ie, small vs large candies) of equal-size food portions on short-term energy intake while snacking. The study used a between-subjects design (n=33) in a randomized experiment conducted in spring 2008. In a psychology laboratory (separate cubicles), participants (undergraduate psychology students, 29 of 33 female, mean age 20.3±2 years, mean body mass index 21.7±3.7) were offered unlimited consumption of candies while participating in an unrelated computerized experiment. For half of the subjects, items were cut in two to make the small food-item size. Food intake (weight in grams, kilocalories, and number of food items) was examined using analysis of variance. Results showed that decreasing the item size of candies led participants to decrease by half their gram weight intake, resulting in an energy intake decrease of 60 kcal compared to the other group. Appetite ratings and subject and food characteristics had no moderating effect. A cognitive bias could explain why people tend to consider that one unit of food (eg, 10 candies) is the appropriate amount to consume, regardless of the size of the food items in the unit. This study suggests a simple dietary strategy, decreasing food-item size without having to alter the portion size offered, may reduce energy intake at snacking occasions.

  18. Transrectal ultrasonography (TRUS)-guided pelvic plexus block to reduce pain during prostate biopsy: a randomised controlled trial.

    PubMed

    Jindal, Tarun; Mukherjee, Subhabrata; Sinha, Rajan K; Kamal, Mir R; Ghosh, Nabankur; Saha, Barun; Mitra, Nilanjan; Sharma, Pramod K; Mandal, Soumendra N; Karmakar, Dilip

    2015-06-01

    To assess the role of pelvic plexus block (PPB) in reducing pain during transrectal ultrasonography(TRUS)-guided prostate biopsy, compared with the conventional periprostatic nerve block (PNB). A prospective, double-blind observational study was conducted with patients being randomised into three groups. Group-1 (47 patients) received intrarectal local anaesthesia (IRLA) with 10 mL 2% lignocaine jelly along with pelvic plexus block (PPB) with 2.5 mL 2% lignocaine injection bilaterally. Group-2 (46 patients) received IRLA with periprostatic nerve block (PNB). Group-3 (46 patients) received only IRLA without any type of nerve block. The patients were requested to rate the level of pain from 0 to 10 on a visual analogue scale (VAS) at two time points: VAS-1: during biopsy procedure and VAS-2: 30 min after the procedure. The mean age of the patients, mean volume of the prostates and mean serum PSA values were comparable among the three groups. The mean pain score during biopsy was significantly less in the PPB group [mean (range) sore of 2.91 (2-4)] compared with the PNB group [mean (range) score of 4 (3-5)], and both these groups were superior to the no nerve block group [mean score of 5.4 (3-7)]. There was no significant difference between the mean pain scores, 30 min after the procedure among the three groups with the mean (range) scores being 2.75 (2-4), 2.83 (2-4) and 2.85 (2-4), respectively. PPB is superior to conventional periprostatic nerve block (PNB) for pain control during TRUS-guided biopsy and both are in turn superior to no nerve block. © 2014 The Authors. BJU International © 2014 BJU International.

  19. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate.

    PubMed

    Miner, Jeffrey N; Chang, William; Chapman, Mark S; Finn, Patricia D; Hong, Mei Hua; López, Francisco J; Marschke, Keith B; Rosen, Jon; Schrader, William; Turner, Russell; van Oeveren, Arjan; Viveros, Humberto; Zhi, Lin; Negro-Vilar, Andres

    2007-01-01

    A number of conditions, including osteoporosis, frailty, and sexual dysfunction in both men and women have been improved using androgens. However, androgens are not widely used for these indications because of the side effects associated with these drugs. We describe an androgen receptor (AR) ligand that maintains expected anabolic activities with substantially diminished activity in the prostate. LGD2226 is a nonsteroidal, nonaromatizable, highly selective ligand for the AR, exhibiting virtually no affinity for the other intracellular receptors. We determined that AR bound to LGD2226 exhibits a unique pattern of protein-protein interactions compared with testosterone, fluoxymesterone (an orally available steroidal androgen), and other steroids, suggesting that LGD2226 alters the conformation of the ligand-binding domain. We demonstrated that LGD2226 is fully active in cell-based models of bone and muscle. LGD2226 exhibited anabolic activity on muscle and bone with reduced impact on prostate growth in rodent models. Biomechanical testing of bones from animals treated with LGD2226 showed strong enhancement of bone strength above sham levels. LGD2226 was also efficacious in a sex-behavior model in male rats measuring mounts, intromissions, ejaculations, and copulation efficiency. These results with an orally available, nonaromatizable androgen demonstrate the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle, and sexual function independent from the conversion of androgens into estrogenic ligands. Taken together, these results suggest that orally active, nonsteroidal selective androgen receptor modulators may be useful therapeutics for enhancing muscle, bone, and sexual function.

  20. Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells.

    PubMed

    Lesinski, Gregory B; Reville, Patrick K; Mace, Thomas A; Young, Gregory S; Ahn-Jarvis, Jennifer; Thomas-Ahner, Jennifer; Vodovotz, Yael; Ameen, Zeenath; Grainger, Elizabeth; Riedl, Kenneth; Schwartz, Steven; Clinton, Steven K

    2015-11-01

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.

  1. Quantitative volumetric imaging of normal, neoplastic and hyperplastic mouse prostate using ultrasound.

    PubMed

    Singh, Shalini; Pan, Chunliu; Wood, Ronald; Yeh, Chiuan-Ren; Yeh, Shuyuan; Sha, Kai; Krolewski, John J; Nastiuk, Kent L

    2015-09-21

    -guided implantation of orthotopic tumor xenografts and monitoring of subsequent tumor growth from ~10 to ~750 mm(3) volume. High frequency ultrasound imaging allows precise determination of normal, neoplastic and hyperplastic mouse prostate. Low cost and small image size allows incorporation of this imaging modality inside clean animal facilities, and thereby imaging of immunocompromised models. 3D reconstruction for volume determination is easily mastered, and both small and large relative changes in volume are accurately visualized. Ultrasound imaging does not rely on penetration of exogenous imaging agents, and so may therefore better measure poorly vascularized or necrotic diseased tissue, relative to bioluminescent imaging (IVIS). Our method is precise and reproducible with very low inter- and intra-observer variability. Because it is non-invasive, mouse models of prostatic disease states can be imaged serially, reducing inter-animal variability, and enhancing the power to detect small volume changes following therapeutic intervention.

  2. Is There a Role for Preoperative 5 Alpha Reductase Inhibitors in Reducing Prostate Vascularity and Blood Loss?

    PubMed

    Bruha, Matthew; Welliver, Charles

    2017-10-01

    Benign prostatic hyperplasia (BPH) and the related medical problems are a major burden as health care costs and as a cause of patient morbidity. The introduction of medical therapy largely offered an alternative to surgical therapy, and these medications have been linked with multiple positive BPH-related outcomes. With ubiquitous use, however, a variety of adverse side effects and unsupported claims to these medications have been reported both in scientific literature and popular press. The use of 5 alpha reductase inhibitors (5ARIs) to reduce recurrent bleeding due to BPH is a reasonable option for men with recurrent trips to the physician or hospital. After a largely anecdotal report of their use in the preoperative period to reduce bleeding during BPH surgery, there was interest in the use of 5ARIs for this indication considering the effusive bleeding that can occur during BPH-related surgery, a dreaded and not uncommon complication. While the pathophysiology for the use of 5ARI to reduce BPH-related bleeding is sound, the actual clinical outcomes still require scrutiny to determine if the efficacy is both scientifically valid and clinically significant. This report will review the current literature on this topic and make attempts to determine if the use of a 5ARI before BPH-related surgery should be encouraged.

  3. Poor glycemic control is associated with reduced prostate specific antigen concentrations in men with type 1 diabetes.

    PubMed

    Sarma, Aruna V; Hotaling, James; Dunn, Rodney L; Cleary, Patricia A; Braffett, Barbara H; Kim, Catherine; Martin, Catherine; Herman, William; Gatcomb, Patricia; Jacobson, Alan M; Holt, Sarah K; Wessells, Hunter

    2015-03-01

    Previous studies have revealed lower prostate specific antigen concentrations in men with type 2 diabetes, paralleling the reported lower prevalence of prostate cancer in diabetic men. Data are lacking on prostate specific antigen in men with type 1 diabetes whose insulin and obesity profiles differ from those with type 2 diabetes mellitus. In this study we examined the relationship between long-term glycemic control and prostate specific antigen in men with type 1 diabetes mellitus. Total prostate specific antigen was measured at one time in 639 men in the EDIC, the observational followup of participants in the DCCT. The relationship between DCCT/EDIC weighted mean hemoglobin A1c and log prostate specific antigen was assessed using linear regression modeling after adjusting for age, body mass index, total testosterone, statin and thiazide medication use, diabetes duration, and DCCT randomization arm and cohort. Median subject age was 52 years, body mass index was 28.4 kg/m(2) and DCCT/EDIC time-weighted hemoglobin A1c was 7.9%. Median prostate specific antigen was 0.64 ng/ml (IQR 0.43, 1.05). Prostate specific antigen increased significantly with age (p <0.0001) and with lower time-weighted hemoglobin A1c (p <0.0001). Each 10% increase in hemoglobin A1c was accompanied by an 11% reduction in prostate specific antigen (p=0.0001). Prostate specific antigen decreases as hemoglobin A1c increases in men with type 1 diabetes mellitus. This relationship is independent of age, body mass index, androgen levels, medication use and measures of diabetes severity, which suggests that factors related to glycemia may directly affect prostate specific antigen levels. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. QUANTITATIVE STUDIES OF PROSTATIC SECRETION

    PubMed Central

    Huggins, Charles; Clark, Philip Johnson

    1940-01-01

    Cystic hyperplasia of the prostate occurs spontaneously in senile dogs only when they possess physiologically effective amounts of androgenic hormone. The cysts are closely grouped and radially arranged in a conical manner with the base of the cone at the periphery of the gland. Flattened and columnar epithelium, varying from about 5 to 25µ are seen in each cyst. The cysts communicate with the urethra by way of ducts. Both normal and cystic prostates undergo marked atrophy when the testes are removed, the chief difference 3 months after orchiectomy being the persistence of slightly dilated clefts and spaces at the site of the former cysts in the senile state. In the castrate dog whose prostate gland is being reconstructed as result of the influence of daily injections of androgen, certain doses of estrogen prevent increase of secretion and still larger doses greatly depress the output of the gland. In dogs so treated by daily injections of testosterone propionate, 10 mg., the amount of secretion is maintained from day to day at a level by daily injections of stilbestrol, 0.4 to 0.6 mg. and greatly depressed by doses of 1 to 1.5 mg. When the larger amounts of estrogen are used, together with androgen, squamous metaplasia occurs in the posterior lobe of the prostate while the epithelium of the acini decreases in height to cuboidal or low columnar form; these histological signs of activity of both androgen and estrogen on the prostate show that inhibition of the male hormone by stilbestrol is incomplete at these ratios. In dogs with either normal or cystic prostate glands, the prostate decreases in size when estrogen is injected in amounts to depress prostatic secretion profoundly. The gland is maintained in an atrophic state and overdosage avoided by controlled periodic injections of stilbestrol until secretion is reduced to the minimum, followed by free intervals, the estrogen being again administered when secretion measurably increases. The shrinkage is related to

  5. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  6. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  7. Do antioxidant vitamins reduce infarct size following acute myocardial ischemia/reperfusion?

    PubMed

    Bellows, S D; Hale, S L; Simkhovich, B Z; Kay, G L; Kloner, R A

    1995-02-01

    There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size.

  8. Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys.

    PubMed

    Bello, Nicholas T; Kemm, Matthew H; Moran, Timothy H

    2008-07-01

    Amylinergic mechanisms are believed to be involved in the control of appetite. This study examined the effects of the amylin agonist, salmon calcitonin, on food intake and meal patterns in adult male rhesus monkeys. Fifteen minutes before the onset of their 6-h daily feeding period, monkeys received intramuscular injections of various doses of salmon calcitonin (0.032, 0.056, 0.1, 0.32, and 1 microg/kg) or saline. Salmon calcitonin dose dependently reduced total daily and hourly food intake, with significant decreases at the 0.1, 0.32, and 1 microg/kg doses. Daily food intake was reduced by approximately 35%, 62%, and 96%, at these doses, respectively. An analysis of meal patterns revealed that size of the first meal was significantly reduced across the dose range of 0.056 to 1 microg/kg, while average meal size was reduced with the 0.32 and 1 microg/kg doses. Meal number was only affected at the 1 microg/kg dose. Repeated 5-day administration of the 0.1 microg/kg dose resulted in a reduction in daily food intake only on injection day 2, while significant reductions in food intake were observed on all five injection days with a 0.32 microg/kg dose. Daily food intake was also reduced for 1 day after the termination of the 5-day injections of the 0.32 microg/kg salmon calcitonin dose. These sustained reductions in intake were expressed through decreases in meal size. These data demonstrate that salmon calcitonin acutely and consistently decreases food intake mainly through reductions in meal sizes in nonhuman primates.

  9. Small portion sizes in worksite cafeterias: do they help consumers to reduce their food intake?

    PubMed Central

    Vermeer, W M; Steenhuis, I H M; Leeuwis, F H; Heymans, M W; Seidell, J C

    2011-01-01

    Background: Environmental interventions directed at portion size might help consumers to reduce their food intake. Objective: To assess whether offering a smaller hot meal, in addition to the existing size, stimulates people to replace their large meal with a smaller meal. Design: Longitudinal randomized controlled trial assessing the impact of introducing small portion sizes and pricing strategies on consumer choices. Setting/participants: In all, 25 worksite cafeterias and a panel consisting of 308 consumers (mean age=39.18 years, 50% women). Intervention: A small portion size of hot meals was offered in addition to the existing size. The meals were either proportionally priced (that is, the price per gram was comparable regardless of the size) or value size pricing was employed. Main outcome measures: Daily sales of small and the total number of meals, consumers' self-reported compensation behavior and frequency of purchasing small meals. Results: The ratio of small meals sales in relation to large meals sales was 10.2%. No effect of proportional pricing was found B=−0.11 (0.33), P=0.74, confidence interval (CI): −0.76 to 0.54). The consumer data indicated that 19.5% of the participants who had selected a small meal often-to-always purchased more products than usual in the worksite cafeteria. Small meal purchases were negatively related to being male (B=−0.85 (0.20), P=0.00, CI: −1.24 to −0.46, n=178). Conclusion: When offering a small meal in addition to the existing size, a percentage of consumers that is considered reasonable were inclined to replace the large meal with the small meal. Proportional prices did not have an additional effect. The possible occurrence of compensation behavior is an issue that merits further attention. PMID:21224829

  10. Reduced clot debris size using standing waves formed via high intensity focused ultrasound

    NASA Astrophysics Data System (ADS)

    Guo, Shifang; Du, Xuan; Wang, Xin; Lu, Shukuan; Shi, Aiwei; Xu, Shanshan; Bouakaz, Ayache; Wan, Mingxi

    2017-09-01

    The feasibility of utilizing high intensity focused ultrasound (HIFU) to induce thrombolysis has been demonstrated previously. However, clinical concerns still remain related to the clot debris produced via fragmentation of the original clot potentially being too large and hence occluding downstream vessels, causing hazardous emboli. This study investigates the use of standing wave fields formed via HIFU to disintegrate the thrombus while achieving a reduced clot debris size in vitro. The results showed that the average diameter of the clot debris calculated by volume percentage was smaller in the standing wave mode than in the travelling wave mode at identical ultrasound thrombolysis settings. Furthermore, the inertial cavitation dose was shown to be lower in the standing wave mode, while the estimated cavitation bubble size distribution was similar in both modes. These results show that a reduction of the clot debris size with standing waves may be attributed to the particle trapping of the acoustic potential well which contributed to particle fragmentation.

  11. Concentration Effect of Reducing Agents on Green Synthesis of Gold Nanoparticles: Size, Morphology, and Growth Mechanism

    NASA Astrophysics Data System (ADS)

    Kim, Hyun-seok; Seo, Yu Seon; Kim, Kyeounghak; Han, Jeong Woo; Park, Youmie; Cho, Seonho

    2016-04-01

    Under various concentration conditions of reducing agents during the green synthesis of gold nanoparticles (AuNPs), we obtain the various geometry (morphology and size) of AuNPs that play a crucial role in their catalytic properties. Through both theoretical and experimental approaches, we studied the relationship between the concentration of reducing agent (caffeic acid) and the geometry of AuNPs. As the concentration of caffeic acid increases, the sizes of AuNPs were decreased due to the adsorption and stabilizing effect of oxidized caffeic acids (OXCAs). Thus, it turns out that optimal concentration exists for the desired geometry of AuNPs. Furthermore, we investigated the growth mechanism for the green synthesis of AuNPs. As the caffeic acid is added and adsorbed on the surface of AuNPs, the aggregation mechanism and surface free energy are changed and consequently resulted in the AuNPs of various geometry.

  12. Clinical efforts to reduce myocardial infarct size--the next step.

    PubMed

    Braunwald, Eugene

    2011-01-01

    Prompt myocardial reperfusion reduces infarct size in patients experiencing coronary occlusion. However, its clinical value is limited because reperfusion also causes ischemic myocardial reperfusion injury (IMRI). Considerable research to reduce IMRI has been conducted. Three interventions appear to be promising: 1) myocardial conditioning, which consists of repetitive occlusions of coronary or other arteries prior to or at the time of myocardial reperfusion; 2) the administration of cyclosporine A; and 3) the administration of adenosine. A plan for the testing of these interventions in patients with acute myocardial infarction is described.

  13. A DRAMATICALLY REDUCED SIZE IN THE GANTRY DESIGN FOR THE PROTON-CARBON THERAPY.

    SciTech Connect

    TRBOJEVIC, D.; GUPTA, R.; PARKER, B.; KEIL, E.; SESSLER, A.M.

    2006-06-23

    Gantries in the proton/carbon cancer therapy machines represent the major cost and are of the largest size. This report explains a new way to the gantry design. The size and cost of the gantries are reduced and their use is simplified by using the fixed magnetic field. The ''new'' gantry is made of a very large momentum acceptance non-scaling Fixed Field Alternating Gradient (FFAG) quarter and half arc beam lines. The gantry is made of combined function magnets with a very strong focusing and small dispersion function. Additional magnets with a fast response are required to allow adjustments of the beam position for different energies at the beginning of the gantry. Additional strong focusing magnets following the gantry have also to be adjustable to provide required spot size and radial scanning above the patients. The fixed field combined function magnets could be made of small permanent magnets for the proton machine, or of the high temperature superconductors or superconductors for the carbon machine, reducing dramatically the size.

  14. Very small size proteoliposomes (VSSP) and Montanide combination enhance the humoral immuno response in a GnRH based vaccine directed to prostate cancer.

    PubMed

    Aguilar, Franklin Fuentes; Barranco, Jesús Junco; Fuentes, Eddy Bover; Aguilera, Lesvia Calzada; Sáez, Yovisleydis Lopez; Santana, María Dolores Castro; Vázquez, Eulogio Pimentel; Baker, Roberto Basulto; Acosta, Osvaldo Reyes; Pérez, Hilda Garay; Nieto, Gerardo Guillén

    2012-10-12

    Very small size proteoliposomes (VSSP) constitute a complex of very small size proteoliposomes that includes proteins, lipids, CpG and gangliosides tumor-associated that provides a potential target for cancer immunotherapy. This compound has been described to stimulate the humoral and cellular response, dendritic cells (DC) activation and differentiation of T-helper cells, specially, in immunocompromised patients with cancer status. This work deals with the stimulating capacity of the VSSP to reach a humoral response when they are used as a component in a peptidic vaccine based on the gonadotrophin releasing hormone (GnRH). This study was carried out in male Copenhagen rats, which were immunized with 750μg of the GnRH mimetic peptide (GnRHm1-TT) with or without the VSSP. The mixtures were always emulsified with the oil adjuvant Montanide ISA 51. The anti GnRH seroconversion analysis revealed that the group immunized with the peptide GnRHm1-TT/VSSP developed a strong anti GnRH seroconversion. These antibody levels proved to be significant superior to those reached by the use of the GnRHm1-TT peptide solely emulsified in Montanide. Post-mortem analysis on the Testosterone ablation target organs (prostate and testicles) yielded a sudden decrease in their size and weight in respect to the control group. On the other hand, the group submitted to the use of GnRHm1-TT/VSSP, showed a significant difference in the reduction of these target organs in comparison with the group only immunized with GnRHm1-TT adjuvated in Montanide ISA 51. These values turned to be of p=0.023 and p=0.009 in the prostate and testicles respectively. These findings foreground the VSSP as a useful immunopotentiator to be used as part of a GnRH based vaccine to treat prostate cancer.

  15. Reduced late rectal mucosal changes after prostate three-dimensional conformal radiotherapy with endorectal balloon as observed in repeated endoscopy

    SciTech Connect

    Lin, Emile van . E-mail: E.vanLin@rther.umcn.nl; Kristinsson, Jon; Philippens, Marielle E.P.; Jong, Dirk J. de; Vight, Lisette P. van der; Kaanders, Johannes; Leer, Jan Willem; Visser, Andries G.

    2007-03-01

    Purpose: The aim of this study was to investigate prospectively the rectal wall (Rwall) spatial dose distribution, toxicity, and mucosal changes after prostate cancer radiotherapy with or without an endorectal balloon (ERB). Methods and Materials: A total of 24 patients with ERB and 24 without ERB (No-ERB) were treated with three-dimensional conformal radiotherapy (3D-CRT) to a dose of 67.5 Gy. The Rwall was divided into 16 mucosal areas and Rwall dose surface maps were constructed. After 3 months, 6 months, 1 year, and 2 years a rectosigmoidoscopy was performed, and each mucosal area was scored on telangiectasia, congestion, ulceration, stricture, and necrosis. Late rectal toxicity was correlated with the endoscopic findings. Results: The ERB significantly reduced the Rwall volume exposed to doses >40 Gy. Late rectal toxicity (grade {>=}1, including excess of bowel movements and slight rectal discharge) was reduced significantly in the ERB group. A total of 146 endoscopies and 2,336 mucosal areas were analyzed. Telangiectases were most frequently seen and appeared after 6 months. At 1 and 2 years, significantly less high-grade telangiectasia (T 2-3) was observed in the ERB group at the lateral and posterior part of the Rwall. In mucosal areas exposed to doses >40 Gy, less high-grade telangiectases (T 2-3) were seen in the ERB group compared with the No-ERB group. Conclusions: An ERB reduced the Rwall volume exposed to doses >40 Gy, resulting in reduction of late rectal mucosal changes and reduced late rectal toxicity. Although further analysis is needed, these data suggest an ERB-induced increased tolerance for late Rwall damage.

  16. Magnitude of observer error using cone beam CT for prostate interfraction motion estimation: effect of reducing scan length or increasing exposure.

    PubMed

    McNair, Helen A; Harris, Emma J; Hansen, Vibeke N; Thomas, Karen; South, Christopher; Hafeez, Shaista; Huddart, Robert; Dearnaley, David P

    2015-10-01

    Cone beam CT (CBCT) enables soft-tissue registration to planning CT for position verification in radiotherapy. The aim of this study was to determine the interobserver error (IOE) in prostate position verification using a standard CBCT protocol, and the effect of reducing CBCT scan length or increasing exposure, compared with standard imaging protocol. CBCT images were acquired using a novel 7 cm length image with standard exposure (1644 mAs) at Fraction 1 (7), standard 12 cm length image (1644 mAs) at Fraction 2 (12) and a 7 cm length image with higher exposure (2632 mAs) at Fraction 3 (7H) on 31 patients receiving radiotherapy for prostate cancer. Eight observers (two clinicians and six radiographers) registered the images. Guidelines and training were provided. The means of the IOEs were compared using a Kruzkal-Wallis test. Levene's test was used to test for differences in the variances of the IOEs and the independent prostate position. No significant difference was found between the IOEs of each image protocol in any direction. Mean absolute IOE was the greatest in the anteroposterior direction. Standard deviation (SD) of the IOE was the least in the left-right direction for each of the three image protocols. The SD of the IOE was significantly less than the independent prostate motion in the anterior-posterior (AP) direction only (1.8 and 3.0 mm, respectively: p = 0.017). IOEs were within 1 SD of the independent prostate motion in 95%, 77% and 96% of the images in the RL, SI and AP direction. Reducing CBCT scan length and increasing exposure did not have a significant effect on IOEs. To reduce imaging dose, a reduction in CBCT scan length could be considered without increasing the uncertainty in prostate registration. Precision of CBCT verification of prostate radiotherapy is affected by IOE and should be quantified prior to implementation. This study shows the importance of quantifying the magnitude of IOEs prior to CBCT implementation.

  17. Arum Palaestinum with isovanillin, linolenic acid and β-sitosterol inhibits prostate cancer spheroids and reduces the growth rate of prostate tumors in mice.

    PubMed

    Cole, Caitlin; Burgoyne, Thomas; Lee, Annie; Stehno-Bittel, Lisa; Zaid, Gene

    2015-08-05

    Arum palaestinum is a plant commonly found in the Middle East that is ingested as an herbal remedy to fight cancer. However, no studies have examined the direct effect of the plant/plant extract on tumor growth in an animal model. Verified prostate cancer cells were plated as 3D spheroids to determine the effect of extract from boiled Arum Palaestinum Boiss roots. In addition, male NU/NU mice (8 weeks old) with xenograft tumors derived from the prostate cancer cell line were treated daily with 1000 mg/kg body weight gavage of the suspension GZ17. The tumor growth was measured repeatedly with calipers and the excised tumors were weighed at the termination of the 3 week study. Control mice (10 mice in each group) received vehicle in the same manner and volume. The number of live prostate cancer cells declined in a dose/dependent manner with a 24 h exposure to the extract at doses of 0.015 to 6.25 mg/mL. A fortified version of the extract (referred to as GZ17) that contained higher levels of isovanillin, linolenic acid and β-sitosterol had a stronger effect on the cell death rate, shifting the percentage of dead cells from 30 % to 55 % at the highest dose while the vehicle control had no effect on cell numbers. When GZ17 was applied to non-cancer tissue, in this case, human islets, there was no cell death at doses that were toxic to treated cancer cells. Preliminary toxicity studies were conducted on rats using an up-down design, with no signs of toxic effect at the highest dose. NU/NU mice with xenograft prostate tumors treated with GZ17 had a dramatic inhibition of tumor progression, while tumors in the control group grew steadily through the 3 weeks. The rate of tumor volume increase was 73 mm(3)/day for the vehicle group and 24 mm(3)/day for the GZ17 treated mice. While there was a trend towards lower excised tumor weight at study termination in the GZ17 treatment group, there was no statistical difference. Fortified Arum palaestinum Boiss caused a reduction in

  18. Do calorie-controlled portion sizes of snacks reduce energy intake?

    PubMed Central

    Stroebele, Nanette; Ogden, Lorraine G.; Hill, James O.

    2009-01-01

    In a cross-over study, participants (n=59) were randomly assigned to receive either 100 kcal packs or standard size packages of snacks for 1-week. After a minimum of a 1-week washout period, participants received the other form of the snack for 1 week. Snack consumption was recorded by participants in a diary. Participants consumed an average of 186.9 fewer grams of snacks per week when receiving 100 kcal snack packs compared to standard size packages of snacks. Post-hoc comparisons revealed the effect of package size depended on both randomization order and study week. Total grams of snacks consumed in week 1 differed significantly between the two randomized groups. In week 2, however, grams of snacks did not differ significantly between the two groups. This interaction was primarily due to a significantly lower consumption of snacks from standard size packages in the week following the portion-controlled packages. The results suggest that portion-controlled packaging reduce total intake from the provided snacks. Further, initial exposure to portion-controlled packages might have increased awareness of portion size such that less was consumed when larger packages were available. PMID:19501784

  19. Electromagnetic transponders indicate prostate size increase followed by decrease during the course of external beam radiation therapy.

    PubMed

    King, Benjamin L; Butler, Wayne M; Merrick, Gregory S; Kurko, Brian S; Reed, Joshua L; Murray, Brian C; Wallner, Kent E

    2011-04-01

    Real-time image guidance enables more accurate radiation therapy by tracking target movement. This study used transponder positions to monitor changes in prostate volume that may be a source of dosimetric and target inaccuracy. Twenty-four men with biopsy-proven T1c-T3a prostate cancer each had three electromagnetic transponders implanted transperineally. Their coordinates were recorded by the Calypso system, and the perimeter of the triangle formed by the transponders was used to calculate prostate volumes at sequential time points throughout the course of radiation therapy to a dose of 81 Gy in 1.8-Gy fractions. There was a significant decrease in mean prostate volume of 10.9% from the first to the final day of radiation therapy. The volume loss did not occur monotonically but increased in most patients (75%) during the first several weeks to a median maximum on Day 7. The volume increased by a mean of 6.1% before decreasing by a mean maximum difference of 18.4% to nadir (p < 0.001 for both increase and decrease). Glandular shrinkage was asymmetric, with the apex to right base dimension varying more than twice that of the lateral dimension. For all dimensions, the mean change was <0.5 cm. Real-time transponder positions indicated a volume increase during the initial days of radiation therapy and then significant and asymmetric shrinkage by the final day. Understanding and tracking volume fluctuations of the prostate during radiation therapy can help real-time imaging technology perform to its fullest potential. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Electromagnetic Transponders Indicate Prostate Size Increase Followed by Decrease During the Course of External Beam Radiation Therapy

    SciTech Connect

    King, Benjamin L.; Butler, Wayne M.; Merrick, Gregory S.; Kurko, Brian S.; Reed, Joshua L.; Murray, Brian C.; Wallner, Kent E.

    2011-04-01

    Purpose: Real-time image guidance enables more accurate radiation therapy by tracking target movement. This study used transponder positions to monitor changes in prostate volume that may be a source of dosimetric and target inaccuracy. Methods and Materials: Twenty-four men with biopsy-proven T1c-T3a prostate cancer each had three electromagnetic transponders implanted transperineally. Their coordinates were recorded by the Calypso system, and the perimeter of the triangle formed by the transponders was used to calculate prostate volumes at sequential time points throughout the course of radiation therapy to a dose of 81 Gy in 1.8-Gy fractions. Results: There was a significant decrease in mean prostate volume of 10.9% from the first to the final day of radiation therapy. The volume loss did not occur monotonically but increased in most patients (75%) during the first several weeks to a median maximum on Day 7. The volume increased by a mean of 6.1% before decreasing by a mean maximum difference of 18.4% to nadir (p < 0.001 for both increase and decrease). Glandular shrinkage was asymmetric, with the apex to right base dimension varying more than twice that of the lateral dimension. For all dimensions, the mean change was <0.5 cm. Conclusion: Real-time transponder positions indicated a volume increase during the initial days of radiation therapy and then significant and asymmetric shrinkage by the final day. Understanding and tracking volume fluctuations of the prostate during radiation therapy can help real-time imaging technology perform to its fullest potential.

  1. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression.

    PubMed

    Ayala, Gustavo; Morello, Matteo; Frolov, Anna; You, Sungyong; Li, Rile; Rosati, Fabiana; Bartolucci, Gianluca; Danza, Giovanna; Adam, Rosalyn M; Thompson, Timothy C; Lisanti, Michael P; Freeman, Michael R; Vizio, Dolores Di

    2013-09-01

    Levels of caveolin-1 (Cav-1) in tumour epithelial cells increase during prostate cancer progression. Conversely, Cav-1 expression in the stroma can decline in advanced and metastatic prostate cancer. In a large cohort of 724 prostate cancers, we observed significantly decreased levels of stromal Cav-1 in concordance with increased Gleason score (p = 0.012). Importantly, reduced expression of Cav-1 in the stroma correlated with reduced relapse-free survival (p = 0.009), suggesting a role for stromal Cav-1 in inhibiting advanced disease. Silencing of Cav-1 by shRNA in WPMY-1 prostate fibroblasts resulted in up-regulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion, and metastasis, including a > 2.5-fold increase in TGF-β1 and γ-synuclein (SNCG) gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. Pharmacological inhibition of Akt caused down-regulation of TGF-β1 and SNCG, suggesting that loss of Cav-1 in the stroma can influence Akt-mediated signalling in the tumour microenvironment. Cav-1-depleted stromal cells exhibited increased levels of intracellular cholesterol, a precursor for androgen biosynthesis, steroidogenic enzymes, and testosterone. These findings suggest that loss of Cav-1 in the tumour microenvironment contributes to the metastatic behaviour of tumour cells by a mechanism that involves up-regulation of TGF-β1 and SNCG through Akt activation. They also suggest that intracrine production of androgens, a process relevant to castration resistance, may occur in the stroma. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression

    PubMed Central

    Frolov, Anna; You, Sungyong; Li, Rile; Rosati, Fabiana; Bartolucci, Gianluca; Danza, Giovanna; Adam, Rosalyn M; Thompson, Timothy C; Lisanti, Michael P; Freeman, Michael R; Vizio, Dolores Di

    2014-01-01

    Levels of caveolin-1 (Cav-1) in tumour epithelial cells increase during prostate cancer progression. Conversely, Cav-1 expression in the stroma can decline in advanced and metastatic prostate cancer. In a large cohort of 724 prostate cancers, we observed significantly decreased levels of stromal Cav-1 in concordance with increased Gleason score (p = 0.012). Importantly, reduced expression of Cav-1 in the stroma correlated with reduced relapse-free survival (p = 0.009), suggesting a role for stromal Cav-1 in inhibiting advanced disease. Silencing of Cav-1 by shRNA in WPMY-1 prostate fibroblasts resulted in up-regulation of Akt phosphorylation, and significantly altered expression of genes involved in angiogenesis, invasion, and metastasis, including a > 2.5-fold increase in TGF-β1 and γ-synuclein (SNCG) gene expression. Moreover, silencing of Cav-1 induced migration of prostate cancer cells when stromal cells were used as attractants. Pharmacological inhibition of Akt caused down-regulation of TGF-β1 and SNCG, suggesting that loss of Cav-1 in the stroma can influence Akt-mediated signalling in the tumour microenvironment. Cav-1-depleted stromal cells exhibited increased levels of intracellular cholesterol, a precursor for androgen biosynthesis, steroidogenic enzymes, and testosterone. These findings suggest that loss of Cav-1 in the tumour microenvironment contributes to the metastatic behaviour of tumour cells by a mechanism that involves up-regulation of TGF-β1 and SNCG through Akt activation. They also suggest that intracrine production of androgens, a process relevant to castration resistance, may occur in the stroma. PMID:23729330

  3. Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function.

    PubMed

    Pischke, Soeren E; Gustavsen, A; Orrem, H L; Egge, K H; Courivaud, F; Fontenelle, H; Despont, A; Bongoni, A K; Rieben, R; Tønnessen, T I; Nunn, M A; Scott, H; Skulstad, H; Barratt-Due, A; Mollnes, T E

    2017-05-01

    Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized that inhibition of C5 before reperfusion will decrease infarct size and improve ventricular function in a porcine model of myocardial infarction. In pigs (Sus scrofa), the left anterior descending coronary artery was occluded (40 min) and reperfused (240 min). Coversin or placebo was infused 20 min after occlusion and throughout reperfusion in 16 blindly randomized pigs. Coversin significantly reduced myocardial infarction in the area at risk by 39% (p = 0.03, triphenyl tetrazolium chloride staining) and by 19% (p = 0.02) using magnetic resonance imaging. The methods correlated significantly (R = 0.92, p < 0.01). Tissue Doppler echocardiography showed increased systolic displacement (31%, p < 0.01) and increased systolic velocity (29%, p = 0.01) in coversin treated pigs. Interleukin-1β in myocardial microdialysis fluid was significantly reduced (31%, p < 0.05) and tissue E-selectin expression was significantly reduced (p = 0.01) in the non-infarcted area at risk by coversin treatment. Coversin ablated plasma C5 activation throughout the reperfusion period and decreased myocardial C5b-9 deposition, while neither plasma nor myocardial LTB4 were significantly reduced. Coversin substantially reduced the size of infarction, improved ventricular function, and attenuated interleukin-1β and E-selectin in this porcine model by inhibiting C5. We conclude that inhibition of C5 in myocardial infarction should be reconsidered.

  4. Polyamine contents in current foods: a basis for polyamine reduced diet and a study of its long term observance and tolerance in prostate carcinoma patients.

    PubMed

    Cipolla, B G; Havouis, R; Moulinoux, J P

    2007-08-01

    Polyamine contents were assessed by mass spectrometry in 233 current foods and beverages. In order to reduce gut polyamine uptake, a polyamine reduced diet (PRD) and partial intermittent intestinal tract decontamination (PIITD) with neomycin or nifuroxazide was proposed as nutritional therapy to 33 prostate carcinoma patients, 30 of whom with hormone refractory prostate cancer (HRPC). Mean PRD observance was 22 +/- 19 (median: 16; range: 3-72) months. 10, 8 and 3 patients were respectively on PRD for more than 30, 36 and 64 months. No diet toxicity was observed. 8 patients had moderate intestinal intolerance due to PIITD which was interrupted. No significant differences in body weight, blood counts or serum protein levels were observed during the follow-up of patients under PRD. Performance status and pain scores were relatively stable during the trial with improved pain scores at 6 months. A PRD associated with intermittent PIITD is a safe and well observed nutritional regimen and long term observance is possible.

  5. A case of liver hemangioma with markedly reduced tumor size after metformin treatment: a case report.

    PubMed

    Ono, Minoru; Sawada, Koji; Okumura, Toshikatsu

    2017-02-01

    A 52-year-old man with a 9-year history of hepatic hemangioma was treated with the anti-diabetic drug metformin, resulting in complete remission of the tumor. In 2006, a hemangioma with diameter of 20 × 25 mm was detected incidentally in the liver. The results of imaging studies including ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) were all compatible with that of hepatic hemangioma. The patient consequently underwent imaging annually from 2006 to 2015. The tumor size increased slightly, to 30 × 35 mm in 2012; however, the general tumor characteristics in imaging were not changed. Beginning May 2012, metformin (750 mg/day) was administered because of an increase in blood sugar and hemoglobin A1c levels. After the start of metformin treatment, the tumor size on US gradually decreased. Finally, in October 2015, the tumor was no longer detected. Dynamic CT study also demonstrated markedly reduced tumor size, with a decrease of 2-3 mm in diameter. These results indicate that metformin treatment strongly suppressed cell proliferation in liver hemangioma. The anti-angiogenic effect of metformin was indicated as a possible cause of the reduction in tumor size.

  6. Deconvolution algorithms for photoacoustic tomography to reduce blurring caused by finite sized detectors

    NASA Astrophysics Data System (ADS)

    Burgholzer, Peter; Roitner, Heinz; Berer, Thomas; Grün, Hubert; O'Leary, D. P.; Nuster, R.; Paltauf, G.; Haltmeier, M.

    2013-03-01

    Most reconstruction algorithms for photoacoustic tomography, like back-projection or time-reversal, work ideally for point-like detectors. For real detectors, which integrate the pressure over their finite size, it was shown that images reconstructed by back-projection or time-reversal show some blurring. Iterative reconstruction algorithms using an imaging matrix can take the finite size of real detectors directly into account, but the numerical effort is significantly higher compared to the use of direct algorithms. For spherical or cylindrical detection surfaces the blurring caused by a finite detector size is proportional to the distance from the rotation center ("spin blur") and is equal to the detector size at the detection surface. In this work we use deconvolution algorithms to reduce this type of blurring on simulated and on experimental data. Experimental data were obtained on a plastisol cylinder with 6 thin holes filled with an absorbing liquid (OrangeG). The holes were located on a spiral emanating from the center of the cylinder. Data acquisition was done by utilization of a piezoelectric detector which was rotated around the plastisol cylinder.

  7. High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice.

    PubMed

    Chang, Seo-Na; Han, Juhee; Abdelkader, Tamer Said; Kim, Tae-Hyoun; Lee, Ji Min; Song, Juha; Kim, Kyung-Sul; Park, Jong-Hwan; Park, Jae-Hak

    2014-09-01

    Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high-fat Western-style diet is a known risk factor for prostate cancer and increases oxidative stress. We evaluated the association between dietary animal fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3 (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Six-week-old male nontransgenic and TRAMP mice were placed on high animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5 or 10 weeks. The histopathological score increased with age and high-fat diet consumption. The histopathological scores in dorsal and lateral lobes increased in the 10-week high-fat diet group (6.2±0.2 and 6.2±0.4, respectively) versus the 10-week control diet group (5.3±0.3 and 5.2±0.2, respectively). GPx3 decreased both at the mRNA and protein levels in mouse prostate. GPx3 mRNA expression decreased (∼36.27% and ∼23.91%, respectively) in the anterior and dorsolateral prostate of TRAMP mice fed a high-fat diet compared to TRAMP mice fed a control diet. Cholesterol treatment increased PC-3 human prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and increased H2 O2 levels in culture medium. Moreover, increasing GPx3 mRNA expression by troglitazone in PC-3 cells decreased cell proliferation and lowered H2 O2 levels. Dietary fat enhances prostate cancer progression, possibly by suppressing GPx3 expression and increasing proliferation of prostate intraepithelial neoplasia (PIN) epithelial cells. © 2014 Wiley Periodicals, Inc.

  8. Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

    PubMed Central

    Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

    2015-01-01

    Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

  9. Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys.

    PubMed

    Gonzales, Lauren A; Benefit, Brenda R; McCrossin, Monte L; Spoor, Fred

    2015-07-03

    Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently.

  10. Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases.

    PubMed

    Chen, Jie-Fu; Ho, Hao; Lichterman, Jake; Lu, Yi-Tsung; Zhang, Yang; Garcia, Mitch A; Chen, Shang-Fu; Liang, An-Jou; Hodara, Elisabeth; Zhau, Haiyen E; Hou, Shuang; Ahmed, Rafi S; Luthringer, Daniel J; Huang, Jiaoti; Li, Ker-Chau; Chung, Leland W K; Ke, Zunfu; Tseng, Hsian-Rong; Posadas, Edwin M

    2015-09-15

    Although enumeration of circulating tumor cells (CTCs) has shown some clinical value, the pool of CTCs contains a mixture of cells that contains additional information that can be extracted. The authors subclassified CTCs by shape features focusing on nuclear size and related this with clinical information. A total of 148 blood samples were obtained from 57 patients with prostate cancer across the spectrum of metastatic states: no metastasis, nonvisceral metastasis, and visceral metastasis. CTCs captured and enumerated on NanoVelcro Chips (CytoLumina, Los Angeles, Calif) were subjected to pathologic review including nuclear size. The distribution of nuclear size was analyzed using a Gaussian mixture model. Correlations were made between CTC subpopulations and metastatic status. Statistical modeling of nuclear size distribution revealed 3 distinct subpopulations: large nuclear CTCs, small nuclear CTCs, and very small nuclear CTCs (vsnCTCs). Small nuclear CTCs and vsnCTC identified those patients with metastatic disease. However, vsnCTC counts alone were found to be elevated in patients with visceral metastases when compared with those without (0.36 ± 0.69 vs 1.95 ± 3.77 cells/mL blood; P<.001). Serial enumeration studies suggested the emergence of vsnCTCs occurred before the detection of visceral metastases. There are morphologic subsets of CTCs that can be identified by fundamental pathologic approaches, such as nuclear size measurement. The results of this observational study strongly suggest that CTCs contain relevant information regarding disease status. In particular, the detection of vsnCTCs was found to be correlated with the presence of visceral metastases and should be formally explored as a putative blood-borne biomarker to identify patients at risk of developing this clinical evolution of prostate cancer. © 2015 American Cancer Society.

  11. Epithelial defect in prostates of Stat5a-null mice.

    PubMed

    Nevalainen, M T; Ahonen, T J; Yamashita, H; Chandrashekar, V; Bartke, A; Grimley, P M; Robinson, G W; Hennighausen, L; Rui, H

    2000-07-01

    The transcription factor Stat5a critically mediates prolactin (PRL)-induced mammary gland development and lactogenesis. PRL also stimulates growth and differentiation of prostate tissue. Specifically, hyperprolactinemia gives rise to prostate hyperplasia, and prostate size is reduced in PRL-deficient mice. We therefore investigated the importance of Stat5a for prostate development and function by examining Stat5a-null mice. The absence of Stat5a in mice was associated with a distinct prostate morphology characterized by an increased prevalence of local disorganization within acinar epithelium of ventral prostates. Affected acini were typically filled with desquamated, granular epithelial cells that had become embedded in dense, coagulated secretory material. These features were reminiscent of acinar cyst formation and degeneration frequently observed in human benign prostate hyperplasia, however, cystic changes in prostate acini of Stat5a-deficient mice were not associated with increased prostate size or morphologic hallmarks of epithelial hyperplasia. Instead, immunohistochemistry of the prostate-specific secretory marker, probasin, suggested that hypersecretory function of the epithelium could underlie local congestion and cyst formation in prostates of Stat5a-null mice. Serum testosterone and PRL levels were normal in Stat5a knockout mice, but prostate PRL receptor expression was reduced as determined by immunohistochemistry. Expression levels or activation states of other PRL signal transduction proteins, including Stat5b, Stat3, Stat1, ERK1, and ERK2 were not altered. The present study offers the first evidence for a direct role of Stat5a in the maintenance of normal tissue architecture and function of the mouse prostate.

  12. The Role of Social Norms in the Portion Size Effect: Reducing Normative Relevance Reduces the Effect of Portion Size on Consumption Decisions

    PubMed Central

    Versluis, Iris; Papies, Esther K.

    2016-01-01

    People typically eat more from large portions of food than from small portions. An explanation that has often been given for this so-called portion size effect is that the portion size acts as a social norm and as such communicates how much is appropriate to eat. In this paper, we tested this explanation by examining whether manipulating the relevance of the portion size as a social norm changes the portion size effect, as assessed by prospective consumption decisions. We conducted one pilot experiment and one full experiment in which participants respectively indicated how much they would eat or serve themselves from a given amount of different foods. In the pilot (N = 63), we manipulated normative relevance by allegedly basing the portion size on the behavior of either students of the own university (in-group) or of another university (out-group). In the main experiment (N = 321), we told participants that either a minority or majority of people similar to them approved of the portion size. Results show that in both experiments, participants expected to serve themselves and to eat more from larger than from smaller portions. As expected, however, the portion size effect was less pronounced when the reference portions were allegedly based on the behavior of an out-group (pilot) or approved only by a minority (main experiment). These findings suggest that the portion size indeed provides normative information, because participants were less influenced by it if it communicated the behaviors or values of a less relevant social group. In addition, in the main experiment, the relation between portion size and the expected amount served was partially mediated by the amount that was considered appropriate, suggesting that concerns about eating an appropriate amount indeed play a role in the portion size effect. However, since the portion size effect was weakened but not eliminated by the normative relevance manipulations and since mediation was only partial, other

  13. The Role of Social Norms in the Portion Size Effect: Reducing Normative Relevance Reduces the Effect of Portion Size on Consumption Decisions.

    PubMed

    Versluis, Iris; Papies, Esther K

    2016-01-01

    People typically eat more from large portions of food than from small portions. An explanation that has often been given for this so-called portion size effect is that the portion size acts as a social norm and as such communicates how much is appropriate to eat. In this paper, we tested this explanation by examining whether manipulating the relevance of the portion size as a social norm changes the portion size effect, as assessed by prospective consumption decisions. We conducted one pilot experiment and one full experiment in which participants respectively indicated how much they would eat or serve themselves from a given amount of different foods. In the pilot (N = 63), we manipulated normative relevance by allegedly basing the portion size on the behavior of either students of the own university (in-group) or of another university (out-group). In the main experiment (N = 321), we told participants that either a minority or majority of people similar to them approved of the portion size. Results show that in both experiments, participants expected to serve themselves and to eat more from larger than from smaller portions. As expected, however, the portion size effect was less pronounced when the reference portions were allegedly based on the behavior of an out-group (pilot) or approved only by a minority (main experiment). These findings suggest that the portion size indeed provides normative information, because participants were less influenced by it if it communicated the behaviors or values of a less relevant social group. In addition, in the main experiment, the relation between portion size and the expected amount served was partially mediated by the amount that was considered appropriate, suggesting that concerns about eating an appropriate amount indeed play a role in the portion size effect. However, since the portion size effect was weakened but not eliminated by the normative relevance manipulations and since mediation was only partial, other

  14. Prostate Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Prostate Cancer What is Prostate Cancer? How Tumors Form The body is made up ... the Escape (Esc) button on your keyboard.) How Prostate Cancer Occurs Prostate cancer occurs when a tumor forms ...

  15. Diosgenin, a Steroidal Saponin, Inhibits Migration and Invasion of Human Prostate Cancer PC-3 Cells by Reducing Matrix Metalloproteinases Expression

    PubMed Central

    Chen, Pin-Shern; Shih, Yuan-Wei; Huang, Hsiang-Ching; Cheng, Hsing-Wen

    2011-01-01

    Background Diosgenin, a steroidal saponin obtained from fenugreek (Trigonella foenum graecum), was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells. Methods and Principal Findings Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 (MMP-2) and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2, -9, -7 and extracellular inducer of matrix metalloproteinase (EMMPRIN) were also suppressed while tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor (VEGF) in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt, extracellular signal regulating kinase (ERK) and c-Jun N-terminal kinase (JNK). In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that diosgenin inhibited NF-κB activity. Conclusion/Significance The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy. PMID:21629786

  16. A retrospective feasibility study of biweekly, reduced-dose docetaxel in Asian patients with castrate-resistant, metastatic prostate cancer.

    PubMed

    Kim, Hae Su; Lee, Ji Yun; Lee, Su Jin; Lim, Ho Yeong; Sung, Hyun Hwan; Jeon, Hwang Gyun; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Park, Se Hoon

    2017-08-22

    The aim of this retrospective study was to evaluate the clinical outcomes of reduced dose, biweekly docetaxel chemotherapy for Korean patients with castrate-resistant prostate cancer (CRPC). We retrospectively reviewed the medical records of 48 patients with metastatic CRPC who were treated with a biweekly regimen (intravenous docetaxel 40 mg/m(2) on day 1 plus prednisolone 5 mg twice daily) between 2012 and 2015 at Samsung Medical Center (Seoul, Korea). Prior to the adoption of a biweekly regimen in Oct 2013, our institutional standard chemotherapy was docetaxel 75 mg/m(2) every 3 weeks for patients with CRPC (n = 24). After Oct 2013, all chemotherapy-naïve patients with CRPC received a 40 mg/m(2) biweekly regimen (n = 24). The primary end point was a PSA response, defined as a greater than 50% decline in PSA level from baseline. The baseline characteristics of the patients in the two treatment groups were similar. The most common cause of treatment discontinuation was disease progression, which was exhibited by 17 patients (71%) in the 3-weekly group and 20 (75%) in the biweekly group. PSA responses were observed in 12 (50%) and 11 (46%) patients in the 3-weekly and biweekly groups, respectively (p = 0.683). Time to treatment failure (TTTF, 4.5 vs 3.9 months) and time-to-progression (TTP, 5.0 vs 4.2 months) were not significantly different between the 3-weekly and biweekly groups. Within the limitations of a retrospective study, the biweekly reduced dose docetaxel regimen was active and well-tolerated in Korean patients with metastatic CRPC.

  17. Radiation damage in protein crystals is reduced with a micron-sized X-ray beam.

    PubMed

    Sanishvili, Ruslan; Yoder, Derek W; Pothineni, Sudhir Babu; Rosenbaum, Gerd; Xu, Shenglan; Vogt, Stefan; Stepanov, Sergey; Makarov, Oleg A; Corcoran, Stephen; Benn, Richard; Nagarajan, Venugopalan; Smith, Janet L; Fischetti, Robert F

    2011-04-12

    Radiation damage is a major limitation in crystallography of biological macromolecules, even for cryocooled samples, and is particularly acute in microdiffraction. For the X-ray energies most commonly used for protein crystallography at synchrotron sources, photoelectrons are the predominant source of radiation damage. If the beam size is small relative to the photoelectron path length, then the photoelectron may escape the beam footprint, resulting in less damage in the illuminated volume. Thus, it may be possible to exploit this phenomenon to reduce radiation-induced damage during data measurement for techniques such as diffraction, spectroscopy, and imaging that use X-rays to probe both crystalline and noncrystalline biological samples. In a systematic and direct experimental demonstration of reduced radiation damage in protein crystals with small beams, damage was measured as a function of micron-sized X-ray beams of decreasing dimensions. The damage rate normalized for dose was reduced by a factor of three from the largest (15.6 μm) to the smallest (0.84 μm) X-ray beam used. Radiation-induced damage to protein crystals was also mapped parallel and perpendicular to the polarization direction of an incident 1-μm X-ray beam. Damage was greatest at the beam center and decreased monotonically to zero at a distance of about 4 μm, establishing the range of photoelectrons. The observed damage is less anisotropic than photoelectron emission probability, consistent with photoelectron trajectory simulations. These experimental results provide the basis for data collection protocols to mitigate with micron-sized X-ray beams the effects of radiation damage.

  18. Radiation damage in protein crystals is reduced with a micron-sized X-ray beam

    PubMed Central

    Sanishvili, Ruslan; Yoder, Derek W.; Pothineni, Sudhir Babu; Rosenbaum, Gerd; Xu, Shenglan; Vogt, Stefan; Stepanov, Sergey; Makarov, Oleg A.; Corcoran, Stephen; Benn, Richard; Nagarajan, Venugopalan; Smith, Janet L.; Fischetti, Robert F.

    2011-01-01

    Radiation damage is a major limitation in crystallography of biological macromolecules, even for cryocooled samples, and is particularly acute in microdiffraction. For the X-ray energies most commonly used for protein crystallography at synchrotron sources, photoelectrons are the predominant source of radiation damage. If the beam size is small relative to the photoelectron path length, then the photoelectron may escape the beam footprint, resulting in less damage in the illuminated volume. Thus, it may be possible to exploit this phenomenon to reduce radiation-induced damage during data measurement for techniques such as diffraction, spectroscopy, and imaging that use X-rays to probe both crystalline and noncrystalline biological samples. In a systematic and direct experimental demonstration of reduced radiation damage in protein crystals with small beams, damage was measured as a function of micron-sized X-ray beams of decreasing dimensions. The damage rate normalized for dose was reduced by a factor of three from the largest (15.6 μm) to the smallest (0.84 μm) X-ray beam used. Radiation-induced damage to protein crystals was also mapped parallel and perpendicular to the polarization direction of an incident 1-μm X-ray beam. Damage was greatest at the beam center and decreased monotonically to zero at a distance of about 4 μm, establishing the range of photoelectrons. The observed damage is less anisotropic than photoelectron emission probability, consistent with photoelectron trajectory simulations. These experimental results provide the basis for data collection protocols to mitigate with micron-sized X-ray beams the effects of radiation damage. PMID:21444772

  19. Grain dissection as a grain size reducing mechanism during ice microdynamics

    NASA Astrophysics Data System (ADS)

    Steinbach, Florian; Kuiper, Ernst N.; Eichler, Jan; Bons, Paul D.; Drury, Martin R.; Griera, Albert; Pennock, Gill M.; Weikusat, Ilka

    2017-04-01

    Ice sheets are valuable paleo-climate archives, but can lose their integrity by ice flow. An understanding of the microdynamic mechanisms controlling the flow of ice is essential when assessing climatic and environmental developments related to ice sheets and glaciers. For instance, the development of a consistent mechanistic grain size law would support larger scale ice flow models. Recent research made significant progress in numerically modelling deformation and recrystallisation mechanisms in the polycrystalline ice and ice-air aggregate (Llorens et al., 2016a,b; Steinbach et al., 2016). The numerical setup assumed grain size reduction is achieved by the progressive transformation of subgrain boundaries into new high angle grain boundaries splitting an existing grain. This mechanism is usually termed polygonisation. Analogue experiments suggested, that strain induced grain boundary migration can cause bulges to migrate through the whole of a grain separating one region of the grain from another (Jessell, 1986; Urai, 1987). This mechanism of grain dissection could provide an alternative grain size reducing mechanism, but has not yet been observed during ice microdynamics. In this contribution, we present results using an updated numerical approach allowing for grain dissection. The approach is based on coupling the full field theory crystal visco-plasticity code (VPFFT) of Lebensohn (2001) to the multi-process modelling platform Elle (Bons et al., 2008). VPFFT predicts the mechanical fields resulting from short strain increments, dynamic recrystallisation process are implemented in Elle. The novel approach includes improvements to allow for grain dissection, which was topologically impossible during earlier simulations. The simulations are supported by microstructural observations from NEEM (North Greenland Eemian Ice Drilling) ice core. Mappings of c-axis orientations using the automatic fabric analyser and full crystallographic orientations using electron

  20. Grape seed proanthocyanidin supplementation reduces adipocyte size and increases adipocyte number in obese rats.

    PubMed

    Pascual-Serrano, A; Arola-Arnal, A; Suárez-García, S; Bravo, F I; Suárez, M; Arola, L; Bladé, C

    2017-08-01

    White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity. The aim of this study was to determine whether grape seed proanthocyanidin extract (GSPE) can modulate WAT expandability. Because GSPE also contains gallic acid, we also studied the capacity of gallic acid to remodel WAT. Male Wistar rats were fed a standard chow diet (n=6) or a cafeteria diet (CAF) for 11 weeks. After 8 weeks, the CAF-fed animals were supplemented with 25 mg GSPE/kg body weight (n=6), 7 mg gallic acid/kg body weight (n=6) or the vehicle (n=6) for 3 weeks. Histological analyses were performed in the retroperitoneal (rWAT) and inguinal (iWAT) WAT to determine adipocyte size and number. Specific markers for adipogenesis and WAT functionality were analysed in rWAT using quantitative RT-PCR. GSPE or gallic acid supplementation did not reduce weight gain or reverse and adiposity. However, GSPE reduced adipocyte size significantly in rWAT and moderately in iWAT and tripled the adipocyte number in rWAT. Gallic acid slightly reduced adipocyte size in rWAT and iWAT and doubled the adipocyte number in both WATs. In accordance with this adipogenic activity, Pref-1 and PPARγ tended to be overexpressed in rWAT of rats supplemented with GSPE. Moreover, GSPE supplementation increased Plin1 and Fabp4 expression and restored adiponectin expression completely, indicating a better functionality of visceral WAT. GSPE supplementation has anti-hypertrophic and hyperplasic activities in rats with established obesity, mainly in visceral WAT inducing a healthier

  1. Interventions to improve decision making and reduce racial and ethnic disparities in the management of prostate cancer: a systematic review.

    PubMed

    Sajid, Saleha; Kotwal, Ashwin A; Dale, William

    2012-08-01

    Ethnic minorities are disproportionately impacted by prostate cancer (PCa) and are at risk for not receiving informed decision making (IDM). We conducted a systematic literature review on interventions to improve: (1) IDM about PCa in screening-eligible minority men, and (2) quality of life (QOL) in minority PCa survivors. MeSH headings for PCa, ethnic minorities, and interventions were searched in MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO. SUBJECT ELIGIBILITY CRITERIA: We identified U.S.-based, English-language articles (1985 - 2010) on interventions to improve PCa IDM and QOL that included 50% or more minority patients or analyses stratified by race/ethnicity. Articles (n = 19) were evaluated and scored for quality using a Downs and Black (DB) system. Interventions were organized by those enhancing 1) IDM about PCa screening and 2) improving QOL and symptom among PCa survivors. Outcomes were reported by intervention type (educational seminar, printed material, telephone-based, video and web-based). Fourteen studies evaluated interventions for enhancing IDM about PCa screening and five evaluated programs to improve outcomes for PCa survivors. Knowledge scores were statistically significantly increased in 12 of 13 screening studies that measured knowledge, with ranges of effect varying across intervention types: educational programs (13% - 48% increase), print (11% - 18%), videotape/DVD (16%), and web-based (7% - 20%). In the final screening study, an intervention to improve decision-making about screening increased decisional self-efficacy by 9%. Five cognitive-behavioral interventions improved QOL among minority men being treated for localized PCa through enhancing problem solving and coping skills. Weak study designs, small sample sizes, selection biases, and variation in follow-up intervals across studies. Educational programs were the most effective intervention

  2. Public School Education: The Case for Reduced Class Size. Why the Present Class Size is Not Working and What Can We Do about It?

    ERIC Educational Resources Information Center

    Graham, Evol

    2009-01-01

    By reducing class size we will close the achievement gap in public school education, caused by prior neglect especially since the civil rights era of the sixties. Additional, highly qualified and specialized teachers will more effectively manage a smaller class size and serve more individual student needs in the crucial early grades, where a solid…

  3. Irradiation testing of full-sized, reduced-enrichment fuel elements

    SciTech Connect

    Snelgrove, J.L.; Copeland, G.L.

    1983-01-01

    The current status of the irradiation testing of full-sized, reduced-enrichment fuel elements and fuel rods under the US Reduced Enrichment Research and Test Reactor Program is reported. Being tested are UAl/sub x/-Al, U/sub 3/O/sub 8/-Al, U/sub 3/Si/sub 2/-Al, and U/sub 3/Si-Al dispersion fuels and UZrH/sub x/ (TRIGA) fuel at uranium densities in the fuel meat ranging from 1.7 to 6.0 Mg/m/sup 3/. Generally good performance has been experienced to date. Some preliminary results of postirradiation examinations are also included. A whole-core demonstration in the Oak Ridge Research Reactor is planned. Some details of this demonstration are provided.

  4. Efficacy and Safety of Medium-to-long-term Use of Tolterodine Extended Release with or without Tamsulosin in Patients with Benign Prostate Hyperplasia and Larger Prostate Size: A Double-blind, Placebo-controlled, Randomized Clinical Trial

    PubMed Central

    Cai, Jian-Liang; Zhou, Zhe; Yang, Yan; Yan, Yi-Fu; Jing, Shuo; Na, Yan-Qun

    2016-01-01

    Background: The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release (ER) with or without tamsulosin in patients with benign prostate hyperplasia (BPH) and larger prostate size. Methods: Totally, 152 patients (age ≥50 years) with BPH, International Prostate Symptom Score (IPSS) ≥12, quality-of-life (QoL) score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups (n = 38 in each) to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS (total, storage, and voiding subscales), QoL, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) were collected at baseline, and at weeks 4, 12, and 24. Results: Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS (−7.15, −12.20, and −14.66 vs. −3.51, −5.78, and −7.23), storage IPSS (−3.56, −5.63, and −6.66 vs. −1.52, −1.21, and −2.43), voiding IPSS (−2.88, −5.10, and −6.48 vs. −1.52, −3.03, and −2.97), QoL (−1.21, −2.40, and −3.21 vs. −0.39, −1.41, and −1.60), Qmax (2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s), and PVR (−17.88, −26.97, and −27.89 ml vs. −12.03, −11.16, and −16.73 ml) at weeks 4, 12, and 24, respectively; the differences were all statistically significant (P < 0.05). Adverse events (AEs) were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS (−4.61, −6.79, and −5.70), voiding IPSS (−0.64, −1.83, and −1.45), QoL (−0.69, −1.21, and −1.41), or Qmax (−0.79, 2

  5. Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase.

    PubMed

    Youn, Dong-Hyun; Park, Jinbong; Kim, Hye-Lin; Jung, Yunu; Kang, JongWook; Jeong, Mi-Young; Sethi, Gautam; Seok Ahn, Kwang; Um, Jae-Young

    2017-02-07

    Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH.

  6. Intraoperative Frozen Section of the Prostate Reduces the Risk of Positive Margin Whilst Ensuring Nerve Sparing in Patients with Intermediate and High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy: First Reported UK Series.

    PubMed

    Vasdev, Nikhil; Agarwal, Samita; Rai, Bhavan P; Soosainathan, Arany; Shaw, Gregory; Chang, Sebastian; Prasad, Venkat; Mohan-S, Gowrie; Adshead, James M

    2016-05-01

    Nerve sparing during robotic radical prostatectomy (RRP) considerably improves post-operative potency and urinary continence as long as it does not compromise oncological outcome. Excision of the neurovascular bundle (NVB) is often performed in patients with intermediate and high risk prostate cancer to reduce the risk of positive surgical margin raising the risk of urinary incontinence and impotence. We present the first UK series outcomes of such patients who underwent an intra-operative frozen section (IOFS) analysis of the prostate during RRP allowing nerve sparing. We prospectively analysed the data of 40 patients who underwent an IOFS during RRP at our centre from November 2012 until November 2014. Our IOFS technique involved whole lateral circumferential analysis of the prostate during RRP with the corresponding neurovascular tissue. An intrafascial nerve spare was performed and the specimen was removed intra-operatively via an extension of the 12 mm Autosuture™ camera port without undocking robotic arms. It was then painted by the surgeon and sprayed with "Ink Aid" prior to frozen section analysis. The corresponding NVB was excised if the histopathologist found a positive surgical margin on frozen section. Median time to extract the specimen, wound closure and re-establishment of pneumoperitoneum increased the operative time by 8 min. Median blood loss for IOFS was 130 ± 97 ml vs. 90 ± 72 ml (p = NS). IOFS was not associated with major complications or with blood transfusion. PSM decreased significantly from non-IOFS RRP series of 28.7 to 7.8% (p < 0.05). Intra-operative PSM on the prostate specimen was seen in 8/40 margin analysis (20%) leading to an excision of the contra-lateral nerve bundle. On analysis of the nerve bundle on a paraffin embedded block, 6 nerve bundle matched tumor on the specimen whereas 2 NVB were retrospectively removed unnecessarily in our series. All 40 patients have undetectable PSA at a mean follow up of 21.2 months (SD 7

  7. Is there a critical endometrioma size associated with reduced ovarian responsiveness in assisted reproduction techniques?

    PubMed

    Coccia, Maria Elisabetta; Rizzello, Francesca; Barone, Stefano; Pinelli, Sara; Rapalini, Erika; Parri, Cristiana; Caracciolo, Domenico; Papageorgiou, Savvas; Cima, Gianpaolo; Gandini, Loredana

    2014-08-01

    This study investigated the relationships between ovarian endometrioma size, ovarian responsiveness and the number of retrieved oocytes following ovarian stimulation. A prospective study was conducted in a public clinical assisted reproduction centre. A total of 64 infertile women with monolateral endometriomas undergoing IVF or intracytoplasmic sperm injection were included in the study. The total number of follicles, number of follicles ≥ 16 mm and number of oocytes retrieved of ovaries containing endometrioma and normal ovaries were compared. Multivariate linear regression was used to assess whether number of follicles and collected oocytes varied by endometrioma size, age, basal FSH concentration. Significantly lower numbers of follicles ≥ 16 mm (P = 0.024) and oocytes retrieved (P = 0.001) in the ovaries containing endometrioma were observed. In patients with endometriomas ≥ 30 mm, endometrioma size was the most influential contributor to the total number of follicles and oocytes retrieved. Ovarian endometriomas result in reduced response to ovarian stimulation, compared with the response of the contralateral normal ovary in the same individual. In case of endometriomas <30 mm, basal FSH concentration remains the most important prognostic factor for oocyte retrieval. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  8. A brief mindfulness intervention reduces unhealthy eating when hungry, but not the portion size effect.

    PubMed

    Marchiori, David; Papies, Esther K

    2014-04-01

    The present research examined the effects of a mindfulness-based intervention to foster healthy eating. Specifically, we tested whether a brief mindfulness manipulation can prevent the portion size effect, and reduce overeating on unhealthy snacks when hungry. 110 undergraduate participants (MAge=20.9±2.3; MBMI=22.3±2.5) were served a small or a large portion of chocolate chip cookies after listening to an audio book or performing a mindfulness exercise (i.e., body scan). Current level of hunger was assessed unobtrusively on a visual analog scale before the eating situation. Calorie intake from chocolate chip cookies. When presented with a large compared to a small portion, participants consumed more cookies (+83kcal). This was not affected by the mindfulness intervention or by hunger. However, while control participants ate more unhealthy food when hungry than when not hungry (+67kcal), participants in the mindfulness condition did not (+1kcal). Findings confirm the prevalence and robustness of the portion size effect and suggest that it may be independent from awareness of internal cues. Prevention strategies may benefit more from targeting awareness of the external environment. However, mindfulness-based interventions may be effective to reduce effects of hunger on unhealthy food consumption. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. REDUCED CHLOROPLAST COVERAGE genes from Arabidopsis thaliana help to establish the size of the chloroplast compartment

    DOE PAGES

    Larkin, Robert M.; Stefano, Giovanni; Ruckle, Michael E.; ...

    2016-02-09

    Eukaryotic cells require mechanisms to establish the proportion of cellular volume devoted to particular organelles. These mechanisms are poorly understood. From a screen for plastid-to-nucleus signaling mutants in Arabidopsis thaliana, we cloned a mutant allele of a gene that encodes a protein of unknown function that is homologous to two other Arabidopsis genes of unknown function and Arabidopsis. In contrast to FRIENDLY, these three homologs of FRIENDLY are found only in photosynthetic organisms. Based on these data, we proposed that FRIENDLY expanded into a small gene family to help regulate the energy metabolism of cells that contain both mitochondria andmore » chloroplasts. Indeed, we found that knocking out these genes caused a number of chloroplast phenotypes, including a reduction in the proportion of cellular volume devoted to chloroplasts to 50% of wild type. Thus, we refer to these genes as REDUCED CHLOROPLAST COVERAGE (REC). The size of the chloroplast compartment was reduced most in rec1 mutants. The REC1 protein accumulated in the cytosol and the nucleus. REC1 was excluded from the nucleus when plants were treated with amitrole, which inhibits cell expansion and chloroplast function. Finally, we conclude that REC1 is an extraplastidic protein that helps to establish the size of the chloroplast compartment, and that signals derived from cell expansion or chloroplasts may regulate REC1.« less

  10. REDUCED CHLOROPLAST COVERAGE genes from Arabidopsis thaliana help to establish the size of the chloroplast compartment

    PubMed Central

    Larkin, Robert M.; Stefano, Giovanni; Ruckle, Michael E.; Stavoe, Andrea K.; Sinkler, Christopher A.; Brandizzi, Federica; Malmstrom, Carolyn M.; Osteryoung, Katherine W.

    2016-01-01

    Eukaryotic cells require mechanisms to establish the proportion of cellular volume devoted to particular organelles. These mechanisms are poorly understood. From a screen for plastid-to-nucleus signaling mutants in Arabidopsis thaliana, we cloned a mutant allele of a gene that encodes a protein of unknown function that is homologous to two other Arabidopsis genes of unknown function and to FRIENDLY, which was previously shown to promote the normal distribution of mitochondria in Arabidopsis. In contrast to FRIENDLY, these three homologs of FRIENDLY are found only in photosynthetic organisms. Based on these data, we proposed that FRIENDLY expanded into a small gene family to help regulate the energy metabolism of cells that contain both mitochondria and chloroplasts. Indeed, we found that knocking out these genes caused a number of chloroplast phenotypes, including a reduction in the proportion of cellular volume devoted to chloroplasts to 50% of wild type. Thus, we refer to these genes as REDUCED CHLOROPLAST COVERAGE (REC). The size of the chloroplast compartment was reduced most in rec1 mutants. The REC1 protein accumulated in the cytosol and the nucleus. REC1 was excluded from the nucleus when plants were treated with amitrole, which inhibits cell expansion and chloroplast function. We conclude that REC1 is an extraplastidic protein that helps to establish the size of the chloroplast compartment, and that signals derived from cell expansion or chloroplasts may regulate REC1. PMID:26862170

  11. REDUCED CHLOROPLAST COVERAGE genes from Arabidopsis thaliana help to establish the size of the chloroplast compartment.

    PubMed

    Larkin, Robert M; Stefano, Giovanni; Ruckle, Michael E; Stavoe, Andrea K; Sinkler, Christopher A; Brandizzi, Federica; Malmstrom, Carolyn M; Osteryoung, Katherine W

    2016-02-23

    Eukaryotic cells require mechanisms to establish the proportion of cellular volume devoted to particular organelles. These mechanisms are poorly understood. From a screen for plastid-to-nucleus signaling mutants in Arabidopsis thaliana, we cloned a mutant allele of a gene that encodes a protein of unknown function that is homologous to two other Arabidopsis genes of unknown function and to FRIENDLY, which was previously shown to promote the normal distribution of mitochondria in Arabidopsis. In contrast to FRIENDLY, these three homologs of FRIENDLY are found only in photosynthetic organisms. Based on these data, we proposed that FRIENDLY expanded into a small gene family to help regulate the energy metabolism of cells that contain both mitochondria and chloroplasts. Indeed, we found that knocking out these genes caused a number of chloroplast phenotypes, including a reduction in the proportion of cellular volume devoted to chloroplasts to 50% of wild type. Thus, we refer to these genes as REDUCED CHLOROPLAST COVERAGE (REC). The size of the chloroplast compartment was reduced most in rec1 mutants. The REC1 protein accumulated in the cytosol and the nucleus. REC1 was excluded from the nucleus when plants were treated with amitrole, which inhibits cell expansion and chloroplast function. We conclude that REC1 is an extraplastidic protein that helps to establish the size of the chloroplast compartment, and that signals derived from cell expansion or chloroplasts may regulate REC1.

  12. Adipocyte mitochondrial function is reduced in human obesity independent of fat cell size.

    PubMed

    Yin, Xiao; Lanza, Ian R; Swain, James M; Sarr, Michael G; Nair, K Sreekumaran; Jensen, Michael D

    2014-02-01

    It has been suggested that mitochondrial dysfunction in adipocytes contributes to obesity-related metabolic complications. However, obesity results in adipocyte hypertrophy, and large and small adipocytes from the same depot have different characteristics, raising the possibility that obesity-related mitochondrial defects are an inherent function of large adipocytes. Our goal was to examine whether obesity, independent of fat cell size and fat depot, is associated with mitochondria dysfunction. We compared adipocyte mitochondrial function using a cross-sectional comparison study design. The studies were performed at Mayo Clinic, an academic medical center. Omental and/or abdominal subcutaneous adipose samples were collected from 20 age-matched obese and nonobese nondiabetic men and women undergoing either elective abdominal surgery or research needle biopsy. Interventions were not conducted as part of these studies. We measured mitochondrial DNA abundance, oxygen consumption rates, and citrate synthase activity from populations of large and small adipocytes (separated with differential floatation). For both omental and subcutaneous adipocytes, at the cell and organelle level, oxygen consumption rates and citrate synthase activity were significantly reduced in cells from obese compared with nonobese volunteers, even when matched for cell size by comparing large adipocytes from nonobese and small adipocytes from obese. Adipocyte mitochondrial content was not significantly different between obese and nonobese volunteers. Mitochondrial function and content parameters were not different between small and large cells, omental, and subcutaneous adipocytes from the same person. Adipocyte mitochondrial oxidative capacity is reduced in obese compared with nonobese adults and this difference is not due to cell size differences. Adipocyte mitochondrial dysfunction in obesity is therefore related to overall adiposity rather than adipocyte hypertrophy.

  13. Fitness reduction for uncooperative fig wasps through reduced offspring size: a third component of host sanctions.

    PubMed

    Jandér, K C; Dafoe, A; Herre, E A

    2016-09-01

    Mutually beneficial interactions between two species-mutualisms-are ancient, diverse, and of fundamental ecological importance. Nonetheless, factors that prevent one partner from reaping the benefits of the interaction without paying the cost are still poorly understood. Fig trees and their unique pollinators, fig wasps, present a powerful model system for studying mutualism stability. Both partners depend completely on each other for reproduction, cooperation levels can be manipulated, and the resulting field-based fitness quantified. Previous work has shown that fig trees can impose two types of host sanctions that reduce the fitness of wasps that do not pollinate: (1) fig abortion, which kills all developing larvae, and (2) reduced number of wasp offspring in figs that are not aborted. Here we demonstrate a third component of host sanctions. Through manipulative field experiments, we show that for four of five studied species, offspring of pollen-free foundresses are only 50-90% the size of offspring of pollinating foundresses. We further show that in all four studied species, smaller wasps are less likely to reach and enter a flowering fig to become foundresses themselves. Therefore, the experimentally determined size reduction of offspring is estimated to cause an additional reduction of up to 80% in fitness for a pollen-free foundress. We determine that the size reduction of pollen-free offspring acts on the level of the entire fig fruit rather than on individual flowers. These results show that estimates of the fitness effect of host sanctions on uncooperative symbionts should consider not only offspring quantity but also offspring quality. We discuss implications beyond the fig tree-fig wasp mutualism.

  14. Antibiotic prophylaxis with intravenous ceftriaxone and fluoroquinolone reduces infectious complications after transrectal ultrasound-guided prostatic biopsy.

    PubMed

    Lee, Chunwoo; You, Dalsan; Jeong, In Gab; Hong, Jun Hyuk; Choo, Myung-Soo; Ahn, Hanjong; Ahn, Tai Young; Kim, Choung-Soo

    2015-06-01

    To assess the rates of infectious complications before and after the change of prophylactic antibiotic regimens in prostate needle biopsy. The records of 5,577 patients who underwent prostate needle biopsy at Asan Medical Center between August 2005 and July 2012 were retrospectively reviewed. Group 1 (n=1,743) included patients treated between 2005 and 2009 with fluoroquinolone for 3 days, group 2 (n=2,723) included those treated between 2009 and 2012 with ceftriaxone once before the biopsy and fluoroquinolone before biopsy and continue therapy for 3 days, and group 3 (n=1,111) received the same treatment for more than 7 days after the biopsy. Univariable and multivariable logistic regression models addressed risk factors associated with infectious complication after prostate needle biopsy. Infectious complication after prostate needle biopsy developed in 18 (group 1), seven (group 2), and two patients (group 3) (p=0.001). In group 1, seven patients with infectious complication had positive blood cultures and harbored fluoroquinolone-resistant Escherichia coli, four had ceftriaxone susceptible isolates, and three had extended spectrum beta-lactamase-positive E. coli. Two patients in group 1 required intensive care because of septic shock. In multivariable analysis, the patients with combination of fluoroquinolone and ceftriaxone had significantly lower infectious complication rate than the fluoroquinolon alone (p=0.003). Antibiotic prophylaxis with ceftriaxone and fluoroquinolone before prostate needle biopsy decreased the risk of potentially serious infectious complications.

  15. Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation.

    PubMed

    Galvão, D A; Taaffe, D R; Spry, N; Joseph, D; Turner, D; Newton, R U

    2009-01-01

    This study examined the effects of androgen suppression therapy (AST) on upper and lower body muscle strength and a range of direct measures of physical performance using a cross-sectional design with 118 men (48 men undertaking AST for prostate cancer and 70 healthy aged-matched controls) from a single tertiary center. Primary end points included muscle strength for the upper- and lower-body; functional performance--repeated chair rise, usual and fast 6-m walk, 6-m backwards walk and 400-m walk time; and dual-energy X-ray absorptiometry assessment--whole body, regional soft tissue composition and bone mineral density (BMD). Men on AST had significantly reduced muscle strength for the upper- and lower-body and impaired functional performance compared to controls (P<0.05). As expected, AST patients had significantly lower whole-body and hip BMD and higher percent of body fat than controls (P<0.05), and tended to have lower whole-body lean mass (-2.3 kg, P=0.077). Appendicular skeletal muscle was positively associated with upper-body (r=0.400-0.606, P<0.001) and lower-body (r=0.549-0.588, P<0.001) muscle strength, and strength was related to functional performance. Men undertaking AST were consistently impaired across a broad range of physical and functional musculoskeletal performance assessments compared with their age-matched normal controls. These findings are relevant for those patients considering AST for subclinical disease management, but whose physical reserve is marginal. Strategies to counter these adverse effects of AST need to be initiated so that independent living and quality of life can be maintained.

  16. Dose-Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

    SciTech Connect

    Gulliford, Sarah L.; Foo, Kerwyn; Morgan, Rachel C.; Aird, Edwin G.; Bidmead, A. Margaret; Critchley, Helen; Evans, Philip M. D.Phil.; Gianolini, Stefano; Mayles, W. Philip; Moore, A. Rollo; Sanchez-Nieto, Beatriz; Partridge, Mike; Sydes, Matthew R. C.Stat; Webb, Steve; Dearnaley, David P.

    2010-03-01

    Purpose: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>=50 Gy). Evidence is emerging that lower doses could also be important. Methods and Materials: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. Results: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<=80%, V40<=65%, V50<=55%, V60<=40%, V65<=30%, V70<=15%, and V75<=3%. Conclusion: Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

  17. Targeting geranylgeranylation reduces adrenal gland tumor burden in a murine model of prostate cancer metastasis

    PubMed Central

    Reilly, Jacqueline E; Neighbors, Jeffrey D; Tong, Huaxiang; Henry, Michael D; Hohl, Raymond J

    2016-01-01

    The isoprenoid biosynthetic pathway (IBP) is critical for providing substrates for the post-translational modification of proteins key in regulating malignant cell properties, including proliferation, invasion, and migration. Inhibitors of the IBP, including statins and nitrogenous bisphosphonates, are used clinically for the treatment of hypercholesterolemia and bone disease respectively. The statins work predominantly in the liver, while the nitrogenous bisphosphonates are highly sequestered to bone. Inhibition of the entire IBP is limited by organ specificity and side effects resulting from depletion of all isoprenoids. We have developed a novel compound, disodium [(6Z,11E,15E)-9-[bis(sodiooxy)phosphoryl]-17-hydroxy-2,6,12,16-tetramethyheptadeca-2,6,11,15-tetraen-9-yl]phosphonate (GGOHBP), which selectively targets geranylgeranyl diphosphate synthase (GGDPS), reducing post-translational protein geranylgeranylation. Intracardiac injection of luciferase-expressing human-derived 22Rv1 PCa cells into SCID mice resulted in tumor development in bone (100%), adrenal glands (72%), mesentery (22%), liver (17%), and the thoracic cavity (6%). Three weeks after tumor inoculation, daily subcutaneous (SQ) injections of 1.5 mg/kg GGOHBP or the vehicle were given for one month. Dissected tumors revealed areduction in adrenal gland tumors corresponding to a 54% (P < 0.005) reduction in total adrenal gland tumor weight of the treated mice as compared to vehicle-treated controls. Western blot analysis of the harvested tissues showed a reduction in Rap1A geranylgeranylation in adrenal glands and mesenteric tumors of the treated mice while non-tumorous tissues and control mice showed no Rap1A alteration. Our findings detail a novel bisphosphonate compound capable of preferentially altering the IBP in tumor-burdened adrenal glands of a murine model of PCa metastasis. PMID:26070429

  18. Targeting geranylgeranylation reduces adrenal gland tumor burden in a murine model of prostate cancer metastasis.

    PubMed

    Reilly, Jacqueline E; Neighbors, Jeffrey D; Tong, Huaxiang; Henry, Michael D; Hohl, Raymond J

    2015-08-01

    The isoprenoid biosynthetic pathway (IBP) is critical for providing substrates for the post-translational modification of proteins key in regulating malignant cell properties, including proliferation, invasion, and migration. Inhibitors of the IBP, including statins and nitrogenous bisphosphonates, are used clinically for the treatment of hypercholesterolemia and bone disease respectively. The statins work predominantly in the liver, while the nitrogenous bisphosphonates are highly sequestered to bone. Inhibition of the entire IBP is limited by organ specificity and side effects resulting from depletion of all isoprenoids. We have developed a novel compound, disodium [(6Z,11E,15E)-9-[bis(sodiooxy)phosphoryl]-17-hydroxy-2,6,12,16-tetramethyheptadeca-2,6,11,15-tetraen-9-yl]phosphonate (GGOHBP), which selectively targets geranylgeranyl diphosphate synthase, reducing post-translational protein geranylgeranylation. Intracardiac injection of luciferase-expressing human-derived 22Rv1 PCa cells into SCID mice resulted in tumor development in bone (100 %), adrenal glands (72 %), mesentery (22 %), liver (17 %), and the thoracic cavity (6 %). Three weeks after tumor inoculation, daily subcutaneous (SQ) injections of 1.5 mg/kg GGOHBP or the vehicle were given for one month. Dissected tumors revealed a reduction in adrenal gland tumors corresponding to a 54 % (P < 0.005) reduction in total adrenal gland tumor weight of the treated mice as compared to vehicle-treated controls. Western blot analysis of the harvested tissues showed a reduction in Rap1A geranylgeranylation in adrenal glands and mesenteric tumors of the treated mice while non-tumorous tissues and control mice showed no Rap1A alteration. Our findings detail a novel bisphosphonate compound capable of preferentially altering the IBP in tumor-burdened adrenal glands of a murine model of PCa metastasis.

  19. Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

    SciTech Connect

    Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly; Zehner, Zendra E

    2008-06-12

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508].

  20. Plant Flavone Apigenin Binds to Nucleic Acid Bases and Reduces Oxidative DNA Damage in Prostate Epithelial Cells

    PubMed Central

    Bhaskaran, Natarajan; Gupta, Sanjay

    2014-01-01

    Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it’s binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2′ deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities. PMID:24614817

  1. Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells.

    PubMed

    Sharma, Haripaul; Kanwal, Rajnee; Bhaskaran, Natarajan; Gupta, Sanjay

    2014-01-01

    Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it's binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2' deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities.

  2. Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats.

    PubMed

    Maranhão, Raul C; Guido, Maria C; de Lima, Aline D; Tavares, Elaine R; Marques, Alyne F; Tavares de Melo, Marcelo D; Nicolau, Jose C; Salemi, Vera Mc; Kalil-Filho, Roberto

    2017-01-01

    Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment. Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery) or with LDE without drug (MI-controls). A sham-surgery group (n=12) was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy. LDE-MTX treatment achieved a 40% improvement in left ventricular (LV) systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine bioavailability in the LV by increasing adenosine receptors and modulating adenosine catabolic enzymes. LDE-MTX increased the expression of myocardial vascular endothelium growth factor (VEGF) associated with adenosine release; this correlated not only with an increase in angiogenesis, but also with other parameters improved by LDE-MTX, suggesting that VEGF increase played an important role in the beneficial effects of LDE-MTX. Overall effects of

  3. Genetic variants reflecting higher vitamin e status in men are associated with reduced risk of prostate cancer.

    PubMed

    Major, Jacqueline M; Yu, Kai; Weinstein, Stephanie J; Berndt, Sonja I; Hyland, Paula L; Yeager, Meredith; Chanock, Stephen; Albanes, Demetrius

    2014-05-01

    Vitamin E (α-tocopherol) plays a key role in the regulation of cell growth and differentiation and has been studied as a potential chemopreventive agent for prostate cancer. The association of serum vitamin E concentrations with cancer risk may be modified by genetic variations in vitamin E-related genes. We examined whether variants in vitamin E-related genes were associated with risk of prostate cancer in a nested case-control study using 483 prostate cancer cases and 542 matched controls of European ancestry from a large U.S. multicenter trial that had available measurements of serum vitamin E concentrations and genotyping of 3 genome-wide association study meta-analysis-identified single-nucleotide polymorphisms (SNPs) associated with circulating vitamin E. ORs and 95% CIs were calculated using unconditional logistic regression adjusted for age, family history of prostate cancer, and serum total cholesterol. Findings suggest lower prostate cancer risk for men whose genotypes reflect higher vitamin E (i.e., α-tocopherol) status. An SNP (rs964184) near budding-site selection protein 13 (yeast) (BUD13), zinc finger protein 259 (ZNF259), and apolipoprotein A5 (APOA5) on 11q23.3 was significantly associated with prostate cancer risk (per-allele OR = 0.75; 95% CI: 0.58, 0.98; P-trend = 0.03). The association between rs964184 and prostate cancer risk was stronger among homozygous carriers of the minor allele (OR = 0.27; 95% CI: 0.09, 0.83). Another variant, rs11057830 in scavenger receptor class-B member 1 (SCARB1) on 12p24.31, approached statistical significance (OR = 0.32; 95% CI: 0.10, 1.01, P = 0.05; 2 minor allele copies). This study suggests that polymorphisms near BUD13/ZNF259/APOA5, involved in vitamin E transport and metabolism, may be associated with lower risk of prostate cancer. This trial was registered at clinicaltrials.gov as NCT00002540.

  4. Diagnosis and management of benign prostatic hyperplasia.

    PubMed

    Edwards, Jonathan L

    2008-05-15

    Benign prostatic hyperplasia is a common condition affecting older men. Typical presenting symptoms include urinary hesitancy, weak stream, nocturia, incontinence, and recurrent urinary tract infections. Acute urinary retention, which requires urgent bladder catheterization, is relatively uncommon. Irreversible renal damage is rare. The initial evaluation should assess the frequency and severity of symptoms and the impact of symptoms on the patient's quality of life. The American Urological Association Symptom Index is a validated instrument for the objective assessment of symptom severity. The initial evaluation should also include a digital rectal examination and urinalysis. Men with hematuria should be evaluated for bladder cancer. A palpable nodule or induration of the prostate requires referral for assessment to rule out prostate cancer. For men with mild symptoms, watchful waiting with annual reassessment is appropriate. Over the past decade, numerous medical and surgical interventions have been shown to be effective in relieving symptoms of benign prostatic hyperplasia. Alpha blockers improve symptoms relatively quickly. Although 5-alpha reductase inhibitors have a slower onset of action, they may decrease prostate size and alter the disease course. Limited evidence shows that the herbal agents saw palmetto extract, rye grass pollen extract, and pygeum relieve symptoms. Transurethral resection of the prostate often provides permanent relief. Newer laser-based surgical techniques have comparable effectiveness to transurethral resection up to two years after surgery with lower perioperative morbidity. Various outpatient surgical techniques are associated with reduced morbidity, but symptom relief may be less durable.

  5. Spectrum of prostatic lesions

    PubMed Central

    2013-01-01

    Background Prostate gland of male reproductive system is about the size of walnut and surrounds the urethra. Most frequently encountered diseases affecting prostate are Prostatitis, Benign prostatic hyperplasia and Prostatic cancer .Our objective of study was to evaluate the spectrum and correlation of prostatic lesions with presenting complaints of patient. Methods It was a cross-sectional study conducted in Pathology Department of Dow Medical College, Dow University of Health Sciences during the period of 1st January 2010 to December 2012. Pathology department of Dow Medical College collected specimens from both Civil Hospital and Lyari General Hospital Karachi, Pakistan. Specimens were taken through transurethral resection of prostate (TURP), simple prostatectomy and radical prostatectomy. A questionnaire was made and information including name, age, ward name of hospital, laboratory number, clinical diagnosis and symptoms were noted in it. Data was entered and analyzed through SPSS 19. Result During the targeted months, 48 prostatic specimens were received with a mean age of 65.7 + -7.6 years. Common presenting complains were urinary retention in 23(47.9%) patients, followed by dribbling in 12(25%). Out of 48 patients, 42 have Benign Prostatic Hyperplasia and 6 have Prostatic Adenocarcinoma. Both Benign Prostatic Hyperplasia and Prostatic Adenocarcinoma were more prevalent in the age group of 60-70 years. Conclusion Frequency of prostatic cancer is on the rise and measures should be taken for its early detection. Screening protocols and awareness programs need to be introduced. Screening programs should be focused on level of androgens and molecular pathogenesis. PMID:24063260

  6. Reduced size liver transplantation from a donor supported by a Berlin Heart.

    PubMed

    Misra, M V; Smithers, C J; Krawczuk, L E; Jenkins, R L; Linden, B C; Weldon, C B; Kim, H B

    2009-11-01

    Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.

  7. Type 2 Diabetes Risk Alleles Are Associated With Reduced Size at Birth

    PubMed Central

    Freathy, Rachel M.; Bennett, Amanda J.; Ring, Susan M.; Shields, Beverley; Groves, Christopher J.; Timpson, Nicholas J.; Weedon, Michael N.; Zeggini, Eleftheria; Lindgren, Cecilia M.; Lango, Hana; Perry, John R.B.; Pouta, Anneli; Ruokonen, Aimo; Hyppönen, Elina; Power, Chris; Elliott, Paul; Strachan, David P.; Järvelin, Marjo-Riitta; Smith, George Davey; McCarthy, Mark I.; Frayling, Timothy M.; Hattersley, Andrew T.

    2009-01-01

    OBJECTIVE Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight. RESEARCH DESIGN AND METHODS We genotyped single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring. RESULTS We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11–31], P = 2 × 10−5, and 14 g [4–23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39–120) lighter at birth than the 8% carrying none (Ptrend = 5 × 10−7). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus. CONCLUSIONS Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype. PMID:19228808

  8. Type 2 diabetes risk alleles are associated with reduced size at birth.

    PubMed

    Freathy, Rachel M; Bennett, Amanda J; Ring, Susan M; Shields, Beverley; Groves, Christopher J; Timpson, Nicholas J; Weedon, Michael N; Zeggini, Eleftheria; Lindgren, Cecilia M; Lango, Hana; Perry, John R B; Pouta, Anneli; Ruokonen, Aimo; Hyppönen, Elina; Power, Chris; Elliott, Paul; Strachan, David P; Järvelin, Marjo-Riitta; Smith, George Davey; McCarthy, Mark I; Frayling, Timothy M; Hattersley, Andrew T

    2009-06-01

    Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight. We genotyped single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring. We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11-31], P = 2 x 10(-5), and 14 g [4-23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39-120) lighter at birth than the 8% carrying none (P(trend) = 5 x 10(-7)). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus. Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype.

  9. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach.

    PubMed

    Rohof, Wout O; Bennink, Roelof J; Boeckxstaens, Guy E

    2014-07-01

    The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P < .001). The pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Reduced size and starvation resistance in adult mosquitoes, Aedes notoscriptus, exposed to predation cues as larvae.

    PubMed

    van Uitregt, Vincent O; Hurst, Timothy P; Wilson, Robbie S

    2012-01-01

    1. Many prey organisms exhibit adaptive phenotypic plasticity in life-history traits that facilitate a better chance of survival in the presence of predators. The evolution of such plastic traits requires that the defensive phenotype incurs a cost in the absence of predation. 2. Model systems that are used to examine predator-induced defences are often organisms with complex life histories that only induce defences during the larval stage. While many studies have detected costs of inducible defences during the larval stage, detecting the costs of larval defences after metamorphosis is also important. 3. We examine the benefits and costs of inducible larval defences in the urban mosquito, Aedes notoscriptus, by rearing them in the presence and absence of predation cues. We compared survival of larvae inducing behavioural defences, when exposed to predation cues, in predation trials with predatory fish Hypseleotris galii to that of larvae reared in the absence predation cues. We also compared life-history traits of predator-exposed larvae to larvae reared in control conditions. 4. Larvae exposed to chemical predation cues limited activity and were able to avoid predation for longer in trials with H. galii. However, predator-exposed larvae suffered retarded larval growth and development, were smaller at metamorphosis and less resistant to starvation as adults. 5. While it is difficult to understand the 'fitness costs' that poorer starvation resistance might confer to adult mosquitoes, it is likely that smaller adult size of predator-exposed individuals would reduce fitness, particularly for females where body size limits the size of blood meal they could take to facilitate egg production. We suggest that the demonstrable costs of inducible defences in mosquito larvae make this a good system for testing theoretical models for the evolutionary maintenance of adaptive phenotypic plasticity.

  11. Xenoendocrine pollutants may reduce size of sexual organs in East Greenland polar bears (Ursus maritimus).

    PubMed

    Sonne, Christian; Leifsson, Pall S; Dietz, Rune; Born, Erik W; Letcher, Robert J; Hyldstrup, Lars; Riget, Frank F; Kirkegaard, Maja; Muir, Derek C G

    2006-09-15

    Reproductive organs from 55 male and 44 female East Greenland polar bears were examined to investigate the potential negative impact from organohalogen pollutants (OHCs). Multiple regressions normalizing for age showed a significant inverse relationship between OHCs and testis length and baculum length and weight, respectively, and was found in both subadults (dichlorodiphenyl trichloroethanes, dieldrin, chlordanes, hexacyclohexanes, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)) and adults (hexachlorobenzene [HCB]) (all p < 0.05). Baculum bone mineral densities decreased with increasing chlordanes, DDTs, and HCB in subadults and adults, respectively (all p < 0.05). In females, a significant inverse relationship was found between ovary length and sigma PCB (p = 0.03) and sigma CHL (p < 0.01), respectively, and between ovary weight and sigma PBDE (p < 0.01) and uterine horn length and HCB (p = 0.02). The study suggests thatthere is an impact from xenoendocrine pollutants on the size of East Greenland polar bear genitalia. This may pose a riskto this polar bear subpopulation in the future because of reduced sperm and egg quality/quantity and uterus and penis size/robustness.

  12. Measuring proteins with greater speed and resolution while reducing sample size.

    PubMed

    Hsieh, Vincent H; Wyatt, Philip J

    2017-08-30

    A multi-angle light scattering (MALS) system, combined with chromatographic separation, directly measures the absolute molar mass, size and concentration of the eluate species. The measurement of these crucial properties in solution is essential in basic macromolecular characterization and all research and production stages of bio-therapeutic products. We developed a new MALS methodology that has overcome the long-standing, stubborn barrier to microliter-scale peak volumes and achieved the highest resolution and signal-to-noise performance of any MALS measurement. The novel design simultaneously facilitates online dynamic light scattering (DLS) measurements. As National Institute of Standards and Technology (NIST) new protein standard reference material (SRM 8671) is becoming the benchmark molecule against which many biomolecular analytical techniques are assessed and evaluated, we present its measurement results as a demonstration of the unique capability of our system to swiftly resolve and measure sharp (20~25 µL full-width-half-maximum) chromatography peaks. Precise measurements of protein mass and size can be accomplished 10 times faster than before with improved resolution. In the meantime the sample amount required for such measurements is reduced commensurately. These abilities will have far-reaching impacts at every stage of the development and production of biologics and bio-therapeutic formulations.

  13. Gripe water as reducing and stabilizing agent for synthesis of size controlled gold nanoparticles.

    PubMed

    Kirubha, E; Palanisamy, P K

    2013-03-01

    Green synthesis techniques are emerging as more facile and eco-friendly approach for the synthesis of metal nanoparticles compared to chemical reduction methods. Herein we report a new approach to synthesize gold nanoparticles (AuNPs) using gripe water as a reducing as well as stabilizing agent. Good control over the size of the nanoparticles from 3.2 nm to 25 nm has been achieved with this method by simply varying the experimental conditions. The Surface Plasmon Resonance bands of tunable gold nanospheres with high monodispersity and polydispersity have been obtained by this technique and monitored using UV-Visible spectrum. The morphology and the size of these AuNPs are determined using High Resolution Transmission Electron Microscope (HR-TEM). X-Ray Diffraction (XRD) analysis confirms the crystalline nature and the phase of the AuNPs. The as-synthesized AuNPs exhibit good optical nonlinearity. The nonlinear optical studies have been carried out by Z-scan technique to demonstrate its optical limiting property. The threshold limit of the AuNPs is obtained at a input intensity of 30 mW. The nonlinear refractive index of the nanoparticles is in the order of 10(-9) cm2/W and the third-order nonlinearity is estimated to be 7 x 10(-5) esu.

  14. Study shows aspirin reduces the risk and recurrence of prostate cancer in African-American men | Center for Cancer Research

    Cancer.gov

    African-American men who take a daily dose of aspirin experience a significantly lower risk of developing advanced prostate cancer – the aggressive and deadly form of the disease – than African-American men who do not regularly use aspirin, according to a study from the Center for Cancer Research (CCR) Laboratory of Human Carcinogenesis. Learn more...

  15. Methyl jasmonate reduces testosterone-induced benign prostatic hyperplasia through regulation of inflammatory and apoptotic processes in rats.

    PubMed

    Adaramoye, Oluwatosin Adekunle; Akanni, Olubukola Oyebimpe; Abiola, Olusoji John; Owumi, Solomon Eduviere; Akinloye, Oluyemi; Olapade-Olaopa, Emiola Olubunmi

    2017-09-20

    Phytotherapy is becoming a treatment option in management of diseases including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH, however the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH. BPH was induced by daily injections of testosterone propionate (TP) (3mg/kg) for 28 days. The weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers; prostatic myeloperoxidase and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl2, while mild expression of p53 and Bax were seen. Serum triglyceride and total cholesterol were significantly increased, while HDL-c was decreased in BPH. Interestingly, MeJA and finasteride (singly or combination) attenuated inflammatory indices and induced apoptotic parameters in BPH rats. MeJA protects against TP-induced BPH via mechanisms that involve anti-inflammation, induction of apoptosis and inhibition of phase I drug metabolizing enzyme. Copyright © 2017. Published by Elsevier Masson SAS.

  16. Improved responsiveness and reduced sample size requirements of PROMIS physical function scales with item response theory.

    PubMed

    Fries, James F; Krishnan, Eswar; Rose, Matthias; Lingala, Bharathi; Bruce, Bonnie

    2011-01-01

    broader range of physical function. This can reduce sample size requirements and thus study costs.

  17. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes

    SciTech Connect

    Serri, O.; Beauregard, H.; Brazeau, P.; Abribat, T.; Lambert, J.; Harris, A.; Vachon, L. Sandoz Canada Inc., Dorval, Quebec )

    1991-02-20

    To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, the authors studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 {mu}g/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group than in the placebo group. Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group than in the placebo group. Glycemic control did not change significantly in either group. They conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

  18. Flaxseed reduces epithelial proliferation but does not affect basal cells in induced benign prostatic hyperplasia in rats.

    PubMed

    de Amorim Ribeiro, Ilma Cely; da Costa, Carlos Alberto Soares; da Silva, Vivian Alves Pereira; Côrrea, Lanna Beatriz Neves Silva; Boaventura, Gilson Teles; Chagas, Mauricio Alves

    2017-04-01

    This study aimed to quantitatively and qualitatively evaluate the effects of a flaxseed-based diet on the histoarchitecture of the prostate of normal Wistar rats and of rats with induced BPH. The study included four experimental groups of ten animals each: casein control group (CCG), who were fed a casein-based diet; flaxseed control group (FCG), who were fed a flaxseed-based diet; hyperplasia-induced casein group (HICG), who were fed a casein-based diet; and hyperplasia-induced flaxseed group (HIFG), who were fed a flaxseed-based diet. Hyperplasia was induced by the subcutaneous implantation of silicone pellets containing testosterone propionate. After 20 weeks, the rats were euthanized and their prostate fixed in buffered formalin. Tissue sections were stained with HE, picrosirius red and immunostained for nuclear antigen p63. Histomorphometric analysis evaluated the epithelial thickness, epithelial area, individual luminal area, and total area of prostatic alveoli. The mean epithelial thickness obtained for HIFG and HICG was 16.52 ± 1.65 and 20.58 ± 2.86 µm, respectively. The mean epithelial thickness in HICG was greater than that in the other groups tested. HIFG had a smaller epithelial thickness and lower percentage of papillary projections in the prostatic alveoli. No significant difference was observed between CCG and FCG. The total area and mean alveolar area showed no significant differences between the groups. The number of cells immunostained for p63 was not significantly different between the groups evaluated. These results suggest that flaxseed has a protective effect on the prostate epithelium in BPH-induced animals.

  19. Enlarged prostate gland

    MedlinePlus

    ... enlarges in size in a process called benign hypertrophy, which means that the gland got larger without ... in several of the symptoms of benign prostatic hypertrophy, or BPH. Symptoms may include a slowed or ...

  20. A high-potassium diet reduces infarct size and improves vascular structure in hypertensive rats.

    PubMed

    Dorrance, Anne M; Pollock, David M; Romanko, Olga P; Stepp, David W

    2007-01-01

    High-potassium diets can improve vascular function, yet the effects of potassium supplementation on ischemic stroke have not been studied. We hypothesized that dietary potassium supplementation would reduce ischemic cerebral infarct size by reversing cerebral artery hypertrophy. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed diets containing 0.79% potassium (LK) or 2.11% potassium (HK) for 6 wk; Wistar-Kyoto (WKY) rats were fed the LK diet. The HK diet did not reduce blood pressure, as measured by telemetry, in the SHRSP. Cerebral ischemia was induced by middle cerebral artery (MCA) occlusion. The resultant infarct was smaller in the HK-SHRSP than in the LK-SHRSP: 55.1 +/- 6.3 vs. 71.4 +/- 2.4% of the hemisphere infarcted (P < 0.05). Infarcts were smaller in WKY rats (33.5 +/- 4.8%) than in LK-SHRSP or HK-SHRSP. The vessel wall of MCAs from LK-SHRSP was hypertrophied compared with WKY rats; this was reversed in HK-SHRSP. RT-PCR analysis of the cerebral vessels showed that expression of platelet-derived growth factor receptors-alpha and -beta, epidermal growth factor receptor, and collagen I and III was increased in the vessels from LK-SHRSP compared with WKY rats and reduced in HK-SHRSP. These results suggest that potassium supplementation provides neuroprotection in a model of ischemic stroke independent of blood pressure and possibly through changes in vascular structure.

  1. Restaurant owners' perspectives on a voluntary program to recognize restaurants for offering reduced-size portions, Los Angeles County, 2012.

    PubMed

    Gase, Lauren; Dunning, Lauren; Kuo, Tony; Simon, Paul; Fielding, Jonathan E

    2014-03-20

    Reducing the portion size of food and beverages served at restaurants has emerged as a strategy for addressing the obesity epidemic; however, barriers and facilitators to achieving this goal are not well characterized. In fall 2012, the Los Angeles County Department of Public Health conducted semistructured interviews with restaurant owners to better understand contextual factors that may impede or facilitate participation in a voluntary program to recognize restaurants for offering reduced-size portions. Interviews were completed with 18 restaurant owners (representing nearly 350 restaurants). Analyses of qualitative data revealed 6 themes related to portion size: 1) perceived customer demand is central to menu planning; 2) multiple portion sizes are already being offered for at least some food items; 3) numerous logistical barriers exist for offering reduced-size portions; 4) restaurant owners have concerns about potential revenue losses from offering reduced-size portions; 5) healthful eating is the responsibility of the customer; and 6) a few owners want to be socially responsible industry leaders. A program to recognize restaurants for offering reduced-size portions may be a feasible approach in Los Angeles County. These findings may have applications for jurisdictions interested in engaging restaurants as partners in reducing the obesity epidemic.

  2. Restaurant Owners’ Perspectives on a Voluntary Program to Recognize Restaurants for Offering Reduced-Size Portions, Los Angeles County, 2012

    PubMed Central

    Dunning, Lauren; Kuo, Tony; Simon, Paul; Fielding, Jonathan E.

    2014-01-01

    Introduction Reducing the portion size of food and beverages served at restaurants has emerged as a strategy for addressing the obesity epidemic; however, barriers and facilitators to achieving this goal are not well characterized. Methods In fall 2012, the Los Angeles County Department of Public Health conducted semistructured interviews with restaurant owners to better understand contextual factors that may impede or facilitate participation in a voluntary program to recognize restaurants for offering reduced-size portions. Results Interviews were completed with 18 restaurant owners (representing nearly 350 restaurants). Analyses of qualitative data revealed 6 themes related to portion size: 1) perceived customer demand is central to menu planning; 2) multiple portion sizes are already being offered for at least some food items; 3) numerous logistical barriers exist for offering reduced-size portions; 4) restaurant owners have concerns about potential revenue losses from offering reduced-size portions; 5) healthful eating is the responsibility of the customer; and 6) a few owners want to be socially responsible industry leaders. Conclusion A program to recognize restaurants for offering reduced-size portions may be a feasible approach in Los Angeles County. These findings may have applications for jurisdictions interested in engaging restaurants as partners in reducing the obesity epidemic. PMID:24650622

  3. Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer.

    PubMed

    Yu, Evan Y; Getzenberg, Robert H; Coss, Christopher C; Gittelman, Marc M; Keane, Thomas; Tutrone, Ronald; Belkoff, Laurence; Given, Robert; Bass, Joel; Chu, Franklin; Gambla, Michael; Gaylis, Franklin; Bailen, James; Hancock, Michael L; Smith, Jordan; Dalton, James T; Steiner, Mitchell S

    2015-02-01

    A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course. To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy. Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot. GTx-758 and leuprolide. The primary end point was the proportion of patients achieving total testosterone ≤ 50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels. Of 159 randomized patients, leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [p<0.001], GTx-758 2000 mg [p=0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%). Although leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs. This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher

  4. Reduced neuronal size and dendritic length in the medial superior olivary nucleus of albino rabbits.

    PubMed

    Conlee, J W; Parks, T N; Creel, D J

    1986-01-15

    We have previously demonstrated that circumscribed structural and functional abnormalities exist in the brainstem auditory system of albino cats. Anomalies in the auditory brainstem evoked response of albino cats were correlated with anatomical defects in the medial superior olivary nucleus (MSO) of the same animals. To examine whether a similar syndrome is present in other albino mammals, we studied the MSO of albino and pigmented rabbits using both Nissl-stained and Golgi-impregnated material. Neurons in the MSO of the albinos were significantly smaller (24%) than those in the pigmented rabbits and there was no overlap in the size distributions between the two groups. Neurons in the abducens nucleus of the albinos were also 14% smaller than in the pigmented rabbits, but this difference was not statistically reliable. The broad overlap in the distributions of neuronal size in the abducens nucleus between groups indicated that not all cells in the albino brainstem are significantly smaller than normal. In the Golgi-impregnated material, the mean total dendritic length for the 'marginal' cell type in the MSO was 39% shorter in albinos than in the pigmented animals. The branching density of dendrites was also significantly reduced in the albinos. Mean total dendritic length for cerebellar granule cells was a statistically insignificant 6% longer in the albinos, demonstrating that dendritic structure is not uniformly affected in all regions of the albino brain. The demonstration of similar anatomical differences in albino rabbits and cats indicates that whatever process produces these effects is not species-specific and may be common to the albinos of other mammalian species. The evidence that the amount of cochlear melanin may be related to differences in auditory function further suggests that the differences in the MSO of the albinos may ultimately be related to absence of inner ear pigmentation and not to other gene effects.

  5. Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion.

    PubMed

    Basch, Ethan; Oliver, Thomas K; Vickers, Andrew; Thompson, Ian; Kantoff, Philip; Parnes, Howard; Loblaw, D Andrew; Roth, Bruce; Williams, James; Nam, Robert K

    2012-08-20

    An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer. Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection. Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic. In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.

  6. Size Dependent Lipidomic Analysis of Urinary Exosomes from Patients with Prostate Cancer by Flow Field-Flow Fractionation and Nanoflow Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Yang, Joon Seon; Lee, Jong Cheol; Byeon, Seul Kee; Rha, Koon Ho; Moon, Myeong Hee

    2017-02-21

    Exosomes are membrane-bound extracellular vesicles involved in intercellular communication and tumor cell metastasis. In this study, flow field-flow fractionation (FlFFF) was utilized to separate urinary exosomes by size, demonstrating a significant difference in exosome sizes between healthy controls and patients with prostate cancer (PCa). Exosome fractions of different sizes were collected for microscopic analysis during an FlFFF run and evaluated with exosome marker proteins using Western blot analysis. The results indicated that exosomes of different sizes originated from different types of cells. Collected exosome fractions were further examined using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUPLC-ESI-MS/MS) for lipidomic analysis. A total of 162 lipids (from 286 identified) were quantified using a selected reaction monitoring (SRM) method. The overall amount of lipids increased by 1.5- to 2-fold in patients with PCa and degree of increase was more significant in the smaller fractions (diameter <150 nm) than in the larger ones (diameter >150 nm) some classes of lipids. In addition, neutral lipids like diacylglycerol (DAG) and triacylglycerol (TAG) decreased in all exosomes without size dependency. Moreover, a dramatic increase in 22:6/22:6-phosphatidylglycerol (PG) was observed and significant decrease in (16:0,16:0)- and (16:1, 18:1)-DAG species (nearly 5-fold) and high abundant TAG species (>2.5-fold) was observed in patients with PCa. The results of this study indicate that FlFFF can be employed for the high-speed screening of urinary exosome sizes in patients with PCa and lipidomic analysis of the fractionated exosomes has potential for developing and distinguishing biomarkers of PCa.

  7. Is there a single spot size and grid for intensity modulated proton therapy? Simulation of head and neck, prostate and mesothelioma cases

    SciTech Connect

    Widesott, Lamberto; Lomax, Antony J.; Schwarz, Marco

    2012-03-15

    Purpose: To assess the quality of dose distributions in real clinical cases for different dimensions of scanned proton pencil beams. The distance between spots (i.e., the grid of delivery) is optimized for each dimension of the pencil beam. Methods: The authors vary the {sigma} of the initial Gaussian size of the spot, from {sigma}{sub x} = {sigma}{sub y} = 3 mm to {sigma}{sub x} = {sigma}{sub y} = 8 mm, to evaluate the impact of the proton beam size on the quality of intensity modulated proton therapy (IMPT) plans. The distance between spots, {Delta}x and {Delta}y, is optimized on the spot plane, ranging from 4 to 12 mm (i.e., each spot size is coupled with the best spot grid resolution). In our Hyperion treatment planning system (TPS), constrained optimization is applied with respect to the organs at risk (OARs), i.e., the optimization tries to satisfy the dose objectives in the planning target volume (PTV) as long as all planning objectives for the OARs are met. Three-field plans for a nasopharynx case, two-field plans for a prostate case, and two-field plans for a malignant pleural mesothelioma case are considered in our analysis. Results: For the head and neck tumor, the best grids (i.e., distance between spots) are 5, 4, 6, 6, and 8 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. {sigma} {<=} 5 mm is required for tumor volumes with low dose and {sigma}{<=} 4 mm for tumor volumes with high dose. For the prostate patient, the best grid is 4, 4, 5, 5, and 5 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Beams with {sigma} > 3 mm did not satisfy our first clinical requirement that 95% of the prescribed dose is delivered to more than 95% of prostate and proximal seminal vesicles PTV. Our second clinical requirement, to cover the distal seminal vesicles PTV, is satisfied for beams as wide as {sigma} = 6 mm. For the mesothelioma case, the low dose PTV prescription is well respected for all values of {sigma}, while there is loss of high dose PTV coverage

  8. Using Ancillary Information to Reduce Sample Size in Discovery Sampling and the Effects of Measurement Error

    SciTech Connect

    Axelrod, M

    2005-08-18

    big sample size might bust the budget, or the number seems intuitively excessive. To reduce the sample size, you can increase the tolerable number of defectives, the ''10'' in the preceding example, or back off on the confidence level, say from 95% to 90%. Auditors also frequently bump up the sample size as a safety factor. They know that something can go wrong. For example, they might find out that the measurements or inspections were subject to errors. Unless the auditors know exactly how measurement error affects sample size, they might be forced to give up the safety factor. Clients often choose to ''live dangerously'' (without a compelling argument to the contrary) to save money. Thus, sometimes the auditor finds that ''you just can't get there from here'', because the goals of the audit and the resources available are inherently in conflict. For discovery audits, there is a way out of this apparent conundrum. It turns out that the classical method of confidence intervals uses an implicit and very conservative assumption. We will see that this assumption is too pessimistic and too conservative in the context of a discovery audit. If we abandon this assumption and use ancillary information about the inventory, then we can significantly reduce the sample size required to achieve the desired confidence level. We will see exactly how the classical method ignores this ancillary information and misses the opportunity for an efficient audit. In the following sections, we first review the standard approach using confidence intervals. Then we present a method that incorporates the ancillary information about the inventory to design a very efficient discovery audit. We also provide results on how measurement errors affect the audit, and how exactly how much the sample size must be modified to compensate for these errors. Finally, we state asymptotic formulas that provide useful approximations for large inventories. It is suggested that the reader review the glossary of

  9. Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble

    NASA Astrophysics Data System (ADS)

    Yongye, Austin B.; Bender, Andreas; Martínez-Mayorga, Karina

    2010-08-01

    Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged- RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged- RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 Å). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1-4), medium (5-9) and high (10-15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments.

  10. Mechanisms of Regulating Tissue Elongation in Drosophila Wing: Impact of Oriented Cell Divisions, Oriented Mechanical Forces, and Reduced Cell Size

    PubMed Central

    Li, Yingzi; Naveed, Hammad; Kachalo, Sema; Xu, Lisa X.; Liang, Jie

    2014-01-01

    Regulation of cell growth and cell division plays fundamental roles in tissue morphogenesis. However, the mechanisms of regulating tissue elongation through cell growth and cell division are still not well understood. The wing imaginal disc of Drosophila provides a model system that has been widely used to study tissue morphogenesis. Here we use a recently developed two-dimensional cellular model to study the mechanisms of regulating tissue elongation in Drosophila wing. We simulate the effects of directional cues on tissue elongation. We also computationally analyze the role of reduced cell size. Our simulation results indicate that oriented cell divisions, oriented mechanical forces, and reduced cell size can all mediate tissue elongation, but they function differently. We show that oriented cell divisions and oriented mechanical forces act as directional cues during tissue elongation. Between these two directional cues, oriented mechanical forces have a stronger influence than oriented cell divisions. In addition, we raise the novel hypothesis that reduced cell size may significantly promote tissue elongation. We find that reduced cell size alone cannot drive tissue elongation. However, when combined with directional cues, such as oriented cell divisions or oriented mechanical forces, reduced cell size can significantly enhance tissue elongation in Drosophila wing. Furthermore, our simulation results suggest that reduced cell size has a short-term effect on cell topology by decreasing the frequency of hexagonal cells, which is consistent with experimental observations. Our simulation results suggest that cell divisions without cell growth play essential roles in tissue elongation. PMID:24504016

  11. From micro- to nanomagnetic dots: evolution of the eigenmode spectrum on reducing the lateral size

    NASA Astrophysics Data System (ADS)

    Carlotti, G.; Gubbiotti, G.; Madami, M.; Tacchi, S.; Hartmann, F.; Emmerling, M.; Kamp, M.; Worschech, L.

    2014-07-01

    Brillouin light scattering experiments and micromagnetic simulations have been exploited to investigate the spectrum of thermally excited magnetic eigenmodes in 10 nm-thick elliptical Permalloy dots, when the longer axis D is scaled down from about 1000 to 100 nm. It is shown that for D larger than about 200 nm the characteristics of the spin-wave eigenmodes are dominated by dipolar energy, while for D in the range of about 100 to 200 nm exchange energy effects cause qualitative and quantitative differences in the spin-wave spectrum. In this ‘mesoscopic’ regime, the usual classification scheme, involving one fundamental mode with large average magnetization and many other modes collected in families with specific symmetries, no longer holds. Rather, one finds the simultaneous presence of two modes with ‘fundamental’ character, i.e. with a significant and comparable value of the average dynamical magnetization: the former is at larger frequency and has its maximum amplitude at the dot's centre, while the latter occurs at lower frequency and is localized at the dot's edges. Interestingly, the maximum intensity swaps from the higher frequency mode to the lower frequency one, just when the dot size is reduced from about 200 to 100 nm. This is relevant in view of the exploitation of nanodots for the design of nanomagnetic devices with lateral dimensions in the above interval, such as memory cells, logic gates, reading heads and spin-torque oscillators.

  12. Impaired egocentric memory and reduced somatosensory cortex size in temporal lobe epilepsy with hippocampal sclerosis.

    PubMed

    Weniger, Godehard; Ruhleder, Mirjana; Lange, Claudia; Irle, Eva

    2012-02-01

    Recent research indicates that longstanding temporal lobe epilepsy (TLE) is associated with extratemporal, i.e. parietal cortex damage. We investigated egocentric and allocentric memory by use of first-person large-scale virtual reality environments in patients with TLE. We expected that TLE patients with parietal cortex damage were impaired in the egocentric memory task. Twenty-two TLE patients with hippocampal sclerosis (HS) and 22 TLE patients without HS were compared with 42 healthy matched controls on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Participants further received a neuropsychological investigation and MRI volumetry at the time of the assessment. When compared with controls, TLE patients with HS had significantly reduced size of the ipsilateral and contralateral somatosensory cortex (postcentral gyrus). When compared with controls or TLE patients without HS, TLE patients with HS were severely impaired learning the virtual maze. Considering all participants, smaller volumes of the left-sided postcentral gyrus were related to worse performance on the virtual maze. It is concluded that the paradigm of egocentric navigation and learning in first-person large-scale virtual environments may be a suitable tool to indicate significant extratemporal damage in individuals with TLE. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Flocculated sediments can reduce the size of sediment basin at construction sites.

    PubMed

    Kang, Jihoon; King, Scott E; McLaughlin, Richard A

    2016-01-15

    Due to stringent water quality regulations on stormwater discharges, there is increasing interest in chemically-assisted settling of suspended sediments at construction sites. This study investigated settling characteristics of flocculated sediment by polyacrylamide (PAM) in a top-loading settling tube. Studied sediment materials were obtained from construction sites in North Carolina, USA: Coastal Plain loamy sand (CPLS), Piedmont sandy clay loam (PSCL), Piedmont silt loam (PSL), and Mountain clay loam (MCL). The four different sediment suspensions mixed with and without dissolved PAM were introduced to the top of the column individually. During a 1-h settling period, samples were taken at 1-m depth from surface at various times and analyzed for total suspended solids (TSS). Flocculated sediment by PAM greatly increased its settled TSS fraction up to 95-97% only in 1-min settling period compared to those of unflocculated sediment (16-72%). The settling improvement by PAM was profound in the finer-textured soils (PSL and MCL) by increasing their median particle settling velocity (>2 cm s(-1)) compared to unflocculated counterparts (<1.1 cm s(-1)). Estimated surface area requirement of sediment basin suggested that the basins receiving flocculated sediment could be reduced in size (surface area) by 2- to 4-times compared to those receiving unflocculated sediment. Our results suggests that current sediment basin design could be modified when chemically-assisted settling is implemented, taking up less space and cost in construction sites.

  14. Walnuts lower TRAMP prostate tumor growth by altering IGF-1, energy and cholesterol metabolism and is not due to their fatty acids

    USDA-ARS?s Scientific Manuscript database

    Dietary changes could potentially reduce prostate cancer morbidity and mortality. Prostate tumor size, gene expression, metabolite and plasma responses to a 100 g of fat/kg diet (whole walnuts, walnut oil and other oils; balanced for macronutrients, tocopherols (a-and ' ) for 18 weeks were assessed ...

  15. Prostate brachytherapy

    MedlinePlus

    Implant therapy - prostate cancer; Radioactive seed placement; Internal radiation therapy - prostate; High dose radiation (HDR) ... plan and then place the seeds that deliver radiation into your prostate. The seeds are placed with ...

  16. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity

    PubMed Central

    Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Dhar, Deepanshi; Panigrahi, Gati K.; Hussain, Anowar; Agarwal, Chapla; El-Elimat, Tamam; Sica, Vincent P.; Oberlies, Nicholas H.; Agarwal, Rajesh

    2016-01-01

    Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1–5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47phox). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity. PMID:26979487

  17. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity.

    PubMed

    Deep, Gagan; Kumar, Rahul; Jain, Anil K; Dhar, Deepanshi; Panigrahi, Gati K; Hussain, Anowar; Agarwal, Chapla; El-Elimat, Tamam; Sica, Vincent P; Oberlies, Nicholas H; Agarwal, Rajesh

    2016-03-16

    Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1-5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47(phox)). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity.

  18. The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells.

    PubMed

    Gravina, Giovanni Luca; Marampon, Francesco; Petini, Foteini; Biordi, Leda; Sherris, David; Jannini, Emmanuele A; Tombolini, Vincenzo; Festuccia, Claudio

    2011-08-01

    One of the major obstacles in the treatment of hormone-refractory prostate cancer (HRPC) is the development of chemo-resistant tumors. The aim of this study is to evaluate the role of Palomid 529 (P529), a novel TORC1/TORC2 inhibitor, in association with docetaxel (DTX) and cisplatin (CP). This work utilizes a wide panel of prostatic cancer cell lines with or without basal activation of Akt as well as two in vivo models of aggressive HRPC. The blockade of Akt/mTOR activity was associated to reduced cell proliferation and induction of apoptosis. Comparison of IC50 values calculated for PTEN-positive and PTEN-negative cell lines as well as the PTEN transfection in PC3 cells or PTEN silencing in DU145 cells revealed that absence of PTEN was indicative for a better activity of the drug. In addition, P529 synergized with DTX and CP. The strongest synergism was achieved when prostate cancer (PCa) cells were sequentially exposed to CP or DTX followed by treatment with P529. Treatment with P529 before the exposure to chemotherapeutic drugs resulted in a moderate synergism, whereas intermediated values of combination index were found when drugs were administered simultaneously. In vivo treatment of a combination of P529 with DTX or CP increased the percentage of complete responses and reduced the number of mice with tumor progression. Our results provide a rationale for combinatorial treatment using conventional chemotherapy and a Akt/mTOR inhibitor as promising therapeutic approach for the treatment of HRPC, a disease largely resistant to conventional therapies.

  19. 30 CFR 203.76 - When might BSEE withdraw or reduce the approved size of my relief?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 2 2012-07-01 2012-07-01 false When might BSEE withdraw or reduce the approved... ENFORCEMENT, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT RELIEF OR REDUCTION IN ROYALTY RATES OCS Oil, Gas, and Sulfur General § 203.76 When might BSEE withdraw or reduce the approved size of my...

  20. Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction

    PubMed Central

    van Hout, Gerardus PJ; Teuben, Michel PJ; Heeres, Marjolein; de Maat, Steven; de Jong, Renate; Maas, Coen; Kouwenberg, Lisanne HJA; Koenderman, Leo; van Solinge, Wouter W; de Jager, Saskia CA; Pasterkamp, Gerard; Hoefer, Imo E

    2015-01-01

    Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies. PMID:26282710

  1. Luteinizing hormone (LH)-releasing hormone agonist reduces serum adrenal androgen levels in prostate cancer patients: implications for the effect of LH on the adrenal glands.

    PubMed

    Nishii, Masahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Oyama, Tetsunari; Suzuki, Kazuhiro

    2012-01-01

    Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing hormone-releasing hormone (LH-RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed. Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone, and estradiol levels were decreased by 90%-95%, and dehydroepiandrosterone-sulfate, dehydroepiandrosterone, and androstenedione levels were significantly decreased by 26%-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. Adrenocorticotropic hormone levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands. The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.

  2. A Randomized Controlled Trial for the Effectiveness of Progressive Muscle Relaxation and Guided Imagery as Anxiety Reducing Interventions in Breast and Prostate Cancer Patients Undergoing Chemotherapy.

    PubMed

    Charalambous, Andreas; Giannakopoulou, Margarita; Bozas, Evangelos; Paikousis, Lefkios

    2015-01-01

    Objective. To test the effectiveness of guided imagery (GI) and progressive muscle relaxation (PMR) as stress reducing interventions in patients with prostate and breast cancer who undergo chemotherapy. Methods. Patients were randomly assigned to either the control group or the intervention group (PMR and GI). Patients were observed for a total duration of 3 weeks and assessed with the SAS and BECK-II questionnaires for anxiety and depression, respectively, in addiotion to two biological markers (saliva cortisol and saliva amylase) (trial registration number: NCT01275872). Results. 256 patients were registered and 236 were randomly assigned. In total 104 were randomised to the control group and 104 to the intervention group. Intervention's mean anxiety score and depression score changes were significantly different compared to the control's (b = -29.4, p < 0.001; b = -29.4, p < 0.001, resp.). Intervention group's cortisol levels before the intervention (0.30 ± 0.25) gradually decreased up to week 3 (0.16 ± 0.18), whilst the control group's cortisol levels before the intervention (0.21 ± 0.22) gradually increased up to week 3 (0.44 ± 0.35). The same interaction appears for the Amylase levels (p < 0.001). Conclusions. The findings showed that patients with prostate and breast cancer undergoing chemotherapy treatment can benefit from PMR and GI sessions to reduce their anxiety and depression.

  3. Reducing Class Size: A Smart Way To Improve America's Urban Schools. Second Edition.

    ERIC Educational Resources Information Center

    Naik, Manish; Casserly, Michael; Uro, Gabriela

    The Council of the Great City Schools, a coalition of the largest urban public schools in the United States, surveyed its membership to determine how they were using federal class size reduction funds in the 2000-2001 school year. Thirty-six major urban school systems responded. Results indicate that the federal class size reduction program is…

  4. Ecological constraints on sensory systems: compound eye size in Daphnia is reduced by resource limitation.

    PubMed

    Brandon, Christopher S; Dudycha, Jeffry L

    2014-08-01

    Eye size is an indicator of visual capability, and macroevolutionary patterns reveal that taxa inhabiting dim environments have larger eyes than taxa from bright environments. This suggests that the light environment is a key driver of variation in eye size. Yet other factors not directly linked with visual tasks (i.e., non-sensory factors) may influence eye size. We sought to jointly investigate the roles of sensory (light) and non-sensory factors (food) in determining eye size and ask whether non-sensory factors could constrain visual capabilities. We tested environmental influences on eye size in four species of the freshwater crustacean Daphnia, crossing bright and dim light levels with high and low resource levels. We measured absolute eye size and eye size relative to body size in early and late adulthood. In general, Daphnia reared on low resources had smaller eyes, both absolutely and relatively. In contrast to the dominant macroevolutionary pattern, phenotypic plasticity in response to light was rarely significant. These patterns of phenotypic plasticity were true for overall diameter of the eye and the diameter of individual facets. We conclude that non-sensory environmental factors can influence sensory systems, and in particular, that resource availability may be an important constraint on visual capability.

  5. Reducing Class Size: A Smart Way To Improve America's Urban Schools. Second Edition.

    ERIC Educational Resources Information Center

    Naik, Manish; Casserly, Michael; Uro, Gabriela

    The Council of the Great City Schools, a coalition of the largest urban public schools in the United States, surveyed its membership to determine how they were using federal class size reduction funds in the 2000-2001 school year. Thirty-six major urban school systems responded. Results indicate that the federal class size reduction program is…

  6. Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

    PubMed

    Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Kenneth; Schleutker, Johanna; Henderson, Brian E; Haiman, Christopher A; Schumacher, Fredrick R; Pashayan, Nora; Pharoah, Paul D P; Ostrander, Elaine A; Stanford, Janet L; Batra, Jyotsna; Clements, Judith A; Chambers, Suzanne K; Weischer, Maren; Nordestgaard, Børge G; Ingles, Sue A; Sorensen, Karina D; Orntoft, Torben F; Park, Jong Y; Cybulski, Cezary; Maier, Christiane; Doerk, Thilo; Dickinson, Joanne L; Cannon-Albright, Lisa; Brenner, Hermann; Rebbeck, Timothy R; Zeigler-Johnson, Charnita; Habuchi, Tomonori; Thibodeau, Stephen N; Cooney, Kathleen A; Chappuis, Pierre O; Hutter, Pierre; Kaneva, Radka P; Foulkes, William D; Zeegers, Maurice P; Lu, Yong-Jie; Zhang, Hong-Wei; Stephenson, Robert; Cox, Angela; Southey, Melissa C; Spurdle, Amanda B; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L; Lophatonanon, Aritaya; Rinckleb, Antje E; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F

    2015-07-01

    Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. ©2015 American Association for Cancer Research.

  7. Evidence for reduced neuromuscular function in men with a history of androgen deprivation therapy for prostate cancer.

    PubMed

    Girard, Danielle; Marino, Frank E; Cannon, Jack

    2014-05-01

    Indices of body composition and muscular strength were compared between men with prostate cancer (PCa) treated with androgen deprivation therapy (ADT) and asymptomatic matched men. Nine subjects aged 63-83 years with PCa who received ADT (PCa+ADT; duration 6-180 months) and 11 asymptomatic aged-matched eugonadal men (HM) aged 59-80 years were assessed for prostate-specific antigen (PSA) and total testosterone (TT). Total body non-osseous lean mass (TBLM) and right thigh non-osseous fat-free mass (RTLM) were assessed using dual-energy X-ray absorptiometry. Peak torque of the right knee extensors at 0° s(-1) (ISO) and 60° s(-1) (CON), maximal handgrip strength of the dominant hand (MHS) and whole-body strength (WBS) were assessed. ISO and CON per unit mass of RTLM and MHS and WBS per unit mass of TBLM were calculated. Age, height, mass, body mass index and prostate-specific antigen were comparable between groups (P>0·05), while TT was lower in PCa+ADT (P<0·01). RTLM was similar between groups (P≥0·075). Absolute ISO and CON were lower for PCa+ADT (P<0·01) as were CON per unit of RTLM and ISO per unit of RTLM (P<0·05). Absolute MHS, WBS and MHS per unit of TBLM and WBS per unit of TBLM were lower for PCa+ADT (P<0·01; P<0·05). Men with PCa who receive ADT experience significant losses in whole-body muscular strength compared with asymptomatic age-matched men, which may impair functional capacity. These losses in muscular strength appear to involve neuromuscular mechanisms that are yet to be identified. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  8. Living in stable social groups is associated with reduced brain size in woodpeckers (Picidae).

    PubMed

    Fedorova, Natalia; Evans, Cara L; Byrne, Richard W

    2017-03-01

    Group size predicts brain size in primates and some other mammal groups, but no such relationship has been found in birds. Instead, stable pair-bonding and bi-parental care have been identified as correlates of larger brains in birds. We investigated the relationship between brain size and social system within the family Picidae, using phylogenetically controlled regression analysis. We found no specific effect of duration or strength of pair-bonds, but brain sizes were systematically smaller in species living in long-lasting social groups of larger sizes. Group-living may only present a cognitive challenge in groups in which members have individually competitive relationships; we therefore propose that groups functioning for cooperative benefit may allow disinvestment in expensive brain tissue.

  9. Molecular Mechanism for Prostate Cancer Resistance to the Anti-Tumor Activity

    DTIC Science & Technology

    2005-11-01

    Interleukin - 6 production in normal prostate cells via MAP Kinase Phosphatase 5: Implications for prostate cancer prevention by... Interleukin - 6 production in normal prostate cells via MAP Kinase Phosphatase 5: Implications for prostate cancer prevention by Vitamin D” (Appendix A...Vitamin D reduces Interleukin - 6 production in normal prostate cells via MAP Kinase Phosphatase 5: Implications for prostate cancer prevention by

  10. High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

    SciTech Connect

    Viani, Gustavo Arruda; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

    2012-08-01

    Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trials showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.

  11. Food extracts consumed in Mediterranean countries and East Asia reduce protein concentrations of androgen receptor, phospho-protein kinase B, and phospho-cytosolic phospholipase A(2)alpha in human prostate cancer cells.

    PubMed

    Singh, Jaskirat; Xie, Chanlu; Yao, Mu; Hua, Sheng; Vignarajan, Soma; Jardine, Greg; Hambly, Brett D; Sved, Paul; Dong, Qihan

    2010-04-01

    Active surveillance is an emerging management option for the rising number of men with low-grade, clinically localized prostate cancer. However, 30-40% of men on active surveillance will progress to high-grade disease over 5 y. With the ultimate aim of developing a food-based chemoprevention strategy to retard cancer progression in these otherwise healthy men, we have developed a blend of food extracts commonly consumed in Mediterranean countries and East Asia. The effect of the food extracts known as Blueberry Punch (BBP) on prostate cancer cell growth and key signaling pathways were examined in vitro and in vivo. BBP reduced prostate cancer cell growth in a dose-dependent manner (0.08-2.5%) at 72 h in vitro due to the reduction in cell proliferation and viability. Prostate cancer cell xenograft-bearing mice, administered 10% BBP in drinking water for 2 wk, had a 25% reduction in tumor volume compared with the control (water only). In vitro, BBP reduced protein concentrations in 3 signaling pathways necessary for the proliferation and survival of prostate cancer cells, namely androgen receptor, phospho-protein kinase B/protein kinase B, and phospho-cytosolic phospholipase A(2)alpha. The downstream effectors of these pathways, including prostate-specific antigen and glycogen synthase kinase 3beta, were also reduced. Thus, this palatable food supplement is a potential candidate for testing in clinical trials and may ultimately prove effective in retarding the progression of low-grade, early-stage prostate cancer in men managed by active surveillance.

  12. Selective endothelin a (ETA) receptor antagonist (BQ-123) reduces both myocardial infarct size and oxidant injury.

    PubMed

    Ozdemir, Ramazan; Parlakpinar, Hakan; Polat, Alaadin; Colak, Cemil; Ermis, Necip; Acet, Ahmet

    2006-02-15

    Endothelins (ET) can be considered stress-responsive regulators working in paracrine and autocrine fashion. It has been suggested that elevated levels of ET may be responsible for the low coronary re-flow phenomena. Ischemia-reperfusion (I/R) was shown to stimulate ET release in rat heart; however, the mechanism(s) of this effect has not been clarified. Therefore, this study was focused to investigate the effect of BQ-123, selective ETA receptor antagonist, on three aspects of myocardial ischemia-reperfusion (MI/R) injury: hemodynamic parameters, infarct size and oxidant-antioxidant status in the absence and presence of ET-1 in an vivo rat model. To produce MI/R, a branch of the descending left coronary artery was occluded for 30 min followed by 2h reperfusion. ECG changes, blood pressure (BP), and heart rate (HR) were measured before occlusion and continued both occlusion and reperfusion. Forty rats were randomly assigned to five groups equally: (1) sham-operated rats without coronary ligation, (2) I/R group, (3) I/R+BQ-123-treated group (10 microg/kg/min i.v.), (4) I/R+ET-treated group (25 ng/kg/min i.v.), (5) I/R+ET+BQ-123-treated group. The results are expressed as mean+/-S.E.M. In the ET-1 plus I/R group, the ratio between the infarcted area and area at risk 56+/-1% was significantly higher than I/R group (49+/-1%). In the BQ-123 group with or without exogenous ET-1 treatment in I/R group, this ratio was significantly lower at 40+/-2 and 37+/-1%, respectively. As compared to sham group, I/R increased lipid peroxidation whereas decreased nitric oxide (NO), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) contents. This decreased antioxidant enzymatic defense could result in aggravated oxidative damage in I/R group rat hearts. ET-1 administration group showed severe oxidative damage. BQ-123 administrations to I/R group with or without ET-1 caused significantly decrease in lipid peroxidation and increased in SOD, CAT activities and NO generation

  13. Use of intradermal botulinum toxin to reduce sebum production and facial pore size.

    PubMed

    Shah, Anil R

    2008-09-01

    Review the safety profile and subjective efficacy of intradermal botulinum toxin type A in facial pore size and sebum production. Retrospective analysis of 20 patients. Twenty consecutive patients with a single application of intradermal botulinum toxin type A were examined: Patients (17/20) noted an improvement in sebum production and a decrease in pores size at 1 month after injection. No complications were observed, and 17/20 patients were satisfied with the procedure. Preliminary data suggests that intradermal botulinum toxin may play a role in decreasing sebum production. Further quantitive study may be necessary to determine effects of intradermal botulinum toxin on pore size.

  14. Living in forest fragments reduces group cohesion in diademed sifakas (Propithecus diadema) in eastern Madagascar by reducing food patch size.

    PubMed

    Irwin, Mitchell T

    2007-04-01

    Forest fragmentation is thought to threaten primate populations, yet the mechanisms by which this occurs remain largely unknown. However, fragmentation is known to cause dietary shifts in several primate species, and links between food resource distribution and within-group spatial dynamics are well documented. Thus, fragmentation has the potential to indirectly affect spatial dynamics, and these changes may present additional stresses to fragmented populations. I present the results from a 12-month study of Propithecus diadema at Tsinjoarivo, eastern Madagascar, including two groups in fragments and two in continuous forest. Instantaneous data on activity and spatial position were collected during all-day focal animal follows. Fragment groups had much lower cohesion, being more likely to have no neighbor within 5 and 10 m. For continuous forest groups, cohesion was highest in the rainy season (when food patches are large) and lowest in winter (when the animals rely on small-crowned mistletoes), and the chance of having no neighbor within 5 m was positively correlated with mistletoe consumption. Thus their decreased cohesion in fragment groups is inferred to result from their increased reliance on mistletoes and other small resources, which causes them to spread out among multiple patches. This scenario is consistent with the reduced body mass of subordinate individuals (males and immatures) in fragments, and suggests the occurrence of steeper within-group fitness gradients. Further research is necessary to determine whether these patterns apply to other primates; however, since fragmentation tends to cause the loss of the largest trees, many primates in fragments may lose their largest food resources and undergo similar behavioral shifts.

  15. Is reduced CAG repeat length in androgen receptor gene associated with risk of prostate cancer in Indian population?

    PubMed

    Mishra, Dk; Thangaraj, K; Mandhani, A; Kumar, A; Mittal, Rd

    2005-07-01

    Shorter CAG repeats in androgen receptor (AR) gene have been found to be associated with an increased risk of prostate cancer (CaP). Ethnic variations in CAG repeat length may contribute to varying risks in different populations. To evaluate the prognostic significance of androgen receptor (AR) CAG repeats in Indian population for CaP, genomic DNA from 113 CaP, 57 benign prostate hyperplasia (BPH) patients and 133 normal healthy controls were examined by using a PCR-based GeneScan analysis. The mean number of CAG repeat in CaP was significantly lower as compared to the healthy controls (20.26 vs 22.98; p = 0.016). The odds ratio for CaP was 2.96 (p < 0.01), when individuals with short CAG repeat (< or =22) were compared with those having longer repeats (>22). A significant association was also observed between short CAG repeat and young age at diagnosis (OR 2.18; p = 0.04). The mean CAG repeat was not significantly different in BPH and healthy controls; however, BPH patients showed a tendency towards short CAG repeats. Thus, our results show that CAG repeat polymorphism in AR gene is significantly associated with CaP risk, suggesting that AR CAG polymorphism may act as a risk modifier to CaP in Indian population.

  16. Prostate Cancer

    MedlinePlus

    Prostate cancer Overview Prostate cancer is cancer that occurs in the prostate — a small walnut-shaped gland in men that produces the seminal fluid that nourishes and transports sperm. Prostate cancer is one of the most common types of ...

  17. Antagonistic effect of Lepidium meyenii (red maca) on prostatic hyperplasia in adult mice.

    PubMed

    Gonzales, G F; Gasco, M; Malheiros-Pereira, A; Gonzales-Castañeda, C

    2008-06-01

    The plants from the Lepidium gender have demonstrated to have effect on the size of the prostate. Lepidium meyenii (Maca) is a Peruvian plant that grows exclusively over 4000 m above sea level. The present study was designed to determine the effect of red maca (RM) in the prostate hyperplasia induced with testosterone enanthate (TE) in adult mice. Prostate hyperplasia was induced by administering TE, and then these animals (n = 6, each group) were treated with RM or Finasteride (positive control) for 21 days. There was an additional group without prostate hyperplasia (vehicle). Mice were killed on days 7, 14 and 21 after treatment with RM. Testosterone and oestradiol levels were measured on the last day of treatment. Prostatic stroma, epithelium and acini were measured histologically. RM reduced prostate weight at 21 days of treatment. Weights of seminal vesicles, testis and epididymis were not affected by RM treatment. The reduction in prostate size by RM was 1.59 times. Histological analysis showed that TE increased 2-fold the acinar area, effect prevented in the groups receiving TE + RM for 14 (P < 0.05) and 21 (P < 0.05) days and the group receiving TE + Finasteride for 21 days (P < 0.05). TE increased prostatic stroma area and this effect was prevented by treatment with RM since 7 days of treatment or Finasteride. The reduction in prostatic stroma area by RM was 1.42 times. RM has an anti-hyperplastic effect on the prostate of adult mice when hyperplasia was induced with TE acting first at prostatic stromal level.

  18. Tree Size Inequality Reduces Forest Productivity: An Analysis Combining Inventory Data for Ten European Species and a Light Competition Model.

    PubMed

    Bourdier, Thomas; Cordonnier, Thomas; Kunstler, Georges; Piedallu, Christian; Lagarrigues, Guillaume; Courbaud, Benoit

    2016-01-01

    Plant structural diversity is usually considered as beneficial for ecosystem functioning. For instance, numerous studies have reported positive species diversity-productivity relationships in plant communities. However, other aspects of structural diversity such as individual size inequality have been far less investigated. In forests, tree size inequality impacts directly tree growth and asymmetric competition, but consequences on forest productivity are still indeterminate. In addition, the effect of tree size inequality on productivity is likely to vary with species shade-tolerance, a key ecological characteristic controlling asymmetric competition and light resource acquisition. Using plot data from the French National Geographic Agency, we studied the response of stand productivity to size inequality for ten forest species differing in shade tolerance. We fitted a basal area stand production model that included abiotic factors, stand density, stand development stage and a tree size inequality index. Then, using a forest dynamics model we explored whether mechanisms of light interception and light use efficiency could explain the tree size inequality effect observed for three of the ten species studied. Size inequality negatively affected basal area increment for seven out of the ten species investigated. However, this effect was not related to the shade tolerance of these species. According to the model simulations, the negative tree size inequality effect could result both from reduced total stand light interception and reduced light use efficiency. Our results demonstrate that negative relationships between size inequality and productivity may be the rule in tree populations. The lack of effect of shade tolerance indicates compensatory mechanisms between effect on light availability and response to light availability. Such a pattern deserves further investigations for mixed forests where complementarity effects between species are involved. When studying the

  19. Tree Size Inequality Reduces Forest Productivity: An Analysis Combining Inventory Data for Ten European Species and a Light Competition Model

    PubMed Central

    Bourdier, Thomas; Cordonnier, Thomas; Kunstler, Georges; Piedallu, Christian; Lagarrigues, Guillaume; Courbaud, Benoit

    2016-01-01

    Plant structural diversity is usually considered as beneficial for ecosystem functioning. For instance, numerous studies have reported positive species diversity-productivity relationships in plant communities. However, other aspects of structural diversity such as individual size inequality have been far less investigated. In forests, tree size inequality impacts directly tree growth and asymmetric competition, but consequences on forest productivity are still indeterminate. In addition, the effect of tree size inequality on productivity is likely to vary with species shade-tolerance, a key ecological characteristic controlling asymmetric competition and light resource acquisition. Using plot data from the French National Geographic Agency, we studied the response of stand productivity to size inequality for ten forest species differing in shade tolerance. We fitted a basal area stand production model that included abiotic factors, stand density, stand development stage and a tree size inequality index. Then, using a forest dynamics model we explored whether mechanisms of light interception and light use efficiency could explain the tree size inequality effect observed for three of the ten species studied. Size inequality negatively affected basal area increment for seven out of the ten species investigated. However, this effect was not related to the shade tolerance of these species. According to the model simulations, the negative tree size inequality effect could result both from reduced total stand light interception and reduced light use efficiency. Our results demonstrate that negative relationships between size inequality and productivity may be the rule in tree populations. The lack of effect of shade tolerance indicates compensatory mechanisms between effect on light availability and response to light availability. Such a pattern deserves further investigations for mixed forests where complementarity effects between species are involved. When studying the

  20. Acarbose reduces myocardial infarct size by preventing postprandial hyperglycemia and hydroxyl radical production and opening mitochondrial KATP channels in rabbits.

    PubMed

    Minatoguchi, Shinya; Zhang, Zengi; Bao, Narentuoya; Kobayashi, Hiroyuki; Yasuda, Shinji; Iwasa, Masamitsu; Sumi, Syouhei; Kawamura, Itta; Yamada, Yoshihisa; Nishigaki, Kazuhiko; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi

    2009-07-01

    Acarbose, an antidiabetic drug, is an alpha-glucosidase inhibitor that can inhibit glucose absorption in the intestine. A recent large-scale clinical trial, STOP-NIDDM, showed that acarbose reduces the risk of myocardial infarction. We examined whether acarbose reduces myocardial infarct size and investigated its mechanisms. Rabbits were fed with 1 of 2 diets in this study: normal chow, 30 mg acarbose per 100 g chow for 7 days. Rabbits were assigned randomly to 1 of 4 groups: control (n = 10), acarbose (n = 10), acarbose + 5HD (n = 10, intravenous 5 mg/kg of 5-hydroxydecanoate), and 5HD (n = 10, intravenous 5 mg/kg of 5HD). Rabbits then underwent 30 minutes of coronary occlusion followed by 48-hour reperfusion. Postprandial blood glucose levels were higher in the control group than in the acarbose group. The infarct size as a percentage of the left ventricular area at risk was reduced significantly in the acarbose (19.4% +/- 2.3%) compared with the control groups (42.8% +/- 5.4%). The infarct size-reducing effect of acarbose was abolished by 5HD (43.4% +/- 4.7%). Myocardial interstitial 2,5-dihydroxybenzoic acid levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 minutes of ischemia, but this increase was inhibited in the acarbose group. This was reversed by 5HD. Acarbose reduces myocardial infarct size by opening mitochondrial KATP channels, which may be related to the prevention of postprandial hyperglycemia and hydroxyl radical production.

  1. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.

    PubMed

    Fowke, Jay H; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E

    2016-01-01

    obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes.

  2. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms

    PubMed Central

    Fowke, Jay H.; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E.

    2016-01-01

    The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes. PMID:27336586

  3. Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

    PubMed

    Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

    2007-12-01

    Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.

  4. Prostate cancer

    SciTech Connect

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  5. Reducing bias in rainfall estimates from microwave links by considering variable drop size distribution

    NASA Astrophysics Data System (ADS)

    Fencl, Martin; Jörg, Rieckermann; Vojtěch, Bareš

    2015-04-01

    Commercial microwave links (MWL) are point-to-point radio systems which are used in backhaul networks of cellular operators. For several years, they have been suggested as rainfall sensors complementary to rain gauges and weather radars, because, first, they operate at frequencies where rain drops represent significant source of attenuation and, second, cellular networks almost completely cover urban and rural areas. Usually, path-average rain rates along a MWL are retrieved from the rain-induced attenuation of received MWL signals with a simple model based on a power law relationship. The model is often parameterized based on the characteristics of a particular MWL, such as frequency, polarization and the drop size distribution (DSD) along the MWL. As information on the DSD is usually not available in operational conditions, the model parameters are usually considered constant. Unfortunately, this introduces bias into rainfall estimates from MWL. In this investigation, we propose a generic method to eliminate this bias in MWL rainfall estimates. Specifically, we search for attenuation statistics which makes it possible to classify rain events into distinct groups for which same power-law parameters can be used. The theoretical attenuation used in the analysis is calculated from DSD data using T-Matrix method. We test the validity of our approach on observations from a dedicated field experiment in Dübendorf (CH) with a 1.85-km long commercial dual-polarized microwave link transmitting at a frequency of 38 GHz, an autonomous network of 5 optical distrometers and 3 rain gauges distributed along the path of the MWL. The data is recorded at a high temporal resolution of up to 30s. It is further tested on data from an experimental catchment in Prague (CZ), where 14 MWLs, operating at 26, 32 and 38 GHz frequencies, and reference rainfall from three RGs is recorded every minute. Our results suggest that, for our purpose, rain events can be nicely characterized based on

  6. [Prostamol-Uno treatment in patients with prostatic adenoma and chronic non-infectious prostatitis].

    PubMed

    Trapeznikova, M F; Dutov, V V; Dolgovq, A G; Urenkov, S B

    2008-01-01

    We studied efficacy and safety of prostamol-Uno (PU) monotherapy in patients with prostatic adenoma (PA) comorbid with chronic abacterial prostatitis (CAP) in a clinical open trial including 45-year-old males aged over 45 years with PA comorbid with CAP, having irritative and obstructive symptoms by IPSS above 8 points and duration 6 months or longer, by NIH-CPSI above 10 points and duration 3 months or longer. The patients had Qmax from 5 to 15 ml/s, urine volume 100-350 ml, residual urine volume under 150 ml, prostate size more than 25 cm3, PSA level under 4 ng/ml and no bacterial growth in the third urine portion seeding and/or prostatic secretion. The effect was assessed by the disease history, complaints, digital rectal examination of the prostate, the disease symptoms by IPSS, quality of life (QoL), NIH-CPSI, bacteriological tests of the urine and prostatic secretion, urinalysis, Nechiporenko test in 3 urine portions. Uroflowmetry, ultrasonic investigation of the urinary bladder and prostate, transrectal energy dopplerography of the prostate, PSA assay in the blood serum were made in all the patients. PU safety was evaluated by arterial pressure, heart rate, 6-lead ECG, total and biochemical blood count. Control examination 3 months after the treatment showed no negative changes. PU patients demonstrated reduction in IPSS index from 14 to 6.8 points and NIH-CPSI (from 18.4 to 12.3 points (from 13 to 11.2 and 17.1 to 16.8 points, respectively, in the controls). QoL reduced from 3.9 to 1.9, from 3.6 to 3.3 points, respectively. Qmax rose from 12.4 to 18.2 ml/s and 13.5 to 14.5 ml/s, respectively. PSA changed insignificantly. Side effects were mild. Spectral doppler examination detected improvement in prostatic blood flow after PU treatment in 16 (53.3%) patients. Resistance index as an index of peripheral vascular resistance increased from 0.48-0.54 to 0.7-0.72 (p < 0.05). Thus, PU effectively reduces irritative and obstructive symptoms typical for prostatic

  7. Increasing age and tear size reduce rotator cuff repair healing rate at 1 year.

    PubMed

    Rashid, Mustafa S; Cooper, Cushla; Cook, Jonathan; Cooper, David; Dakin, Stephanie G; Snelling, Sarah; Carr, Andrew J

    2017-09-07

    Background and purpose - There is a need to understand the reasons why a high proportion of rotator cuff repairs fail to heal. Using data from a large randomized clinical trial, we evaluated age and tear size as risk factors for failure of rotator cuff repair. Patients and methods - Between 2007 and 2014, 65 surgeons from 47 hospitals in the National Health Service (NHS) recruited 447 patients with atraumatic rotator cuff tendon tears to the United Kingdom Rotator Cuff Trial (UKUFF) and 256 underwent rotator cuff repair. Cuff integrity was assessed by imaging in 217 patients, at 12 months post-operation. Logistic regression analysis was used to determine the influence of age and intra-operative tear size on healing. Hand dominance, sex, and previous steroid injections were controlled for. Results - The overall healing rate was 122/217 (56%) at 12 months. Healing rate decreased with increasing tear size (small tears 66%, medium tears 68%, large tears 47%, and massive tears 27% healed). The mean age of patients with a healed repair was 61 years compared with 64 years for those with a non-healed repair. Mean age increased with larger tear sizes (small tears 59 years, medium tears 62 years, large tears 64 years, and massive tears 66 years). Increasing age was an independent factor that negatively influenced healing, even after controlling for tear size. Only massive tears were an independent predictor of non-healing, after controlling for age. Interpretation - Although increasing age and larger tear size are both risks for failure of rotator cuff repair healing, age is the dominant risk factor.

  8. Reduced-size microchips for identification of horses: response to implantation and readability during a six-month period.

    PubMed

    Wulf, M; Aurich, C; von Lewinski, M; Möstl, E; Aurich, J E

    2013-11-09

    In this study, readability of reduced-size microchips in horses and the response to implantation were analysed. It was hypothesised that small microchips can be implanted stress-free but are less readable than larger microchips. Adult mares (n=40) were implanted with a reduced-size microchip (10.9×1.6 mm) at the left side of the neck (size of conventional microchips 11.4×2.2 mm). Microchips were identified with three different scanners (A, B, C) immediately, and at 6, 12 and 28 weeks after implantation. Twelve out of the 40 mares were submitted to microchip implantation and control treatments and cortisol, heart rate and heart rate variability (HRV) were determined. From the chip-bearing side of the neck, microchips were identified with all scanners in all horses at all times. From the contralateral side, correct readings were always 100 per cent with scanner C and with scanners A and B ranged between 60 and 100 per cent. Heart rate and HRV variable sd of beat-to-beat interval increased slightly (P<0.01) at microchip implantation and control treatment, but cortisol concentration did not increase. In conclusion, reduced-size microchips are highly reliable for identification of horses. Compared with conventional microchips, the reduction in size did not impair readability. Microchip implantation is no pronounced stressor for horses.

  9. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    SciTech Connect

    Oorschot, Bregje van; Hovingh, Suzanne E.; Moerland, Perry D.; Medema, Jan Paul; Stalpers, Lukas J.A.; Vrieling, Harry; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  10. An Evaluation of a Community-Academic-Clinical Partnership to Reduce Prostate Cancer Disparities in the South

    PubMed Central

    Friedman, Daniela B.; Owens, Otis L.; Jackson, Dawnyea D.; Johnson, Kim M.; Gansauer, Lucy; Dickey, Joe; Miller, Ron; Payne, Johnny; Bearden, James D.; Hebert, James R.

    2013-01-01

    Background Engaging partners in the planning, implementation, and evaluation of cancer education programs is critical for improving the health of our communities. A two-year pilot education intervention on prostate cancer decision making and participation in medical research was funded by the National Cancer Institute. The partnership involving community members and clinical staff at a cancer center was used to develop recruitment strategies and plan for the implementation of the intervention with African-American (AA) middle-age and older men and female family members. We assessed partners’ perceptions of this community-academic-clinical research collaboration. Methods In year 2, eight project advisory council members were selected among existing partners and year 1 participants to serve as a formal committee. Council members were required to participate in telephone and in-person meetings and actively support recruitment/implementation efforts. At the conclusion of the project, 20 individuals (all clinical and community partners, including the eight advisory council members) were invited to complete a survey to assess their perceived impact of the collaboration on the community and provide suggestions for future collaborations. Results Most partners agreed that their organization benefitted from the collaboration and that various aspects of the advisory council process (e.g., both formal and informal communication) worked well. The most noted accomplishment of the partnership related to leveraging the collaboration to make men more knowledgeable about prostate cancer decision making. Suggested improvements for future collaborations included distributing more frequent updates regarding project successes. Conclusions Evaluating partners’ perceptions of this collaboration provided important recommendations for future planning, implementation, and evaluation of community-based cancer education programs. PMID:24078315

  11. POOR GLYCEMIC CONTROL IS ASSOCIATED WITH REDUCED PROSTATE-SPECIFIC ANTIGEN CONCENTRATIONS IN MEN WITH TYPE 1 DIABETES

    PubMed Central

    Sarma, Aruna V.; Hotaling, James; Dunn, Rodney L.; Cleary, Patricia A.; Braffett, Barbara H.; Kim, Catherine; Martin, Catherine; Herman, William; Gatcomb, Patricia; Jacobson, Alan M.; Holt, Sarah K.; Wessells, Hunter

    2015-01-01

    PURPOSE Previous studies have demonstrated lower prostate-specific antigen (PSA) concentrations in men with type 2 diabetes (T2DM), paralleling the reported lower prevalence of prostate cancer among diabetic men. Data on PSA in men with type 1 diabetes (T1DM), in whom insulin and obesity profiles differ from those in T2DM, are lacking. The objective of this study was to examine the relationship between long-term glycemic control and PSA in men with T1DM. MATERIALS & METHODS Total PSA was measured at one time in 639 men in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow up of participants in the Diabetes Control and Complications Trial (DCCT). The relationship between DCCT/EDIC weighted mean HbA1c and log PSA was assessed using linear regression modeling after adjusting for age, body mass index (BMI), total testosterone, statin and thiazide medication use, diabetes duration, and DCCT randomization arm and cohort. RESULTS The subjects had a median age of 52 years, BMI of 28.4 kg/m2 and DCCT/EDIC time weighted HbA1c of 7.9%. Total median (interquartile range) for PSA levels was 0.64 (0.43, 1.05). PSA levels increased significantly with age (p<0.0001) and with lower time weighted HbA1c (p<0.0001). Each 10% increase in HbA1c was accompanied by an 11% reduction in PSA (p=0.0001). CONCLUSIONS PSA levels decrease as HbA1c increases in men with T1DM. This relationship is independent of age, BMI, androgen levels, medication use and measures of diabetes severity, which suggest that factors related to glycemia may be directly affecting PSA levels. PMID:25218922

  12. Motor-Reducer Sizing through a MATLAB-Based Graphical Technique

    ERIC Educational Resources Information Center

    Giberti, H.; Cinquemani, S.

    2012-01-01

    The design of the drive system for an automatic machine and its correct sizing is a very important competence for an electrical or mechatronic engineer. This requires knowledge that crosses the fields of electrical engineering, electronics and mechanics, as well as the skill to choose commercial components based upon their technical documentation.…

  13. Size sorting of citrate reduced gold nanoparticles by sedimentation field-flow fractionation.

    PubMed

    Contado, Catia; Argazzi, Roberto

    2009-12-25

    Gold nanoparticles (GNPs) have been synthesized through the citrate reduction method; the citrate/gold(III) ratio was changed from 1:1 up to 10:1 and the size of the resulting nanoparticles was measured by sedimentation field-flow fractionation (SdFFF). Experimental data showed that the GNPs size decreases in the ratio range 1:1-3:1 and then increases from 5:1 to 10:1 passing through a plateau region in between, and is almost independent of the precursor solution concentrations. In the zone of minimum diameters the synthetic process does not produce monodispersed GNPs but often multiple distributions, very close in size, are observed as evidenced by the particle size distributions (PSDs) derived from the SdFFF fractograms. UV-vis spectrophotometry, being the most common technique employed in the optical characterization of nanoparticles suspensions, was used throughout this work. A confirmation of the nucleation-aggregation-fragmentation mechanism was inferred from the cross-correlation between UV-vis and SdFFF results.

  14. Winter grazing can reduce wildfire size, intensity, and behavior in a shrub-grassland

    USDA-ARS?s Scientific Manuscript database

    1. An increase in mega-fires and wildfires in general is a global issue that is expected to become worse with climate change. Fuel treatments are often recommended to decrease the risk, size, intensity, and severity of wildfires; however, the extensive nature of rangelands limits the use of many po...

  15. Motor-Reducer Sizing through a MATLAB-Based Graphical Technique

    ERIC Educational Resources Information Center

    Giberti, H.; Cinquemani, S.

    2012-01-01

    The design of the drive system for an automatic machine and its correct sizing is a very important competence for an electrical or mechatronic engineer. This requires knowledge that crosses the fields of electrical engineering, electronics and mechanics, as well as the skill to choose commercial components based upon their technical documentation.…

  16. 30 CFR 203.76 - When might BSEE withdraw or reduce the approved size of my relief?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Oil, Gas, and Sulfur General § 203.76 When might BSEE withdraw or reduce the approved size of my... our approval, we will withdraw the relief we granted. (c) Your actual development costs are less than 80 percent of the eligible development costs estimated in your application's most likely scenario...

  17. Brokering Dialogue between Secondary Students and Teachers to Co-Construct Appropriate Pedagogy in Reduced-Size Classes

    ERIC Educational Resources Information Center

    Harfitt, Gary James

    2014-01-01

    This study focuses on how two teachers working in reduced-size secondary classes of the same grade adapted their pedagogy as a result of a brokered dialogue between myself as researcher and 43 grade 10 students from the teachers' classes. Research was carried out over the course of one academic year. First, students' perspectives on studying in a…

  18. BIOREACTOR ECONOMICS, SIZE AND TIME OF OPERATION (BEST) COMPUTER SIMULATOR FOR DESIGNING SULFATE-REDUCING BACTERIA FIELD BIOREACTORS

    EPA Science Inventory

    BEST (bioreactor economics, size and time of operation) is an Excel™ spreadsheet-based model that is used in conjunction with the public domain geochemical modeling software, PHREEQCI. The BEST model is used in the design process of sulfate-reducing bacteria (SRB) field bioreacto...

  19. Testing Probation Outcomes in an Evidence-Based Practice Setting: Reduced Caseload Size and Intensive Supervision Effectiveness

    ERIC Educational Resources Information Center

    Jalbert, Sarah Kuck; Rhodes, William; Flygare, Christopher; Kane, Michael

    2010-01-01

    Probation and parole professionals argue that supervision outcomes would improve if caseloads were reduced below commonly achieved standards. Criminal justice researchers are skeptical because random assignment and strong observation studies have failed to show that criminal recidivism falls with reductions in caseload sizes. One explanation is…

  20. Testing Probation Outcomes in an Evidence-Based Practice Setting: Reduced Caseload Size and Intensive Supervision Effectiveness

    ERIC Educational Resources Information Center

    Jalbert, Sarah Kuck; Rhodes, William; Flygare, Christopher; Kane, Michael

    2010-01-01

    Probation and parole professionals argue that supervision outcomes would improve if caseloads were reduced below commonly achieved standards. Criminal justice researchers are skeptical because random assignment and strong observation studies have failed to show that criminal recidivism falls with reductions in caseload sizes. One explanation is…

  1. BIOREACTOR ECONOMICS, SIZE AND TIME OF OPERATION (BEST) COMPUTER SIMULATOR FOR DESIGNING SULFATE-REDUCING BACTERIA FIELD BIOREACTORS

    EPA Science Inventory

    BEST (bioreactor economics, size and time of operation) is an Excel™ spreadsheet-based model that is used in conjunction with the public domain geochemical modeling software, PHREEQCI. The BEST model is used in the design process of sulfate-reducing bacteria (SRB) field bioreacto...

  2. The Cumulative Effects of Indiana PRIME TIME: A State Sponsored Reduced Class Size Program, on Basic Skills Achievement.

    ERIC Educational Resources Information Center

    Malloy, Leanne; Gilman, David

    The purpose of this paper was to analyze the initial results of statewide implementation of the PRIME TIME program in Indiana. PRIME TIME is a state-wide program to reduce class size in the primary grades. Mean scores from 65,911 third graders who had completed the Indiana Competency Test in the spring of 1987 after completing 3 years of the…

  3. Size inequality in regenerating yellow birch stands is reduced by elevated CO[sub 2] atmospheres

    SciTech Connect

    Wayne, P.W.; Bazzaz, F.A. )

    1994-06-01

    Dense stands of yellow birch (Betula alleghaniensis) seedlings comprised of equal numbers of three maternal families were established in forest soil profiles in low (350 [mu]l l[sup [minus]1]) and high (700 [mu]l l[sup [minus]1]) CO[sub 2] atmospheres in a glasshouse. In both CO[sub 2] treatments, seedling size inequality (% CV) within stands increased through time with total with total stand biomass. However, while stands in high CO[sub 2] maintained greater final above and below ground biomass than stands at low CO[sub 2], inequalities in total seedling mass, shoot height, and leaf area were significantly lower in high CO[sub 2] throughout the growing season. This effect of elevated CO[sub 2] on stand development differs from the effects of other resources additions (e.g. light, nutrients) which generally increase inter-individual size inequality. Lower size inequalities in high CO[sub 2] may have occurred because sub-canopy plants in low light exhibited greater proportional responsiveness to elevated CO[sub 2] than did canopy plants in high light. Other studies with yellow birch suggest CO[sub 2]-induced photosynthetic and growth enhancements are proportionally greater at low vs. high light. Hypothesis which may explain greater CO[sub 2] enhancements at low light are presented. Strong correlations were found between individuals' final positions in stand size hierarchies and seedlings' initial sizes and abilities to preempt light and soil nutrients. The three maternal lines differed in their responsiveness to elevated CO[sub 2], and thus contributed differently to total stand biomass in the two CO[sub 2] treatments.

  4. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

    Loeb, Stacy; Sanda, Martin G.; Broyles, Dennis L.; Shin, Sanghyuk S.; Bangma, Chris H.; Wei, John T.; Partin, Alan W.; Klee, George G.; Slawin, Kevin M.; Marks, Leonard S.; van Schaik, Ron H. N.; Chan, Daniel W.; Sokoll, Lori J.; Cruz, Amabelle B.; Mizrahi, Isaac A.; Catalona, William J.

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  5. Delayed Treatment With Hypothermia Protects Against the No‐Reflow Phenomenon Despite Failure to Reduce Infarct Size

    PubMed Central

    Hale, Sharon L.; Herring, Michael J.; Kloner, Robert A.

    2013-01-01

    Background Many studies have shown that when hypothermia is started after coronary artery reperfusion (CAR), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no‐reflow. Our aim was to test the effects of hypothermia on no‐reflow when initiated close to reperfusion and 30 minutes after reperfusion, times not associated with a protective effect on myocardial infarct size. Methods and Results Rabbits received 30 minutes coronary artery occlusion/3 hours CAR. In protocol 1, hearts were treated for 1 hour with topical hypothermia (myocardial temperature ≈32°C) initiated at 5 minutes before or 5 minutes after CAR, and the results were compared with a normothermic group. In protocol 2, hypothermia was delayed until 30 minutes after CAR and control hearts remained normothermic. In protocol 1, risk zones were similar and infarct size was not significantly reduced by hypothermia initiated close to CAR. However, the no‐reflow defect was significantly reduced by 43% (5 minutes before CAR) and 38% (5 minutes after CAR) in hypothermic compared with normothermic hearts (P=0.004, ANOVA, P=ns between the 2 treated groups). In protocol 2, risk zones and infarct sizes were similar, but delayed hypothermia significantly reduced no‐reflow in hypothermic hearts by 30% (55±6% of the necrotic region in hypothermia group versus 79±6% with normothermia, P=0.008). Conclusion These studies suggest that treatment with hypothermia reduces no‐reflow even when initiated too late to reduce infarct size and that the microvasculature is especially receptive to the protective properties of hypothermia and confirm that microvascular damage is in large part a form of true reperfusion injury. PMID:23525431

  6. Obesity and prostate enlargement in men with localized prostate cancer.

    PubMed

    Kopp, Ryan P; Han, Misop; Partin, Alan W; Humphreys, Elizabeth; Freedland, Stephen J; Parsons, J Kellogg

    2011-12-01

    What's known on the subject? and What does the study add? Obesity is associated with prostate enlargement in men without prostate cancer. This study demonstrates an association between obesity and prostate enlargement in men with prostate cancer, and leads to possible implications for prostate cancer screening and diagnosis. • To determine if obesity is associated with prostate size in men with prostate cancer. • We examined preoperative body mass index (BMI) and whole prostate weight in a cohort of 16,325 patients undergoing radical prostatectomy for localized prostate cancer from 1975 to 2008 at a single institution. • We used multivariable regression modelling adjusting for age, year of surgery, preoperative serum prostate-specific antigen (PSA), pathological stage and Gleason grade. • Of the entire cohort, 13,343 (82%) patients had a prostate weight of at least 40 g. These men were older (P < 0.001), had a higher preoperative BMI (P < 0.002), higher preoperative PSA (P < 0.001), and were more likely to have pT2 disease (P < 0.001). • In multivariable regression, preoperative BMI was associated with increased prostate weight: for each 1 kg/m(2) increase in BMI, prostate weight increased by 0.45 g (95% CI 0.35-0.55, P-trend < 0.001). • Compared with men with BMI < 25 kg/m(2) , men with a BMI ≥35 kg/m(2) had a 40% (odds ratio 1.40, 95% CI 1.01-1.95) increased risk of prostate weight of at least 40 g and a 70% (odds ratio 1.70, 95% CI 1.32-2.20) increased risk of prostate weight of at least 50 g. • In men with localized prostate cancer, obesity is associated with an increased risk of prostate enlargement. • These data validate other observations linking obesity with prostate enlargement and may have important ramifications for prostate cancer diagnosis in obese men. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  7. Faltering lemming cycles reduce productivity and population size of a migratory Arctic goose species.

    PubMed

    Nolet, Bart A; Bauer, Silke; Feige, Nicole; Kokorev, Yakov I; Popov, Igor Yu; Ebbinge, Barwolt S

    2013-07-01

    The huge changes in population sizes of Arctic-nesting geese offer a great opportunity to study population limitation in migratory animals. In geese, population limitation seems to have shifted from wintering to summering grounds. There, in the Arctic, climate is rapidly changing, and this may impact reproductive performance, and perhaps population size of geese, both directly (e.g. by changes in snow melt) or indirectly (e.g. by changes in trophic interactions). Dark-bellied brent geese (Branta bernicla bernicla L.) increased 20-fold since the 1950s. Its reproduction fluctuates strongly in concert with the 3-year lemming cycle. An earlier analysis, covering the growth period until 1988, did not find evidence for density dependence, but thereafter the population levelled off and even decreased. The question is whether this is caused by changes in lemming cycles, population density or other factors like carry-over effects. Breeding success was derived from proportions of juveniles. We used an information-theoretical approach to investigate which environmental factors best explained the variation in breeding success over nearly 50 years (1960-2008). We subsequently combined GLM predictions of breeding success with published survival estimates to project the population trajectory since 1991 (year of maximum population size). In this way, we separated the effects of lemming abundance and population density on population development. Breeding success was mainly dependent on lemming abundance, the onset of spring at the breeding grounds, and the population size of brent goose. No evidence was found for carry-over effects (i.e. effects of conditions at main spring staging site). Negative density dependence was operating at a population size above c. 200 000 individuals, but the levelling off of the population could be explained by faltering lemming cycles alone. Lemmings have long been known to affect population productivity of Arctic-nesting migratory birds and, more

  8. Faltering lemming cycles reduce productivity and population size of a migratory Arctic goose species

    PubMed Central

    Nolet, Bart A; Bauer, Silke; Feige, Nicole; Kokorev, Yakov I; Popov, Igor Yu; Ebbinge, Barwolt S

    2013-01-01

    1. The huge changes in population sizes of Arctic-nesting geese offer a great opportunity to study population limitation in migratory animals. In geese, population limitation seems to have shifted from wintering to summering grounds. There, in the Arctic, climate is rapidly changing, and this may impact reproductive performance, and perhaps population size of geese, both directly (e.g. by changes in snow melt) or indirectly (e.g. by changes in trophic interactions). 2. Dark-bellied brent geese (Branta bernicla bernicla L.) increased 20-fold since the 1950s. Its reproduction fluctuates strongly in concert with the 3-year lemming cycle. An earlier analysis, covering the growth period until 1988, did not find evidence for density dependence, but thereafter the population levelled off and even decreased. The question is whether this is caused by changes in lemming cycles, population density or other factors like carry-over effects. 3. Breeding success was derived from proportions of juveniles. We used an information-theoretical approach to investigate which environmental factors best explained the variation in breeding success over nearly 50 years (1960–2008). We subsequently combined GLM predictions of breeding success with published survival estimates to project the population trajectory since 1991 (year of maximum population size). In this way, we separated the effects of lemming abundance and population density on population development. 4. Breeding success was mainly dependent on lemming abundance, the onset of spring at the breeding grounds, and the population size of brent goose. No evidence was found for carry-over effects (i.e. effects of conditions at main spring staging site). Negative density dependence was operating at a population size above c. 200 000 individuals, but the levelling off of the population could be explained by faltering lemming cycles alone. 5. Lemmings have long been known to affect population productivity of Arctic-nesting migratory

  9. Chemoprevention of prostate cancer.

    PubMed

    Vemana, Goutham; Hamilton, Robert J; Andriole, Gerald L; Freedland, Stephen J

    2014-01-01

    Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence.

  10. Reduced-size plutonium sample processing and packaging for the PAT-2 package

    SciTech Connect

    Kuhn, E.; Deron, S.; Aigner, H.; Andersen, J.A.

    1982-01-01

    A light-water container for the air transport of plutonium safeguards samples, the PAT-2 package, has been developed in the USA and is now licensed by the US NRC (Certificate of Compliance) and the US DOT (IAEA Certificate of Competent Authority). The very limited available space in this package for plutonium-bearing samples required the design of small-size canisters to meet the needs of international safeguards. The suitability of a new small canister and vial for powder and solution samples has been tested in an intralaboratory experiment. The results of the experiment, based on the concept of pre-weighed samples, show that the tested canister and quartz vial can be used successfully for containing small size PuO/sub 2/ powder samples of homogeneous source material, as well as for dried aliguands of plutonium nitrate solutions.

  11. Cryptic female choice: frogs reduce clutch size when amplexed by undesired males.

    PubMed

    Reyer, H U; Frei, G; Som, C

    1999-10-22

    In species with internal fertilization, females can 'cryptically' choose (e.g. through sperm selection) which individuals sire their offspring, even when their overt preferences for copulatory partners are overrun by male-male competition and sexual coercion. The experiment presented here reveals that control of paternity after copulation has begun is also possible in species with external fertilization. Females of the hybridogenetic Rana essonae-Rana esculenta (LL-LR) waterfrog complex adjust their clutch size in response to mate type: they release fewer eggs when amplexed by hybrid LR males who--jeopardize successful reproduction--than when amplexed by parental LL males. This reduction in the number of eggs laid can increase a female's residual reproductive value through a second mating in the same breeding season or a larger clutch size in the next year. We argue that cryptic female choice through clutch size adjustment (i) may have evolved more often than previously assumed, and (ii) can arise even where females mate only once during a reproductive period.

  12. Reducing the availability of food to control feral pigeons: changes in population size and composition.

    PubMed

    Senar, Juan C; Montalvo, Tomás; Pascual, Jordi; Peracho, Victor

    2017-02-01

    As feeding by humans is one of the main food resources to pigeons (Columba livia), there is general agreement that public education that aims to reduce the food base may be the most feasible way to reduce pigeon abundance. However, except for the classic example of Basel, the method has rarely been tested or implemented. We provide results from a 1 year study in the city of Barcelona where we tested the effect of public education on pigeon population abundance and composition. The quantity of food provided by people to pigeons was significantly reduced during the study. Feral pigeon density was reduced by 40% in the two experimental districts, but no variation was detected in the control district. Detailed analyses in one of the districts showed that the reduction was mainly related to the reduction in food availability but not to culling. Pigeons captured at the end of the experiment were larger than at the start of the study, but body condition was reduced. Results show the effectiveness of public information to manage feral pigeon populations in a large city, and that control operations can exert important selection pressure on the population, leading to changes in population composition. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  13. Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3β?

    PubMed Central

    2010-01-01

    Background Male Irs2-/- mice develop fatal type 2 diabetes at 13-14 weeks. Defects in neuronal proliferation, pituitary development and photoreceptor cell survival manifest in Irs2-/- mice. We identify retarded renal growth in male and female Irs2-/- mice, independent of diabetes. Results Kidney size and kidney:body weight ratio were reduced by approximately 20% in Irs2-/- mice at postnatal day 5 and was maintained in maturity. Reduced glomerular number but similar glomerular density was detected in Irs2-/- kidney compared to wild-type, suggesting intact global kidney structure. Analysis of insulin signalling revealed renal-specific upregulation of PKBβ/Akt2, hyperphosphorylation of GSK3β and concomitant accumulation of β-catenin in Irs2-/- kidney. Despite this, no significant upregulation of β-catenin targets was detected. Kidney-specific increases in Yes-associated protein (YAP), a key driver of organ size were also detected in the absence of Irs2. YAP phosphorylation on its inhibitory site Ser127 was also increased, with no change in the levels of YAP-regulated genes, suggesting that overall YAP activity was not increased in Irs2-/- kidney. Conclusions In summary, deletion of Irs2 causes reduced kidney size early in mouse development. Compensatory mechanisms such as increased β-catenin and YAP levels failed to overcome this developmental defect. These data point to Irs2 as an important novel mediator of kidney size. PMID:20604929

  14. Salt stress reduces root meristem size by nitric oxide-mediated modulation of auxin accumulation and signaling in Arabidopsis.

    PubMed

    Liu, Wen; Li, Rong-Jun; Han, Tong-Tong; Cai, Wei; Fu, Zheng-Wei; Lu, Ying-Tang

    2015-05-01

    The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor N(ω)-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels. © 2015 American Society of Plant Biologists. All Rights Reserved.

  15. Herniated disks unchanged over time: Size reduced after oxygen–ozone therapy

    PubMed Central

    Bonetti, Matteo; Zambello, Alessio; Princiotta, Ciro

    2016-01-01

    The spontaneous regression of disk herniation secondary to dehydration is a much-debated topic in medicine. Some physicians wonder whether surgical removal of the extruded nucleus pulposus is really necessary when the spontaneous disappearance of a herniated lumbar disk is a well-known phenomenon. Unfortunately, without spontaneous regression, chronic pain leads to progressive disability for which surgery seems to be the only solution. In recent years, several studies have demonstrated the utility of oxygen–ozone therapy in the treatment of disk herniation, resulting in disk shrinkage. This retrospective study evaluates the outcomes of a series of patients with a history of herniated disks neuroradiologically unchanged in size for over two years, treated with oxygen–ozone therapy at our center over the last 15 years. We treated 96 patients, 84 (87.5%) presenting low back pain complicated or not by chronic sciatica. No drug therapy had yielded significant benefits. A number of specialists had been consulted in two or more years resulting in several neuroradiological scans prior to the decision to undertake oxygen–ozone therapy. Our study documents how ozone therapy for slipped disks “unchanged over time” solved the problem, with disk disruption or a significant reduction in the size of the prolapsed disk material extruded into the spinal canal. PMID:27066816

  16. Effect of sample size and reduced number of principle components on the Gillette Gait Index.

    PubMed

    Tulchin, Kirsten; Campbell, Scott; Browne, Richard; Orendurff, Michael

    2009-06-01

    The Gillette Gait Index uses principle components analysis of 16 variables to determine the deviation of an individual's gait compared to a normal control set. Previous literature has not reported on the effects of altering the size of the control set used to create the principle components, or described the effects of using less than the maximum number of principle components, 16, to calculate the Gillette Gait Index (GGI). Calculations of the GGI were determined for a group of 24 able-bodied normal subjects and 24 cerebral palsy subjects using 128 control subjects allotted into 15 subsets of varying sizes, from N=16-128. A minimum of 40 controls were needed for GGI estimates to achieve less than approximately 20% error, and 96 controls were needed for less than 10% error, if all 16 principle components were used. With smaller control sets, an alternative method to increase the accuracy would be to use only those principle components that represent 95% of the variance. Caution must still be used when describing differences in GGI among groups, or changes in an individual's GGI over time. In addition, absolute changes in GGI should always be reported, as differences as great as 150 were seen in cerebral palsy patients across control groups, even when greater than 40 controls are used to create the principle components.

  17. Herniated disks unchanged over time: Size reduced after oxygen-ozone therapy.

    PubMed

    Bonetti, Matteo; Zambello, Alessio; Leonardi, Marco; Princiotta, Ciro

    2016-08-01

    The spontaneous regression of disk herniation secondary to dehydration is a much-debated topic in medicine. Some physicians wonder whether surgical removal of the extruded nucleus pulposus is really necessary when the spontaneous disappearance of a herniated lumbar disk is a well-known phenomenon. Unfortunately, without spontaneous regression, chronic pain leads to progressive disability for which surgery seems to be the only solution. In recent years, several studies have demonstrated the utility of oxygen-ozone therapy in the treatment of disk herniation, resulting in disk shrinkage. This retrospective study evaluates the outcomes of a series of patients with a history of herniated disks neuroradiologically unchanged in size for over two years, treated with oxygen-ozone therapy at our center over the last 15 years. We treated 96 patients, 84 (87.5%) presenting low back pain complicated or not by chronic sciatica. No drug therapy had yielded significant benefits. A number of specialists had been consulted in two or more years resulting in several neuroradiological scans prior to the decision to undertake oxygen-ozone therapy. Our study documents how ozone therapy for slipped disks "unchanged over time" solved the problem, with disk disruption or a significant reduction in the size of the prolapsed disk material extruded into the spinal canal.

  18. Transient response in longitudinal grain size to reduced sediment supply in a large river

    NASA Astrophysics Data System (ADS)

    Singer, Michael

    2010-05-01

    Bed material grain size is an important degree of freedom in fluvial systems as they adjust to system-wide perturbations such as sediment supply changes. However, little is known about processes and patterns of such adjustment in longitudinal grain size sorting in large rivers. This research uses unprecedented datasets collected in a large fluvial system to investigate transient response to recent supply changes associated with anthropogenic activities. Separate fining trends for gravel and fines, a protracted gravel-sand (G-S) transition, and bed patchiness identified in Singer (2008) were interrogated using output from a hydraulic model with grain size distributions (GSDs) extracted from ~125 cross sections spanning ~400 river kilometers of the Sacramento River, California. The analysis suggests that interactions between hydraulics, bed material sorting, and sediment flux explain these previously identified anomalies. Highest values of sorting occur in the G-S transition and represent the overlap of separate fining trends for gravel and fines, where the long profile is jagged with evidence of progressive incision. Much of the sediment in this poorly sorted zone is organized into patches, where transport apparently occurs as bedload sheets. Patchiness occurs over short length scales leading to strong differences in entrainment and flux, regardless of hydraulic conditions. A modified Shields stress is proposed that is scaled by GSD sorting to improve characterization of entrainment/disentrainment. Sediment flux calculations based on an equation sensitive bed material conditions (Singer and Dunne, 2004) reveal a strong relationship between fine sediment flux and d90, suggesting that the efficiency of fine patch flux controls bed material bed surface roughness. Results are in part consistent with Paola and Seal (1995) suggesting that patches are a result of overlapping pdfs of shear stress and sorting and with Ferguson (2003) in that the final end of the protracted G

  19. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-05

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. [Drugs for the treatment of benign prostatic hypertrophy].

    PubMed

    Caprino, L

    2000-06-01

    Benign Prostatic Hyperplasia (BPH) usually occurs in males 45-50 old and progressively involves 75% of the male population over 75 years of age. The clinical manifestations of BPH are related primarily to bladder outlet obstructions resulting from enlargement (mechanical component) of the prostate gland, and from extrinsic and intrinsic sympathetic activation of alpha-adrenoceptors (dynamic component) present in the prostatic muscle tissue, prostatic urethra, bladder base and neck. Several drugs have been employed in the last decades: LHRH analogs (Leuprorelin and Goserelin) which can reduce the testicular production of androgens with reduction in prostate size; Serenoa repens for its anti-androgenic and anti-estrogenic activities; Finasteride (5-alpha-reductase inhibitor) which blocks the conversion of testosterone into the more active dihydrotestosterone. Finally, the alpha 1 blocking agents (Terazosin, Doxazosin, Tamsulosin) that improve urinary symptoms by acting on dynamic component. Clinical improvements derive from their antagonist action on alpha 1 adrenergic receptors which mediate contraction of the prostate gland, proximal urethra, bladder base and neck, with the consequent reduction of urethral pressure, bladder outlet resistance, and increase of urinary flow. Due to its pharmacodynamic and pharmacokinetic properties, as well as the clinical results obtained, Terazosin, alpha 1 blocker, appears to be particularly useful in the treatment of patients with mild- to moderate symptomatic BPH.

  1. One size does not fit all: evaluating an intervention to reduce antibiotic prescribing for acute bronchitis

    PubMed Central

    2013-01-01

    Background Overuse of antibiotics for upper respiratory tract infections (URIs) and acute bronchitis is a persistent and vexing problem. In the U.S., more than half of all patients with upper respiratory tract infections and acute bronchitis are treated with antibiotics annually, despite the fact that most cases are viral in etiology and are not responsive to antibiotics. Interventions aiming to reduce unnecessary antibiotic prescribing have had mixed results, and successes have been modest. The objective of this evaluation is to use mixed methods to understand why a multi-level intervention to reduce antibiotic prescribing for acute bronchitis among primary care providers resulted in measurable improvement in only one third of participating clinicians. Methods Clinician perspectives on print-based and electronic intervention strategies, and antibiotic prescribing more generally, were elicited through structured telephone surveys at high and low performing sites after the first year of intervention at the Geisinger Health System in Pennsylvania (n = 29). Results Compared with a survey on antibiotic use conducted 10 years earlier, clinicians demonstrated greater awareness of antibiotic resistance and how it is impacted by individual prescribing decisions—including their own. However, persistent perceived barriers to reducing prescribing included patient expectations, time pressure, and diagnostic uncertainty, and these factors were reported as differentially undermining specific intervention components’ effectiveness. An exam room poster depicting a diagnostic algorithm was the most popular strategy. Conclusions Future efforts to reduce antibiotic prescribing should address multi-level barriers identified by clinicians and tailor strategies to differences at individual clinician and group practice levels, focusing in particular on changing how patients and providers make decisions together about antibiotic use. PMID:24188573

  2. Face inversion and acquired prosopagnosia reduce the size of the perceptual field of view.

    PubMed

    Van Belle, Goedele; Lefèvre, Philippe; Rossion, Bruno

    2015-03-01

    Using a gaze-contingent morphing approach, we asked human observers to choose one of two faces that best matched the identity of a target face: one face corresponded to the reference face's fixated part only (e.g., one eye), the other corresponded to the unfixated area of the reference face. The face corresponding to the fixated part was selected significantly more frequently in the inverted than in the upright orientation. This observation provides evidence that face inversion reduces an observer's perceptual field of view, even when both upright and inverted faces are displayed at full view and there is no performance difference between these conditions. It rules out an account of the drop of performance for inverted faces--one of the most robust effects in experimental psychology--in terms of a mere difference in local processing efficiency. A brain-damaged patient with pure prosopagnosia, viewing only upright faces, systematically selected the face corresponding to the fixated part, as if her perceptual field was reduced relative to normal observers. Altogether, these observations indicate that the absence of visual knowledge reduces the perceptual field of view, supporting an indirect view of visual perception.

  3. Kava components down-regulate expression of AR and AR splice variants and reduce growth in patient-derived prostate cancer xenografts in mice.

    PubMed

    Li, Xuesen; Liu, Zhongbo; Xu, Xia; Blair, Christopher A; Sun, Zheng; Xie, Jun; Lilly, Michael B; Zi, Xiaolin

    2012-01-01

    Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5'6'-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR.

  4. Kava Components Down-Regulate Expression of AR and AR Splice Variants and Reduce Growth in Patient-Derived Prostate Cancer Xenografts in Mice

    PubMed Central

    Li, Xuesen; Liu, Zhongbo; Xu, Xia; Blair, Christopher A.; Sun, Zheng; Xie, Jun; Lilly, Michael B.; Zi, Xiaolin

    2012-01-01

    Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5′6′-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR. PMID:22347450

  5. Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced pro-inflammatory cytokines and immune suppressive cells

    PubMed Central

    Lesinski, Gregory B.; Reville, Patrick K.; Mace, Thomas A.; Young, Gregory S.; Ahn-Jarvis, Jennifer; Thomas-Ahner, Jennifer; Vodovotz, Yael; Ameen, Zeenath; Grainger, Elizabeth; Riedl, Kenneth; Schwartz, Steven; Clinton, Steven K.

    2015-01-01

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may impact prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 prostate cancer patients with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to 2 slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on Day 56 versus baseline. Subgroup analysis indicated reduced Th1 (p=0.028) and MDSC-associated cytokines (p=0.035). Th2 and Th17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8+ or CD4+ T cells, but showed increased CD56+ NK cells (p=0.038). The percentage of cells with a T regulatory cell phenotype (CD4+CD25+FoxP3+) were significantly decreased after 56 days of soy bread (p=0.0136). Significantly decreased monocytic (CD33+HLADRnegCD14+) MDSC were observed in patients consuming soy bread (p=0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required. PMID:26276751

  6. Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria: a prospective open-label long-term study using frequency-volume chart.

    PubMed

    Kojima, Yoshiyuki; Sasaki, Shoichi; Imura, Makoto; Kubota, Yasue; Hayashi, Yutaro; Kohri, Kenjiro

    2012-01-01

    The effects of tamsulosin treatment on changes in frequency-volume chart (FVC) data, especially nighttime urine production, over time were assessed, and the mechanisms underlying the improvement of nocturia in benign prostatic hyperplasia (BPH) patients with nocturnal polyuria (NP) are discussed. A total of 104 patients with lower urinary tract symptoms secondary to BPH were enrolled. After enrollment in the study, the patients were treated with tamsulosin (0.2 mg) once daily. Visits were scheduled every 4 weeks until week 12 (month 3) after study entry, and then every 12 weeks subsequently. All patients completed the International Prostate Symptom Score (IPSS), quality of life (QOL) index, and 3-day FVC, and underwent uroflowmetry at enrollment and on each visit. Eighty-two patients (mean age: 70.9 ± 7.1 years) were analyzed for 24 months after treatment. Patients were divided into two groups, NP and nonNP, based on FVC outcome. The IPSS, QOL index, and maximum flow rate improved during the 24-month period after treatment in both groups. Mean daytime urine volume significantly increased in the NP group, but no changes were detected in the nonNP group. Mean nighttime urine frequency significantly decreased in the NP group over a 24-month period, and was associated with a significant decrease in nighttime urine volume that was not found in the nonNP group. Maximum voided volume increased most months after treatment in both groups. The present long-term prospective study using FVC demonstrated that tamsulosin reduced nighttime urine production in BPH patients with NP. Copyright © 2011 Wiley Periodicals, Inc.

  7. Reducing Size, Weight, and Power (SWaP) of Perception Systems in Small Autonomous Aerial Systems

    NASA Technical Reports Server (NTRS)

    Jones, Kennie H.; Gross, Jason

    2014-01-01

    The objectives are to examine recent trends in the reduction of size, weight, and power (SWaP) requirements of sensor systems for environmental perception and to explore new technology that may overcome limitations in current systems. Improving perception systems to facilitate situation awareness is critical in the move to introduce increasing autonomy in aerial systems. Whether the autonomy is in the current state-of-the-art of increasing automation or is enabling cognitive decisions that facilitate adaptive behavior, collection of environmental information and fusion of that information into knowledge that can direct actuation is imperative to decisions resulting in appropriate behavior. Artificial sensory systems such as cameras, radar, LIDAR, and acoustic sensors have been in use on aircraft for many years but, due to the large size and weight of the airplane and electrical power made available through powerful engines, the SWaP requirements of these sensors was inconsequential. With the proliferation of Remote Piloted Vehicles (RPV), the trend is in significant reduction in SWaP of the vehicles. This requires at least an equivalent reduction in SWaP for the sensory systems. A survey of some currently available sensor systems and changing technology will reveal the trend toward reduction of SWaP of these systems and will predict future reductions. A new technology will be introduced that provides an example of a desirable new trend. A new device replaces multiple conventional sensory devices facilitating synchronization, localization, altimetry, collision avoidance, terrain mapping, and data communication in a single integrated, small form-factor, extremely lightweight, and low power device that it is practical for integration into small autonomous vehicles and can facilitate cooperative behavior. The technology is based on Ultra WideBand (UWB) radio using short pulses of energy rather than continuous sine waves. The characteristics of UWB yield several

  8. Laser system refinements to reduce variability in infarct size in the rat photothrombotic stroke model

    PubMed Central

    Alaverdashvili, Mariam; Paterson, Phyllis G.; Bradley, Michael P.

    2015-01-01

    Background The rat photothrombotic stroke model can induce brain infarcts with reasonable biological variability. Nevertheless, we observed unexplained high inter-individual variability despite using a rigorous protocol. Of the three major determinants of infarct volume, photosensitive dye concentration and illumination period were strictly controlled, whereas undetected fluctuation in laser power output was suspected to account for the variability. New method The frequently utilized Diode Pumped Solid State (DPSS) lasers emitting 532 nm (green) light can exhibit fluctuations in output power due to temperature and input power alterations. The polarization properties of the Nd:YAG and Nd:YVO4 crystals commonly used in these lasers are another potential source of fluctuation, since one means of controlling output power uses a polarizer with a variable transmission axis. Thus, the properties of DPSS lasers and the relationship between power output and infarct size were explored. Results DPSS laser beam intensity showed considerable variation. Either a polarizer or a variable neutral density filter allowed adjustment of a polarized laser beam to the desired intensity. When the beam was unpolarized, the experimenter was restricted to using a variable neutral density filter. Comparison with existing method(s) Our refined approach includes continuous monitoring of DPSS laser intensity via beam sampling using a pellicle beamsplitter and photodiode sensor. This guarantees the desired beam intensity at the targeted brain area during stroke induction, with the intensity controlled either through a polarizer or variable neutral density filter. Conclusions Continuous monitoring and control of laser beam intensity is critical for ensuring consistent infarct size. PMID:25840363

  9. Individual thorax geometry reduces position and size differences in reconstructed images of electrical impedance tomography.

    PubMed

    Zhao, Zhanqi; Frerichs, Inéz; Pulletz, Sven; Müller-Lisse, Ullrich; Möller, Knut

    2014-01-01

    Due to the ill-posed problem, the electrical impedance within the thorax cannot be exactly reconstructed. The aim of our study was to prove that reconstruction with individual thorax geometry improved the quality of EIT (electrical impedance tomography) images. Seven mechanically ventilated patients with acute respiratory distress syndrome were examined by EIT. The thorax contours were determined from routine computed tomography (CT) images based on automatic threshold filtering. EIT raw data was reconstructed offline with (1) back-projection with circular forward model; (2) GREIT reconstruction method with circular forward model and (3) GREIT with individual thorax geometry. The resulting EIT images were compared to rescaled CT images. The distance between the lung contour and the thorax contour was calculated for each method and the differences to that in CT were denoted as position differences. Shape differences was defined as the ratio of thorax (or lungs) size in EIT and that in rescaled CT. Method (3) has the smallest position differences (6.6 ± 2.8, 5.3 ± 3.3, 2.3 ± 1.4 in pixel, for each reconstruction method respectively; mean ± SD). The thorax and lungs sizes in the transformed CT images were 514 ± 73 and 177 ± 39. Shape differences of thorax were 1.81 ± 0.26, 1.81 ± 0.26, 1.10 ± 0.12 and that of lungs were 1.69 ± 0.45, 1.52 ± 0.45, 1.34 ± 0.35 for each method respectively. The reconstructed images using the GREIT method with individual thorax geometry were more realistic. Improvement of EIT image quality may foster the acceptance of EIT in routine clinical use.

  10. Prostate Cancer

    MedlinePlus

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  11. Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats.

    PubMed

    Kiss, Krisztina; Csonka, Csaba; Pálóczi, János; Pipis, Judit; Görbe, Anikó; Kocsis, Gabriella F; Murlasits, Zsolt; Sárközy, Márta; Szűcs, Gergő; Holmes, Christopher P; Pan, Yijun; Bhandari, Ashok; Csont, Tamás; Shamloo, Mehrdad; Woodburn, Kathryn W; Ferdinandy, Péter; Bencsik, Péter

    2016-11-01

    Erythropoietin (EPO) has been shown to protect the heart against acute myocardial infarction in pre-clinical studies, however, EPO failed to reduce infarct size in clinical trials and showed significant safety problems. Here, we investigated cardioprotective effects of two selective non-erythropoietic EPO receptor ligand dimeric peptides (AF41676 and AF43136) lacking erythropoietic activity, EPO, and the prolonged half-life EPO analogue, darbepoetin in acute myocardial infarction (AMI) in rats. In a pilot study, EPO at 100U/mL significantly decreased cell death compared to vehicle (33.8±2.3% vs. 40.3±1.5%, p<0.05) in rat neonatal cardiomyocytes subjected to simulated ischemia/reperfusion. In further studies (studies 1-4), in vivo AMI was induced by 30min coronary occlusion and 120min reperfusion in male Wistar rats. Test compounds and positive controls for model validation (B-type natriuretic peptide, BNP or cyclosporine A, CsA) were administered iv. before the onset of reperfusion. Infarct size (IS) was measured by standard TTC staining. In study 1, 5000U/kg EPO reduced infarct size significantly compared to vehicle (45.3±4.8% vs. 59.8±4.5%, p<0.05). In study 2, darbepoetin showed a U-shaped dose-response curve with maximal infarct size-reducing effect at 5μg/kg compared to the vehicle (44.4±5.7% vs. 65.9±2.7%, p<0.01). In study 3, AF41676 showed a U-shaped dose-response curve, where 3mg/kg was the most effective dose compared to the vehicle (24.1±3.9% vs. 44.3±2.5%, p<0.001). The positive control BNP significantly decreased infarct size in studies 1-3 by approximately 35%. In study 4, AF43136 at 10mg/kg decreased infarct size, similarly to the positive control CsA compared to the appropriate vehicle (39.4±5.9% vs. 58.1±5.4% and 45.9±2.4% vs. 63.8±4.1%, p<0.05, respectively). This is the first demonstration that selective, non-erythropoietic EPO receptor ligand dimeric peptides AF41676 and AF43136 administered before reperfusion are able to reduce

  12. Reducing Capsule Based on Electron Programming: Versatile Synthesizer for Size-Controlled Ultra-Small Metal Clusters.

    PubMed

    Kambe, Tetsuya; Imaoka, Takane; Yamamoto, Kimihisa

    2016-11-07

    Controlled reducing capsules with a specific number of reducing electrons were achieved by appropriately placed BH3 units in the dendritic polyphenylazomethines (DPAs). Using the 1:1 coordination fashion on their basic branches with radius affinity gradient, the 4th generation DPA (DPAG4) possessing four BH3 units in the central positions was prepared as a template synthesizer for size-controlled ultra-small metal clusters. This was well-demonstrated by reduction of Ag, Pt, and other metal ions resulting in monodispersed ultra-small clusters.

  13. Intermittent exposure to reduced oxygen levels affects prey size selection and consumption in swimming crab Thalamita danae Stimpson.

    PubMed

    Shin, P K S; Cheung, P H; Yang, F Y; Cheung, S G

    2005-01-01

    Portunid crabs Thalamita danae (carapace width: 46-56 mm) were exposed to low oxygen level (4.0 mg O2 l(-1)) and hypoxia (1.5 mg O2 l(-1)) for 6 h each day with three size classes (large: 15.0-19.9 mm, medium: 10.0-14.9 mm, small: 5.0-9.9 mm) of mussels Brachidontes variabilis offered as food. Consumption rate, prey size preference, and prey handling including breaking time, handling time, eating time and prey value, were studied during the time the crabs were exposed to reduced oxygen levels and results were compared with the crabs maintained at high oxygen level (8.0 mg O2 l(-1)) throughout the experiment. Consumption of mussels from all size classes was significantly higher at high oxygen level than at reduced oxygen levels. No mussel size preference was observed for crabs exposed to 4.0 or 8.0 mg O2 l(-1) but those crabs exposed to 1.5 mg O2 l(-1) preferred medium mussels. Both breaking time and handling time increased with mussel size but did not vary with oxygen level. Prey value of each mussel consumed (mg dry wt eaten crab(-1) s(-1)) was calculated by dividing the estimated dry weight of the mussel by the observed handling time. Mean prey value varied significantly with mussel size, with values obtained for large mussels being higher than small mussels at 4.0 and 8.0 mg O2 l(-1); the effect of oxygen level, however, was insignificant. In view of portunid crabs as major predators of mussels, results may help explain dominance of mussels in eutrophic harbours in Hong Kong.

  14. Imatinib mesylate (Glivec) inhibits Schwann cell viability and reduces the size of human plexiform neurofibroma in a xenograft model.

    PubMed

    Demestre, Maria; Herzberg, Jan; Holtkamp, Nikola; Hagel, Christian; Reuss, David; Friedrich, Reinhard E; Kluwe, Lan; Von Deimling, Andreas; Mautner, Victor-F; Kurtz, Andreas

    2010-05-01

    Plexiform neurofibromas (PNF), one of the major features of neurofibromatosis type 1 (NF1), are characterized by complex cellular composition and mostly slow but variable growth patterns. In this study, we examined the effect of imatinib mesylate, a receptor tyrosine kinase inhibitor, on PNF-derived Schwann cells and PNF tumour growth in vitro and in vivo. In vitro, PNF-derived primary Schwann cells express platelet-derived growth factors receptors (PDGFR) alpha and beta, both targets of imatinib, and cell viability was reduced by imatinib mesylate, with 50% inhibition concentration (IC(50)) of 10 microM. For in vivo studies, PNF tumour fragments xenografted onto the sciatic nerve of athymic nude mice were first characterized. The tumours persisted for at least 63 days and maintained typical characteristics of PNFs such as complex cellular composition, low proliferation rate and angiogenesis. A transient enlargement of the graft size was due to inflammation by host cells. Treatment with imatinib mesylate at a daily dose of 75 mg/kg for 4 weeks reduced the graft size by an average of 80% (n = 8), significantly different from the original sizes within the group and from sizes of the grafts in 11 untreated mice in the control group (P < 0.001). We demonstrated that grafting human PNF tumour fragments into nude mice provides an adequate in vivo model for drug testing. Our results provide in vivo and in vitro evidence for efficacy of imatinib mesylate for PNF.

  15. Reducing sample sizes in two-stage phase II cancer trials by using continuous tumour shrinkage end-points.

    PubMed

    Wason, James M S; Mander, Adrian P; Eisen, Tim G

    2011-05-01

    Reducing the number of patients required for a clinical trial is important for shortening development time. Phase II cancer trials assess the tumour-shrinking effect of a novel compound through a binary end-point formed from the percentage change in total lesion diameter. We compare single-arm two-stage designs which use the binary end-point to those which directly use the continuous end-point. Using the continuous end-point results in lower expected and maximum sample sizes. For larger trials the reduction is around 37%. This assumes that the dichotomisation point of the continuous end-point is chosen to give the best sample size, with the trial design using the binary end-point performing even worse otherwise. We consider a previous trial designed using a Simon two-stage design and show that if the continuous end-point had been used, the expected and maximum sample sizes of the trial would be reduced by around 50%. Using the continuous end-point in a two-stage cancer trial results in large sample size reductions. The methods discussed in this paper work best when the number of complete responses is low, as is true in several types of cancer. We discuss what could be done if this is not the case.

  16. Use of pharmacogenetics in bioequivalence studies to reduce sample size: an example with mirtazapine and CYP2D6.

    PubMed

    González-Vacarezza, N; Abad-Santos, F; Carcas-Sansuan, A; Dorado, P; Peñas-Lledó, E; Estévez-Carrizo, F; Llerena, A

    2013-10-01

    In bioequivalence studies, intra-individual variability (CV(w)) is critical in determining sample size. In particular, highly variable drugs may require enrollment of a greater number of subjects. We hypothesize that a strategy to reduce pharmacokinetic CV(w), and hence sample size and costs, would be to include subjects with decreased metabolic enzyme capacity for the drug under study. Therefore, two mirtazapine studies, two-way, two-period crossover design (n=68) were re-analysed to calculate the total CV(w) and the CV(w)s in three different CYP2D6 genotype groups (0, 1 and ≥ 2 active genes). The results showed that a 29.2 or 15.3% sample size reduction would have been possible if the recruitment had been of individuals carrying just 0 or 0 plus 1 CYP2D6 active genes, due to the lower CV(w). This suggests that there may be a role for pharmacogenetics in the design of bioequivalence studies to reduce sample size and costs, thus introducing a new paradigm for the biopharmaceutical evaluation of drug products.

  17. Arginase inhibition improves coronary microvascular function and reduces infarct size following ischemia-reperfusion in a rat model

    PubMed Central

    Grönros, Julia; Kiss, Attila; Palmér, Malin; Jung, Christian; Berkowitz, Dan; Pernow, John

    2013-01-01

    Aim Ischemia-reperfusion injury is associated with reduced bioavailability of nitric oxide and microvascular dysfunction. One emerging mechanism behind reduced nitric oxide bioavailability is upregulation of arginase which metabolizes the nitric oxide synthase substrate L-arginine. This study investigated the effects of arginase inhibition on coronary flow velocity and infarct size during reperfusion. Methods Anaesthetized rats, subjected to 30 min coronary artery ligation and reperfusion up to 8 days, were treated with vehicle or the arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA; 100 mg/kg) intravenously 15 min before ischemia. Coronary flow velocity was determined repeatedly during reperfusion. Results Arginase activity in the ischemic-reperfused myocardium was increased already at 20 min of reperfusion and maintained at 8 days. Infarct size was reduced by arginase inhibition at 2 h (39 ± 3% of the area at risk vs. 51 ± 2% in the vehicle group, P<0.01) and at 8 days of reperfusion (13 ± 2% of the left ventricle vs. 22 ± 2%, P<0.05). Basal coronary flow velocity was higher during reperfusion in the group given nor-NOHA and it correlated inversely to infarct size (P<0.01, r=−0.60). Hyperemic coronary flow velocity was also increased in the nor-NOHA treated group compared to vehicle at 24 h and at day 8 (P<0.05). Conclusion It is concluded that arginase activity is increased already during early reperfusion. Arginase inhibition increases coronary flow velocity and reduces infarct size that is sustained 8 days after reperfusion. Inhibition of arginase may thus be a promising therapeutic target to prevent the development of microvascular dysfunction and myocardial injury following ischemia-reperfusion. PMID:23497275

  18. Awns reduce grain number to increase grain size and harvestable yield in irrigated and rainfed spring wheat

    PubMed Central

    Rebetzke, G. J.; Bonnett, D. G.; Reynolds, M. P.

    2016-01-01

    Genotypic variation in ear morphology is linked to differences in photosynthetic potential to influence grain yield in winter cereals. Awns contribute to photosynthesis, particularly under water-limited conditions when canopy assimilation is restricted. We assessed performance of up to 45 backcross-derived, awned–awnletted NILs representing four diverse genetic backgrounds in 25 irrigated or rainfed, and droughted environments in Australia and Mexico. Mean environment grain yields were wide-ranging (1.38–7.93 t ha−1) with vegetative and maturity biomass, plant height, anthesis date, spike number, and harvest index all similar (P >0.05) for awned and awnletted NILs. Overall, grain yields of awned–awnletted sister-NILs were equivalent, irrespective of yield potential and genetic background. Awnletted wheats produced significantly more grains per unit area (+4%) and per spike (+5%) reflecting more fertile spikelets and grains in tertiary florets. Increases in grain number were compensated for by significant reductions in grain size (–5%) and increased frequency (+0.8%) of small, shrivelled grains (‘screenings’) to reduce seed-lot quality of awnletted NILs. Post-anthesis canopies of awnletted NILs were marginally warmer over all environments (+0.27 °C) but were not different and were sometimes cooler than awned NILs at cooler air temperatures. Awns develop early and represented up to 40% of total spikelet biomass prior to ear emergence. We hypothesize that the allocation of assimilate to large and rapidly developing awns decreases spikelet number and floret fertility to reduce grain number, particularly in distal florets. Individual grain size is increased to reduce screenings and to increase test weight and milling quality, particularly in droughted environments. Despite the average reduction in grain size, awnless lines could be identified that combined higher grain yield with larger grain size, increased grain protein concentration, and reduced

  19. Preventive effects of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

    PubMed

    Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

    2007-12-01

    Plant extracts are useful in the management of benign prostatic hyperplasia (BPH). This study investigates whether ACTICOA (Barry Callebaut France, Louviers, France) powder (AP), a cocoa polyphenolic extract, could prevent prostate hyperplasia induced by testosterone propionate (TP) in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one negative control group receiving subcutaneous injections of corn oil and treated with vehicle and three groups injected subcutaneously with TP and treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments were given orally and started 2 weeks before the induction of prostate hyperplasia. The influence of TP and AP on body weights and food and water consumption of rats was examined. On day 36, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumption, while AP at both doses tested reduced significantly these differences. TP significantly increased prostate size ratio (P < .001), and this induced increase was significantly inhibited in AP-treated rats in comparison with positive controls (P < .001) in a dose-dependent manner. We conclude that AP can prevent TP-induced prostate hyperplasia and therefore may be beneficial in the management of BPH.

  20. Pigment epithelial-derived factor and melanoma differentiation associated gene-7 cytokine gene therapies delivered by adipose-derived stromal/mesenchymal stem cells are effective in reducing prostate cancer cell growth.

    PubMed

    Zolochevska, Olga; Yu, Gang; Gimble, Jeffrey M; Figueiredo, Marxa L

    2012-05-01

    Adipose-derived stromal/mesenchymal stem cells (ASC) have gained interest as promising tools for delivering cancer therapy. Adipose tissue can be obtained readily in amounts sufficient for ASC isolation, which can be expanded rapidly, allowing its use at low passage numbers, and can be transduced by viral and nonviral means. Our goal was to examine the potential of ASC to deliver cytokine gene therapies melanoma differentiation associated gene-7 (MDA-7) or pigment epithelial-derived factor (PEDF) to cancer cells. These novel cytokines are a potent proapoptotic and an antiangiogenesis mediator, respectively, with potential as antitumor agents. Expression of cytokine therapies did not adversely affect ASC biology, and these cells were still able to differentiate and retain normal viability. The ASC cytokine therapies were efficient in reducing tumor cell growth in coculture and also in suppressing in vitro angiogenesis phenotypes. We also observed that ASC retained their innate ability to migrate toward tumor cells in coculture, and this ability could be blocked by inhibition of CXCR4 signaling. The ASC were found to be nontumorigenic in vitro using a soft agar assay, as well as in vivo, utilizing 2 prostate cancer xenograft models. The ASC-MDA7 only reduced tumor growth in the TRAMP-C2-Ras (TC2Ras) prostate cancer model. The ASC-PEDF, however, reduced growth in both the TC2Ras and the PC3 highly aggressive prostate cancer models, and it was able to completely prevent prostate tumor establishment in vivo. In conclusion, ASC expressing PEDF and MDA7 could effectively reduce prostate tumor growth in vivo, suggesting ASC-cytokine therapies might have translational applications, especially the PEDF modality.

  1. Low Sociability is Associated with Reduced Size of the Corpus Callosum in the BALB/cJ Inbred Mouse Strain

    PubMed Central

    Fairless, Andrew H.; Dow, Holly C.; Toledo, Monica M.; Malkus, Kristen A.; Edelmann, Michele; Li, Hongzhe; Talbot, Konrad; Arnold, Steven E.; Abel, Ted; Brodkin, Edward S.

    2008-01-01

    The behavioral manifestations of autism, including reduced sociability (reduced tendency to seek social interaction), may be related to underdevelopment of the corpus callosum (CC). The BALB/cJ inbred mouse strain is a useful model system for testing the relationship between reduced sociability and CC underdevelopment. BALB/cJ mice show low levels of sociability, on average, but substantial intrastrain variability in sociability, as well as striking variability in CC development. This study tested the hypothesis that sociability is positively correlated with CC size within the BALB/cJ inbred strain. 30-day-old BALB/cJ and C57BL/6J mice were tested for sociability towards gonadectomized A/J stimulus mice in a social choice task. The size of the corpus callosum was measured histologically at the mid-sagittal plane. BALB/cJ mice showed a significant positive correlation between the tendency to sniff the stimulus mouse and size of the CC relative to brain weight. C57BL/6J mice showed consistently high levels of sociability and normal corpus callosum development. These results suggest that abnormal white matter structure is associated with deficits in sociability in BALB/cJ mice. Additional studies are warranted to elucidate the relationship between brain connectivity and sociability in this model system. PMID:18662677

  2. Low sociability is associated with reduced size of the corpus callosum in the BALB/cJ inbred mouse strain.

    PubMed

    Fairless, Andrew H; Dow, Holly C; Toledo, Monica M; Malkus, Kristen A; Edelmann, Michele; Li, Hongzhe; Talbot, Konrad; Arnold, Steven E; Abel, Ted; Brodkin, Edward S

    2008-09-16

    The behavioral manifestations of autism, including reduced sociability (reduced tendency to seek social interaction), may be related to underdevelopment of the corpus callosum (CC). The BALB/cJ inbred mouse strain is a useful model system for testing the relationship between reduced sociability and CC underdevelopment. BALB/cJ mice show low levels of sociability, on average, but substantial intrastrain variability in sociability, as well as striking variability in CC development. This study tested the hypothesis that sociability is positively correlated with CC size within the BALB/cJ inbred strain. 30-day-old BALB/cJ and C57BL/6J mice were tested for sociability towards gonadectomized A/J stimulus mice in a social choice task. The size of the corpus callosum was measured histologically at the midsagittal plane. BALB/cJ mice showed a significant positive correlation between the tendency to sniff the stimulus mouse and size of the CC relative to brain weight. C57BL/6J mice showed consistently high levels of sociability and normal corpus callosum development. These results suggest that abnormal white matter structure is associated with deficits in sociability in BALB/cJ mice. Additional studies are warranted to elucidate the relationship between brain connectivity and sociability in this model system.

  3. Use of implanted markers and interportal adjustment with real-time tracking radiotherapy system to reduce intrafraction prostate motion.

    PubMed

    Shimizu, Shinichi; Osaka, Yasuhiro; Shinohara, Nobuo; Sazawa, Ataru; Nishioka, Kentaro; Suzuki, Ryusuke; Onimaru, Rikiya; Shirato, Hiroki

    2011-11-15

    Interportal adjustment was applied to patients with prostate cancer using three fiducial markers and two sets of fluoroscopy in a real-time tumor-tracking radiotherapy (RTRT) system. The incidence of table position adjustment required to keep intrafractional uncertainty within 2.0 mm was investigated in this study. The coordinates of the center of gravity of the three fiducial markers were measured at the start of every portal irradiation in intensity-modulated radiotherapy (IMRT) with seven ports. The table position was adjusted to the planned position if the discrepancy was larger than 2.0 mm in the anterior-posterior (AP), cranial-caudal (CC), or left-right (LR) directions. In total, we analyzed 4,541 observations in 20 patients who received 70 Gy in 30 fractions (7.6 times a day on average). The incidence of table position adjustment at 10 minutes from the initial setup of each treatment was 14.2%, 12.3%, and 5.0% of the observations in the AP, CC, and LR directions, respectively. The accumulated incidence of the table position adjustment was significantly higher at 10 minutes than at 2 minutes for AP (p = 0.0033) and CC (p = 0.0110) but not LR (p = 0.4296). An adjustment greater than 5 mm was required at least once in the treatment period in 11 (55%) patients. Interportal adjustment of table position was required in more than 10% of portal irradiations during the 10-minute period after initial setup to maintain treatment accuracy within 2.0 mm. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. A reduced estimate of the number of kilometre-sized near-Earth asteroids.

    PubMed

    Rabinowitz, D; Helin, E; Lawrence, K; Pravdo, S

    2000-01-13

    Near-Earth asteroids are small (diameters < 10 km), rocky bodies with orbits that approach that of the Earth (they come within 1.3 AU of the Sun). Most have a chance of approximately 0.5% of colliding with the Earth in the next million years. The total number of such bodies with diameters > 1 km has been estimated to be in the range 1,000-2,000, which translates to an approximately 1% chance of a catastrophic collision with the Earth in the next millennium. These numbers are, however, poorly constrained because of the limitations of previous searches using photographic plates. (One kilometre is below the size of a body whose impact on the Earth would produce global effects.) Here we report an analysis of our survey for near-Earth asteroids that uses improved detection technologies. We find that the total number of asteroids with diameters > 1 km is about half the earlier estimates. At the current rate of discovery of near-Earth asteroids, 90% will probably have been detected within the next 20 years.

  5. Efficacy of a 2% climbazole shampoo for reducing Malassezia population sizes on the skin of naturally infected dogs.

    PubMed

    Cavana, P; Petit, J-Y; Perrot, S; Guechi, R; Marignac, G; Reynaud, K; Guillot, J

    2015-12-01

    Shampoo therapy is often recommended for the control of Malassezia overgrowth in dogs. The aim of this study was to evaluate the in vivo activity of a 2% climbazole shampoo against Malassezia pachydermatis yeasts in naturally infected dogs. Eleven research colony Beagles were used. The dogs were distributed randomly into two groups: group A (n=6) and group B (n=5). Group A dogs were washed with a 2% climbazole shampoo, while group B dogs were treated with a physiological shampoo base. The shampoos were applied once weekly for two weeks. The population size of Malassezia yeasts on skin was determined by fungal culture through modified Dixon's medium contact plates pressed on left concave pinna, axillae, groins, perianal area before and after shampoo application. Samples collected were compared by Wilcoxon rank sum test. Samples collected after 2% climbazole shampoo application showed a significant and rapid reduction of Malassezia population sizes. One hour after the first climbazole shampoo application, Malassezia reduction was already statistically significant and 15 days after the second climbazole shampoo, Malassezia population sizes were still significantly decreased. No significant reduction of Malassezia population sizes was observed in group B dogs. The application of a 2% climbazole shampoo significantly reduced Malassezia population sizes on the skin of naturally infected dogs. Application of 2% climbazole shampoo may be useful for the control of Malassezia overgrowth and it may be also proposed as prevention when recurrences are frequent. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Effective size of a wild salmonid population is greatly reduced by hatchery supplementation

    PubMed Central

    Christie, M R; Marine, M L; French, R A; Waples, R S; Blouin, M S

    2012-01-01

    Many declining and commercially important populations are supplemented with captive-born individuals that are intentionally released into the wild. These supplementation programs often create large numbers of offspring from relatively few breeding adults, which can have substantial population-level effects. We examined the genetic effects of supplementation on a wild population of steelhead (Oncorhynchus mykiss) from the Hood River, Oregon, by matching 12 run-years of hatchery steelhead back to their broodstock parents. We show that the effective number of breeders producing the hatchery fish (broodstock parents; Nb) was quite small (harmonic mean Nb=25 fish per brood-year vs 373 for wild fish), and was exacerbated by a high variance in broodstock reproductive success among individuals within years. The low Nb caused hatchery fish to have decreased allelic richness, increased average relatedness, more loci in linkage disequilibrium and substantial levels of genetic drift in comparison with their wild-born counterparts. We also documented a substantial Ryman–Laikre effect whereby the additional hatchery fish doubled the total number of adult fish on the spawning grounds each year, but cut the effective population size of the total population (wild and hatchery fish combined) by nearly two-thirds. We further demonstrate that the Ryman–Laikre effect is most severe in this population when (1) >10% of fish allowed onto spawning grounds are from hatcheries and (2) the hatchery fish have high reproductive success in the wild. These results emphasize the trade-offs that arise when supplementation programs attempt to balance disparate goals (increasing production while maintaining genetic diversity and fitness). PMID:22805657

  7. Total Mechanical Unloading Minimizes Metabolic Demand of Left Ventricle and Dramatically Reduces Infarct Size in Myocardial Infarction

    PubMed Central

    Kakino, Takamori; Arimura, Takahiro; Sakamoto, Takafumi; Nishikawa, Takuya; Sakamoto, Kazuo; Ikeda, Masataka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

    2016-01-01

    Background Left ventricular assist device (LVAD) mechanically unloads the left ventricle (LV). Theoretical analysis indicates that partial LVAD support (p-LVAD), where LV remains ejecting, reduces LV preload while increases afterload resulting from the elevation of total cardiac output and mean aortic pressure, and consequently does not markedly decrease myocardial oxygen consumption (MVO2). In contrast, total LVAD support (t-LVAD), where LV no longer ejects, markedly decreases LV preload volume and afterload pressure, thereby strikingly reduces MVO2. Since an imbalance in oxygen supply and demand is the fundamental pathophysiology of myocardial infarction (MI), we hypothesized that t-LVAD minimizes MVO2 and reduces infarct size in MI. The purpose of this study was to evaluate the differential impact of the support level of LVAD on MVO2 and infarct size in a canine model of ischemia-reperfusion. Methods In 5 normal mongrel dogs, we examined the impact of LVAD on MVO2 at 3 support levels: Control (no LVAD support), p-LVAD and t-LVAD. In another 16 dogs, ischemia was induced by occluding major branches of the left anterior descending coronary artery (90 min) followed by reperfusion (300 min). We activated LVAD from the beginning of ischemia until 300 min of reperfusion, and compared the infarct size among 3 different levels of LVAD support. Results t-LVAD markedly reduced MVO2 (% reduction against Control: -56 ± 9%, p<0.01) whereas p-LVAD did less (-21 ± 14%, p<0.05). t-LVAD markedly reduced infarct size compared to p-LVAD (infarct area/area at risk: Control; 41.8 ± 6.4, p-LVAD; 29.1 ± 5.6 and t-LVAD; 5.0 ± 3.1%, p<0.01). Changes in creatine kinase-MB paralleled those in infarct size. Conclusions Total LVAD support that minimizes metabolic demand maximizes the benefit of LVAD in the treatment of acute myocardial infarction. PMID:27124411

  8. Anabolic steroids activate calcineurin-NFAT signaling and thereby increase myotube size and reduce denervation atrophy.

    PubMed

    Qin, Weiping; Pan, Jiangping; Wu, Yong; Bauman, William A; Cardozo, Christopher

    2015-01-05

    Anabolic androgens have been shown to reduce muscle loss due to immobilization, paralysis and many other medical conditions, but the molecular basis for these actions is poorly understood. We have recently demonstrated that nandrolone, a synthetic androgen, slows muscle atrophy after nerve transection associated with down-regulation of regulator of calcineurin 2 (RCAN2), a calcineurin inhibitor, suggesting a possible role of calcineurin-NFAT signaling. To test this possibility, rat gastrocnemius muscle was analyzed at 56 days after denervation. In denervated muscle, calcineurin activity declined and NFATc4 was excluded from the nucleus and these effects were reversed by nandrolone. Similarly, nandrolone increased calcineurin activity and nuclear NFATc4 levels in cultured L6 myotubes. Nandrolone also induced cell hypertrophy that was blocked by cyclosporin A or overexpression of RCAN2. Finally protection against denervation atrophy by nandrolone in rats was blocked by cyclosporin A. These results demonstrate for the first time that nandrolone activates calcineurin-NFAT signaling, and that such signaling is important in nandrolone-induced cell hypertrophy and protection against paralysis-induced muscle atrophy.

  9. Reduced size of the amygdala in individuals with 47,XXY and 47,XXX karyotypes.

    PubMed

    Patwardhan, Anil J; Brown, Wendy E; Bender, Bruce G; Linden, Mary G; Eliez, Stephan; Reiss, Allan L

    2002-01-08

    The excess of 47,XXX and 47,XXY karyotypes found in cytogenetic screening studies of individuals with schizophrenia has given support for an increased risk of psychiatric illness among men and women with sex chromosomal aneuploidy (SCA). Mesial temporal lobe structures, including the amygdala and hippocampus, are thought to be associated with abnormalities of mood and behavior in humans and in the neurobiology of schizophrenia. This study focuses on variations in volumes of mesial temporal lobe structures in men and women with SCA. Utilizing an unselected birth cohort of subjects with SCA and high-resolution magnetic resonance imaging (MRI), we investigated the neuroanatomical consequences of a supernumerary X chromosome on the morphology of the amygdala and hippocampus. Regional and total brain volumes were measured in 10 subjects with 47,XXY, 10 subjects with 47,XXX, and 20 euploid controls. Amygdala volumes were significantly reduced in men with 47,XXY, compared to control men, while the decrease in women with 47,XXX was not as pronounced. Hippocampus volumes were preserved in both groups, compared to same-gender controls. Longitudinal studies of SCA individuals have shown an increased incidence of mild psychopathology and behavioral dysfunction in men with 47,XXY and more overt psychiatric illness in women with 47,XXX, compared to control populations. The alteration in amygdala volumes in individuals with a supernumerary X chromosome may provide a neuroanatomic basis for these findings. Copyright 2001 Wiley-Liss, Inc.

  10. Microarray analysis of prostate cancer progression to reduced androgen dependence: studies in unique models contrasts early and late molecular events.

    PubMed

    Sirotnak, F M; She, Yuhong; Khokhar, Nushmia Z; Hayes, Paula; Gerald, William; Scher, Howard I

    2004-11-01

    Three unique variants of the CWR22 human prostate cancer xenograft model (CWR22LD1, LD2, and LD3) with a decrease in dependence on androgens were selected under noncastrate conditions, i.e., by outgrowth after transplantation into male NCR (AT) nu mice without testosterone supplementation. These variants were unable to grow in castrated male mice. For comparison, a second set of variants with even less dependence on androgens (castrate-resistant) were derived following outgrowth from CWR22 (CWR22Rv1 and RC) or CWRLD1 (CWR22RS) after transplantion in castrated male mice. The androgen receptor (AR) gene in the CWR22LD variants was transcriptionally active and was neither mutated nor significantly overexpressed compared to CWR22. Oligonucleotide microarray analysis showed distinctly different profiles of dysregulated gene expression among the CWR22LD variants. Groups of only 26-41 genes were dysregulated greater than threefold with a different proportion of up versus downregulated genes in each variant. Only one of the castrate-resistant variants (CWR22Rv1) had a highly overexpressed AR gene but AR in this variant and the two other castrate-resistant variants, CWR22 RS and RC, was not mutated beyond that seen in CWR22. In contrast to the CWR22LD variants, a total of 342, 295, and 222 genes were dysregulated at least threefold in CWR22Rv1, CWR22RS, and CWR22RC, respectively, differing as well in the proportion of up versus downregulated genes. Many of the genes dysregulated in CWR22LD1, LD2, and LD3 were further dysregulated in CWR22Rv1, RC, or RS. The most downregulated gene was microseminoprotein beta (MSPB). Along with cyclin D1, the most upregulated gene by an order of magnitude compared to other upregulated genes was hepatocyte growth factor (HGF) (scatter factor). These results suggest that the onset in the loss of androgen dependence in CWR22 proceeds through multiple pathways and does not require any direct change in the status of AR. However, upregulation of

  11. Tumor volume in insignificant prostate cancer: Increasing the threshold is a safe approach to reduce over-treatment.

    PubMed

    Ting, Francis; van Leeuwen, Pim J; Delprado, Warick; Haynes, Anne-Maree; Brenner, Phillip; Stricker, Phillip D

    2015-11-01

    There are conflicting results in the literature regarding the tumor volume (TV) threshold that defines insignificant prostate cancer (PCa). In this study, we retrospectively evaluate the association of an increasing TV with biochemical recurrence (BCR) following radical prostatectomy (RP) in order to provide further clarification surrounding the TV threshold definition for insignificant PCa. RP patients were recruited from January 2004 to December 2009. Inclusion criteria were localized (stage ≤pT2c, negative surgical margins) Gleason 6 PCa with a total TV of ≤2.50 cm(3) . BCR was the primary outcome and defined as a PSA of ≥0.1. All cases with BCR were re-evaluated by the pathologist with reassessment of tumor grade, pathological stage and surgical margin status. From 1,636 patients, 178 men (10.9%) met all inclusion criteria. Ninety-six patients (53.9%) had a TV <0.5 cm(3) and 82 patients (46.1%) had a TV 0.5-2.5 cm(3) . Three out of 178 patients (1.7%) presented with BCR during follow-up. One of these had TV <0.5 cm(3) and two had TV 0.5-2.5 cm(3) . These three cases of BCR underwent re-review of pathology; one patient was found to have a positive surgical margin and one patient was upgraded to Gleason 3 + 4 = 7. The third patient was re-reported as having positive margins for a benign hyperplastic nodule (incomplete RP specimen). Subsequently, these three cases were excluded from final analysis as they did not fit inclusion criteria. Median follow-up duration was 84 months (IQR 70-102 months). On final analysis, there were no patients with BCR, corresponding with a final BCR rate of 0% for both patients with a TV of <0.5 cm(3) and 0.5-2.5 cm(3) . Our results have shown that, with a median follow-up of 84 (IQR 70-102) months, patients in our cohort with localized Gleason 6 PCa with a total TV 0.5-2.5 cm(3) have a BCR rate of 0%. We would support a more liberal total TV threshold of 2.5 cm(3) for the further development of

  12. Prostate Cancer Screening

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Prostate Cancer Key Points Prostate cancer is a disease in ...

  13. Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo

    PubMed Central

    2012-01-01

    Background Neuroglobin is considered to be a novel important pharmacological target in combating stroke and neurodegenerative disorders, although the mechanism by which this protection is accomplished remains an enigma. We hypothesized that if neuroglobin is directly involved in neuroprotection, then permanent cerebral ischemia would lead to larger infarct volumes in neuroglobin-null mice than in wild-type mice. Methods Using neuroglobin-null mice, we estimated the infarct volume 24 hours after permanent middle cerebral artery occlusion using Cavalieri’s Principle, and compared the infarct volume in neuroglobin-null and wild-type mice. Neuroglobin antibody staining was used to examine neuroglobin expression in the infarct area of wild-type mice. Results Infarct volumes 24 hours after permanent middle cerebral artery occlusion were significantly smaller in neuroglobin-null mice than in wild-types (p < 0.01). Neuroglobin immunostaining of the penumbra area revealed no visible up-regulation of neuroglobin protein in ischemic wild-type mice when compared to uninjured wild-type mice. In uninjured wild-type mice, neuroglobin protein was seen throughout cortical layer II and sparsely in layer V. In contrast, no neuroglobin-immunoreactive neurons were observed in the aforementioned layers of the ischemia injured cortical area, or in the surrounding penumbra of ischemic wild-type mice. This suggests no selective sparing of neuroglobin expressing neurons in ischemia. Conclusions Neuroglobin-deficiency resulted in reduced tissue infarction, suggesting that, at least at endogenous expression levels, neuroglobin in itself is non-protective against ischemic injury. PMID:22901501

  14. Dipeptidyl peptidase-4 inhibitors and GLP-1 reduce myocardial infarct size in a glucose-dependent manner.

    PubMed

    Hausenloy, Derek J; Whittington, Hannah J; Wynne, Abigail M; Begum, Shah S; Theodorou, Louise; Riksen, Niels; Mocanu, Mihaela M; Yellon, Derek M

    2013-10-22

    The dipeptidyl peptidase-4 (DPP-4) inhibitors Sitagliptin and Vildagliptin lower blood glucose by augmenting endogenous levels of glucagon-like peptide-1 (GLP-1), an incretin which also confers cardioprotection. As such, we hypothesized that treatment with DPP-4 inhibitors are also cardioprotective. In ex vivo experiments: Male Sprague-Dawley rats were randomized to receive by oral gavage either Vildagliptin (20 mg/kg/day), Sitagliptin (100 mg/kg/day), or water for 2 weeks. Excised hearts were Langendorff-perfused with buffer containing either 5 mmol/L or 11 mmol/L glucose and subjected to 35 minutes ischaemia/120 minutes reperfusion. In in vivo experiments: Male young Wistar and Sprague-Dawley rats, middle aged Wistar and Goto-Kakizaki diabetic rats were randomized to receive by oral gavage either Sitagliptin (100 mg/kg/day), or water for 2 weeks. Rats were then subjected to 30 minutes ischaemia/120 minutes reperfusion and infarct size ascertained. Two weeks pre-treatment with either Vildagliptin or Sitagliptin reduced ex vivo myocardial infarction (MI) size in hearts perfused with buffer containing 11 mmol/L glucose but not 5 mmol/L glucose. This effect was abolished by Exendin 9-39 (GLP-1 receptor antagonist) and H-89 (PKA antagonist). Treatment of perfused hearts with native GLP-1 was also glucose-sensitive, reducing MI size, at glucose concentrations 7, 9, and 11 mmol/L but not at 5 mmol/L. Finally, Sitagliptin reduced in vivo MI size in middle aged Wistar (7-8 mmol/L glucose) and Goto-Kakizaki (9-10 mmol/L glucose) rats where blood glucose was elevated, but not in young Wistar (5 mmol/L glucose) or Sprague-Dawley (5 mmol/L glucose) rats, where blood glucose was normal. We find that chronic treatment with DPP-4 inhibitors reduced MI size, via the GLP-1 receptor-PKA pathway, in a glucose-dependent manner. Glucose-sensitive cardioprotection of endogenous GLP-1 in diabetic patients may in part explain why intensive control of serum glucose

  15. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

    PubMed Central

    Rodríguez-Castelán, J.; Méndez-Tepepa, M.; Carrillo-Portillo, Y.; Anaya-Hernández, A.; Zambrano, E.

    2017-01-01

    Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood. PMID:28133606

  16. Investigation of the InAs/GaAs Quantum Dots’ Size: Dependence on the Strain Reducing Layer’s Position

    PubMed Central

    Souaf, Manel; Baira, Mourad; Nasr, Olfa; Hadj Alouane, Mohamed Helmi; Maaref, Hassen; Sfaxi, Larbi; Ilahi, Bouraoui

    2015-01-01

    This work reports on theoretical and experimental investigation of the impact of InAs quantum dots (QDs) position with respect to InGaAs strain reducing layer (SRL). The investigated samples are grown by molecular beam epitaxy and characterized by photoluminescence spectroscopy (PL). The QDs optical transition energies have been calculated by solving the three dimensional Schrödinger equation using the finite element methods and taking into account the strain induced by the lattice mismatch. We have considered a lens shaped InAs QDs in a pure GaAs matrix and either with InGaAs strain reducing cap layer or underlying layer. The correlation between numerical calculation and PL measurements allowed us to track the mean buried QDs size evolution with respect to the surrounding matrix composition. The simulations reveal that the buried QDs’ realistic size is less than that experimentally driven from atomic force microscopy observation. Furthermore, the average size is found to be slightly increased for InGaAs capped QDs and dramatically decreased for QDs with InGaAs under layer. PMID:28793465

  17. Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits.

    PubMed

    Rodríguez-Castelán, J; Méndez-Tepepa, M; Carrillo-Portillo, Y; Anaya-Hernández, A; Rodríguez-Antolín, J; Zambrano, E; Castelán, F; Cuevas-Romero, E

    2017-01-01

    Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

  18. [Prostate localization systems for prostate radiotherapy].

    PubMed

    de Crevoisier, R; Lagrange, J-L; Messai, T; M'Barek, B; Lefkopoulos, D

    2006-11-01

    The development of sophisticated conformal radiation therapy techniques for prostate cancer, such as intensity-modulated radiotherapy, implies precise and accurate targeting. Inter- and intrafraction prostate motion can be significant and should be characterized, unless the target volume may occasionally be missed. Indeed, bony landmark-based portal imaging does not provide the positional information for soft-tissue targets (prostate and seminal vesicles) or critical organs (rectum and bladder). In this article, we describe various prostate localization systems used before or during the fraction: rectal balloon, intraprostatic fiducials, ultrasound-based localization, integrated CT/linear accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical benefit in using such prostate localization tools is not proven by randomized studies and the feasibility has just been established for some of these techniques. Nevertheless, these systems should improve local control by a more accurate delivery of an increased prescribed dose in a reduced planning target volume.

  19. Inhibitor of p52 NF-κB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated ARser81

    PubMed Central

    Mehraein-Ghomi, Farideh; Church, Dawn R.; Schreiber, Cynthia L.; Weichmann, Ashley M.; Basu, Hirak S.; Wilding, George

    2015-01-01

    Accumulating evidence shows that androgen receptor (AR) activation and signaling plays a key role in growth and progression in all stages of prostate cancer, even under low androgen levels or in the absence of androgen in the castration-resistant prostate cancer. Sustained activation of AR under androgen-deprived conditions may be due to its interaction with co-activators, such as p52 NF-κB subunit, and/or an increase in its stability by phosphorylation that delays its degradation. Here we identified a specific inhibitor of AR/p52 interaction, AR/p52-02, via a high throughput screen based on the reconstitution of Gaussia Luciferase. We found that AR/p52-02 markedly inhibited growth of both castration-resistant C4-2 (IC50 ∼6 μM) and parental androgen-dependent LNCaP (IC50 ∼4 μM) human prostate cancer cells under low androgen conditions. Growth inhibition was associated with significantly reduced nuclear p52 levels and DNA binding activity, as well as decreased phosphorylation of AR at serine 81, increased AR ubiquitination, and decreased AR transcriptional activity as indicated by decreased prostate-specific antigen (PSA) mRNA levels in both cell lines. AR/p52-02 also caused a reduction in levels of p21WAF/CIP1, which is a direct AR targeted gene in that its expression correlates with androgen stimulation and mitogenic proliferation in prostate cancer under physiologic levels of androgen, likely by disrupting the AR signaling axis. The reduced level of cyclinD1 reported previously for this compound may be due to the reduction in nuclear presence and activity of p52, which directly regulates cyclinD1 expression, as well as the reduction in p21WAF/CIP1, since p21WAF/CIP1 is reported to stabilize nuclear cyclinD1 in prostate cancer. Overall, the data suggest that specifically inhibiting the interaction of AR with p52 and blocking activity of p52 and pARser81 may be an effective means of reducing castration-resistant prostate cancer cell growth. PMID:26622945

  20. Inhibitor of p52 NF-κB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated AR(ser81).

    PubMed

    Mehraein-Ghomi, Farideh; Church, Dawn R; Schreiber, Cynthia L; Weichmann, Ashley M; Basu, Hirak S; Wilding, George

    2015-09-01

    Accumulating evidence shows that androgen receptor (AR) activation and signaling plays a key role in growth and progression in all stages of prostate cancer, even under low androgen levels or in the absence of androgen in the castration-resistant prostate cancer. Sustained activation of AR under androgen-deprived conditions may be due to its interaction with co-activators, such as p52 NF-κB subunit, and/or an increase in its stability by phosphorylation that delays its degradation. Here we identified a specific inhibitor of AR/p52 interaction, AR/p52-02, via a high throughput screen based on the reconstitution of Gaussia Luciferase. We found that AR/p52-02 markedly inhibited growth of both castration-resistant C4-2 (IC50 ∼6 μM) and parental androgen-dependent LNCaP (IC50 ∼4 μM) human prostate cancer cells under low androgen conditions. Growth inhibition was associated with significantly reduced nuclear p52 levels and DNA binding activity, as well as decreased phosphorylation of AR at serine 81, increased AR ubiquitination, and decreased AR transcriptional activity as indicated by decreased prostate-specific antigen (PSA) mRNA levels in both cell lines. AR/p52-02 also caused a reduction in levels of p21(WAF/CIP1), which is a direct AR targeted gene in that its expression correlates with androgen stimulation and mitogenic proliferation in prostate cancer under physiologic levels of androgen, likely by disrupting the AR signaling axis. The reduced level of cyclinD1 reported previously for this compound may be due to the reduction in nuclear presence and activity of p52, which directly regulates cyclinD1 expression, as well as the reduction in p21(WAF/CIP1), since p21(WAF/CIP1) is reported to stabilize nuclear cyclinD1 in prostate cancer. Overall, the data suggest that specifically inhibiting the interaction of AR with p52 and blocking activity of p52 and pARser81 may be an effective means of reducing castration-resistant prostate cancer cell growth.

  1. Reducing and Uniforming the Co3 O 4 Particle Size by Sulfonated Graphenal Polymers for Electrochemical Applications

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Liu, Xubo; Zeng, Sha; Fang, Jianhui; Men, Chuanling; Zhang, Xiaohua; Li, Qingwen

    2017-03-01

    A novel two-dimensional (2D) nanomaterial, namely sulfonated graphenal polymer (SGP), is used to tune the hydrothermal growth of Co3O4 nanoparticles. SGP provides abundant nucleation sites to grow Co3O4 nanoparticles and effectively reduces the particle size and dimension. As a result, with considering the improved size uniformity of Co3O4 and the tight wrapping of SGP around Co3O4 as well, the Co3O4/SGP hybrid electrode exhibits a high specific electrochemical capacitance of 234.28 F/g at a current density of 0.2 A/g, 237% higher than that of the pure Co3O4 electrode. By using the hybrid as the anode of an all-solid-state asymmetric supercapacitor, the capacitance can be well maintained up to 93% after 5000 cycles even at 2 A/g.

  2. Enhanced hydrogenation and reduced lattice distortion in size selected Pd-Ag and Pd-Cu alloy nanoparticles

    SciTech Connect

    Sengar, Saurabh K.; Mehta, B. R.; Kulriya, P. K.; Khan, S. A.

    2013-10-21

    Important correlation between valence band spectra and hydrogenation properties in Pd alloy nanoparticles is established by studying the properties of size selected and monocrystalline Pd, Ag, Cu, Pd-Ag, and Pd-Cu nanoparticles. The X-ray photoelectron spectroscopy and elastic recoil detection analysis show that size induced Pd4d centroid shift is related to enhanced hydrogenation with H/Pd ratio of 0.57 and 0.49 in Pd-Ag and Pd-Cu nanoparticles in comparison to reported bulk values of 0.2 and 0.1, respectively. Pd-alloy nanoparticles show lower hydrogen induced lattice distortion. The reduced distortion and higher hydrogen reactivity of Pd-alloy nanoparticles is important for numerous hydrogen related applications.

  3. Reduced microsatellite heterozygosity in island endemics supports the role of long-term effective population size in avian microsatellite diversity

    PubMed Central

    2011-01-01

    Because of the high mutation rate of microsatellites, polymorphism at microsatellite loci might be predicted to reflect the effective population size over a time span of about 10,000 years and thus to be associated with biogeographic factors impacting species on that time frame. This prediction was tested by comparing heterozygosity at microsatellite loci from 294 bird species, including 58 species endemic to oceanic islands. Controlling statistically for phylogenetic effects, mean heterozygosity was significantly reduced in oceanic island endemics compared to other species. There was also an effect of current endangerment, statistically independent of the effect of island endemicity. These results support the hypothesis that long-term effective population size can be an important causative factor behind differences among species with respect to microsatellite heterozygosity. PMID:21104002

  4. Use of High-Frequency In-Home Monitoring Data May Reduce Sample Sizes Needed in Clinical Trials

    PubMed Central

    Dodge, Hiroko H.; Zhu, Jian; Mattek, Nora C.; Austin, Daniel; Kornfeld, Judith; Kaye, Jeffrey A.

    2015-01-01

    individual-specific distributions of walking speed collected at baseline, 262 subjects are required. Similarly for computer use, 26 subjects are required. Conclusions Individual-specific thresholds of low functional performance based on high-frequency in-home monitoring data distinguish trajectories of MCI from NC and could substantially reduce sample sizes needed in dementia prevention RCTs. PMID:26379170

  5. Reduction in patient-reported acute morbidity in prostate cancer patients treated with 81-Gy Intensity-modulated radiotherapy using reduced planning target volume margins and electromagnetic tracking: assessing the impact of margin reduction study.

    PubMed

    Sandler, Howard M; Liu, Ping-Yu; Dunn, Rodney L; Khan, David C; Tropper, Scott E; Sanda, Martin G; Mantz, Constantine A

    2010-05-01

    To investigate whether patient-reported quality of life after high-dose external beam intensity-modulated radiotherapy for prostate cancer can be improved by decreasing planning target volume margins while using real-time tumor tracking. Study patients underwent radiotherapy with nominal 3-mm margins and electromagnetic real-time tracking. Morbidity was assessed before and at the end of radiotherapy using Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Changes in scores were compared between the Assessing Impact of Margin Reduction (AIM) study cohort and the comparator Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROST-QA) cohort, treated with conventional margins. The 64 patients in the prospective AIM study had generally less favorable clinical characteristics than the 153 comparator patients. Study patients had similar or slightly poorer pretreatment EPIC scores than comparator patients in bowel, urinary, and sexual domains. AIM patients receiving radiotherapy had less bowel morbidity than the comparator group as measured by changes in mean bowel and/or rectal domain EPIC scores from pretreatment to 2 months after start of treatment (-1.5 vs -16.0, P = .001). Using a change in EPIC score >0.5 baseline standard deviation as the measure of clinical relevance, AIM study patients experienced meaningful decline in only 1 health-related quality of life domain (urinary) whereas decline in 3 health-related quality of life domains (urinary, sexual, and bowel/rectal) was observed in the PROST-QA comparator cohort. Prostate cancer patients treated with reduced margins and tumor tracking had less radiotherapy-related morbidity than their counterparts treated with conventional margins. Highly contoured intensity-modulated radiotherapy shows promise as a successful strategy for reducing morbidity in prostate cancer treatment. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Cytochrome P450 omega-hydroxylase inhibition reduces infarct size during reperfusion via the sarcolemmal KATP channel.

    PubMed

    Gross, Eric R; Nithipatikom, Kasem; Hsu, Anna K; Peart, Jason N; Falck, John R; Campbell, William B; Gross, Garrett J

    2004-12-01

    Inhibition of 20-hydroxyeicosatrienoic acid (20-HETE), by pretreatment with pharmacological inhibitors of cytochrome P450 (CYP) omega-hydroxylase, has been shown to reduce infarct size in canines when administered prior to ischemia. However, it is unknown whether these agents reduce infarct size when administered just prior to reperfusion and if the sarcolemmal and/or mitochondrial K(ATP) channels (sK(ATP) and mK(ATP)) contribute to cardioprotection. Therefore, we determined whether specific CYP inhibitors for epoxygenases and omega-hydroxylases are cardioprotective when given either prior to ischemia or prior to reperfusion and furthermore, if selective inhibition of the sK(ATP) by HMR-1098 or mK(ATP) by 5-hydroxydecanoic acid (5-HD) could abrogate this effect. Male Sprague-Dawley rats underwent 30 minutes of ischemia followed by 2 hours of reperfusion. Groups received either miconazole (MIC, non-selective CYP inhibitor, 3 mg/kg), 17-octadecynoic acid (17-ODYA, CYP omega-hydroxylase inhibitor, 0,3 or 3 mg/kg), N-methylsulfonyl-12, 12-dibromododec-11-enamide (DDMS, CYP omega-hydroxylase inhibitor, 0,4 or 4 mg/kg), N-methanesulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH, CYP epoxygenase inhibitor, 3 mg/kg), or vehicle either 10 minutes prior to ischemia or 5 minutes prior to reperfusion. Rats also received either HMR-1098 (6 mg/kg) or 5-HD (10 mg/kg) 10 minutes prior to reperfusion, with subsets of rats also receiving either MIC or 17-ODYA 5 minutes prior to reperfusion. DDMS and 17-ODYA dose dependently reduced infarct size. Rats treated with MIC, 17-ODYA and DDMS, but not MS-PPOH, produced comparable reductions in infarct size when administered prior to ischemia or reperfusion compared to vehicle. HMR-1098, but not 5-HD, also blocked the infarct size reduction afforded by MIC and 17-ODYA. These data suggest a novel cardioprotective pathway involving CYP omega-hydroxylase inhibition and subsequent activation of the sK(ATP) channel during reperfusion.

  7. Plasmodesmata formation and cell-to-cell transport are reduced in decreased size exclusion limit 1 during embryogenesis in Arabidopsis

    PubMed Central

    Xu, Min; Cho, Euna; Burch-Smith, Tessa M.; Zambryski, Patricia C.

    2012-01-01

    In plants, plasmodesmata (PD) serve as channels for micromolecular and macromolecular cell-to-cell transport. Based on structure, PD in immature tissues are classified into two types, simple and branched (X- and Y-shaped) or twinned. The maximum size of molecules capable of PD transport defines PD aperture, known as the PD size exclusion limit. Here we report an Arabidopsis mutation, decreased size exclusion limit1 (dse1), that exhibits reduced cell-to-cell transport of the small (524 Da) fluorescent tracer 8-hydroxypyrene-1,3,6-trisulfonic acid at the midtorpedo stage of embryogenesis. Correspondingly, the fraction of X- and Y-shaped and twinned PD was reduced in dse1 embryos compared with WT embryos at this stage, suggesting that the frequency of PD is related to transport capability. dse1 is caused by a point mutation in At4g29860 (previously termed TANMEI) at the last donor splice site of its transcript, resulting in alternative splicing in both the first intron and the last intron. AtDSE1 is a conserved eukaryotic 386-aa WD-repeat protein critical for Arabidopsis morphogenesis and reproduction. Similar to its homologs in mouse, null mutants are embryo-lethal. The weak loss-of-function mutant dse1 exhibits pleiotropic phenotypes, including retarded vegetative growth, delayed flowering time, dysfunctional male and female organs, and delayed senescence. Finally, silencing of DSE1 in Nicotiana benthamiana leaves leads to reduced movement of GFP fused to tobacco mosaic virus movement protein. Thus, DSE1 is important for regulating PD transport between plant cells. PMID:22411811

  8. Plasmodesmata formation and cell-to-cell transport are reduced in decreased size exclusion limit 1 during embryogenesis in Arabidopsis.

    PubMed

    Xu, Min; Cho, Euna; Burch-Smith, Tessa M; Zambryski, Patricia C

    2012-03-27

    In plants, plasmodesmata (PD) serve as channels for micromolecular and macromolecular cell-to-cell transport. Based on structure, PD in immature tissues are classified into two types, simple and branched (X- and Y-shaped) or twinned. The maximum size of molecules capable of PD transport defines PD aperture, known as the PD size exclusion limit. Here we report an Arabidopsis mutation, decreased size exclusion limit1 (dse1), that exhibits reduced cell-to-cell transport of the small (524 Da) fluorescent tracer 8-hydroxypyrene-1,3,6-trisulfonic acid at the midtorpedo stage of embryogenesis. Correspondingly, the fraction of X- and Y-shaped and twinned PD was reduced in dse1 embryos compared with WT embryos at this stage, suggesting that the frequency of PD is related to transport capability. dse1 is caused by a point mutation in At4g29860 (previously termed TANMEI) at the last donor splice site of its transcript, resulting in alternative splicing in both the first intron and the last intron. AtDSE1 is a conserved eukaryotic 386-aa WD-repeat protein critical for Arabidopsis morphogenesis and reproduction. Similar to its homologs in mouse, null mutants are embryo-lethal. The weak loss-of-function mutant dse1 exhibits pleiotropic phenotypes, including retarded vegetative growth, delayed flowering time, dysfunctional male and female organs, and delayed senescence. Finally, silencing of DSE1 in Nicotiana benthamiana leaves leads to reduced movement of GFP fused to tobacco mosaic virus movement protein. Thus, DSE1 is important for regulating PD transport between plant cells.

  9. Peri-procedural povidone-iodine rectal preparation reduces microorganism counts and infectious complications following ultrasound-guided needle biopsy of the prostate.

    PubMed

    Gyorfi, Justin R; Otteni, Christopher; Brown, Kevin; Patel, Amar; Lehman, Kathleen; Phillips, Brett E; Dewan, Kalyan; Kirimanjeswara, Girish; Raman, Jay D

    2014-08-01

    The purpose of the study was to evaluate whether a peri-procedural povidone-iodine rectal preparation (PIRP) prior to transrectal ultrasound-guided prostate needle biopsy (TRUS PNB) can reduce microorganism colony counts and infectious complications. Our institutional TRUS PNB database was reviewed to identify infectious post-biopsy complications (defined as fever >38.5 °C with positive culture). The last 570 biopsy patients were divided into those administered only preoperative oral and/or parenteral antibiotics (n = 456; chronologically cohorts A-D) versus men receiving peri-procedural PIRP in conjunction with standard preoperative antibiotics (n = 114; cohort E). Rectal cultures were obtained in the PIRP cohort to quantify changes in microorganism colony counts. Mean baseline PSA for patients was 11.6 ng/ml, 63 % were undergoing an initial biopsy, and 17 % had documented use of antibiotic therapy within the previous 6 months. A reduction in infectious complications was observed when comparing the conventional antibiotic (cohorts A-D) versus PIRP (cohort E) group (1.8 vs. 0 %), with the largest magnitude of decline occurring in the concurrent contemporary cohorts (cohort D-5.3 % vs. cohort E-0 %, p = 0.03). Rectal cultures obtained in 92 men before and after PIRP administration noted a 97 % reduction in microorganism colonies (2.1 × 10(5) vs. 6.3 × 10(3) CFU/ml, p < 0.001). No adverse reactions to the PIRP were reported by patients 7 days post-biopsy. Peri-procedural PIRP decreased microorganism colony counts and effectively reduced infectious complications following TRUS PNB. This safe, cheap, and simple strategy may be a reasonable alternative to systemic or targeted antibiotic therapy to reduce post-biopsy infections.

  10. Ad5/48 hexon oncolytic virus expressing sTGFβRIIFc produces reduced hepatic and systemic toxicities and inhibits prostate cancer bone metastases.

    PubMed

    Xu, Weidong; Zhang, Zhenwei; Yang, Yuefeng; Hu, Zebin; Wang, Chi-Hsiung; Morgan, Melanie; Wu, Ying; Hutten, Ryan; Xiao, Xianghui; Stock, Stuart; Guise, Theresa; Prabhakar, Bellur S; Brendler, Charles; Seth, Prem

    2014-08-01

    We are interested in developing oncolytic adenoviruses for the treatment of prostate cancer (PCa) bone metastases. A key limitation of Adenovirus 5 (Ad5) is that upon systemic administration, it produces major liver and systemic toxicities. To address this issue, a chimaeric Ad5/48 adenovirus mHAd.sTβRFc was created. Seven hypervariable regions of Ad5 hexon present in Ad5-based Ad.sTβRFc expressing soluble transforming growth factor beta receptor II-Fc fusion protein (sTGβRIIFc), were replaced by those of Ad48. mHAd.sTβRFc, like Ad.sTβRFc, was replication competent in the human PCa cells, and produced high levels of sTGβRIIFc expression. Compared to Ad.sTβRFc, the systemic delivery of mHAd.sTβRFc in nude mice resulted in much reduced systemic toxicity, and reduced liver sequestration. Ad.sTβRFc produced significant liver necrosis, and increases in alanine transaminase, aspartate transaminase, lactate dehydrogenase, tumor necrosis factor-α, and interleukin-6 levels, while mHAd.sTβRFc produced much reduced responses of these markers. Intravenous delivery of Ad.sTβRFc or mHAd.sTβRFc (5 × 10(10) viral particles/mouse) in nude mice bearing PC-3-luc PCa bone metastases produced inhibition of bone metastases. Moreover, a larger dose of the mHAd.sTβRFc (4 × 10(11) viral particles /mouse) was also effective in inhibiting bone metastases. Thus, mHAd.sTβRFc could be developed for the treatment of PCa bone metastases.

  11. [Prostate cancer].

    PubMed

    Bey, P; Beckendorf, V; Stinès, J

    2001-10-01

    Radiation therapy of prostate carcinoma with a curative intent implies to treat the whole prostate at high dose (at least 66 Gy). According to clinical stage, PSA level, Gleason's score, the clinical target volume may include seminal vesicles and less often pelvic lymph nodes. Microscopic extracapsular extension is found in 15 to 60% of T1-T2 operated on, specially in apex tumors. On contrary, cancers developing from the transitional zone may stay limited to the prostate even with a big volume and with a high PSA level. Zonal anatomy of the prostate identifies internal prostate, including the transitional zone (5% of the prostate in young people). External prostate includes central and peripheral zones. The inferior limit of the prostate is not lower than the inferior border of the pubic symphysis. Clinical and radiological examination: ultrasonography, nuclear magnetic resonance (NMR), CT-scan identify prognostic factors as tumor volume, capsule effraction, seminal vesicles invasion and lymph node extension. The identification of the clinical target volume is now done mainly by CT-Scan which identifies prostate and seminal vesicles. NMR could be helpful to identify more precisely prostate apex. The definition of margins around the clinical target volume has to take in account daily reproducibility and organ motion and of course the maximum tolerable dose for organs at risk.

  12. Alendronate decreases orthotopic PC-3 prostate tumor growth and metastasis to prostate-draining lymph nodes in nude mice

    PubMed Central

    Tuomela, Johanna M; Valta, Maija P; Väänänen, Kalervo; Härkönen, Pirkko L

    2008-01-01

    Background Metastatic prostate cancer is associated with a high morbidity and mortality but the spreading mechanisms are still poorly understood. The aminobisphosphonate alendronate, used to reduce bone loss, has also been shown to inhibit the invasion and migration of prostate cancer cells in vitro. We used a modified orthotopic PC-3 nude mouse tumor model of human prostate cancer to study whether alendronate affects prostate tumor growth and metastasis. Methods PC-3 cells (5 × 105) were implanted in the prostates of nude mice and the mice were treated with alendronate (0.5 mg/kg/day in PBS, s.c.) or vehicle for 4 weeks. After sacrifice, the sizes of tumor-bearing prostates were measured and the tumors and prostate-draining regional iliac and sacral lymph nodes were excised for studies on markers of proliferation, apoptosis, angiogenesis and lymphangiogenesis, using histomorphometry and immunohistochemistry. Results Tumor occurrence in the prostate was 73% in the alendronate-treated group and 81% in the control group. Mean tumor size (218 mm3, range: 96–485 mm3, n = 11) in the alendronate-treated mice was 41% of that in the control mice (513 mm3, range: 209–1350 mm3, n = 13) (p < 0.05). In the iliac and sacral lymph nodes of alendronate-treated mice, the proportion of metastatic area was only about 10% of that in control mice (p < 0.001). Immunohistochemical staining of tumor sections showed that alendronate treatment caused a marked decrease in the number of CD34-positive endothelial cells in tumors (p < 0.001) and an increase in that of ISEL positive apoptotic cells in tumors as well as in lymph node metastases (p < 0.05) compared with those in the vehicle-treated mice. The density of m-LYVE-1-stained lymphatic capillaries was not changed. Conclusion Our results demonstrate that alendronate treatment opposes growth of orthotopic PC-3 tumors and decreases tumor metastasis to prostate-draining lymph nodes. This effect could be at least partly explained by

  13. Microwave thermotherapy for benign prostatic hyperplasia.

    PubMed

    Hoffman, Richard M; Monga, Manoj; Elliott, Sean P; Macdonald, Roderick; Langsjoen, Jens; Tacklind, James; Wilt, Timothy J

    2012-09-12

    -blocker. Study durations ranged from 3 to 60 months. The mean age of participants was 66.8 years and the baseline symptom scores and urinary flow rates, which did not differ across treatment groups, demonstrated moderately severe lower urinary tract symptoms. The pooled mean urinary symptom scores decreased by 65% with TUMT and by 77% with TURP. The weighted mean difference (WMD) with 95% confidence interval (CI) for the International Prostate Symptom Score (IPSS) was -1.00 (95% CI -2.03 to -0.03), favoring TURP. The pooled mean peak urinary flow increased by 70% with TUMT and by 119% with TURP. The WMD for peak urinary flow was 5.08 mL/s (95% CI 3.88 to 6.28 mL/s), favoring TURP. Compared to TURP, TUMT was associated with decreased risks for retrograde ejaculation, treatment for strictures, hematuria, blood transfusions, and the transurethral resection syndrome, but increased risks for dysuria, urinary retention, and retreatment for BPH symptoms. Microwave thermotherapy improved IPSS symptom scores (WMD -5.15, 95% CI -4.26 to -6.04) and peak urinary flow (WMD 2.01 mL/s, 95% CI 0.85 to 3.16) compared with sham procedures. Microwave thermotherapy also improved IPSS symptom scores (WMD -4.20, 95% CI -3.15 to -5.25) and peak urinary flow (WMD 2.30 mL/s, 95% CI 1.47 to 3.13) in the one comparison with alpha-blockers. No studies evaluated the effects of symptom duration, patient characteristics, prostate-specific antigen levels, or prostate volume on treatment response. Microwave thermotherapy techniques are effective alternatives to TURP and alpha-blockers for treating symptomatic BPH in men with no history of urinary retention or previous prostate procedures and prostate volumes between 30 to 100 mL. However, TURP provided greater symptom score and urinary flow improvements and reduced the need for subsequent BPH treatments compared to TUMT. Small sample sizes and differences in study design limit comparisons between devices with different designs and energy levels. The effects of

  14. The importance of prostate bed tilt during postprostatectomy intensity-modulated radiotherapy

    SciTech Connect

    Bell, Linda J.; Cox, Jennifer; Eade, Thomas; Rinks, Marianne; Kneebone, Andrew

    2014-10-01

    Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle change between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1 cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by more

  15. The importance of prostate bed tilt during postprostatectomy intensity-modulated radiotherapy.

    PubMed

    Bell, Linda J; Cox, Jennifer; Eade, Thomas; Rinks, Marianne; Kneebone, Andrew

    2014-01-01

    Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle change between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by more

  16. Reduced Cardiovascular Capacity and Resting Metabolic Rate in Men with Prostate Cancer Undergoing Androgen Deprivation: A Comprehensive Cross-Sectional Investigation.

    PubMed

    Wall, Bradley A; Galvão, Daniel A; Fatehee, Naeem; Taaffe, Dennis R; Spry, Nigel; Joseph, David; Newton, Robert U

    2015-01-01

    Objectives. To investigate if androgen deprivation therapy exposure is associated with additional risk factors for cardiovascular disease and metabolic treatment-related toxicities. Methods. One hundred and seven men (42-89 years) with prostate cancer undergoing androgen deprivation therapy completed a maximal graded objective exercise test to determine maximal oxygen uptake, assessments for resting metabolic rate, body composition, blood pressure and arterial stiffness, and blood biomarker analysis. A cross-sectional analysis was undertaken to investigate the potential impact of therapy exposure with participants stratified into two groups according to duration of androgen deprivation therapy (<3 months and ≥3 months). Results. Maximal oxygen uptake (26.1 ± 6.0 mL/kg/min versus 23.2 ± 5.8 mL/kg/min, p = 0.020) and resting metabolic rate (1795 ± 256 kcal/d versus 1647 ± 236 kcal/d, p = 0.005) were significantly higher in those with shorter exposure to androgen deprivation. There were no differences between groups for peripheral and central blood pressure, arterial stiffness, or metabolic profile. Conclusion. Three months or longer exposure to androgen deprivation therapy was associated with reduced cardiorespiratory capacity and resting metabolic rate, but not in a range of blood biomarkers. These findings suggest that prolonged exposure to androgen deprivation therapy is associated with negative alterations in cardiovascular outcomes. Trial registry is: ACTRN12609000200280.

  17. Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells

    PubMed Central

    Pifano, Marina; Garona, Juan; Capobianco, Carla S.; Gonzalez, Nazareno; Alonso, Daniel F.; Ripoll, Giselle V.

    2017-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects. Desmopressin (dDAVP) is a synthetic analog of AVP that acts as a selective agonist for the V2r, which shows antitumor properties in breast and colorectal cancer models. Recently, we developed a derivative of dDAVP named [V4Q5]dDAVP, which presents higher antitumor effects in a breast cancer model compared to the parental compound. The goal of present work was to explore the antitumor properties of the V2r agonist dDAVP and its novel analog [V4Q5]dDAVP on aggressive human lung (NCI-H82) and prostate cancer (PC-3) cell lines with neuroendocrine (NE) characteristics. We study the presence of specific NE markers (CgA and NSE) and V2r expression in NCI-H82 and PC-3. Both cell lines express high levels of NE markers NSE and CgA but then incubation with dDAVP diminished expression levels of both markers. DDAVP and [V4Q5]dDAVP significantly reduced proliferation, doubling time, and migration in both tumor cell cultures. [V4Q5]dDAVP analog showed a higher cytostatic effect than dDAVP, on cellular proliferation in the NCI-H82 cell line. Silencing of V2r using small interfering RNA significantly attenuated the inhibitory effects of [V4Q5]dDAVP on NCI-H82 cell proliferation. We, preliminarily, explored the in vivo effect of dDAVP and [V4Q5]dDAVP on NCI-H82 small cell lung cancer xenografts. Treated tumors (0.3 μg kg−1, thrice a week) grew slower in comparison to vehicle-treated animals. In this work, we demonstrated

  18. Reduced neuronal size and mTOR pathway activity in the Mecp2 A140V Rett syndrome mouse model.

    PubMed

    Rangasamy, Sampathkumar; Olfers, Shannon; Gerald, Brittany; Hilbert, Alex; Svejda, Sean; Narayanan, Vinodh

    2016-01-01

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene, encoding methyl-CpG-binding protein 2. We have created a mouse model ( Mecp2 A140V "knock-in" mutant) expressing the recurrent human MECP2 A140V mutation linked to an X-linked mental retardation/Rett syndrome phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed on primary hippocampus and cerebellum granule neuron (CGN) cultures from mutant ( Mecp2(A140V/y)) and wild type ( Mecp2(+/y)) male mice. Cultured hippocampus and cerebellar granule neurons from mutant animals were significantly smaller than neurons from wild type animals. We also examined soma size in hippocampus neurons from individual female transgenic mice that express both a mutant  (maternal allele) and a wild type Mecp2 gene linked to an eGFP transgene (paternal allele). In cultures from such doubly heterozygous female mice, the size of neurons expressing the mutant (A140V) allele also showed a significant reduction compared to neurons expressing wild type MeCP2, supporting a cell-autonomous role for MeCP2 in neuronal development. IGF-1 (insulin growth factor-1) treatment of neuronal cells from Mecp2 mutant mice rescued the soma size phenotype. We also found that Mecp2  mutation leads to down-regulation of the mTOR signaling pathway, known to be involved in neuronal size regulation. Our results suggest that i) reduced neuronal size is an important in vitro cellular phenotype of Mecp2 mutation in mice, and ii) MeCP2 might play a critical role in the maintenance of neuronal structure by modulation of the mTOR pathway. The definition of a quantifiable cellular phenotype supports using neuronal size as a biomarker in the development of a high-throughput, in vitro assay to screen for compounds that rescue small neuronal phenotype ("phenotypic assay").

  19. Reduced neuronal size and mTOR pathway activity in the Mecp2 A140V Rett syndrome mouse model

    PubMed Central

    Rangasamy, Sampathkumar; Olfers, Shannon; Gerald, Brittany; Hilbert, Alex; Svejda, Sean; Narayanan, Vinodh

    2016-01-01

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene, encoding methyl-CpG-binding protein 2. We have created a mouse model ( Mecp2 A140V “knock-in” mutant) expressing the recurrent human MECP2 A140V mutation linked to an X-linked mental retardation/Rett syndrome phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed on primary hippocampus and cerebellum granule neuron (CGN) cultures from mutant ( Mecp2 A140V/y) and wild type ( Mecp2 +/y) male mice. Cultured hippocampus and cerebellar granule neurons from mutant animals were significantly smaller than neurons from wild type animals. We also examined soma size in hippocampus neurons from individual female transgenic mice that express both a mutant  (maternal allele) and a wild type Mecp2 gene linked to an eGFP transgene (paternal allele). In cultures from such doubly heterozygous female mice, the size of neurons expressing the mutant (A140V) allele also showed a significant reduction compared to neurons expressing wild type MeCP2, supporting a cell-autonomous role for MeCP2 in neuronal development. IGF-1 (insulin growth factor-1) treatment of neuronal cells from Mecp2 mutant mice rescued the soma size phenotype. We also found that Mecp2   mutation leads to down-regulation of the mTOR signaling pathway, known to be involved in neuronal size regulation. Our results suggest that i) reduced neuronal size is an important in vitro cellular phenotype of Mecp2 mutation in mice, and ii) MeCP2 might play a critical role in the maintenance of neuronal structure by modulation of the mTOR pathway. The definition of a quantifiable cellular phenotype supports using neuronal size as a biomarker in the development of a high-throughput, in vitro assay to screen for compounds that rescue small neuronal phenotype (“phenotypic assay”). PMID:27781091

  20. Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways

    SciTech Connect

    Aguado, Andrea; Galán, María; Zhenyukh, Olha; Wiggers, Giulia A.; Roque, Fernanda R.; Redondo, Santiago; Peçanha, Franck; Martín, Angela; Fortuño, Ana; Cachofeiro, Victoria; Tejerina, Teresa; Salaices, Mercedes; and others

    2013-04-15

    MAPK activation, oxidative stress and COX-2 expression. ► Inhibition of MAPK reduces HgCl{sub 2}-induced oxidative stress and COX-2 expression. ► Inhibition of MAPK, oxidative stress and COX-2 restores the altered cell proliferation and size.

  1. Using a Reduced Spot Size for Intensity-Modulated Proton Therapy Potentially Improves Salivary Gland-Sparing in Oropharyngeal Cancer

    SciTech Connect

    Water, Tara A. van de; Lomax, Antony J.; Bijl, Hendrik P.; Schilstra, Cornelis; Hug, Eugen B.; Langendijk, Johannes A.

    2012-02-01

    Purpose: To investigate whether intensity-modulated proton therapy with a reduced spot size (rsIMPT) could further reduce the parotid and submandibular gland dose compared with previously calculated IMPT plans with a larger spot size. In addition, it was investigated whether the obtained dose reductions would theoretically translate into a reduction of normal tissue complication probabilities (NTCPs). Methods: Ten patients with N0 oropharyngeal cancer were included in a comparative treatment planning study. Both IMPT plans delivered simultaneously 70 Gy to the boost planning target volume (PTV) and 54 Gy to the elective nodal PTV. IMPT and rsIMPT used identical three-field beam arrangements. In the IMPT plans, the parotid and submandibular salivary glands were spared as much as possible. rsIMPT plans used identical dose-volume objectives for the parotid glands as those used by the IMPT plans, whereas the objectives for the submandibular glands were tightened further. NTCPs were calculated for salivary dysfunction and xerostomia. Results: Target coverage was similar for both IMPT techniques, whereas rsIMPT clearly improved target conformity. The mean doses in the parotid glands and submandibular glands were significantly lower for three-field rsIMPT (14.7 Gy and 46.9 Gy, respectively) than for three-field IMPT (16.8 Gy and 54.6 Gy, respectively). Hence, rsIMPT significantly reduced the NTCP of patient-rated xerostomia and parotid and contralateral submandibular salivary flow dysfunction (27%, 17%, and 43% respectively) compared with IMPT (39%, 20%, and 79%, respectively). In addition, mean dose values in the sublingual glands, the soft palate and oral cavity were also decreased. Obtained dose and NTCP reductions varied per patient. Conclusions: rsIMPT improved sparing of the salivary glands and reduced NTCP for xerostomia and parotid and submandibular salivary dysfunction, while maintaining similar target coverage results. It is expected that rsIMPT improves quality

  2. Multiparametric magnetic resonance imaging guided diagnostic biopsy detects significant prostate cancer and could reduce unnecessary biopsies and over detection: a prospective study.

    PubMed

    Thompson, James E; Moses, Daniel; Shnier, Ron; Brenner, Phillip; Delprado, Warick; Ponsky, Lee; Pulbrook, Marley; Böhm, Maret; Haynes, Anne-Maree; Hayen, Andrew; Stricker, Phillip D

    2014-07-01

    Multiparametric magnetic resonance imaging appears to improve prostate cancer detection but prospective studies are lacking. We determined the accuracy of multiparametric magnetic resonance imaging for detecting significant prostate cancer before diagnostic biopsy in men with abnormal prostate specific antigen/digital rectal examination. In this single center, prospective study men older than 40 years with abnormal prostate specific antigen/digital rectal examination and no previous multiparametric magnetic resonance imaging underwent T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging without an endorectal coil. Imaging was allocated alternately to 1.5/3.0 Tesla. Imaging was double reported independently using PI-RADS (Prostate Imaging Reporting and Data System) by specialist radiologists. Transperineal grid directed 30-core biopsy was performed with additional magnetic resonance imaging directed cores for regions of interest outside template locations. Four significant cancer definitions were tested. Chi-square and logistic regression analysis was done. Men undergoing prostatectomy were analyzed. Of the 165 men who enrolled in the study 150 were analyzed. Median age was 62.4 years, median prostate specific antigen was 5.6 ng/ml, 29% of patients had an abnormal digital rectal examination and 88% underwent initial biopsy. Multiparametric magnetic resonance imaging was positive (PI-RADS 3 to 5) in 66% of patients, 61% had prostate cancer and 30% to 41% had significant prostate cancer (definitions 1 to 4). For significant cancer sensitivity was 93% to 96%, specificity was 47% to 53%, and negative and positive predictive values were 92% to 96% and 43% to 57%, respectively (definitions 1 to 4). Radical prostatectomy results in 48 men were similar. Aggregate PI-RADS (4 to 20) performed similarly to overall PI-RADS (1 to 5). Negative and positive predictive values (100% and 71%, respectively) were similar in men at higher risk, defined as prostate

  3. Impact of particle size distribution on rheological and textural properties of chocolate models with reduced fat content.

    PubMed

    Do, T-A L; Hargreaves, J M; Wolf, B; Hort, J; Mitchell, J R

    2007-11-01

    With an increasing consumption of lipids nowadays, decreasing the fat content in food products has become a trend. Chocolate is a fat-based suspension that contains about 30%wt fat. Reducing fat content causes an increase in the molten chocolate viscosity. This leads to 2 major issues: difficulties in the process and a loss of eating quality in the final product, reported to have poor in-mouth melting properties, remain hard, and difficult to swallow. Literature shows that optimizing the particle size distribution (PSD), that is, having one with an increased packing fraction, can decrease the viscosity of highly concentrated suspensions. This study focuses on the impact of the PSD and fat content on the rheological properties, melting behavior, and hardness of chocolate models (dispersions of sugar in fat). We show that optimizing the PSD while reducing the fat content to a critical amount (22%wt) can decrease the viscosity of the molten material and reduce the hardness of the crystallized chocolate models. Melting in the mouth, characterized by an in vitro collapse speed, is faster for the samples with an optimized PSD. The decrease in the viscosity by optimizing the PSD in systems with a constant fraction of medium phase is based on the decrease of interparticle contact, reducing the particle aggregates strength, and structure buildup during flow or meltdown. In its crystallized state, the particle network is less interconnected, providing less resistance to breakage and meltdown.

  4. Analysis of stunter1, a maize mutant with reduced gametophyte size and maternal effects on seed development.

    PubMed

    Phillips, Allison R; Evans, Matthew M S

    2011-04-01

    Many higher eukaryotes have evolved strategies for the maternal control of growth and development of their offspring. In higher plants this is achieved in part by postmeiotic gene activity controlling the development of the haploid female gametophyte. stunter1 (stt1) is a novel, recessive, maternal effect mutant in maize that displays viable, miniature kernels. Maternal inheritance of stt1 results in seeds with reduced but otherwise normal endosperms and embryos. The stt1 mutation displays reduced transmission through the male and female parents and causes significant changes in the sizes of both male and female gametophytes. stt1 pollen grains are smaller than wild type, have reduced germination efficiency, and reduced pollen tube growth. stt1 embryo sacs have smaller central cells and abnormal antipodal cells that are larger, more vacuolated, and fewer in number than wild type. Embryos and endosperms produced by fertilization of stt1 embryo sacs develop and grow more slowly than wild type. The data suggest that the morphology of mutant embryo sacs influences endosperm development, leading to the production of miniature kernels in stt1. Analysis of seeds carrying a mutant maternal allele of stt1 over a deletion of the paternal allele demonstrates that both parental alleles are active after fertilization in both the endosperm and embryo. This analysis also indicates that embryo development until the globular stage in maize can proceed without endosperm development and is likely supported directly by the diploid mother plant.

  5. The Educational Effects of a State Supported Reduced Class Size Program. A Comprehensive Evaluation of Indiana's Project PRIME TIME at the North Gibson School Corporation.

    ERIC Educational Resources Information Center

    Swan, Edward; And Others

    Research studies on class size date back to 1900. Common sense has suggested that small classes lead to greater academic achievement, but most research on the effects of class size on achievement have been inconclusive. Furthermore, the financial costs and political consequences of reducing class size have generally prohibited the adoption of…

  6. A facile completely 'green' size tunable synthesis of maltose-reduced silver nanoparticles without the use of any accelerator.

    PubMed

    Oluwafemi, Oluwatobi S; Lucwaba, Yolisa; Gura, Akhona; Masabeya, Moffat; Ncapayi, Vuyelwa; Olujimi, Olanrewaju O; Songca, Sandile P

    2013-02-01

    A simple, straightforward, cost effective and environmentally benign method for the synthesis of highly stable and small sized silver nanoparticles (Ag-NPs) with narrow size distribution without the use of an accelerator is reported. Silver nitrate, gelatin and maltose, a non-toxic disaccharide sugar were used as silver precursor, stabiliser and reducing agent. By varying the precursor concentration and reaction time, we monitored the temporal evolution of the optical and structural properties of the as-synthesised Ag-NPs. The as-synthesised Ag-NPs were characterised using UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The absorption maxima of the surface plasmon resonance (SPR) were blue-shifted as the reaction time increased indicating decrease in particle size. The TEM images showed that, the particles are small, well dispersed and spherical in shape. The smallest particles with an average particle diameter of 3.76±1.00 nm and 4.09±1.83 nm were obtained at 24h for the 1.0M and 0.5M silver ion precursor solution concentration respectively. The smaller particles produced were attributed to the higher concentration of the reducing saccharides in the reaction system, which in turn increases the formation of stable silver ions in the reaction system. The HRTEM images confirmed the crystalline nature of the material while the FTIR confirmed the stabilisation of the Ag-NPs by the gelatin. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

    PubMed Central

    Komaba, Hirotaka; Nakanishi, Shohei; Fujimori, Akira; Tanaka, Motoko; Shin, Jeongsoo; Shibuya, Koji; Nishioka, Masato; Hasegawa, Hirohito; Kurosawa, Takeshi

    2010-01-01

    Background and objectives: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume. Design, setting, participants, & measurements: This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was performed to measure the parathyroid gland size at baseline, week 26, and week 52. Findings were also compared with those of historical controls. Results: Of the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm3 (group S) and 25 had at least one enlarged gland larger than 500 mm3 (group L). Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. A slightly greater proportion of patients in group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a >30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n = 87) where parathyroid gland volume progressively increased with traditional therapy alone. Conclusions: Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia. PMID:20798251

  8. The Educational Effects of a State Supported Reduced Class Size Program: A Comprehensive Evaluation of Indiana's Project PRIME TIME at the North Gibson School Corporation.

    ERIC Educational Resources Information Center

    Gilman, David Alan; And Others

    1988-01-01

    After describing the pros and cons of reduced class size, this article evaluates the effectiveness of a pilot project sponsored by the Indiana Department of Education to reduce the size of its primary grade classes. Methodology and results are presented and discussed. (JL)

  9. Cryptococcal prostatitis.

    PubMed

    Hinchey, W W; Someren, A

    1981-02-01

    A case of granulomatous prostatitis due to Cryptococcus neoformans is reported. The patient, who had a history of diabetes mellitus and chronic active hepatitis, had symptoms of prostatic hypertrophy. Tissue obtained from surgery showed granulomatous prostatitis, and a cryptococcal organism was identified by special stains. Postoperative cultures grew Cryptococcus neoformans, and the patient was treated successfully with surgery and a short course of amphotericin B. After nine months of follow-up, there is no evidence of systemic infection.

  10. Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

    PubMed

    McVary, Kevin T; Gange, Steven N; Gittelman, Marc C; Goldberg, Kenneth A; Patel, Kalpesh; Shore, Neal D; Levin, Richard M; Rousseau, Michael; Beahrs, J Randolf; Kaminetsky, Jed; Cowan, Barrett E; Cantrill, Christopher H; Mynderse, Lance A; Ulchaker, James C; Larson, Thayne R; Dixon, Christopher M; Roehrborn, Claus G

    2016-05-01

    This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezūm® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. The Akt inhibitor ISC-4 activates Prostate apoptosis response protein-4 and reduces colon tumor growth in a nude mouse model

    PubMed Central

    Sharma, Arun K.; Kline, Christina L; Berg, Arthur; Amin, Shantu; Irby, Rosalyn B.

    2011-01-01

    Purpose Prostate apoptosis response protein-4 (Par-4) sensitizes cells to chemotherapy; however, Akt1 inactivates Par-4. Previously we showed that Par-4 overexpressing colon cancer cells responded more readily to 5-FU than did wild type counterparts. In this study we investigated: 1) the effects of the Akt inhibitor, phenylbutyl isoselenocyanate (ISC-4), on tumor growth in nude mice and 2) bystander effect of Par-4 overexpressing cells on wild type tumor growth. Experimental design Mice (80) were injected with wild type HT29 human colon cancer cells in the right flank. Forty of the mice were also injected in the left flank with HT29 cells engineered to overexpress Par-4. Mice were treated with 5-FU, ISC-4, a combination, or vehicle. Results ISC-4 reduced tumor growth, with or without 5-FU. When Par-4 overexpressing tumors were present, wild type tumors grew more slowly than when no Par-4 overexpressing tumors were present. The level of Par-4 protein as well as the Par-4 binding protein, GRP78, was increased in wild type cells growing in the same mouse as Par-4 overexpressing tumors compared to wild type tumors growing without Par-4 overexpressing tumors. Conclusions Par-4 overexpressing tumors exhibited a bystander effect on wild type tumors growing distally in the same mouse. This suggests that gene therapy need not achieve total penetration to have a positive effect on tumor treatment. Inhibition of Akt with ISC-4 inhibited tumor growth and had a greater effect on cells overexpressing Par-4. The data indicate ISC-4 alone or in combination with Par-4 can greatly reduce tumor growth. PMID:21555373

  12. Consultation audio-recording reduces long-term decision regret after prostate cancer treatment: A non-randomised comparative cohort study.

    PubMed

    Good, Daniel W; Delaney, Harry; Laird, Alexander; Hacking, Belinda; Stewart, Grant D; McNeill, S Alan

    2016-12-01

    The life expectancy of prostate patients is long and patients will spend many years carrying the burdens & benefits of the treatment decisions they have made, therefore, it is vital that decisions on treatments are shared between patient and physician. The objective was to determine if consultation audio-recording improves quality of life, reduces regret or improves patient satisfaction in comparison to standard counselling. In 2012 we initiated consultation audio-recordings, where patients are given a CD of their consultation to keep and replay at home. We conducted a prospective non-randomised study of patient satisfaction, quality of life (QOL) and decision regret at 12 months follow-up using posted validated questionnaires for the audio-recording (AR) patients and a control cohort. Qualitative and thematic analyses were used. Forty of 59 patients in the AR group, and 27 of 45 patients in the control group returned the questionnaires. Patient demographics were similar in both groups with no statistically significant differences between the two groups. Decision regret was lower in the audio-recording group (11/100) vs control group (19/100) (p = 0.04). The risk ratio for not having any long-term decision regret was 5.539 (CI 1.643-18.674), with NNT to prevent regret being 4. Regression analysis showed that receiving audio-recording was strongest predictor for absence of regret even greater than potency and incontinence. The study has shown that audio-recording clinic consultation reduces long-term decision regret, increases patient information recall, understanding and confidence in their decision. There is great potential for further expansion of this low-cost intervention. Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  13. SU-E-T-385: Evaluation of DVH Change for PTV Due to Patient Weight Loss in Prostate VMAT Using Gaussian Error Function

    SciTech Connect

    Viraganathan, H; Jiang, R; Chow, J

    2015-06-15

    Purpose: We proposed a method to predict the change of dose-volume histogram (DVH) for PTV due to patient weight loss in prostate volumetric modulated arc therapy (VMAT). This method is based on a pre-calculated patient dataset and DVH curve fitting using the Gaussian error function (GEF). Methods: Pre-calculated dose-volume data from patients having weight loss in prostate VMAT was employed to predict the change of PTV coverage due to reduced depth in external contour. The effect of patient weight loss in treatment was described by a prostate dose-volume factor (PDVF), which was evaluated by the prostate PTV. Along with the PDVF, the GEF was used to fit into the DVH curve for the PTV. To predict a new DVH due to weight loss, parameters from the GEF describing the shape of DVH curve were determined. Since the parameters were related to the PDVF as per the specific reduced depth, we could first predict the PDVF at a reduced depth based on the prostate size from the pre-calculated dataset. Then parameters of the GEF could be determined from the PDVF to plot the new DVH for the PTV corresponding to the reduced depth. Results: A MATLAB program was built basing on the patient dataset with different prostate sizes. We input data of the prostate size and reduced depth of the patient into the program. The program then calculated the PDVF and DVH for the PTV considering the patient weight loss. The program was verified by different patient cases with various reduced depths. Conclusion: Our method can estimate the change of DVH for the PTV due to patient weight loss quickly without CT rescan and replan. This would help the radiation staff to predict the change of PTV coverage, when patient’s external contour reduced in prostate VMAT.

  14. Benign prostatic hyperplasia: An overview of existing treatment

    PubMed Central

    Dhingra, Neelima; Bhagwat, Deepak

    2011-01-01

    Benign prostatic hyperplasia (BPH) is the most common condition in aging men, associated with lower urinary tract symptoms (LUTS). A better understanding of the prostate physiology, function, and pathogenesis has led to the development of promising agents, useful in the management of LUTS in men. The specific approach used to treat BPH depends upon number of factors like age, prostrate size, weight, prostate-specific antigen level, and severity of the symptoms. 5α-reductase inhibitors decrease the production of dihydrotestosterone within the prostate, which results in decreased prostate volume, increased peak urinary flow rate, improvement of symptoms, decreased risk of acute urinary retention, and need for surgical intervention. α1-adrenergic receptor (α1-AR) antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Clinical efficacy of either 5α-reductase inhibitor or α1-AR antagonist has been further improved by using combination therapy; however, long-term outcomes are still awaited. Many more potential new therapies are under development that may improve the treatment of BPH. This article gives a brief account of rationale and efficacy of different treatment options presently available in the management of BPH. PMID:21455413

  15. Hypofractionation for prostate cancer.

    PubMed

    Ritter, Mark; Forman, Jeffrey; Kupelian, Patrick; Lawton, Colleen; Petereit, Daniel

    2009-01-01

    Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience but has now attracted greatly renewed interest based upon a hypothesis that prostate cancers have a higher sensitivity to fraction size, reflected in a low alpha/beta ratio, than do late responding organs at risk such as the rectum or bladder. Tumor control and acceptable toxicity outcomes from several hypofractionation or brachytherapy analyses do in fact support an alpha/beta ratio for prostate cancer that is low, perhaps even lower that that for the normal organs that ordinarily constrain the delivery of radiation therapy. However, many of these studies lack sufficient patient numbers and follow-up, are clouded by dose inhomogeneity issues in the case of brachytherapy, or delivered effective doses that were too low by contemporary standards. Thus, the clinical efficacy of the approach has yet to be fully validated. However, a number of newer prospective trials, some randomized, are underway or have reached accrual but await sufficient follow-up for analysis. These studies, which cover a wide range of doses per fraction, should ultimately be capable of validating the utility of prostate hypofractionation and the models that predict its effects. With hypofractionation's significant potential for therapeutic gain, cost savings, and improved patient convenience, the future management of localized prostate cancer could be profoundly altered in the process.

  16. Geometric systematic prostate biopsy.

    PubMed

    Chang, Doyoung; Chong, Xue; Kim, Chunwoo; Jun, Changhan; Petrisor, Doru; Han, Misop; Stoianovici, Dan

    2017-04-01

    The common sextant prostate biopsy schema lacks a three-dimensional (3D) geometric definition. The study objective was to determine the influence of the geometric distribution of the cores on the detection probability of prostate cancer (PCa). The detection probability of significant (>0.5 cm(3)) and insignificant (<0.2 cm(3)) tumors was quantified based on a novel 3D capsule model of the biopsy sample. The geometric distribution of the cores was optimized to maximize the probability of detecting significant cancer for various prostate sizes (20-100cm(3)), number of biopsy cores (6-40 cores) and biopsy core lengths (14-40 mm) for transrectal and transperineal biopsies. The detection of significant cancer can be improved by geometric optimization. With the current sextant biopsy, up to 20% of tumors may be missed at biopsy in a 20 cm(3) prostate due to the schema. Higher number and longer biopsy cores are required to sample with an equal detection probability in larger prostates. Higher number of cores increases both significant and insignificant tumor detection probability, but predominantly increases the detection of insignificant tumors. The study demonstrates mathematically that the geometric biopsy schema plays an important clinical role, and that increasing the number of biopsy cores is not necessarily helpful.

  17. Role of MAPK Activation in Prostate Cancer Development and Progression

    DTIC Science & Technology

    2008-03-01

    tumor progression and maintenance. (A) Schematic representation of CI-1040 (a MEK inhibitor ) treatment protocol using tissue recombination. Tissue...However, the tumor size with the treatment of a MEK inhibitor significantly increased compared to vehicle treated ones in tissue recombination...expression is often found to be elevated and B- Raf inhibitor expression reduced in human prostate tumors (25). Lastly, ETV1/ER85, a partner in the

  18. Role of plant residues in determining temporal patterns of the activity, size, and structure of nitrate reducer communities in soil.

    PubMed

    Chèneby, D; Bru, D; Pascault, N; Maron, P A; Ranjard, L; Philippot, L

    2010-11-01

    The incorporation of plant residues into soil not only represents an opportunity to limit soil organic matter depletion resulting from cultivation but also provides a valuable source of nutrients such as nitrogen. However, the consequences of plant residue addition on soil microbial communities involved in biochemical cycles other than the carbon cycle are poorly understood. In this study, we investigated the responses of one N-cycling microbial community, the nitrate reducers, to wheat, rape, and alfalfa residues for 11 months after incorporation into soil in a field experiment. A 20- to 27-fold increase in potential nitrate reduction activity was observed for residue-amended plots compared to the nonamended plots during the first week. This stimulating effect of residues on the activity of the nitrate-reducing community rapidly decreased but remained significant over 11 months. During this period, our results suggest that the potential nitrate reduction activity was regulated by both carbon availability and temperature. The presence of residues also had a significant effect on the abundance of nitrate reducers estimated by quantitative PCR of the narG and napA genes, encoding the membrane-bound and periplasmic nitrate reductases, respectively. In contrast, the incorporation of the plant residues into soil had little impact on the structure of the narG and napA nitrate-reducing community determined by PCR-restriction fragment length polymorphism (RFLP) fingerprinting. Overall, our results revealed that the addition of plant residues can lead to important long-term changes in the activity and size of a microbial community involved in N cycling but with limited effects of the type of plant residue itself.

  19. Increased fat mass is associated with increased bone size but reduced volumetric density in pre pubertal children.

    PubMed

    Cole, Z A; Harvey, N C; Kim, M; Ntani, G; Robinson, S M; Inskip, H M; Godfrey, K M; Cooper, C; Dennison, E M

    2012-02-01

    Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired. We recruited 530 children at 6 years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany). Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=-14.6 mg/mm(3) per sd, p=0.003; β=-7.7 mg/mm(3) per sd, p=0.02 respectively). These results suggest that fat mass is negatively associated with volumetric bone density at 6 years old, independent of lean mass, despite positive associations with bone size. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury

    PubMed Central

    Haar, Cole Vonder; Anderson, Gail D.; Hoane, Michael R.

    2011-01-01

    Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B3) in animal models of TBI with systemic dosing at 50 and 500 mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150 mg/kg/day) or saline (1 ml/kg) pumps 30 min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50 mg/kg) or saline (1 ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies. PMID:21704653

  1. Systematic adjustment of charge densities and size of polyglycerol amines reduces cytotoxic effects and enhances cellular uptake.

    PubMed

    Hellmund, Markus; Achazi, Katharina; Neumann, Falko; Thota, Bala N S; Ma, Nan; Haag, Rainer

    2015-11-01

    Excessive cationic charge density of polyplexes during cellular uptake is still a major hurdle in the field of non-viral gene delivery. The most efficient cationic vectors such as polyethylene imine (PEI) or polyamidoamine (PAMAM) can be highly toxic and may induce strong side effects due to their high cationic charge densities. Alternatives like polyethylene glycol (PEG) are used to 'shield' these charges and thus to reduce the cytotoxic effects known for PEI/PEG-core-shell architectures. In this study, we compared the ability of hyperbranched polyglycerol amines (hPG amines) with different amine densities and molecular weights as non-viral cationic vectors for DNA delivery. By adjusting the hydroxyl to amine group ratio on varying molecular weights, we were able to perform a systematic study on the cytotoxic effects caused by the effective charge density in correlation to size. We could demonstrate that carriers with moderate charge density have a higher potential for effective DNA delivery as compared to high/low charged ones independent of their size, but the final efficiency can be optimized by the molecular weight. We analyzed the physicochemical properties and cellular uptake capacity as well as the cytotoxicity and transfection efficiency of these new vector systems.

  2. Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury.

    PubMed

    Vonder Haar, Cole; Anderson, Gail D; Hoane, Michael R

    2011-10-31

    Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B(3)) in animal models of TBI with systemic dosing at 50 and 500 mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150 mg/kg day) or saline (1 ml/kg) pumps 30 min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1 ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies.

  3. Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients.

    PubMed

    Thoeny, Harriet C; Triantafyllou, Maria; Birkhaeuser, Frederic D; Froehlich, Johannes M; Tshering, Dechen W; Binser, Tobias; Fleischmann, Achim; Vermathen, Peter; Studer, Urs E

    2009-04-01

    Lymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret. To assess whether combined USPIO and DW-MRI (USPIO-DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients. Twenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery. Patients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors. Diagnostic accuracies of the new combined USPIO-DW-MRI approach compared with the "classic" reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient. Diagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO-DW-MRI reading method, while time of analysis with 80 min (range 45-180 min) for the classic and 13 min (range 5-90 min) for the USPIO-DW-MRI method was significantly shorter (p<0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO-DW-MRI. In two patients, one micrometastasis each (1.0x0.2 mm; 0.7x0.4 mm) was missed in all imaging studies. USPIO-DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.

  4. Prostatic aspergillosis.

    PubMed

    Abbas, F; Kamal, M K; Talati, J

    1995-03-01

    Prostatic aspergillosis is rare with only 3 cases reported previously. We report a case of localized invasive aspergillosis of the prostate in a nonimmunocompromised patient with chronic urinary retention and recurrent urinary tract infections. Transurethral resection followed by open prostatectomy was performed for massive prostatomegaly. No systemic antifungal therapy was required for cure. The literature is reviewed, and diagnostic and management options are discussed.

  5. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    SciTech Connect

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  6. Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

    SciTech Connect

    Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2011-06-01

    Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

  7. Optical coherence tomography of the prostate nerves

    NASA Astrophysics Data System (ADS)

    Chitchian, Shahab

    Preservation of the cavernous nerves during prostate cancer surgery is critical in preserving a man's ability to have spontaneous erections following surgery. These microscopic nerves course along the surface of the prostate within a few millimeters of the prostate capsule, and they vary in size and location from one patient to another, making preservation of the nerves difficult during dissection and removal of a cancerous prostate gland. These observations may explain in part the wide variability in reported sexual potency rates (9--86%) following prostate cancer surgery. Any technology capable of providing improved identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery would be of great assistance in improving sexual function after surgery, and result in direct patient benefit. Optical coherence tomography (OCT) is a noninvasive optical imaging technique capable of performing high-resolution cross-sectional in vivo and in situ imaging of microstructures in biological tissues. OCT imaging of the cavernous nerves in the rat and human prostate has recently been demonstrated. However, improvements in the OCT system and the quality of the images for identification of the cavernous nerves is necessary before clinical use. The following chapters describe complementary approaches to improving identification and imaging of the cavernous nerves during OCT of the prostate gland. After the introduction to OCT imaging of the prostate gland, the optimal wavelength for deep imaging of the prostate is studied in Chapter 2. An oblique-incidence single point measurement technique using a normal-detector scanning system was implemented to determine the absorption and reduced scattering coefficients, mua and m's , of fresh canine prostate tissue, ex vivo, from the diffuse reflectance profile of near-IR light as a function of source-detector distance. The effective attenuation coefficient, mueff, and the Optical Penetration Depth (OPD) were

  8. Morphology, structural properties and reducibility of size-selected CeO2− x nanoparticle films

    PubMed Central

    D’Addato, Sergio; Gasperi, Gabriele; Benedetti, Francesco; Luches, Paola; Grillo, Vincenzo; Bertoni, Giovanni; Valeri, Sergio

    2015-01-01

    Summary Non-stoichiometric ceria nanoparticles (NPs) were obtained by a gas aggregation source with a magnetron and were mass-selected with a quadrupole mass filter. By varying magnetron power, Ar gas flow, and the length of the aggregation tube, NPs with an average diameter of 6, 9, and 14 nm were synthesized and deposited onto a substrate, thus obtaining NP films. The morphology of the films was studied with scanning electron microscopy, while high resolution transmission electron microscopy was used to gain a deeper insight into the atomic structure of individual NPs. By using X-ray photoelectron spectroscopy we analyzed the degree of reduction of the NPs of different diameters, before and after thermal treatments in vacuum (reduction cycle) and in O2 atmosphere (oxidation cycle) at different temperatures. From this analysis we inferred that the size is an important parameter only at intermediate temperatures. As a comparison, we evaluated the reducibility of an ultra-thin ceria film with the same surface to volume ratio as the 9 nm diameter NPs film, observing that NPs are more reducible than the ceria film. PMID:25671152

  9. A prospective, randomized, controlled trial assessing diazepam to reduce perception and recall of pain during transrectal ultrasonography-guided biopsy of the prostate.

    PubMed

    Li, Roger; Ruckle, Herbert C; Creech, Jon D; Culpepper, David J; Lightfoot, Michelle A; Alsyouf, Muhannad; Nicolay, Lesli; Jellison, Forrest; Baldwin, D Duane

    2014-07-01

    The effect of oral anxiolytics in diminishing patient discomfort and pain perception has been demonstrated in GI endoscopy, percutaneous coronary interventions, and various procedures in the emergency department setting, but has not been prospectively studied in the setting of prostate biopsy. The purpose of this study was to investigate the effect of diazepam on pain perception during and after prostate biopsy. Sixty patients undergoing prostate biopsy at a single academic institution were enrolled into a prospective, randomized, placebo-controlled study. A questionnaire was administered prebiopsy to determine baseline discomfort and pain history. A visual analog pain scale was used to determine pain associated with each step of the transrectal Ultrasonography-guided prostate biopsy and was administered 20 minutes after biopsy and 1 week later. Responses were compared between groups using the Mann-Whitney U test, Fisher exact test, and Wilcoxon signed rank test as appropriate. A total of 60 patients (29 diazepam, 31 placebo) completed pre- and postbiopsy surveys for analysis. The number of cores sampled during biopsy was controlled during analysis and was found to have no correlation with total pain measured. There were no differences between diazepam and placebo groups in age, prebiopsy survey results, immediate and 1 week postbiopsy survey results. There was no difference in the patients' willingness to undergo a repeated procedure in the control and treatment groups. Complications of taking diazepam prebiopsy included drowsiness, chills, and ankle injury. Diazepam does not improve patient pain perception immediately after or at 1-week recall after prostate biopsy. Omitting diazepam simplifies the biopsy regimen and allows the patient to drive himself home. Based on these results, routine use of diazepam in prostate biopsy is not recommended.

  10. Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

    PubMed Central

    Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

    2015-01-01

    Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

  11. Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

    PubMed

    Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y

    2015-08-01

    Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

  12. Effect of endorectal balloon positioning errors on target deformation and dosimetric quality during prostate SBRT.

    PubMed

    Jones, Bernard L; Gan, Gregory; Kavanagh, Brian; Miften, Moyed

    2013-11-21

    An inflatable endorectal balloon (ERB) is often used during stereotactic body radiation therapy (SBRT) for treatment of prostate cancer in order to reduce both intrafraction motion of the target and risk of rectal toxicity. However, the ERB can exert significant force on the prostate, and this work assessed the impact of ERB position errors on deformation of the prostate and treatment dose metrics. Seventy-one cone-beam computed tomography (CBCT) image datasets of nine patients with clinical stage T1cN0M0 prostate cancer were studied. An ERB (Flexi-Cuff, EZ-EM, Westbury, NY) inflated with 60 cm(3) of air was used during simulation and treatment, and daily kilovoltage (kV) CBCT imaging was performed to localize the prostate. The shape of the ERB in each CBCT was analyzed to determine errors in position, size, and shape. A deformable registration algorithm was used to track the dose received by (and deformation of) the prostate, and dosimetric values such as D95, PTV coverage, and Dice coefficient for the prostate were calculated. The average balloon position error was 0.5 cm in the inferior direction, with errors ranging from 2 cm inferiorly to 1 cm superiorly. The prostate was deformed primarily in the AP direction, and tilted primarily in the anterior-posterior/superior-inferior plane. A significant correlation was seen between errors in depth of ERB insertion (DOI) and mean voxel-wise deformation, prostate tilt, Dice coefficient, and planning-to-treatment prostate inter-surface distance (p < 0.001). Dosimetrically, DOI is negatively correlated with prostate D95 and PTV coverage (p < 0.001). For the model of ERB studied, error in ERB position can cause deformations in the prostate that negatively affect treatment, and this additional aspect of setup error should be considered when ERBs are used for prostate SBRT. Before treatment, the ERB position should be verified, and the ERB should be adjusted if the error is observed to exceed tolerable values.

  13. Testosterone stimulates growth and secretory activity of the female prostate in the adult gerbil (Meriones unguiculatus).

    PubMed

    Santos, Fernanda C A; Leite, Rodrigo P; Custódio, Ana M G; Carvalho, Karina P; Monteiro-Leal, Luiz H; Santos, Adriana B; Góes, Rejane M; Carvalho, Hernandes F; Taboga, Sebastião R

    2006-09-01

    The prostate of the female gerbil (Meriones unguiculatus) is similar to the human female prostate (Skene gland) and, despite its reduced size, it is functional and shows secretory activity. However, virtually nothing is known about its physiological regulation. This study was thus undertaken to evaluate the behavior of the gerbil female prostate in a hyperandrogenic condition. Adult females received subcutaneous injections of testosterone cypionate (1 mg/kg body weight every 48 h) up to 21 days. Circulating levels of testosterone and estradiol were monitored, and the prostate and ovaries subjected to structural and immunocytochemical analyses. The treatment resulted in sustained high levels of circulating testosterone, and caused a transient increase in estradiol. There was an increase in epithelial cell proliferation accompanied by significant reorganization of the epithelium and an apparent reduction in secretory activity, followed by a progressive increase in luminal volume density and accumulation of secretory products. Immunocytochemistry identified the expression of androgen receptor and a prostate-specific antigen (PSA)-related antigen in prostatic epithelial cells. A circulating PSA-related antigen was also found, and its concentration showed strong negative correlation with circulating estrogen. Epithelial dysplasia was detected in the prostate of treated females. Analysis of the ovaries showed the occurrence of a polycystic condition and stromal cell hyperplasia. The results indicate that testosterone has a stimulatory effect on the female prostate, inducing epithelial cell proliferation, differentiation, secretory activity, and dysplasia. The results also suggest that prostatic growth and activity, polycystic ovaries, and ovarian stromal cell hyperplasia are related to a hyperandrogenic condition in females.

  14. Prostate cancer screening

    MedlinePlus

    Prostate cancer screening - PSA; Prostate cancer screening - digital rectal exam; Prostate cancer screening - DRE ... level of PSA could mean you have prostate cancer. But other conditions can also cause a high ...

  15. A natural antipredation experiment: predator control and reduced sea ice increases colony size in a long-lived duck

    PubMed Central

    Hanssen, Sveinn A; Moe, Børge; Bårdsen, Bård-Jørgen; Hanssen, Frank; Gabrielsen, Geir W

    2013-01-01

    Anthropogenic impact on the environment and wildlife are multifaceted and far-reaching. On a smaller scale, controlling for predators has been increasing the yield from local natural prey resources. Globally, human-induced global warming is expected to impose severe negative effects on ecosystems, an effect that is expected to be even more pronounced in the scarcely populated northern latitudes. The clearest indication of a changing Arctic climate is an increase in both air and ocean temperatures leading to reduced sea ice distribution. Population viability is for long-lived species dependent on adult survival and recruitment. Predation is the main mortality cause in many bird populations, and egg predation is considered the main cause of reproductive failure in many birds. To assess the effect of predation and climate, we compared population time series from a natural experiment where a trapper/down collector has been licensed to actively protect breeding common eiders Somateria mollissima (a large seaduck) by shooting/chasing egg predators, with time series from another eider colony located within a nature reserve with no manipulation of egg predators. We found that actively limiting predator activity led to an increase in the population growth rate and carrying capacity with a factor of 3–4 compared to that found in the control population. We also found that population numbers were higher in years with reduced concentration of spring sea ice. We conclude that there was a large positive impact of human limitation of egg predators, and that this lead to higher population growth rate and a large increase in size of the breeding colony. We also report a positive effect of warming climate in the high arctic as reduced sea-ice concentrations was associated with higher numbers of breeding birds. PMID:24223290

  16. A natural antipredation experiment: predator control and reduced sea ice increases colony size in a long-lived duck.

    PubMed

    Hanssen, Sveinn A; Moe, Børge; Bårdsen, Bård-Jørgen; Hanssen, Frank; Gabrielsen, Geir W

    2013-09-01

    Anthropogenic impact on the environment and wildlife are multifaceted and far-reaching. On a smaller scale, controlling for predators has been increasing the yield from local natural prey resources. Globally, human-induced global warming is expected to impose severe negative effects on ecosystems, an effect that is expected to be even more pronounced in the scarcely populated northern latitudes. The clearest indication of a changing Arctic climate is an increase in both air and ocean temperatures leading to reduced sea ice distribution. Population viability is for long-lived species dependent on adult survival and recruitment. Predation is the main mortality cause in many bird populations, and egg predation is considered the main cause of reproductive failure in many birds. To assess the effect of predation and climate, we compared population time series from a natural experiment where a trapper/down collector has been licensed to actively protect breeding common eiders Somateria mollissima (a large seaduck) by shooting/chasing egg predators, with time series from another eider colony located within a nature reserve with no manipulation of egg predators. We found that actively limiting predator activity led to an increase in the population growth rate and carrying capacity with a factor of 3-4 compared to that found in the control population. We also found that population numbers were higher in years with reduced concentration of spring sea ice. We conclude that there was a large positive impact of human limitation of egg predators, and that this lead to higher population growth rate and a large increase in size of the breeding colony. We also report a positive effect of warming climate in the high arctic as reduced sea-ice concentrations was associated with higher numbers of breeding birds.

  17. A giant prostatic hyperplasia treated by open surgery