Combined treatment with oral finasteride and topical minoxidil in male androgenetic alopecia: a randomized and comparative study in Chinese patients.

PubMed

Hu, Ruiming; Xu, Feng; Sheng, Youyu; Qi, Sisi; Han, Yumei; Miao, Ying; Rui, Wenlong; Yang, Qinping

2015-01-01

Finasteride at 1 mg/day and 5% topical minoxidil are effective in male androgenetic alopecia (MAGA). However, studies describing their effects in Chinese individuals are scarce. 450 Chinese MAGA patients were randomly assigned to receive finasteride (n = 160), minoxidil (n = 130) and combined medication (n = 160) for 12 months. The patients returned to the clinic every 3 months for efficacy evaluation. And efficacy was evaluated in 428 men at treatment end, including 154, 122, and 152 in the finasteride, 5% minoxidil, and combination groups, respectively. All groups showed similar baseline characteristics, including age at enrollment, and duration and severity of alopecia (p > 0.05). At 12 months, 80.5, 59, and 94.1% men treated with finasteride, 5% minoxidil and the combination therapy showed improvement, respectively. Adverse reactions were rare (finasteride, 1.8%; minoxidil, 6.1%), and disappeared right after drug withdrawal. In conclusion, finasteride is superior to 5% minoxidil, while the combined medication showed the best efficacy. © 2015 Wiley Periodicals, Inc.

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

DTIC Science & Technology

2006-02-01

1-0113 TITLE: Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models...To) 14 JAN 2002 - 13 JAN 2006 4. TITLE AND SUBTITLE Enhancement of Intermittent Androgen Ablation Therapy by Finasteride 5a. CONTRACT NUMBER... finasteride , an inhibitor of T to DHT conversion. We have tested our hypothesis using LNCaP xenograft tumors in nude mice. Our experiments showed

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

DTIC Science & Technology

2003-02-01

that intermittent androgen ablation therapy can be enhanced by finasteride , an inhibitor of T to DHT conversion, To test our hypothesis in animal...models, it is necessary to deliver exogenous T at physiologic levels and finasteride over a long period of time, We have worked out conditions to deliver T and finasteride in nude mice, which will allow us to test our hypothesis.

Finasteride topical delivery systems for androgenetic alopecia.

PubMed

Khan, Muhammad Zia Ullah; Khan, Shujaat Ali; Ubaid, Muhammad; Shah, Aamna; Kousar, Rozina; Murtaza, Ghulam

2018-01-23

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes, ointments, pastes, creams, gel and lotions are still to be worthy regarding finasteride topical delivery in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The antiandrogenic effect of finasteride against a mutant androgen receptor

PubMed Central

Chhipa, Rishi Raj; Zhang, Haitao; Ip, Clement

2011-01-01

Finasteride is known to inhibit Type 2 5α-reductase and thus block the conversion of testosterone to dihydrotestosterone (DHT). The structural similarity of finasteride to DHT raises the possibility that finasteride may also interfere with the function of the androgen receptor (AR). Experiments were carried out to evaluate the antiandrogenic effect of finasteride in LNCaP, C4-2 and VCaP human prostate cancer cells. Finasteride decreased DHT binding to AR, and DHT-stimulated AR activity and cell growth in LNCaP and C4-2 cells, but not in VCaP cells. LNCaP and C4-2 (derived from castration-resistant LNCaP) cells express the T877A mutant AR, while VCaP cells express the wild-type AR. When PC-3 cells, which are AR-null, were transfected with either the wild-type or the T877A mutant AR, only the mutant AR-expressing cells were sensitive to finasteride inhibition of DHT binding. Peroxiredoxin-1 (Prx1) is a novel endogenous facilitator of AR binding to DHT. In Prx1-rich LNCaP cells, the combination of Prx1 knockdown and finasteride was found to produce a greater inhibitory effect on AR activity and cell growth than either treatment alone. The observation suggests that cells with a low expression of Prx1 are likely to be more responsive to the antiandrogenic effect of finasteride. Additional studies showed that the efficacy of finasteride was comparable to that of bicalutamide (a widely used non-steroidal antiandrogen). The implication of the above findings is discussed in the context of developing strategies to improve the outcome of androgen deprivation therapy. PMID:21386657

In Vitro Analysis of Finasteride Activity against Candida albicans Urinary Biofilm Formation and Filamentation

PubMed Central

Chavez-Dozal, Alba A.; Lown, Livia; Jahng, Maximillian; Walraven, Carla J.

2014-01-01

Candida albicans is the 3rd most common cause of catheter-associated urinary tract infections, with a strong propensity to form drug-resistant catheter-related biofilms. Due to the limited efficacy of available antifungals against biofilms, drug repurposing has been investigated in order to identify novel agents with activities against fungal biofilms. Finasteride is a 5-α-reductase inhibitor commonly used for the treatment of benign prostatic hyperplasia, with activity against human type II and III isoenzymes. We analyzed the Candida Genome Database and identified a C. albicans homolog of type III 5-α-reductase, Dfg10p, which shares 27% sequence identity and 41% similarity to the human type III 5-α-reductase. Thus, we investigated finasteride for activity against C. albicans urinary biofilms, alone and in combination with amphotericin B or fluconazole. Finasteride alone was highly effective in the prevention of C. albicans biofilm formation at doses of ≥16 mg/liter and the treatment of preformed biofilms at doses of ≥128 mg/liter. In biofilm checkerboard analyses, finasteride exhibited synergistic activity in the prevention of biofilm formation in a combination of 4 mg/liter finasteride with 2 mg/liter fluconazole. Finasteride inhibited filamentation, thus suggesting a potential mechanism of action. These results indicate that finasteride alone is highly active in the prevention of C. albicans urinary biofilms in vitro and has synergistic activity in combination with fluconazole. Further investigation of the clinical utility of finasteride in the prevention of urinary candidiasis is warranted. PMID:25049253

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

DTIC Science & Technology

2006-10-01

dihydrotestosterone in the prostate by the enzyme 5α-reductase. The Prostate Cancer Prevention Trial (PCPT) demonstrated that treatment with finasteride , an...demand. Finasteride , despite being an older drug, has several advantages over dutasteride. First, its efficacy has been proven by a phase III trial... finasteride treatment. No such information is available with dutasteride. Third, finasteride is available commercially from Steraloids (Newport, RI

Finasteride for Chronic Central Serous Chorioretinopathy

PubMed Central

Forooghian, Farzin; Meleth, Annal D.; Cukras, Catherine; Chew, Emily Y.; Wong, Wai T.; Meyerle, Catherine B.

2010-01-01

Purpose To evaluate the safety and efficacy of finasteride, an inhibitor of dihyroxytestosterone (DHT) synthesis, in the treatment of chronic central serous chorioretinopathy (CSC). Methods Five patients with chronic CSC were prospectively enrolled in this pilot study. Patients were administered finasteride (5mg) daily for 3 months, following which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity (BCVA), center-subfield macular thickness and subretinal fluid volume as assessed by optical coherence tomography (OCT). Serum DHT, serum testosterone, and urinary cortisol were also measured. Results There was no change in mean BCVA. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months, and rose to levels that were below baseline by 6 months. The changes in both OCT parameters paralleled changes in serum DHT level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased following discontinuation of finasteride. In the remaining patient, both OCT parameters normalized with finasteride and remained stable when the study medication was discontinued. Conclusion Finasteride may represent a novel medical treatment for chronic CSC. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of CSC. Summary Pilot study to evaluate finasteride for treatment of chronic central serous chorioretinopathy suggests efficacy and tolerability. PMID:21273946

Finasteride treatment of patterned hair loss in normoandrogenic postmenopausal women.

PubMed

Trüeb, Ralph M

2004-01-01

Finasteride, an inhibitor of type 2 5alpha-reductase, inhibits conversion of testosterone to dihydrotestosterone, resulting in a decrease in serum and scalp dihydrotestosterone levels believed to be pathogenic in androgenetic alopecia. Oral finasteride has been shown to be effective in the treatment of hair loss in men, while its efficacy in women has remained controversial. 5 postmenopausal women without clinical or laboratory signs of hyperandrogenism were given 2.5 or 5 mg/day oral finasteride for the treatment of pattern hair loss. Efficacy was evaluated by patient and investigator assessments, and review of photographs taken at baseline and at months 6, 12 and 18 by an expert panel. Finasteride treatment improved scalp hair by all evaluation techniques. The patients' self-assessment demonstrated that finasteride treatment decreased hair loss, increased hair growth and improved appearance of hair. These improvements were confirmed by investigator assessment and assessments of photographs. No adverse effects were noted. Oral finasteride in a dosage of 2.5 mg/day or more may be effective for the treatment of pattern hair loss in postmenopausal women in the absence of clinical or laboratory signs of hyperandrogenism.

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

DTIC Science & Technology

2010-04-01

reductase. The Prostate Cancer Prevention Trial (PCPT) demonstrated that treatment with finasteride , an inhibitor of 5α-reductase, reduced prostate...Statement of Work (SOW). B. BODY Task 1. Determine the optimal dose of finasteride to achieve growth inhibition of tumor xenografts in nude mice... finasteride and we found in the literature doses of finasteride effective in inhibiting the growth of LNCaP xenografts in nude mice inhibiting LNCaP

A PHARMACOKINETIC-PHARMACODYNAMIC MODEL FOR GENE-REGULATED PROSTATE MAINTENANCE: COMPARING THE EFFECTS OF CASTRATION WITH ANTIANDROGEN EXPOSURE IN THE RAT

EPA Science Inventory

Antiandrogens affect prostate maintenance in two ways. Androgen antagonists, such as the fungicide vinclozolin, act as competitive ligands for the androgen receptor (AR). Enzyme inhibitors, such as the therapeutic drug Finasteride, inhibit the enzyme 5 -reductase (5 R) from metab...

Finasteride induced depression: a prospective study

PubMed Central

Rahimi-Ardabili, Babak; Pourandarjani, Ramin; Habibollahi, Peiman; Mualeki, Amir

2006-01-01

Background Finasteride is a competitive inhibitor of 5 alpha-reductase enzyme, and is used for treatment of benign prostatic hyperplasia and androgenetic alopecia. Animal studies have shown that finasteride might induce behavioral changes. Additionally, some cases of finasteride-induced depression have been reported in humans. The purpose of this study was to examine whether depressive symptoms or anxiety might be induced by finasteride administration. Methods One hundred and twenty eight men with androgenetic alopecia, who were prescribed finasteride (1 mg/day) were enrolled in this study. Information on depressed mood and anxiety was obtained by Beck Depression Inventory (BDI), and Hospital Anxiety and Depression Scale (HADS). Participants completed BDI and HADS questionnaires before beginning the treatment and also two months after it. Results Mean age of the subjects was 25.8(± 4.4) years. At baseline, mean BDI and HADS depression scores were 12.11(± 7.50) and 4.04(± 2.51), respectively. Finasteride treatment increased both BDI (p < 0.001) and HADS depression scores significantly (p = 0.005). HADS anxiety scores were increased, but the difference was not significant (p = 0.061). Conclusion This preliminary study suggests that finasteride might induce depressive symptoms; therefore this medication should be prescribed cautiously for patients with high risk of depression. It seems that further studies would be necessary to determine behavioral effects of this medication in higher doses and in more susceptible patients. PMID:17026771

Structural characterization of polymorphs and molecular complexes of finasteride

NASA Astrophysics Data System (ADS)

Wawrzycka, Irena; Stȩpniak, Krystyna; Matyjaszczyk, Sławomir; Kozioł, Anna E.; Lis, Tadeusz; Abboud, Khalil A.

1999-01-01

The molecular structure of finasteride, 17 β-( N-tert-butylcarbamoyl)-4-aza-5 α-androst-1-en-3-one, and structures of three related crystalline forms have been determined by X-ray analysis. The rigid steroid skeleton of the molecule adopts a half-chair/chair/chair/half-chair conformation. Two peptide groups, one cyclic (lactam) in the ring A and a second being a part of the substituent at C17, are the main factors influencing intermolecular contacts. Different hydrogen-bond interactions of these hydrophilic groups are observed in the crystal structures. An infinite ribbon of finasteride molecules is formed between lactam groups in the orthorhombic homomolecular crystal ( 1) obtained from an ethanol solution. The linear molecular complex finasteride-acetic acid ( 1a) is connected by hydrogen bonds between the lactam of finasteride and the carboxyl group of acetic acid. The crystallization from an ethyl acetate solution gives a complex structure of bis-finasteride monohydrate ethyl acetate clathrate ( 1b) with guest molecule disordered in channels. Crystals of a second (monoclinic) finasteride polymorph ( 2) were obtained during thermal decomposition of 1a, and sublimation of 1, 1a and 1b. Two polymorphic forms show different IR spectra.

Anti-proliferative activities of finasteride in benign prostate epithelial cells require stromal fibroblasts and c-Jun gene.

PubMed

Wang, Kai; Jin, Song; Fan, Dongdong; Wang, Mingshuai; Xing, Nianzeng; Niu, Yinong

2017-01-01

This study aimed to identify the role of mouse fibroblast-mediated c-Jun and IGF-1 signaling in the therapeutic effect of finasteride on benign prostatic epithelial cells. BPH-1 cells, alone or with fibroblasts (c-Jun+/+ or c-Jun-/-), were implanted subcutaneously in male nude mice who were then treated with finasteride. The degrees of cell proliferation, apoptosis, and sizes of the xenografts were determined. BPH-1 cells were grown alone or co-cultured with mouse fibroblasts in the presence of finasteride and the level of IGF-1 secreted into the medium by the fibroblasts was determined. The proliferation-associated signaling pathway in BPH-1 cells was also evaluated. Fibroblasts and c-Jun promoted xenograft growth, stimulated Ki-67 expression, and inhibited BPH-1 apoptosis. Finasteride did not induce the shrinkage of xenografts in the combined-grafted groups despite repressing Ki-67 expression and inducing cell apoptosis. The addition of c-Jun-/- fibroblasts did not promote xenograft growth. In the absence of c-Jun and fibroblasts, finasteride did not alter xenograft growth, Ki-67 expression, or cell apoptosis. The in vitro results demonstrated that when BPH-1 cells were grown in monoculture, treatment with finasteride did not induce cell death and stimulated the expression of pro-proliferative signaling molecules, while in the presence of fibroblasts containing c-Jun, finasteride treatment repressed epithelial cell proliferation, the level of IGF-1 in the medium, and the activation of downstream pro-proliferative signaling pathways. Taken together, our results suggest that fibroblasts, c-Jun, and IGF-1 play key roles in mediating stromal-epithelial interactions that are required for the therapeutic effects of finasteride in benign prostate epithelial cells.

Anti-proliferative activities of finasteride in benign prostate epithelial cells require stromal fibroblasts and c-Jun gene

PubMed Central

Fan, Dongdong; Wang, Mingshuai; Xing, Nianzeng; Niu, Yinong

2017-01-01

This study aimed to identify the role of mouse fibroblast-mediated c-Jun and IGF-1 signaling in the therapeutic effect of finasteride on benign prostatic epithelial cells. BPH-1 cells, alone or with fibroblasts (c-Jun+/+ or c-Jun-/-), were implanted subcutaneously in male nude mice who were then treated with finasteride. The degrees of cell proliferation, apoptosis, and sizes of the xenografts were determined. BPH-1 cells were grown alone or co-cultured with mouse fibroblasts in the presence of finasteride and the level of IGF-1 secreted into the medium by the fibroblasts was determined. The proliferation-associated signaling pathway in BPH-1 cells was also evaluated. Fibroblasts and c-Jun promoted xenograft growth, stimulated Ki-67 expression, and inhibited BPH-1 apoptosis. Finasteride did not induce the shrinkage of xenografts in the combined-grafted groups despite repressing Ki-67 expression and inducing cell apoptosis. The addition of c-Jun-/- fibroblasts did not promote xenograft growth. In the absence of c-Jun and fibroblasts, finasteride did not alter xenograft growth, Ki-67 expression, or cell apoptosis. The in vitro results demonstrated that when BPH-1 cells were grown in monoculture, treatment with finasteride did not induce cell death and stimulated the expression of pro-proliferative signaling molecules, while in the presence of fibroblasts containing c-Jun, finasteride treatment repressed epithelial cell proliferation, the level of IGF-1 in the medium, and the activation of downstream pro-proliferative signaling pathways. Taken together, our results suggest that fibroblasts, c-Jun, and IGF-1 play key roles in mediating stromal-epithelial interactions that are required for the therapeutic effects of finasteride in benign prostate epithelial cells. PMID:28196103

Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy

PubMed Central

CARVER, BRETT S.; KATTAN, MICHAEL W.; SCARDINO, PETER T.; EASTHAM, JAMES A.

2007-01-01

OBJECTIVE To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence. PATIENTS AND METHODS Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for ≥6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate-specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5-year freedom from recurrence using the Kaplan-Meier method. RESULTS The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5-year actuarial freedom from recurrence was 86%. CONCLUSION Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5-year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer. PMID:15705069

Finasteride Does Not Increase the Risk of High-grade Prostate Cancer: A Bias-adjusted Modeling Approach

PubMed Central

Redman, Mary W.; Tangen, Catherine M.; Goodman, Phyllis J.; Parnes, Howard; Ford, Leslie G.; Lucia, M. Scott; Coltman, Charles A.; Thompson, Ian M.

2010-01-01

The Prostate Cancer Prevention Trial found that seven years of administration of finasteride reduced the risk of prostate cancer by 25% but with an apparent increased risk of high grade disease. Subsequent analyses found that finasteride affects cancer detection and improves accuracy of tumor grading at biopsy. We herein estimate the impact of finasteride on the risk of overall and high grade prostate cancer, accounting for these biases. Study endpoints (biopsy-proven cancer or a 7-year end-of-study biopsy) were available in 10,182 of 15,990 subjects assessable for 7-year status and grading information from 500 subjects diagnosed with cancer who underwent radical prostatectomy. Prostate cancer was observed in 22.9% (4.8% with high grade) in the placebo group versus 16.6% (5.8% with high grade) in the finasteride group. In this bias-adjusted analysis, the estimated rates are 21.1% (4.2%) and 14.7% (4.8%), respectively, a 30% risk reduction in prostate cancer (RR =0.70 (95% confidence interval (CI) =0.64-0.76, p<0.0001) and a non-significant 14% increase in high grade cancer (RR=1.14 (95% CI = (0.96-1.35), p=0.12) with finasteride. Incorporating the prostatectomy data, estimated rates of high grade cancers are 8.2% (placebo) versus 6.0% (finasteride), a 27% risk reduction (RR = 0.73 (95% CI=0.56-0.96, p=0.02)) with finasteride. While the observed risk of high grade disease is greater with finasteride, this appears to be through facilitated diagnosis, primarily due to increased biopsy sensitivity. Men undergoing regular prostate cancer screening or who express an interest in cancer prevention should be informed of this prevention opportunity. PMID:19138953

Patterns of finasteride use in the male populations of four Nordic countries: A cross-national drug utilization study.

PubMed

Kjærulff, T M; Ersbøll, A K; Green, A; Emneus, M; Pukkala, E; Bolin, K; Stavem, K; Iversen, P; Brasso, K; Hallas, J; Thygesen, L C

2016-06-01

Objective Finasteride 5 mg is a drug used to treat prostate hyperplasia. Little is known about its pattern of usage. This cross-national analysis of individual-level data from Denmark, Finland, Norway and Sweden was undertaken to appraise its usage and describe cross-national differences. Materials and methods Individual-level data from nationwide prescription registers in Denmark (1995-2009), Finland (1997-2010), Norway (2004-2009) and Sweden (July 2005-2011) were used to examine cross-national finasteride utilization patterns in the adult male population (≥15 years). The study presents period prevalences, incidence rates, waiting time distributions and Lorenz curves. Results During the study period, 295,620 men had at least one prescription redemption of finasteride 5 mg, and there were approximately 3 million dispensing events of finasteride prescriptions in the four Nordic countries. Different patterns of finasteride use were observed among the four Nordic countries. The period prevalence was markedly higher in Finland and Sweden than in Denmark and Norway. In 2009, period prevalences were 18.2/1000 males in Finland and 12.0/1000 males in Sweden compared to 6.7/1000 males in Norway and 4.9/1000 males in Denmark. Incidence rates of finasteride use for Finland, Norway and Sweden were about three times that for Denmark in 2008-2009. Long-term use of finasteride was found in all four Nordic countries with a high ratio between prevalent and incident users. Conclusion Despite resemblances regarding political systems and healthcare services in the Nordic countries, differences in finasteride utilization were found across Denmark, Finland, Norway and Sweden.

Prolongation of Off-Cycle Interval by Finasteride Is Not Associated with Survival Improvement in Intermittent Androgen Deprivation Therapy in LNCaP Tumor Model

PubMed Central

Wang, Yujuan; Gupta, Shubham; Hua, Vi; Ramos-Garcia, Raquel; Shevrin, Daniel; Jovanovic, Borko D.; Nelson, Joel B

2009-01-01

BACKGROUND We have previously reported that finasteride administration in intermittent androgen deprivation therapy (IADT) can improve survival of nude mice bearing LNCaP xenograft tumors when the duration of off-cycle in IADT was fixed. A recent retrospective study showed that addition of finasteride doubled the duration of the off-cycle, without changing progression to castration resistance. In view of the above difference, we attempted to investigate the relationship of 5α-reductase inhibition with the off-cycle interval and overall survival in a murine model. METHODS Subcutaneous LNCaP tumors were established in nude mice (Balb/C-Nu). After the tumors reached a size of 0.5 cm in diameter, the mice were castrated and followed up for 2 weeks after which they were randomized to continuous androgen deprivation (CAD), CAD plus finasteride, IADT, and IADT plus finasteride. The off-cycle was discontinued when the tumor volume was doubled. Subsequent cycles were carried out similarly. RESULTS Use of finasteride during the off-cycle of IADT doubled the first off-cycle duration. However, prolongation of the off-cycle by finasteride did not translate into an increase in overall survival. CONCLUSIONS The survival advantage of IADT+F over IADT that we previously reported was lost when the off-cycle prolongation by finasteride was allowed. Maximum possible lengthening of the off-cycle by 5α-reductase inhibition is not associated with survival improvement in this animal model. PMID:19739129

Finasteride for chronic central serous chorioretinopathy.

PubMed

Forooghian, Farzin; Meleth, Annal D; Cukras, Catherine; Chew, Emily Y; Wong, Wai T; Meyerle, Catherine B

2011-04-01

To evaluate the safety and efficacy of finasteride, an inhibitor of dihydrotestosterone synthesis, in the treatment of chronic central serous chorioretinopathy. Five patients with chronic central serous chorioretinopathy were prospectively enrolled in this pilot study. Patients were administered finasteride (5 mg) daily for 3 months, after which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity, central subfield macular thickness, and subretinal fluid volume as assessed by optical coherence tomography. Serum dihydrotestosterone, serum testosterone, and urinary cortisol were also measured. There was no change in mean best-corrected visual acuity. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months and rose to levels that were below baseline by 6 months. The changes in both optical coherence tomography parameters paralleled those in serum dihydrotestosterone level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased after discontinuation of finasteride. In the remaining patient, both optical coherence tomography parameters normalized with finasteride and remained stable when the study medication was discontinued. Finasteride may represent a novel medical treatment for chronic central serous chorioretinopathy. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of central serous chorioretinopathy.

Drug Treatment for Androgenetic Alopecia: First Italian Questionnaire Survey on What Dermatologists Think about Finasteride.

PubMed

Sorbellini, Elisabetta; Pinto, Daniela; Marzani, Barbara; Rinaldi, Fabio

2018-06-01

Treatment with finasteride 1 mg/day represents the therapy of choice for androgenetic alopecia (AGA). We investigated how Italian dermatologists approach use of finasteride for treatment of AGA and common side effects reported by patients. A tablet-based survey was conducted from February 2017 to January 2018 in Italy to investigating use of 1 mg/day finasteride in the treatment of AGA. Approximately 1153 Italian dermatologists were surveyed about prescription frequency, therapy duration, treatment practices, and side effects eventually reported. Dermatologists considered treatment with 1 mg/day finasteride to be the most efficacious treatment for AGA, as reflecting by its long-term (5 years) prescription. Data on sexual side effects from our survey are in line with previous scientific evidence, especially regarding loss of libido, erectile dysfunction, and problems with ejaculation, but also in the psychological sphere and regarding physical impairments such as myalgia and loss of muscle tone. This is the first preliminary observational study on how Italian dermatologists approach use of finasteride to treat AGA. Although side effects have been reported, especially in the sexual sphere, lack of alternative treatments with the same efficacy leads dermatologists to prescribe 1 mg/day finasteride with a tendency to prolong therapy in the long term. Giuliani S.p.A.

Finasteride inhibited brain dopaminergic system and open-field behaviors in adolescent male rats.

PubMed

Li, Li; Kang, Yun-Xiao; Ji, Xiao-Ming; Li, Ying-Kun; Li, Shuang-Cheng; Zhang, Xiang-Jian; Cui, Hui-Xian; Shi, Ge-Ming

2018-02-01

Finasteride inhibits the conversion of testosterone to dihydrotestosterone. Because androgen regulates dopaminergic system in the brain, it could be hypothesized that finasteride may inhibit dopaminergic system. The present study therefore investigates the effects of finasteride in adolescent and early developmental rats on dopaminergic system, including contents of dopamine and its metabolites (dihydroxy phenyl acetic acid and homovanillic acid) and tyrosine hydroxylase expressions both at gene and protein levels. Meanwhile, open-field behaviors of the rats are examined because of the regulatory effect of dopaminergic system on the behaviors. Open-field behaviors were evaluated by exploratory and motor behaviors. Dopamine and its metabolites were assayed by liquid chromatography-mass spectrometry. Tyrosine hydroxylase mRNA and protein expressions were determined by real-time qRT-PCR and western blot, respectively. It was found that in adolescent male rats, administration of finasteride at doses of 25 and 50 mg/kg for 14 days dose dependently inhibited open-field behaviors, reduced contents of dopamine and its metabolites in frontal cortex, hippocampus, caudate putamen, nucleus accumbens, and down-regulated tyrosine hydroxylase mRNA and protein expressions in substantia nigra and ventral tegmental area. However, there was no significant change of these parameters in early developmental rats after finasteride treatment. These results suggest that finasteride inhibits dopaminergic system and open-field behaviors in adolescent male rats by inhibiting the conversion of testosterone to dihydrotestosterone, and imply finasteride as a potential therapeutic option for neuropsychiatric disorders associated with hyperactivities of dopaminergic system and androgen. © 2017 John Wiley & Sons Ltd.

Rates of prostate surgery and acute urinary retention for benign prostatic hyperplasia in men treated with dutasteride or finasteride.

PubMed

Kuiper, Josephina G; Bezemer, Irene D; Driessen, Maurice T; Vasylyev, Averyan; Roehrborn, Claus G; Penning-van Beest, Fernie J A; Herings, Ron M C

2016-08-31

Previous studies have suggested a greater benefit for various outcomes in men diagnosed with benign prostatic hyperplasia (BPH) who are treated with dutasteride than for men treated with finasteride. This study investigates whether the rates of BPH-related prostate surgery and acute urinary retention (AUR) differ between dutasteride and finasteride users in the Netherlands. From the PHARMO Database Network, men aged ≥50 years with a dispensing of dutasteride or finasteride with or without concomitant alpha-blocker treatment between March 1, 2003 and December 31, 2011 were selected. The incidence of BPH-related prostate surgery and AUR was determined during dutasteride or finasteride treatment and stratified by type of initial BPH-treatment (5-ARI monotherapy or combination with alpha-blocker) and prescriber (general practitioner (GP) or urologist). Comparison of the incidence of BPH-related prostate surgery and AUR between the treatment groups was done by Cox proportional hazard regression. 11,822 dutasteride users and 5,781 finasteride users were identified. Most users started treatment in combination with an alpha-blocker. Overall, dutasteride users had a lower risk of BPH-related prostate surgery was lower among dutasteride users than finasteride users (HR: 0.75; 95 % CI: 0.56-0.99). This lower risk among dutasteride users was also seen when stratifying by monotherapy or combination therapy (HR: 0.73; 95 % CI: 0.54-0.98 for monotherapy and HR: 0.85; 95 % CI: 0.74-0.97 for combination therapy). However, the association was only present among men treated by urologists. For AUR the rates were low and no statistical significant difference was observed between dutasteride and finasteride users. The risk of undergoing BPH-related prostate surgery was lower among men using dutasteride compared to men using finasteride. The association was observed for monotherapy as well as combination therapy, however, only among men who received their prescription from a urologist.

Long-term Treatment with Finasteride Resulted in a Significant Improvement Relative to Placebo in Clinical Progression of Benign Prostatic Hyperplasia (BPH) in Men with Enlarged Prostates (≥30 mL), But Not in Those with Smaller Prostates (<30 mL): Data from the Medical Therapy of Prostatic Symptoms (MTOPS) Trial

PubMed Central

Kaplan, Steven A.; Lee, Jeannette Y.; Meehan, Alan G.; Kusek, John W.

2013-01-01

Purpose This post hoc analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial examined the effect of finasteride alone compared to placebo on clinical progression of benign prostatic hyperplasia (BPH) in men with baseline prostate volume (PV) <30 mL and ≥30 mL. Materials and Methods Men were randomized to placebo (n=737), doxazosin alone (4 to 8 mg) (n=756), finasteride alone (5 mg) (n=768), or doxazosin plus finasteride (n=786) (average duration of follow-up was 4.5 yrs); ~50% of patients had a baseline PV ≥30 mL. The present analysis was based on the finasteride alone and placebo arms only and included patients for whom baseline and end of study data were available. We examined the effect of treatment on the cumulative percentage of men who did not experience clinical progression of BPH by study end. Results In men with baseline PV ≥30 mL, treatment with finasteride produced a significant (p<0.001) increase relative to placebo in the cumulative percentage of patients who did not experience clinical progression of BPH (finasteride, 88.1%, versus placebo, 77.8%). There was no significant (p=0.441) between-group difference in men with baseline PV <30 mL (91.4% versus 89.1%, respectively). Conclusions Long-term treatment with finasteride led to a significant beneficial effect compared to placebo on clinical progression of BPH in LUTS patients with enlarged prostates (baseline PV ≥30 mL). Finasteride had no significant effect, compared to placebo on clinical progression of BPH in LUTS patients with smaller prostates (baseline PV <30 mL). PMID:21334655

Prescribing Habits for Androgenic Alopecia Among Dermatologists in Spain in 2017: A Cross-Sectional Study.

PubMed

Pindado-Ortega, C; Saceda-Corralo, D; Buendía-Castaño, D; Fernández-González, P; Moreno-Arrones, Ó M; Fonda-Pascual, P; Alegre-Sánchez, A; Rodrigues-Barata, A R; Vañó-Galván, S

2018-04-12

Topical minoxidil and oral finasteride are the only drugs approved for the treatment of androgenetic alopecia (AGA) in Spain. However, the management of this condition is highly variable because numerous treatments are used off-label. The main aim of this study was to describe the prescribing habits of dermatologists in Spain for male AGA (MAGA) and female AGA (FAGA). Descriptive cross-sectional study using online questionnaires completed by dermatologists working in Spain. The responses of 241 dermatologists were analyzed. The most common treatments prescribed for MAGA were minoxidil (98%), oral finasteride (96%), nutricosmetics (44%), topical finasteride (37%), oral dutasteride (33%), platelet-rich plasma (14%), and low-level laser therapy (8%). For premenopausal FAGA, the most common treatments were topical minoxidil (98%), oral contraceptives (81%), nutricosmetics (72%), cyproterone acetate (58%), oral finasteride (39%), topical finasteride (39%), spironolactone (27%), platelet-rich plasma (20%), oral dutasteride (20%), oral flutamide (18%), and low-level laser therapy (7%). Finally, for postmenopausal FAGA, the most common treatments prescribed were topical minoxidil (98%), oral finasteride (84%), nutricosmetics (68%), topical finasteride (50%), oral dutasteride (35%), platelet-rich plasma (21%), spironolactone (16%), cyproterone acetate (16%), oral flutamide (9%), and low-level laser therapy (9%). A limitation of our study is that we did not analyze novel AGA treatments such as oral minoxidil and dutasteride mesotherapy. The most common treatments prescribed for AGA by dermatologists in Spain are topical minoxidil, oral finasteride, and nutricosmetics for MAGA and postmenopausal FAGA and topical minoxidil, oral contraceptives, and nutricosmetics for premenopausal FAGA. Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Long-term Consequences of Finasteride vs Placebo in the Prostate Cancer Prevention Trial

PubMed Central

Till, Cathee; Thompson, Ian M.; Tangen, Catherine M.; Goodman, Phyllis J.; Wright, Jason D.; Barlow, William E.; Ramsey, Scott D.; Minasian, Lori M.; Hershman, Dawn L.

2016-01-01

Background: Finasteride has been found to reduce the risk of low-grade prostate cancer but to have no impact on overall survival. The long-term adverse and beneficial consequences of finasteride have not been examined. Methods: We used a linkage between data from the Prostate Cancer Prevention Trial (PCPT) and Medicare claims. Patients were examined by randomized study arm (finasteride vs placebo for 7 years) for long-term consequences of the intervention, including cardiac, endocrine, and sexual dysfunction, depression, diabetes, and benign prostatic hyperplasia (BPH)–related events. To examine time to events, we used cumulative incidence and Cox regression, adjusting for covariates. All statistical tests were two-sided. Results: A total of 13 935 of 18 880 participants (73.8%) in the PCPT were linked to Medicare claims, with median Medicare follow-up assessment time of 16 years from trial registration. There were no differences between finasteride and placebo participants with respect to important baseline factors or amount of Medicare follow-up assessment time. Finasteride patients had a 10% higher risk of new claims for depression (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.01 to 1.19, P = .04) and a 6% lower risk of procedures for BPH-related events (primarily lower urinary tract symptoms; HR = 0.94, 95% CI = 0.89 to 1.00, P = .03). No other differences were found in rates of long-term consequences of intervention in the two study arms. Conclusions: Finasteride use is associated with reduced need for procedures for relief of BPH-related events and a modest increase in depression. Overall, there is little need to worry about long-term noncancer consequences of finasteride use in those who use it for treatment of symptomatic BPH, hair growth, or prevention of cancer. PMID:27565902

Reduction of Racial Disparities in Prostate Cancer

DTIC Science & Technology

2008-12-01

inhibitors, aspirin, anti-TNF medications), and other medications of interest (testosterone, finasteride , alpha receptor blockers). 12 We...0.01. There were 14 (7%) control-patients who had finasteride use, with an average of 398.6 doses per individual. None of the prostate cancer...patients had prior finasteride use. In a multiple logistic regression model (Table 2, see supporting materials), after adjustment for the matching

New Approaches for Prostate Cancer Combination Therapy

DTIC Science & Technology

2007-04-01

in DU145 cells. Strong inducers of apoptosis included Sulindac sulfide, Finasteride , Diclofenac, Flufenamic acid, Flurbiprofen, Sulindac sulfone and... Finasteride , a selective 5-alpha-reductase inhibitor, is not known to inhibit COX-2, strongly induces MDA-7/IL-24 expression and apoptosis, whereas the...ibuprofen, aspirin, acet- aminophen, and naproxen were obtained from Sigma-Aldrich (St. Louis, MO). Meloxicam, celecoxib, diclofenac, finasteride , and

Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases

PubMed Central

Li, Qingfeng

2016-01-01

Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products. PMID:27738338

A population-based study of the risk of osteoporosis and fracture with dutasteride and finasteride.

PubMed

Antoniou, Tony; Macdonald, Erin M; Yao, Zhan; Gomes, Tara; Tadrous, Mina; Ho, Joanne M-W; Mamdani, Muhammad M; Juurlink, David N

2018-05-22

Dutasteride is a potent inhibitor of 5-alpha reductase enzymes that reduces concentrations of dihydrotestosterone to a greater extent than finasteride. Whether this has adverse implications for bone health is unknown. We compared the risk of osteoporosis and fractures in older men treated with dutasteride or finasteride. We conducted a population-based retrospective cohort study with high-dimensional propensity score matching of Ontario men aged 66 years or older who started treatment with dutasteride or finasteride between January 1, 2006 and December 31, 2012. The primary outcome was a diagnosis of osteoporosis within 2 years of treatment initiation. A secondary outcome was osteoporotic or fragility fractures. We studied 31,615 men treated with dutasteride and an equal number of men treated with finasteride. Dutasteride-treated patients had a lower incidence of osteoporosis than those receiving finasteride [2.2 versus 2.6 per 100 person years; hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.72 to 0.93]. This effect was no longer statistically significant following adjustment for specialty of prescribing physician (HR 0.90; 95% CI 0.78 to 1.02)]. There was no differential risk of fractures with dutasteride (HR 1.04; 95% 0.86 to 1.25). Despite differential effects on 5-alpha reductase, dutasteride is not associated with an increased risk of osteoporosis or fractures in older men relative to finasteride. These findings suggest that dutasteride does not adversely affect bone health.

New topical antiandrogenic formulations can stimulate hair growth in human bald scalp grafted onto mice.

PubMed

Sintov, A; Serafimovich, S; Gilhar, A

2000-01-20

The purpose of this study was to test the ability of topical formulations of finasteride and flutamide to re-enlarge hair follicles in male-pattern baldness. This was evaluated by an experimental model of human scalp skin graft transplanted onto SCID mice. A comparison was made between formulations containing finasteride and flutamide, and a vehicle formulation in terms of the mean hairs per graft, length, diameter of the shafts, and structures of the growth stages of the hair. Flutamide and finasteride had a significantly higher effect (P<0.05) than the placebo in all the tested parameters, but flutamide demonstrated more hair per graft and longer hair shafts than finasteride (P<0.05). The number of hairs per graft for flutamide and finasteride groups were 1.22+/-0. 47 and 0.88+/-0.95 hairs/0.5 mm2 graft, respectively, versus 0. 35+/-0.6 hairs/graft for vehicle-treated graft. Similarly, hair lengths for flutamide and finasteride were 5.82+/-0.50 and 4.50+/-0. 32 mm, respectively, versus 2.83+/-0.18 mm for the vehicle-treated grafts. An in vitro diffusion study of flutamide gel using hairless mouse skin demonstrated the beneficial effect of the vehicle composition in comparison with a hydroalcoholic solution or a gel containing no penetration enhancer. It is therefore suggested that this topical composition containing flutamide or finasteride may effectively result in regression of male-pattern baldness.

Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors.

PubMed

Wu, Yue; Godoy, Alejandro; Azzouni, Faris; Wilton, John H; Ip, Clement; Mohler, James L

2013-09-01

Blocking 5α-reductase-mediated testosterone conversion to dihydrotestosterone (DHT) with finasteride or dutasteride is the driving hypothesis behind two prostate cancer prevention trials. Factors affecting intracellular androgen levels and the androgen receptor (AR) signaling axis need to be examined systematically in order to fully understand the outcome of interventions using these drugs. The expression of three 5α-reductase isozymes, as determined by immunohistochemistry and qRT-PCR, was studied in five human prostate cancer cell lines. Intracellular testosterone and DHT were analyzed using mass spectrometry. A luciferase reporter assay and AR-regulated genes were used to evaluate the modulation of AR activity. Prostate cancer cells were capable of accumulating testosterone to a level 15-50 times higher than that in the medium. The profile and expression of 5α-reductase isozymes did not predict the capacity to convert testosterone to DHT. Finasteride and dutasteride were able to depress testosterone uptake in addition to lowering intracellular DHT. The inhibition of AR activity following drug treatment often exceeded the expected response due to reduced availability of DHT. The ability to maintain high intracellular testosterone might compensate for the shortage of DHT. The biological effect of finasteride or dutasteride appears to be complex and may depend on the interplay of several factors, which include testosterone turnover, enzymology of DHT production, ability to use testosterone and DHT interchangeably, and propensity of cells for off-target AR inhibitory effect. © 2013 Wiley Periodicals, Inc.

Cell Cycle Target-Based Therapy of Ovarian Cancer

DTIC Science & Technology

2008-03-01

inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride , whereas treatment with ibuprofen in low levels of apoptosis...Ibuprofen, Exisulind, Acetaminophen, Naproxen, NS-398, Celecoxib, Diclofenac, Finasteride , Flufenamic acid, Meloxican, Ebselen and Flurbiprofen was...Diclofenac, 50µM Finasteride , 200µM Flufenamic acid, 40µM Meloxican, 50µM Ebselen, 20nM Flurbiprofen or 50µM Sulindac sulfide. Apoptosis was measured 24

Reduction of Racial Disparities in Prostate Cancer

DTIC Science & Technology

2007-12-01

anti-inflammatory medication, COX-2 inhibitors, aspirin, anti-TNF medications), and other medications of interest (testosterone, finasteride , alpha...compared to control-patients (mean 123) P=0.01. There were 14 (7%) control-patients who had Finasteride use, with an average of 398.6 doses per...individual. None of the prosate cancer patients had prior finasteride use. In a multiple logistic regression model (Table 2), after adjustment for the

A prospective, 1-year trial using saw palmetto versus finasteride in the treatment of category III prostatitis/chronic pelvic pain syndrome.

PubMed

Kaplan, Steven A; Volpe, Michael A; Te, Alexis E

2004-01-01

This study was designed to assess the safety and efficacy of saw palmetto or finasteride in men with category III prostatitis/chronic pelvic pain syndrome (CP/CPPS). A prospective, randomized, open label, 1-year study was designed to assess the safety and efficacy of saw palmetto and finasteride in the treatment of men diagnosed with CP/CPPS. Patients were randomized to finasteride (5 mg once daily) or saw palmetto (325 mg daily) for 1 year. Patients were evaluated using the National Institutes of Health Chronic Prostatitis Symptom Index, individual domains (pain, urinary symptoms, quality of life and mean pain score) and the American Urological Association Symptom Score at baseline, 3, 6 and 12 months. A total of 64 consecutive men 24 to 58 years old (mean age 43.2) with a diagnosis of CP/CPPS were equally randomized to the 2 treatment arms. All 64 men had previously received antibiotics (duration of 3 to 93 weeks), 52 (82%) had been on alpha-blockade. There were 61, 57 and 56 patients evaluable at 3, 6 and 12 months, respectively. At 1 year mean total National Institutes of Health Chronic Prostatitis Symptom Index score decreased from 23.9 to 18.1 in the finasteride group (p <0.003), and from 24.7 to 24.6 in the saw palmetto arm (p = 0.41). In the finasteride arm the quality of life and pain domains were significantly improved at 1 year; however, urination was not. Adverse events included headache (3 cases) in the saw palmetto group and decreased libido (2 cases) in the finasteride group. At the end of the trial 13 of 32 (41%) and 21 of 32 (66%) opted to continue saw palmetto and finasteride, respectively. CP/CPPS treated with saw palmetto had no appreciable long-term improvement. In contrast, patients treated with finasteride had significant and durable improvement in all various parameters except voiding. Further studies are warranted to ascertain the mechanism and reproducibility of these effects in a placebo controlled trial.

BCL-2 and Bax Expression in Skin Flaps Treated with Finasteride or Azelaic Acid.

PubMed

Ayatollahi, Seyyed Abdulmajid; Ajami, Marjan; Reyhanfard, Hamed; Asadi, Yasin; Nassiri-Kashani, Mansour; Rashighi Firoozabadi, Mehdi; Davoodi, Sayed Hossein; Habibi, Esmaeil; Pazoki-Toroudi, Hamidreza

2012-01-01

Despite all modern surgical techniques, skin flap that is considered as the main method in most reconstructive surgeries puts the skin tissue at danger of necrosis and apoptosis derived from ischemia. Therefore, finding a treatment for decreasing the apoptosis derived from flap ischemia will be useful in clinic. In present study, we evaluated the effect of azelaic acid 20% and finasteride on expression of BCL-2 and bax proteins after the skin flap surgery. For this purpose, 21 rats were entered in three groups including control, azelaic acid 20% and finasteride, all experienced skin flap surgery and then flap tissue was assessed for determining the expression of proteins in 5 slices prepared from each rat that were graded between - to +++ scales. Both azelaic acid and finasteride increased the expression of BCL-2 protein (p < 0.05) and decrease the expression of bax protein (p < 0.05). These results suggested an antiapoptotic role for finasteride and azelaic acid in preserving the flap after the ischemia reperfusion insult.

BCL-2 and Bax Expression in Skin Flaps Treated with Finasteride or Azelaic Acid

PubMed Central

Ayatollahi, Seyyed Abdulmajid; Ajami, Marjan; Reyhanfard, Hamed; Asadi, Yasin; Nassiri-Kashani, Mansour; Rashighi Firoozabadi, Mehdi; Davoodi, Sayed Hossein; Habibi, Esmaeil; Pazoki-Toroudi, Hamidreza

2012-01-01

Despite all modern surgical techniques, skin flap that is considered as the main method in most reconstructive surgeries puts the skin tissue at danger of necrosis and apoptosis derived from ischemia. Therefore, finding a treatment for decreasing the apoptosis derived from flap ischemia will be useful in clinic. In present study, we evaluated the effect of azelaic acid 20% and finasteride on expression of BCL-2 and bax proteins after the skin flap surgery. For this purpose, 21 rats were entered in three groups including control, azelaic acid 20% and finasteride, all experienced skin flap surgery and then flap tissue was assessed for determining the expression of proteins in 5 slices prepared from each rat that were graded between – to +++ scales. Both azelaic acid and finasteride increased the expression of BCL-2 protein (p < 0.05) and decrease the expression of bax protein (p < 0.05). These results suggested an antiapoptotic role for finasteride and azelaic acid in preserving the flap after the ischemia reperfusion insult. PMID:24250563

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2012-11-01

randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer...and that this risk differed between men who took finasteride versus those who took the placebo. The strongest association was seen for a cluster of 9...SNPs in NPAS2, which was associated with total prostate cancer risk in the finasteride group but not in the placebo group. The most significant NPAS2

Cell Cycle Target-based Therapy for Ovarian Cancer

DTIC Science & Technology

2008-09-01

induces apoptosis in quiescent ovarian cancer cells. Strong inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride ...Thus, a whole panel of NSAIDs including Aspirin, Ibuprofen, Exisulind, Acetaminophen, Naproxen, NS-398, Celecoxib, Diclofenac, Finasteride ...Naproxen, 200µM NS-398, 50µM Celecoxib, 200µM Diclofenac, 50µM Finasteride , 200µM Flufenamic acid, 40µM Meloxican, 50µM Ebselen, 20nM Flurbiprofen or

Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway.

PubMed

Soni, Kiran Kumar; Shin, Yu Seob; Choi, Bo Ram; Karna, Keshab Kumar; Kim, Hye Kyung; Lee, Sung Won; Kim, Chul Young; Park, Jong Kwan

2017-01-01

Finasteride is used to treat male pattern baldness and benign prostatic hyperplasia. This study investigated the toxicity of finasteride and recovery by DA-9401 using Sprague Dawley (SD) rats. Forty adult male SD rats were assigned to four groups: control (CTR), finasteride 1 mg/kg/day (F), finasteride 1 mg/kg + DA-9401 100 mg/kg/day (F + DA 100) and finasteride 1 mg/kg + DA-9401 200 mg/kg/day (F + DA 200). Treatments were by oral delivery once daily for 90 consecutive days. The gross anatomical parameters assessed included: genital organ weight; vas deferens sperm count and sperm motility; testosterone, dihydrotestosterone (DHT) and malondialdehyde levels; and histological and terminal deoxynucleotidyl transferase enzyme mediated dUTP nick-end labeling (TUNEL) staining of testis for spermatogenic cell density, Johnsen's score and apoptosis. Testicular tissue was also used for evaluating endoplasmic reticulum (ER) stress and apoptotic proteins. Epididymis weight, seminal vesicle weight, prostate weight, penile weight and vas deferens sperm motility showed significant differences between the F group and the CTR, F + DA 100 and F + DA 200 groups. There was no significant change in the testosterone level. DHT level decreased significantly in the F group compared with the CTR group. Testis tissue revealed significant changes in spermatogenic cell density, Johnsen's score and apoptotic index. Western blot showed significant changes in the ER stress and apoptotic markers. Finasteride resulted in reduced fertility and increased ER stress and apoptotic markers, which were recovered by administration of DA-9401 in the SD rats.

Photostability and toxicity of finasteride, diclofenac and naproxen under simulating sunlight exposure: evaluation of the toxicity trend and of the packaging photoprotection

PubMed Central

2013-01-01

Background Drugs photostability plays two different opposite roles; a real advantage arises considering the longer expiration time of the drugs while the consequent persistence in the environment involves an obvious negative effect bound to their harmfulness. On this basis we tested the photostability and toxicity of three pharmaceutical active principles: Finasteride, Diclofenac and Naproxen. The pure active principles, as well as commercial drugs containing them, were considered; for the last, the protective effect of the packaging was also evaluated. Samples were irradiated according to the ICH Guidelines for photostability testing (The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use); a simulating sunlight source (a mercury-vapor lamp coupled to a tungsten filament one) was used to cover the wavelength range 300–2000 nm; Temperature, Relative Humidity, Irradiance and Illuminance were maintained constant during the photodegradation. The concentrations of the pharmaceutical active principles during the photodegradation were monitored by HPLC with UV/Vis detector. Toxicity tests were performed by means of an amperometric biosensor based on suspended yeast cells. Since the products obtained by the photodegradation process can result as toxic or more toxic than the original molecules, tests were performed first and after the photodegadation. Results After 90 hours of exposure the concentration resulted lowered by 42.9%, 88.4% and 91% for Finasteride, Naproxen and Diclofenac respectively. Toxicity of the pure active principles follows the same order of the photostability. After photodegradation a contribute of the reaction products was evidenced. Conclusions The simple and cheap analytical procedure here proposed, allowed to obtain not only data on photostability and toxicity of the pure active principles but, even if roughly, also useful information on the reactions kinetic and toxicity of the photodegradation products. PMID:24325844

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

DTIC Science & Technology

2009-10-01

efficacy of methylselenocysteine (MSC) and finasteride in preventing the clonal expansion of early stage, small volume prostate cancer using a tumor...xenograft model. When used alone, MSC had little effect on tumor growth, whereas finasteride was only effective for a short duration. However, the...repeat of the experiment with larger sample size is needed to corroborate the findings. We also demonstrated a synergy between emodin and finasteride in

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

DTIC Science & Technology

2007-10-01

regulates androgen receptor, and finasteride , a 5α-reductase inhibitor, has a synerigistic effect in inhibiting the growth of prostate cancer cells...impact of the selenium and finasteride combination on androgen signaling; 2) Identifying the pro-apoptotic target genes of FOXO1 that are induced by...selenium; 3) studying the potential AR antagonistic effect of finasteride . The last was not proposed in the original application. But we strongly

Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome.

PubMed

Sökeland, J

2000-09-01

To test the hypothesis that in patients with benign prostatic hyperplasia (BPH), the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL, using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy. A subgroup of 431 patients was analysed from a randomized, multicentre, double-blind clinical trial involving 543 patients with the early stages of BPH. Patients received a fixed combination of extracts of saw palmetto fruit (Serenoa repens) and nettle root (Urtica dioica) (PRO 160/120) or the synthetic 5alpha-reductase inhibitor finasteride. The patients assessed had valid ultrasonographic measurements and baseline prostate volumes of either 40 mL. All 516 patients were included in the safety analysis. The results of the original trial showed equivalent efficacy for both treatments. The mean (SD) maximum urinary flow (the main outcome variable) increased (from baseline values) after 24 weeks by 1.9 (5.6) mL/s with PRO 160/120 and by 2.4 (6.3) mL/s with finasteride. There were no statistically significant group differences (P = 0.52). The subgroups with small prostates ( 40 mL were similar, at 2.3 (6.1) and 2. 2 (5.3) mL/s, respectively. There were improvements in the International Prostate Symptom Score in both treatment groups, with no statistically significant differences. The subgroup analysis showed slightly better results for voiding symptoms in the patients with prostates of > 40 mL, but there were also improvements in the subgroup with smaller prostates. The safety analysis showed that more patients in the finasteride group reported adverse events and also there were more adverse events in this group than in patients treated with PRO 160/120. The present analysis showed that the efficacy of both PRO 160/120 and finasteride was equivalent and unrelated to prostate volume. However, PRO 160/120 had better tolerability than finasteride.

Isotope Dilution-Based Targeted and Nontargeted Carbonyl Neurosteroid/Steroid Profiling.

PubMed

Sharp, Sheila; Mitchell, Scott J; Vallée, Monique; Kuzmanova, Elena; Cooper, Michelle; Belelli, Delia; Lambert, Jeremy J; Huang, Jeffrey T-J

2018-04-17

Neurosteroids are brain-derived steroids, capable of rapidly modulating neuronal excitability in a nongenomic manner. Dysregulation of their synthesis or metabolism has been implicated in many pathological conditions. Here, we describe an isotope dilution based targeted and nontargeted (ID-TNT) profiling of carbonyl neurosteroids/steroids. The method combines stable isotope dilution, hydroxylamine derivatization, high-resolution MS scanning, and data-dependent MS/MS analysis, allowing absolute quantification of pregnenolone, progesterone, 5α-dihydroprogesterone, 3α,5α-tetrahydroprogesterone, and 3β,5α-tetrahydroprogesterone, and relative quantification of other carbonyl containing steroids. The utility and validity of this approach was tested in an acute stress mouse model and via pharmacological manipulation of the steroid metabolic pathway with finasteride. We report that brain levels of 3α,5α-tetrahydroprogesterone, a potent enhancer of GABA A receptor (GABA A R-mediated inhibitory function, from control mice is in the 5-40 pmol/g range, a value greater than previously reported. The approach allows the use of data from targeted analysis to guide the normalization strategy for nontargeted data. Furthermore, novel findings, including a striking increase of brain pregnenolone following finasteride administration were discovered in this study. Collectively, our results indicate that this approach has distinct advantages for examining targeted and nontargeted neurosteroid/steroid pathways in animal models and could facilitate a better understanding of the physiological and pathological roles of neurosteroids as modulators of brain excitability.

Does Variation in Either Age at Start of Therapy or Duration of Therapy Make Chemoprevention with Finasteride Cost-Effective?

PubMed Central

Stewart, Suzanne Biehn; Scales, Charles D.; Moul, Judd W.; Reed, Shelby D.

2013-01-01

Background Incremental cost-effectiveness ratios (ICER) of finasteride for prostate cancer prevention are consistent with estimates beyond $100,000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50–55yrs. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. Methods A probabilistic Markov model was designed to estimate lifetime prostate health related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. Results The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88,800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142,300 per when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64,700 per QALY (base case 1) and $118,600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention. Conclusion Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100,000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug. PMID:22777393

Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial*

PubMed Central

Murtola, Teemu J.; Gurel, Bora; Umbehr, Martin; Lucia, M. Scott; Thompson, Ian M.; Goodman, Phyllis J.; Kristal, Alan R.; Parnes, Howard L.; Lippman, Scott M.; Sutcliffe, Siobhan; Peskoe, Sarah B.; Barber, John R.; Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

2015-01-01

Background A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here we studied these associations in the PCPT finasteride arm. Methods Prostate cancer cases (N=197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N=248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of H&E stained sections. Logistic regression was used for statistical analysis. Results In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas; p < 0.001 for difference compared to placebo arm. Overall, the odds of prostate cancer did not differ by prevalence (OR=0.90, 95% CI 0.44-1.84) or extent (P-trend=0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR=1.07, 95% CI 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammationin either cases or controls. Conclusion The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. Impact Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation. PMID:26715424

New Approaches for Prostate Cancer Combination Therapy

DTIC Science & Technology

2008-04-01

5 times whereas Finasteride , Diclofenac and Sulindac Sulfone 5 can be reduced 2 times when compared with the solvent controls, and still resulting...Flufenamic acid and Sulindac Sulfide; 20, 10, 5 and 2nM Flurbiprofen; 50, 25,10 and 5 µM Finasteride ; 200, 100,50 and 25 µM NS-398 and Sulindac...Diclofenac, Sulindac Sulfide, Finasteride and NS398 and NF-B inhibitors 6-Amino-4-(4-phenoxyphenylethylamino) quinazoline and IKK- 2 inhibitor SC-514

Cost effectiveness comparison of dutasteride and finasteride in patients with benign prostatic hyperplasia--The Markov model based on data from Montenegro.

PubMed

Dabanović, Vera; Kostić, Marina; Janković, Slobodan

2016-01-01

Benign prostatic hyperplasia (BPH) is one of the most common disease among males aging 50 years and more. The rise of the prevalence of BPH is related to aging, and since duration of life time period has the tendency of rising the prevalence of BPH will rise as costs of BPH treatment will and its influence on health economic budget. Dutasteride is a new drug similar to finasteride, inhibits enzyme testosterone 5-alpha reductase, diminish symptoms of BPH, reduce risk of the complications and increases quality of life in patients with BPH. But, the use of dutasteride is limited by its high costs. The aim of this study was to compare cost effectiveness of dutasteride and finasteride from the perspective of a purchaser of health care service (Republic Institute for Health Insuranse, Montenegro). We constructed a Markov model to compare cost effectivenss of dutasteride and finasteride using data from the available pharmacoeconomic literature and data about socioeconomic sphere actual in Montenegro. A time horizon was estimated to be 20 years, with the duration of 1 year per one cycle. The discount rate was 3%. We performed Monte Carlo simulation for virtual cohort of 1,000 patients with BPH. The total costs for one year treatment of BPH with dutasteride were estimated to be 6,458.00 € which was higher comparing with finasteride which were 6,088.56 €. The gain in quality adjusted life years (QALY) were higher with dutasteride (11.97 QALY) than with finasteride (11.19 QALY). The results of our study indicate that treating BPH with dutasteride comparing to finasteride is a cost effective option since the value of incremental cost-effectiveness ratio (ICER) is 1,245.68 €/QALY which is below estimated threshold (1,350.00 € per one gained year of life). Dutasteride is a cost effective option for treating BPH comparing to finasteride. The results of this study provide new information for health care decision makers about treatment of BPH in socioeconomic environment which is actual both in Montenegro and other countries with a recent history of socioeconomic transition.

An open, randomized, comparative study of oral finasteride and 5% topical minoxidil in male androgenetic alopecia.

PubMed

Arca, Ercan; Açikgöz, Gürol; Taştan, Halis Bülent; Köse, Osman; Kurumlu, Zafer

2004-01-01

Androgenetic alopecia (AGA) is undoubtedly the most common form of hair loss in males. It is a condition which may cause cosmetic and psychosocial problems in androgen-dependent cases. In this open, randomized and comparative study we evaluated the efficacy of oral finasteride and 5% topical minoxidil treatment for 12 months in 65 male patients with mild to severe AGA. We randomly assigned 40 (61.53%) patients to receive 1 mg/day oral finasteride for 12 months, and 25 (38.47%) patients applied 5% topical minoxidil solution twice daily for 12 months. There were no significant differences between the 2 groups considering age, age of onset of hair loss, family history and type of hair loss (p > 0.05). In the clinical evaluation at the endpoint of treatment, the clinical cure rates (i.e. increased intensity of hair) were 80% (32/40) for the oral finasteride group and 52% (13/25) for the 5% topical minoxidil group. Encountered side effects were all mild, and there was no need to stop the treatment. In the group given oral finasteride, side effects were noted in 7 patients: 6 patients suffered from loss of libido, and 1 patient had an increase in other body hairs; irritation of the scalp was seen in 1 patient in the group administered 5% minoxidil. These adverse events disappeared as soon as the treatment was stopped. The laboratory data on both drug groups did not show any statistically or clinically significant intragroup changes from baseline values to the endpoint (p > 0.05), except the level of serum total testosterone which was increased, and free testosterone and serum prostate-specific antigen in the finasteride group which were statistically decreased from baseline values to the endpoint (p < 0.05). In this comparative study of systemic finasteride and topical minoxidil, it was concluded that both drugs were effective and safe in the treatment of mild to severe AGA, although oral finasteride treatment was more effective (p < 0.05). Adverse events were not considered important either, and these side effects disappeared as soon as the treatment was stopped.

Finasteride (Propecia/Proscar) and Pregnancy

MedlinePlus

... treatment is stopped, and there will be a reversal of any benefits within twelve months of stopping ... uses finasteride while I am breastfeeding? No. Having sexual intercourse with your partner while he is taking ...

An economic evaluation of finasteride for treatment of benign prostatic hyperplasia.

PubMed

Baladi, J F; Menon, D; Otten, N

1996-05-01

This evaluation was conducted at the request of a Canadian provincial government considering finasteride for formulary inclusion. The comparator therapies, in accordance with Canadian pharmacoeconomic guidelines, were the most prevalent treatment [transurethral resection of the prostate (TURP)] and the lowest cost treatment (watchful waiting). All costs were measured in 1994 Canadian dollars ($Can), and both costs and outcomes were discounted at 5% per annum. Cost-effectiveness and cost-utility ratios were calculated, and were found to be dependent on initial symptom severity and the anticipated duration of treatment with finasteride. The drug was shown to be the dominant alternative compared with both TURP and watchful waiting for patients with moderate symptoms, when the duration of drug therapy is 3 years or less. However, finasteride is a weak alternative for patients with severe symptoms who are treated for 4 years or more. For other groups of patients (i.e. moderate symptoms and on finasteride for 4 years or more; severe symptoms and on treatment for 3 years or less), the drug can improve health-related quality of life, but at a cost of between $Can3000 and $Can97,000 per incremental quality-adjusted life year (1994 dollars). Our study also indicated that it would cost between $Can2.7 million and $Can5.6 million, depending on the severity mix of the patients, to treat cohort of 10,000 men aged 60 years or older with finasteride.

Finasteride therapy does not alter bone turnover in men with benign prostatic hyperplasia--a Clinical Research Center study.

PubMed

Tollin, S R; Rosen, H N; Zurowski, K; Saltzman, B; Zeind, A J; Berg, S; Greenspan, S L

1996-03-01

Benign prostatic hyperplasia is often treated with finasteride, which inhibits the conversion of testosterone to dihydrotestosterone (DHT). Aside from the prostate, other androgen-dependent tissues seem to be unaffected by selective DHT deficiency, but the effect on bone density in humans has not yet been defined. To study this question, we compared indices of bone turnover and bone mineral density in 35 men treated with finasteride with controls. Bone resorption was assessed by measuring urinary excretion of N-telopeptide cross-links of type I collagen and hydroxyproline, and bone formation was assessed by measuring serum osteoncalcin and bone-specific alkaline phosphatase. Bone density of the spine and hip were assessed by dual energy x-ray absorptiometry. We found that finasteride-treated patients had mean DHT levels 81% lower than controls (P < 0.0001). There were no significant differences between the two groups in any of the markers of bone turnover or measures of bone density. These results suggest that testosterone can maintain bone density in men even in the absence of DHT. Although long term studies are needed, our results suggest that men who take finasteride are not at increased risk for bone loss.

Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial

PubMed Central

Yarrow, Joshua F.; Conover, Christine F.; Nseyo, Unyime; Meuleman, John R.; Lipinska, Judyta A.; Braith, Randy W.; Beck, Darren T.; Martin, Jeffrey S.; Morrow, Matthew; Roessner, Shirley; Beggs, Luke A.; McCoy, Sean C.; Cannady, Darryl F.; Shuster, Jonathan J.

2013-01-01

Testosterone acts directly at androgen receptors and also exerts potent actions following 5α-reduction to dihydrotestosterone (DHT). Finasteride (type II 5α-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged ≥60 yr with a serum testosterone concentration of ≤300 ng/dl or bioavailable testosterone ≤70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8–14% (P = 0.015 to <0.001), fat-free mass 4.04 kg (P = 0.032), lumbar spine bone mineral density (BMD) 4.19% (P < 0.001), and total hip BMD 1.96% (P = 0.024) while reducing total body fat −3.87 kg (P < 0.001) and trunk fat −1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P < 0.001). Coadministration of finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm3 (P = 0.0051), an effect that was completely prevented by finasteride (P = 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue. PMID:24326421

The 5α-reductase inhibitor finasteride is not associated with alterations in sleep spindles in men referred for polysomnography

PubMed Central

Goldstein, Michael R.; Cook, Jesse D.; Plante, David T.

2015-01-01

Objective Endogenous neurosteroids that potentiate the GABAA receptor are thought to enhance the generation of sleep spindles. This study tested the hypothesis that the 5α-reductase inhibitor finasteride, an agent associated with reductions in neurosteroids, would be associated with reduced sleep spindles in men referred for polysomnography. Methods Spectral analysis and spindle waveform detection were performed on electroencephalographic (EEG) sleep data in the 11–16Hz sigma band, as well as several subranges, from 27 men taking finasteride and 27 matched comparison patients (ages 18 to 81 years). Results No significant differences between groups were observed for spectral power or sleep spindle morphology measures, including spindle density, amplitude, duration, and integrated spindle activity. Conclusions Contrary to our hypothesis, these findings demonstrate that finasteride is not associated with alterations in sleep spindle range activity or spindle morphology parameters. PMID:26494125

Determination of finasteride and its metabolite in urine by dispersive liquid-liquid microextraction combined with field-enhanced sample stacking and sweeping.

PubMed

Chen, Chun-Hsien; Chao, Yu-Ying; Lin, Yi-Hui; Chen, Yen-Ling

2018-04-27

The on-line preconcentration technique of field-enhanced sample stacking and sweeping (FESS-sweeping) are combined with dispersive liquid-liquid microextraction (DLLME) to monitor the concentrations of finasteride, which is used in the treatment of androgenetic alopecia, and its metabolite, finasteride carboxylic acid (M3), in urine samples. DLLME is used to concentrate and eliminate the interferences of urine samples and uses chloroform as an extracting solvent and acetonitrile as a disperser solvent. A high conductivity buffer (HCB) was introduced into capillary and then sample plug (90.7% capillary length) was injected into capillary. After applying voltage, the sodium dodecyl sulfate (SDS) swept the analytes from the low conductivity sample solution into HCB. The analytes were concentrated on the field-enhanced sample stacking boundary. The limit of detection for the analytes is 20 ng mL -1 . The sensitivity enrichment of finasteride and M3 are 362-fold and 480-fold, respectively, compared with the conventional MEKC method. The on-line preconcentration technique of field-enhanced sample stacking and sweeping possess good selectivity because the endogenous steroid did not interfere the detection of finasteride and M3. The analytical technique is applied to investigate the concentrations in urine samples from patients who have been administered finasteride for the treatment of androgenetic alopecia; the amount of M3 detected in 12 h was 72.69 ± 4.18 μg. Copyright © 2018 Elsevier B.V. All rights reserved.

Emotional Consequences of Finasteride: Fool’s Gold

PubMed Central

Ganzer, Christine Anne; Jacobs, Alan Roy

2016-01-01

Androgenetic alopecia, the gradual, progressive loss of hair frequently results in psychological despair, in part related to changes in self-image. Current androgenetic alopecia treatments are limited to hair transplantation and medications that inhibit dihydrotestosterone, a potent androgen associated with follicular micronization. Users of finasteride, which prevents dihydrotestosterone production, report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome. Psychiatric illnesses and personality traits, specifically neuroticism influence emotional well-being. Limited research exists exploring the psychological corollaries of post-finasteride syndrome and preexisting Axis I and Axis II mental health conditions. The aim of this study was to explore how having a preexisting personal and/or familial history of a psychiatric diagnosis and certain personality traits may influence anxiety and depression among finasteride users. Participants in this online survey completed the Beck Depression Inventory, the Beck Anxiety Inventory, and Ten-Item Personality Inventory. An important finding in this study was that almost 57% (n = 97) of men reported a psychiatric diagnosis and 28% (n = 27) had a first-degree relative with a mental health disorder, of this group 17 only had a family history. Nearly 50% of the men surveyed reported clinically significant depression as evidenced by Beck Depression Inventory score and 34% experienced anxiety on the Beck Anxiety Inventory. There were no statistically significant trends in personality traits reported. Results provide evidence on the need to screen for psychiatric history and counseling patients about the potential psychological consequences of finasteride. Prescribing clinicians should carefully weigh the risk/benefit ratio with these patients. PMID:26868914

Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling.

PubMed

Zhao, Ruizhe; Wang, Xingjie; Jiang, Chenyi; Shi, Fei; Zhu, Yiping; Yang, Boyu; Zhuo, Jian; Jing, Yifeng; Luo, Guangheng; Xia, Shujie; Han, Bangmin

2018-06-01

Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling. TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated. Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction. Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization. © 2017 John Wiley & Sons Ltd.

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2011-09-01

placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

T cell-mediated acute localized exanthematous pustulosis caused by finasteride.

PubMed

Tresch, Sandra; Cozzio, Antonio; Kamarashev, Jivko; Harr, Thomas; Schmid-Grendelmeier, Peter; French, Lars E; Feldmeyer, Laurence

2012-02-01

A 21-year-old man presented with multiple erythematous nonfollicular papules partially confluent to plaques on his breast and lower abdomen that had been present for 1 month. Grouped pustules were present under the right breast. The patient had been taking finasteride over the past 3 months for androgenetic alopecia. His medical history was negative for psoriasis. Our initial differential diagnosis included dyskeratosis follicularis Darier, allergic contact dermatitis, infectious folliculitis, varicella zoster virus infection, fixed drug eruption, and IgA pemphigus. The white blood cell count and differential were within the normal limits. Results of viral cultures and PCR, as well as bacterial and fungal cultures of skin lesions proved negative. A lesional biopsy specimen showed a slight psoriasiform acanthosis in association with spongiosis and infiltration of both the epidermis and dermis by neutrophils and eosinophils, resulting in formation of subcorneal, intraepidermal, and subepidermal pustules. The results of direct immunofluorescence were negative, excluding an IgA pemphigus. The result of a lymphocyte transformation test was positive for finasteride. On the basis of the time relationship between the administration of finasteride and the development of the skin disease in combination with symptoms resolution on cessation of the drug, the histologic findings, and the positive lymphocyte transformation test result, we consider this to be an unusual type of acute generalized exanthematous pustulosis defined as acute localized exanthematous pustulosis caused by finasteride. Within 4 weeks after withdrawal of finasteride, the rash resolved without any specific therapy. Transient discrete residual hyperpigmentation and scaling were present. The patient refused an oral provocation challenge. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The corpus cavernosum after treatment with dutasteride or finasteride: A histomorphometric study in a benign prostatic hyperplasia rodent model.

PubMed

Da Silva, Marcello H A; Costa, Waldemar S; B Sampaio, Francisco J; De Souza, Diogo B

2018-06-08

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia (BPH) rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups: C, untreated control rats; C + D, control rats receiving dutasteride; C + F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats (SHRs); H + D, SHRs treated with dutasteride; and H + F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density (Sv) of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni's posttest. Groups C + D and C + F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C + D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H + D and H + F had less smooth muscle Sv than Group H. Group H + D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was greater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

Preparation, Optimization, In vitro Evaluation and Ex vivo Permeation Studies of Finasteride loaded gel Formulations Prepared by using Response Surface Methodology.

PubMed

Khan, Muhammad Zia Ullah; Makreski, Petre; Murtaza, Ghulam

2018-05-02

The aim of present explorative study was to prepare and optimize finasteride loaded topical gel formulations by using three factor [propylene glycol (PG), Tween® 80, and sodium lauryl sulphate (SLS)], five level central composite design. Optimized finasteride topical gel formulation (F4), containing PG, Tween® 80, and SLS in a concentration of 0.8 mg, 0.4 mg and 0.2 mg, respectively, showed 6-fold higher values of cumulative drug release, flux, partition coefficient, input rate, lag time, and diffusion coefficient, when compared to control formulation without permeation enhancer. Finally, it can be concluded that finasteride permeation was enhanced by PG, tween® 80 and SLS individually, while in combination only PG along with tween® 80 had synergistic and more pronounced effect on flux, permeability coefficient and input rate while antagonistic effect on lag time and diffusion coefficient was observed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Health-Related Quality-of-Life Findings for the Prostate Cancer Prevention Trial

PubMed Central

2012-01-01

Background The Prostate Cancer Prevention Trial (PCPT)—a randomized placebo-controlled study of the efficacy of finasteride in preventing prostate cancer—offered the opportunity to prospectively study effects of finasteride and other covariates on the health-related quality of life of participants in a multiyear trial. Methods We assessed three health-related quality-of-life domains (measured with the Health Survey Short Form–36: Physical Functioning, Mental Health, and Vitality scales) via questionnaires completed by PCPT participants at enrollment (3 months before randomization), at 6 months after randomization, and annually for 7 years. Covariate data obtained at enrollment from patient-completed questionnaires were included in our model. Mixed-effects model analyses and a cross-sectional presentation at three time points began at 6 months after randomization. All statistical tests were two-sided. Results For the physical function outcome (n = 16 077), neither the finasteride main effect nor the finasteride interaction with time were statistically significant. The effects of finasteride on physical function were minor and accounted for less than a 1-point difference over time in Physical Functioning scores (mixed-effect estimate = 0.07, 95% confidence interval [CI] = −0.28 to 0.42, P = .71). Comorbidities such as congestive heart failure (estimate = −5.64, 95% CI = −7.96 to −3.32, P < .001), leg pain (estimate = −2.57, 95% CI = −3.04 to −2.10, P < .001), and diabetes (estimate = −1.31, 95% CI = −2.04 to −0.57, P < .001) had statistically significant negative effects on physical function, as did current smoking (estimate = −2.34, 95% CI = −2.97 to −1.71, P < .001) and time on study (estimate = −1.20, 95% CI = −1.36 to −1.03, P < .001). Finasteride did not have a statistically significant effect on the other two dependent variables, mental health and vitality, either in the mixed-effects analyses or in the cross-sectional analysis at any of the three time points. Conclusion Finasteride did not negatively affect SF–36 Physical Functioning, Mental Health, or Vitality scores. PMID:22972968

Preventive and Therapeutic Efficacy of Finasteride and Dutasteride in TRAMP Mice

PubMed Central

Opoku-Acheampong, Alexander B.; Unis, Dave; Henningson, Jamie N.; Beck, Amanda P.; Lindshield, Brian L.

2013-01-01

Background The prostate cancer prevention trial (PCPT) and Reduction by dutasteride of Prostate Cancer Events (REDUCE) trial found that 5α-reductase (5αR) inhibitors finasteride and dutasteride respectively, decreased prostate cancer prevalence but also increased the incidence of high-grade tumors. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have high 5αR1 and low 5αR2 expression. Because finasteride inhibits only 5αR2, we hypothesized that it would not be as efficacious in preventing prostate cancer development and/or progression in C57BL/6 TRAMP x FVB mice as dutasteride, which inhibits both 5αR1 and 5αR2. Method/Principal Findings Six-week-old C57BL/6 TRAMP x FVB male mice were randomized to AIN93G control or pre- and post- finasteride and dutasteride diet (83.3 mg drug/kg diet) groups (n =30–33) that began at 6 and 12 weeks of age, respectively, and were terminated at 20 weeks of age. The pre- and post- finasteride and dutasteride groups were designed to test the preventive and therapeutic efficacy of the drugs, respectively. Final body weights, genitourinary tract weights, and genitourinary tract weights as percentage of body weights were significantly decreased in the Pre- and Post-dutasteride groups compared with the control. The Post-dutasteride group showed the greatest inhibition of prostatic intraepithelial neoplasia progression and prostate cancer development. Surprisingly, the Post-dutasteride group showed improved outcomes compared with the Pre-dutasteride group, which had increased incidence of high-grade carcinoma as the most common and most severe lesions in a majority of prostate lobes. Consistent with our hypothesis, we found little benefit from the finasteride diets, and they increased the incidence of high-grade carcinoma. Conclusion Our findings have commonalities with previously reported PCPT, REDUCE, and the Reduction by dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial results. Our results may support the therapeutic use of dutasteride, but not finasteride, for therapeutic or preventive use. PMID:24204943

Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day in women with female pattern hair loss.

PubMed

Won, Yong-Yon; Lew, Bark-Lynn; Sim, Woo-Young

2018-03-01

Female pattern hair loss (FPHL) presents with diffuse thinning over the mid-frontal scalp, for which various treatment modalities have been tried. Although currently, oral 5 α-reductase inhibitors such as finasteride are being used, their clinical efficacy remains controversial. We retrospectively investigated 544 premenopausal or postmenopausal patients with FPHL who were prescribed finasteride at a dose of 2.5 mg/day. Our study excluded patients with a follow-up period of < 3 months and patients who were prescribed other FPHL treatment modalities including topical minoxidil. Finally, 112 patients were evaluated based on their medical records and clinical photographs. Based on assessment using the Ludwig scale at the time of their initial visit, among 112 patients studied, 59 patients were classified as belonging to grade I, 47 were grade II, and 6 were grade III. Using global photographs, we found that 33 (29.5%) of the 112 patients studied showed slight improvement, 73 (65.2%) showed significant improvement, whereas no change was recorded in 6 (5.4%). We could demonstrate efficacy of administration of finasteride at a dose of 2.5 mg/day for patients with FPHL and also found that finasteride has a better effect on hair growth when patients had a lower Ludwig score and an older age at onset. © 2018 Wiley Periodicals, Inc.

Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice.

PubMed

Rashid, Davood; Panda, B P; Vohora, Divya

2015-11-01

Neurosteroids, such as testosterone and their metabolites, are known to modulate neuronal excitability. The enzymes regulating the metabolism of these neurosteroids, thus, may be targeted as a noval strategy for the development of new antiepileptic drugs. The present work targeted two such enzymes i,e aromatase and 5α-reductase in order to explore the potential of letrozole (an aromatase inhibitor) on pentylenetetrazole (PTZ)-induced kindling in mice and the ability of finasteride (a 5α-reductase inhibitor) to modulate any such effects. PTZ (30 mg/kg, i.p.), when administered once every two days (for a total of 24 doses) induced kindling in Swiss albino mice. Letrozole (1 mg/kg, p.o.), administered prior to PTZ, significantly reduced the % incidence of kindling, delayed mean onset time of seizures and reduced seizure severity score. Letrozole reduced the levels of plasma 17β-estradiol after induction of kindling. The concurrent administration of finasteride and letrozole produced effects similar to letrozole on PTZ-kindling and on estradiol levels. This implies that the ability of letrozole to redirect the synthesis of dihydrotestosterone (DHT) and 5α-androstanediol from testosterone doesn't appear to play a significant role in the protective effects of letrozole against PTZ kindling. Letrozole, however, increased the levels of 5α-DHT in mice plasma. The aromatase inhibitors, thus, may be exploited for inhibiting the synthesis of proconvulsant (17β-estradiol) and/or redirecting the synthesis of anticonvulsant (DHT and 5α-androstanediol) neurosteroids. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improvement of Tissue Survival of Skin Flaps by 5α-Reductase Inhibitors: Possible Involvement of Nitric Oxide and Inducible Nitric Oxide Synthase

PubMed Central

Karimi, Ali Asghar; Ajami, Marjan; Asadi, Yasin; Aboutaleb, Nahid; Gorjipour, Fazel; Malekloo, Roya; Pazoki-Toroudi, Hamidreza

2015-01-01

Background: Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5α-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase (iNOS) in graft survival mediated by these agents. Methods: A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid (100 mg/flap); 3, finasteride (1 mg/flap); 4, injection of L-NG-nitroarginine methyl ester (L-NAME) (i.p., 20 mg/kg); 5, L-NAME (20 mg/kg, i.p.) + azelaic acid (100 mg/flap, topical); 6, L-NAME (20 mg/kg, i.p.) + finasteride (1 mg/flap, topical). Tissue survival, level of nitric oxide, and iNOS expression in groups were measured. Results: Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide (NO) levels in graft tissue (P < 0.05). These increases in iNOS expression and NO level were associated with higher survival of the graft tissue. Conclusion: It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps. PMID:25864816

Finasteride treatment of female pattern hair loss.

PubMed

Iorizzo, Matilde; Vincenzi, Colombina; Voudouris, Stylianos; Piraccini, Bianca Maria; Tosti, Antonella

2006-03-01

To evaluate the efficacy of oral finasteride therapy associated with an oral contraceptive containing drospirenone and ethinyl estradiol in premenopausal women with female pattern hair loss. Outpatient consultation for hair disorders at the Department of Dermatology, University of Bologna. Thirty-seven women with female pattern hair loss were treated with oral finasteride, 2.5 mg/d, while taking an oral contraceptive containing drospirenone and ethinyl estradiol. Treatment efficacy was evaluated using global photography and the hair density score from videodermoscopy. A self-administered questionnaire was used to assess patient evaluation of treatment effectiveness. At 12-month follow-up, 23 of the 37 patients were rated as improved using global photography (12 were slightly improved, 8 were moderately improved, and 3 were greatly improved). No improvement was recorded in 13 patients. One patient experienced worsening of the condition. There was a statistically significant (P = .002) increase in the hair density score in 12 patients. No adverse reactions to the drug were reported. Sixty-two percent of the patients demonstrated some improvement of their hair loss with the use of finasteride, 2.5 mg/d, while taking the oral contraceptive. It is unclear whether the success was due to a higher dosage of finasteride (2.5 mg instead of 1 mg) or to its association with the oral contraceptive containing drospirenone, which has an antiandrogenic effect. Further studies are necessary to understand which patterns of female pattern hair loss respond better to this treatment.

Cognitive effects of testosterone and finasteride administration in older hypogonadal men

PubMed Central

Borst, Stephen E; Yarrow, Joshua F; Fernandez, Carmen; Conover, Christine F; Ye, Fan; Meuleman, John R; Morrow, Matthew; Zou, Baiming; Shuster, Jonathan J

2014-01-01

Serum concentrations of neuroactive androgens decline in older men and, in some studies, low testosterone is associated with decreased cognitive function and incidence of depression. Existing studies evaluating the effect of testosterone administration on cognition in older men have been largely inconclusive, with some studies reporting minor to moderate cognitive benefit, while others indicate no cognitive effect. Our objective was to assess the cognitive effects of treating older hypogonadal men for 1 year with a supraphysiological dose of testosterone, either alone or in combination with finasteride (a type II 5α-reductase inhibitor), in order to determine whether testosterone produces cognitive benefit and whether suppressed dihydrotestosterone influences cognition. Sixty men aged ≥60 years with a serum testosterone concentration of ≤300 ng/dL or bioavailable testosterone ≤70 ng/dL and no evidence of cognitive impairment received testosterone-enanthate (125 mg/week) versus vehicle, paired with finasteride (5 mg/day) versus placebo using a 2×2 factorial design. Testosterone caused a small decrease in depressive symptoms as assessed by the Geriatric Depression Scale and a moderate increase in visuospatial memory as assessed by performance on a recall trial of the Rey-Osterrieth Complex Figure Test. Finasteride caused a small increase in performance on the Benton Judgment of Line Orientation test. In total, major improvements in cognition were not observed either with testosterone or finasteride. Further studies are warranted to determine if testosterone replacement may improve cognition in other domains. PMID:25143719

Finasteride is effective for the treatment of central serous chorioretinopathy

PubMed Central

Moisseiev, E; Holmes, A J; Moshiri, A; Morse, L S

2016-01-01

Purpose To evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC). Methods Retrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded. Results Initial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 μm, and was significantly reduced after 1 month of treatment (284±77 μm; P=0.002) and this was maintained to the end of follow-up (247±85 μm; P=0.001). A significant reduction in SRF presence was found at all time points, with an overall 75.9% rate of complete resolution. Following discontinuation, SRF recurrence was noted in 37.5% of cases. No adverse events were recorded. Conclusions Finasteride is a safe and effective treatment for CSC. It may be a possible new option for the initial management of patient with CSC, and a suggested treatment approach is presented. PMID:27055675

Investigation of intermolecular interactions in finasteride drug crystals in view of X-ray and Hirshfeld surface analysis

NASA Astrophysics Data System (ADS)

Bojarska, Joanna; Maniukiewicz, Waldemar

2015-11-01

The N,N-dimethylformamide (DMF) solvate hemihydrate (1) of finasteride, has been structurally characterized by single-crystal X-ray diffraction at 100 K and compared with previously reported finasteride crystalline forms. In addition, in order to resolve ambiguity concerning H-bond interactions, the crystal structure of finasteride hemihydrate, (2), originally reported by Schultheiss et al. in 2009, has been redetermined with higher precision. The (1) and (2) pseudopolymorphs of finasteride crystallize as orthorhombic in chiral P212121 space group with two very similar host molecules in the asymmetric unit. The conformation of fused 6-membered rings are screw-boat, chair and chair for both molecules, while 5-membered rings assume chair in (1), and half-chair in (2). There is a fairly close resemblance of the molecular geometry for all analyzed compounds, arising due to the rigid host molecule. Inter- and intramolecular host-host, host-guest strong O-H⋯O, N-H⋯O hydrogen bonds and weak C-H⋯O interactions form 3D net conferring stability to the crystal packing. Finasterides can be classified as synthon pseudopolymorphs. Isostructural solvates crystallizing in the orthorhombic space group P212121, with Z‧ = 2, exhibit R22(8) C22(15) network, monoclinic solvate (Z‧ = 1) possess D11(2), while both orthorhombic and monoclinic polymorphs have C(4) motifs, respectively. The structural similarities and subtle differences have been interpreted in view of the 3D Hirshfeld surface analysis and associated 2D fingerprint plots, which enabled detailed qualitative and quantitative insight into the intermolecular interactions. The 97-100% of Hirshfeld surface areas are due to H···H, O···H/H⋯O, C···H/H⋯C and N⋯H/H⋯N contacts. Furthermore, the electrostatic potential has been mapped over the Hirshfeld surfaces to decode the electrostatic complementarities, which exist in the crystal packing.

Efficacy of non-surgical treatments for androgenetic alopecia: a systematic review and network meta-analysis.

PubMed

Gupta, Aditya K; Mays, Rachel R; Dotzert, Michelle S; Versteeg, Sarah G; Shear, Neil H; Piguet, Vincent

2018-05-24

Androgenetic alopecia, or male/female pattern baldness, is the most common type of progressive hair loss disorder. The aim of this paper is to review recent advances in non-surgical treatments for androgenetic alopecia and identify the most effective treatments. A network meta-analysis (NMA) was conducted of the available literature of the six most common non-surgical treatment options for treating androgenetic alopecia in both men and women; dutasteride 0.5mg, finasteride 1mg, low level laser therapy (LLLT), minoxidil 2%, minoxidil 5% and platelet rich plasma (PRP). Seventy-eight studies met the inclusion criteria and twenty-two studies had the data necessary for a network meta-analysis. Relative effects show LLLT as the superior treatment. Relative effects show PRP, finasteride 1 mg (male), finasteride 1 mg (female), minoxidil 5%, minoxidil 2% and dutasteride (male) are approximately equivalent in mean change hair count following treatment. Minoxidil 5% and minoxidil 2% reported the most drug-related adverse events (n=45 and n=23, respectively). The quality of evidence of minoxidil 2% vs. minoxidil 5% was high; minoxidil 5% vs. placebo was moderate; dutasteride (male) vs. placebo, finasteride (female) vs placebo, minoxidil 2% vs. placebo, minoxidil 5% vs. LLLT was low and finasteride (male) vs. placebo, LLLT vs. sham, PRP vs. placebo, finasteride vs. minoxidil 2% was very low. Results of this NMA indicate the emergence of novel, non-hormonal therapies as effective treatments for hair loss; however, the quality of evidence is generally low. High quality randomized controlled trials and head to head trials are required to support these findings and aid in the development of more standardized protocols, particularly for PRP. Regardless, this analysis may aid physicians in clinical decision making and highlight the variety of non-surgical hair restoration options for patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Influence of Finasteride on Mean and Relative Spectral Density of EEG Bands in Rat Model of Thioacetamide-Induced Hepatic Encephalopathy.

PubMed

Mladenović, D; Hrnčić, D; Rašić-Marković, A; Macut, Dj; Stanojlović, O

2016-08-01

Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE). Finasteride, inhibitor of neurosteroid synthesis, may improve the course of HE. The aim of our study was to investigate the influence of finasteride on mean and relative power density of EEG bands, determined by spectral analysis, in rat model of thioacetamide-induced HE. Male Wistar rats were divided into groups: (1) control; (2) thioacetamide-treated group, TAA (900 mg/kg); (3) finasteride-treated group, FIN (150 mg/kg); and (4) group treated with finasteride (150 mg/kg) and thioacetamide (900 mg/kg), FIN + TAA. Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered during 3 subsequent days, and in FIN + TAA group FIN was administered 2 h before every dose of TAA. EEG was recorded 22-24 h after treatment and analyzed by fast Fourier transformation. While TAA did not induce significant changes in the beta band, mean and relative power in this band were significantly higher in FIN + TAA versus control group (p < 0.01). TAA caused a significant decline in mean power in alpha, theta, and delta band, and in FIN + TAA group the mean power in these bands was significantly higher compared with control. While in TAA group relative power was significantly decreased in theta (p < 0.01) and increased in delta band (p < 0.01) versus control, the opposite changes were found in FIN + TAA group: an increase in theta (p < 0.01) and a decrease in delta relative power (p < 0.01). In this study, finasteride pretreatment caused EEG changes that correspond to mild TAA-induced HE.

The Effect of Finasteride and Dutasteride on the Growth of WPE1-NA22 Prostate Cancer Xenografts in Nude Mice

PubMed Central

Opoku-Acheampong, Alexander B.; Nelsen, Michelle K.; Unis, Dave; Lindshield, Brian L.

2012-01-01

Background 5α-reductase 1 (5αR1) and 5α-reductase 2 (5αR2) convert testosterone into the more potent androgen dihydrotestosterone. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have increased 5αR1 and decreased 5αR2 expression. Previously, finasteride (5αR2 inhibitor) treatment begun 3 weeks post-tumor implantation had no effect on Dunning R3327-H rat prostate tumor growth. We believe the tumor compensated for finasteride treatment by increasing tumor 5αR1 expression or activity. We hypothesize that finasteride treatment would not significantly alter tumor growth even if begun before tumor implantation, whereas dutasteride (5αR1 and 5αR2 inhibitor) treatment would decrease tumor growth regardless of whether treatment was initiated before or after tumor implantation. Methodology/Principal Findings Sixty 8-week-old male nude mice were randomized to Control, Pre- and Post-Finasteride, and Pre- and Post-Dutasteride (83.3 mg drug/kg diet) diet groups. Pre- and post-groups began their treatment diets 1–2 weeks prior to or 3 weeks after subcutaneous injection of 1×105 WPE1-NA22 human prostate cancer cells, respectively. Tumors were allowed to grow for 22 weeks; tumor areas, body weights, and food intakes were measured weekly. At study's conclusion, prostate and seminal vesicle weights were significantly decreased in all treatment groups versus the control; dutasteride intake significantly decreased seminal vesicle weights compared to finasteride intake. No differences were measured in final tumor areas or tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 prostate cancer cells and parent line RWPE-1 prostate epithelial cells were unaltered by treatment with testosterone, dihydrotestosterone, or mibolerone, suggesting that these cell lines are not androgen-sensitive. Conclusion The lack of response of WPE1-NA22 prostate cancer cells to androgen treatment may explain the inadequate tumor growth observed. Additional studies are needed to determine whether finasteride and dutasteride are effective in decreasing prostate cancer development/growth. PMID:22242155

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2009-03-01

a randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer... finasteride  (an inhibitor of androgen bioactivation) could  prevent prostate cancer. Included in our study are approximately 1,800 case‐control pairs

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2010-09-01

determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 2 of the award, we were approved by the...Trial (PCPT), a randomized placebo‐ controlled clinical trial to determine if  finasteride  (an inhibitor of androgen bioactivation) could  prevent

Neonatal allopregnanolone or finasteride administration modifies hippocampal K(+) Cl(-) co-transporter expression during early development in male rats.

PubMed

Mòdol, Laura; Casas, Caty; Llidó, Anna; Navarro, Xavier; Pallarès, Marc; Darbra, Sònia

2014-09-01

The maintenance of levels of endogenous neurosteroids (NS) across early postnatal development of the brain, particularly to the hippocampus, is crucial for their maturation. Allopregnanolone (Allop) is a NS that exerts its effect mainly through the modulation of the GABAA receptor (GABAAR). During early development, GABA, acting through GABAAR, that predominantly produces depolarization shifts to hyperpolarization in mature neurons, around the second postnatal week in rats. Several factors contribute to this change including the progressive increase of the neuron-specific K(+)/Cl(-) co-transporter 2 (KCC2) (a chloride exporter) levels. Thus, we aimed to analyze whether a different profile of NS levels during development is critical and can alter this natural progression of KCC2 stages. We administrated sustained Allop (20mg/kg) or Finasteride (5α-reductase inhibitor, 50mg/kg) from the 5th postnatal day (PD5) to PD9 and assessed changes in the hippocampal expression of KCC2 at transcript and protein levels as well as its active phosphorylated state in male rats. Taken together data indicated that manipulation of NS levels during early development influence KCC2 levels and point out the importance of neonatal NS levels for the hippocampal development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Expression of basic fibroblast growth factor and its receptors FGFR1 and FGFR2 in human benign prostatic hyperplasia treated with finasteride.

PubMed

Sáez, C; González-Baena, A C; Japón, M A; Giráldez, J; Segura, D I; Rodríguez-Vallejo, J M; González-Esteban, J; Miranda, G; Torrubia, F

1999-07-01

The development of benign prostatic hyperplasia (BPH) is an androgen-dependent process which may be mediated by a number of locally produced growth factors. One of these, the basic fibroblast growth factor (bFGF or FGF2), has a mitogenic effect on prostatic stroma. High expression levels of bFGF have been reported in BPH. FGFR1 and FGFR2 receptors, that exhibit affinity for bFGF, have been identified in normal and hyperplastic prostate. Finasteride, a 5alpha-reductase inhibitor, is an effective drug in the treatment of BPH, inducing regressive changes in the prostate of treated patients, even though its mechanisms of action are not yet completely elucidated. This study was designed to assess the effects of finasteride on the expression levels of bFGF, FGFR1, and FGFR2 in patients with BPH. The expression levels of bFGF, FGFR1, and FGFR2 in 9 patients with prostatic hyperplasia treated with finasteride were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA expression and were compared with those of 9 control patients with untreated BPH. Immunohistochemistry showed strong bFGF immunoreactivity in the prostatic stroma of untreated patients, this being somewhat weaker in the epithelium. In treated patients, epithelial immunoreactivity was practically negative, and a considerable reduction in stromal immunoreactivity was seen. These findings were also confirmed by RT-PCR. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR1 showed a weak immunoreactivity in the stroma and in basal epithelial cells. FGFR2 exhibited strong stromal immunoreactivity, becoming weaker in the basal epithelium. No differences were seen in the expression of both receptors between the groups of treated and untreated patients. A marked reduction in bFGF levels is seen in BPH treated with finasteride in comparison to untreated BPH. In our opinion, finasteride may act as a negative regulator of bFGF expression, counteracting the role of bFGF in the development of BPH.

The inductive effect of ginsenoside F2 on hair growth by altering the WNT signal pathway in telogen mouse skin.

PubMed

Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Song, Hyun-Geun; Mavlonov, Gafurjon T; Yi, Tae-Hoo

2014-05-05

This study was conducted to confirm the possibility of using minor ginseng saponin F2 by oral administration on hair anagen induction effects. The signaling pathway and anagen induction effect of ginsenoside F2 were investigated and compared with finasteride on the effect of hair growth induction. The cell-based MTT assay results indicated that the proliferation rates of HHDPC and HaCaT treated with F2 significantly increased by 30% compared with the finasteride-treated group. A western blot study showed that the expression of β-catenin Lef-1 and DKK-1 increased by 140, 200% and decreased by 40% in the F2-treated group, respectively compared to that of finasteride-treated group. C57BL/6 mice were subjected to the same treatments. The hair growth promotion rates were compared with groups treated with finasteride, which was 20% higher in the F2-treated group. Tissue histological analysis results showed the number of hair follicles, thickness of the epidermis, and follicles of the anagen phase which increased in the F2-treated group, compared with the finasteride-treated groups. Moreover, the effect of F2 on hair growth was confirmed through the immunofluorescence (IF) methods indicating the expression aspect of Wnt signal pathway-related factors in the tissue of C57BL/6 mouse. Our results considered the expression increase in β-catenin, Lef-1 which was suggested as a major factor related to the development and growth of hair follicle and the decrease in DKK-1 when entering catagen by F2. As the data showed, F2 might be a potential new therapeutic source for anagen induction and hair growth through the Wnt signal pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization and validation of spectrophotometric methods for determination of finasteride in dosage and biological forms

PubMed Central

Amin, Alaa S.; Kassem, Mohammed A.

2012-01-01

Aim and Background: Three simple, accurate and sensitive spectrophotometric methods for the determination of finasteride in pure, dosage and biological forms, and in the presence of its oxidative degradates were developed. Materials and Methods: These methods are indirect, involve the addition of excess oxidant potassium permanganate for method A; cerric sulfate [Ce(SO4)2] for methods B; and N-bromosuccinimide (NBS) for method C of known concentration in acid medium to finasteride, and the determination of the unreacted oxidant by measurement of the decrease in absorbance of methylene blue for method A, chromotrope 2R for method B, and amaranth for method C at a suitable maximum wavelength, λmax: 663, 528, and 520 nm, for the three methods, respectively. The reaction conditions for each method were optimized. Results: Regression analysis of the Beer plots showed good correlation in the concentration ranges of 0.12–3.84 μg mL–1 for method A, and 0.12–3.28 μg mL–1 for method B and 0.14 – 3.56 μg mL–1 for method C. The apparent molar absorptivity, Sandell sensitivity, detection and quantification limits were evaluated. The stoichiometric ratio between the finasteride and the oxidant was estimated. The validity of the proposed methods was tested by analyzing dosage forms and biological samples containing finasteride with relative standard deviation ≤ 0.95. Conclusion: The proposed methods could successfully determine the studied drug with varying excess of its oxidative degradation products, with recovery between 99.0 and 101.4, 99.2 and 101.6, and 99.6 and 101.0% for methods A, B, and C, respectively. PMID:23781478

The Direct Inhibitory Effect of Dutasteride or Finasteride on Androgen Receptor Activity is Cell Line Specific

PubMed Central

Chhipa, Rishi Raj; Halim, Danny; Cheng, Jinrong; Zhang, Huan Yi; Mohler, James L.; Ip, Clement; Wu, Yue

2014-01-01

BACKGROUND Finasteride and dutasteride were developed originally as 5α-reductase inhibitors to block the conversion of testosterone to dihydrotestosterone (DHT). These drugs may possess off-target effects on the androgen receptor (AR) due to their structural similarity to DHT. METHODS A total of 4 human prostate cancer cell models were examined: LNCaP (T877A mutant AR), 22Rv1 (H874Y mutant AR), LAPC4 (wild type AR) and VCaP (wild type AR). Cells were cultured in 10% charcoal-stripped fetal bovine serum, either with or without DHT added to the medium. AR activity was evaluated using the ARE-luciferase assay or the expression of AR regulated genes. RESULTS Dutasteride was more potent than finasteride in interfering with DHT-stimulated AR signaling. Disruption of AR function was accompanied by decreased cell growth. Cells that rely on DHT for protection against death were particularly vulnerable to dutasteride. Different prostate cancer cell models exhibited different sensitivities to dutasteride and finasteride. LNCaP was most sensitive, LAPC4 and VCaP were intermediate, while 22Rv1 was least sensitive. Regardless of the AR genotype, if AR was transfected into drug-sensitive cells, AR was inhibited by drug treatment; and if AR was transfected into drug-resistant cells, AR was not inhibited. CONCLUSIONS The direct inhibitory effect of dutasteride or finasteride on AR signaling is cell line specific. Mutations in the ligand binding domain of AR do not appear to play a significant role in influencing the AR antagonistic effect of these drugs. Subcellular constituent is an important factor in determining the drug effect on AR function. PMID:23813737

Efficacy and safety of 3% minoxidil versus combined 3% minoxidil / 0.1% finasteride in male pattern hair loss: a randomized, double-blind, comparative study.

PubMed

Tanglertsampan, Chuchai

2012-10-01

Topical minoxidil and oral finasteride have been used to treat men with androgenetic alopecia (AGA). There are concerns about side effects of oral finasteride especially erectile dysfunction. To compare the efficacy and safety of the 24 weeks application of 3% minoxidil lotion (MNX) versus combined 3% minoxidil and 0.1% finasteride lotion (MFX) in men with AGA. Forty men with AGA were randomized treated with MNX or MFX. Efficacy was evaluated by hair counts and global photographic assessment. Safety assessment was performed by history and physical examination. At week 24, hair counts were increased from baseline in both groups. However paired t-test revealed statistical difference only in MFX group (p = 0.044). Unpaired t-test revealed no statistical difference between two groups with respect to change of hair counts at 24 weeks from baseline (p = 0.503). MFX showed significantly higher efficacy than MNX by global photographic assessment (p = 0.003). There was no significant difference in side effects between both groups. Although change of hair counts was not statistically different between two groups, global photographic assessment showed significantly greater improvement in the MFX group than the MNX group. There was no sexual side effect. MFX may be a safe and effective treatment option.

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

DTIC Science & Technology

2010-04-01

finasteride decreases the formation of DHT, while MSA depresses the abundance of AR protein. To study the effect of finasteride/MSA on FOXO1...chemoprevention based on selenium suppression of androgen signaling”. 4. AACR Centennial Meeting, Los Angeles, CA, April 15-18, poster presentation...AR mRNA level was depressed by 0%, 20%, or 60%, respec- tively; AR transactivation was inhibited by 35%, 10%, or 60%, respectively; whereas the PSA

Effect of a novel steroid (PM-9) on the inhibition of 5alpha-reductase present in Penicillium crustosum broths.

PubMed

Flores, Eugenio; Cabeza, Marisa; Quiroz, Alexandra; Bratoeff, Eugene; García, Genoveva; Ramírez, Elena

2003-03-01

The conversion of testosterone (T) to 5alpha-dihydrotestosterone (DHT) has been demonstrated in Penicillium crustosum broth obtained from fermented pistachios, lemons and corn tortillas. Furthermore, the presence of 5alpha-reductase enzyme, which is responsible for this conversion, has been established by electrophoretical techniques in these cultures.5alpha-Reductase enzyme is also present in animal and human androgen-dependent tissues as well as in prostate and seminal vesicles. The increase of the conversion of T to DHT in prostate gland, has been related to some illnesses such as benign prostate hyperplasia and prostate cancer. Furthermore, treatment with 5alpha-reductase inhibitors such as finasteride reduces the prostate growth. These data have stimulated research for the synthesis of new molecules with antiandrogenic activity, whose biological effect needs to be demonstrated. The purpose of this study is to determine the inhibition pattern of 5alpha-reductase in P. crustosum by finasteride and the new steroidal compound PM-9. K(m) and V(max) values for T, were determined in the broths by Lineweaver-Burk plots using different testosterone concentrations. The inhibition pattern of finasteride and PM-9 was also determined by Lineweaver-Burk using different concentrations of T and inhibitors. Results show that finasteride and PM-9 inhibit 5alpha-reductase present in the broth in a competitive manner.

Androgens and alopecia.

PubMed

Kaufman, Keith D

2002-12-30

Androgens have profound effects on scalp and body hair in humans. Scalp hair grows constitutively in the absence of androgens, while body hair growth is dependent on the action of androgens. Androgenetic alopecia, referred to as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is due to the progressive miniaturization of scalp hair. Observations in both eunuchs, who have low levels of testicular androgens, and males with genetic 5alpha-reductase (5alphaR) deficiency, who have low levels of dihydrotestosterone (DHT), implicate DHT as a key androgen in the pathogenesis of MPHL in men. The development of finasteride, a type 2-selective 5alphaR inhibitor, further advanced our understanding of the role of DHT in the pathophysiology of scalp alopecia. Controlled clinical trials with finasteride demonstrated improvements in scalp hair growth in treated men associated with reductions in scalp DHT content, and a trend towards reversal of scalp hair miniaturization was evident by histopathologic evaluation of scalp biopsies. In contrast to its beneficial effects in men, finasteride did not improve hair growth in postmenopausal women with FPHL. Histopathological evaluation of scalp biopsies confirmed that finasteride treatment produced no benefit on scalp hair in these women. These findings suggest that MPHL and FPHL are distinct clinical entities, with disparate pathophysiologies. Studies that elucidate the molecular mechanisms by which androgens regulate hair growth would provide greater understanding of these differences. Copyright 2002 Elsevier Science Ireland Ltd.

Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5α-reductase by finasteride

PubMed Central

Roth, M. Y.; Dudley, R. E.; Hull, L.; Leung, A.; Christenson, P.; Wang, C.; Swerdloff, R.; Amory, J. K.

2014-01-01

Summary Oral testosterone undecanoate (TU) is used to treat testosterone deficiency; however, oral TU treatment elevates dihydrotestosterone (DHT), which may be associated with an increased risk of acne, male pattern baldness and prostate hyperplasia. Co-administration of 5α-reductase inhibitors with other formulations of oral testosterone suppresses DHT production and increases serum testosterone. We hypothesized that finasteride would increase serum testosterone and lower DHT during treatment with oral TU. Therefore, we studied the steady-state pharmacokinetics of oral TU, 200 mg equivalents of testosterone twice daily for 7 days, alone and with finasteride 0.5 and 1.0 mg po twice daily in an open-label, three-way crossover study in 11 young men with experimentally induced hypogonadism. On the seventh day of each dosing period, serum testosterone, DHT and oestradiol were measured at baseline and 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 h after the morning dose. Serum testosterone and DHT were significantly increased into and above their normal ranges similarly by all three treatments. Co-administration of finasteride at 0.5 and 1.0 mg po twice daily had no significant effect on either serum testosterone or DHT. Oral TU differs from other formulations of oral testosterone in its response to concomitant inhibition of 5α-reductase, perhaps because of its unique lymphatic route of absorption. PMID:20969601

Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology.

PubMed

Melcangi, Roberto Cosimo; Caruso, Donatella; Abbiati, Federico; Giatti, Silvia; Calabrese, Donato; Piazza, Fabrizio; Cavaletti, Guido

2013-10-01

Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation. A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology. The levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls. Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls. At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17β-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5α-androstane-3α,17β-diol and 17β-estradiol were observed in plasma. The present observations confirm that an impairment of neuroactive steroid levels, associated with depression symptoms, is still present in androgenic alopecia patients treated with finasteride despite the discontinuation of the treatment. © 2013 International Society for Sexual Medicine.

Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.

PubMed

Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Mavlonov, Gafurjon Turdalievich; Yi, Tae-Hoo

2014-01-01

This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-β) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-β2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-β2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays.

PubMed

Chen, Li; Wang, Jiaolong; Mouser, Glen; Li, Yan Chun; Marcovici, Geno

2016-06-01

Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Molecular Determinants of Prostate Cancer Progression Across Race-Ethnicity

DTIC Science & Technology

2003-05-01

finasteride (from 5-180 nM (Table 1). We have also uncovered similar phamacogenetic variation for the other two drugs we examined: PNU and GG745 (Table 1...NADPH; ( finasteride ; (PNU; (GG745; JAM)U 11) M) PM) wt 2 0.6 8 6.0 60 6 17 V31 5 3 12 5.5-6.0 27 3 93 A49T 9.8 1.5 7 6.0 180 1.1 1.1 V63M 1.6 1.5 11

Finasteride Inhibits the Disease-Modifying Activity of Progesterone in the Hippocampus Kindling Model of Epileptogenesis

PubMed Central

Reddy, Doodipala Samba; Ramanathan, G.

2012-01-01

Progesterone (P) plays an important role in seizure susceptibility in women with epilepsy. Preclinical and experimental studies suggest that P appears to interrupt epileptogenesis, which is a process whereby a normal brain becomes progressively epileptic due to precipitating risk factors. P has not been investigated widely for its potential disease-modifying activity in epileptogenic models. Recently, P has been shown to exert disease-modifying effects in the kindling model of epileptogenesis. However, the mechanisms underlying the protective effects of P against epileptogenesis remain unclear. In this study, we investigated the role of P-derived neurosteroids in the disease-modifying activity of P. It is hypothesized that 5α-reductase converts P to allopregnanolone and related neurosteroids that retard epileptogenesis in the brain. To test this hypothesis, we utilized the mouse hippocampus kindling model of epileptogenesis and investigated the effect of finasteride, a 5α-reductase and neurosteroid synthesis inhibitor. P markedly retarded the development of epileptogenesis and inhibited the rate of kindling acquisition to elicit stage 5 seizures. Pretreatment with finasteride led to complete inhibition of the P-induced retardation of limbic epileptogenesis in mice. Finasteride did not significantly influence the acute seizure expression in fully-kindled mice expressing stage 5 seizures. Thus, neurosteroids that potentiate phasic and tonic inhibition in the hippocampus, such as allopregnanolone, may mediate the disease-modifying effect of P, indicating a new role of neurosteroids in acquired limbic epileptogenesis and temporal lobe epilepsy. PMID:22835430

Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice.

PubMed

Iqbal, Ramsha; Jain, Gaurav K; Siraj, Fouzia; Vohora, Divya

2018-07-01

Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABA A receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an adjuvant in the treatment of status epilepticus and can be pursued further. Copyright © 2018 Elsevier B.V. All rights reserved.

11β-Hydoxylase Inhibitors Protect Against Seizures in Mice by Increasing Endogenous Neurosteroid Synthesis

PubMed Central

Kaminski, Rafal M.; Rogawski, Michael A.

2011-01-01

Steroid 11β-hydroxylase (CYP11B1; EC 1.14.15.4) is a mitochondrial enzyme located in the zona fasciculata of the adrenal cortex and also in the brain that mediates the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone (DOC) to corticosterone. Inhibitors of CYP11B1, such as metyrapone and etomidate, reduce glucocorticoid synthesis and raise levels of DOC providing greater availability for metabolic conversion to the GABAA receptor modulating neurosteroid allotetrahydrodeoxycorticosterone (THDOC). Because THDOC is a potent anticonvulsant, it is plausible that CYP11B1 inhibitors could protect against seizures. Here we demonstrate that metyrapone affords dose-dependent protection against 6-Hz seizures 30 min after injection (ED50, 191 mg/kg), but is markedly more potent at 6 h (ED50, 30 mg/kg). Similarly, etomidate is also protective at 30 min and 6 h (ED50 values, 4.5 and 1.7 mg/kg). Finasteride, an inhibitor of neurosteroid synthesis, attenuated the anticonvulsant effects of both CYP11B1 inhibitors at 6 h, but not 30 min following their injection. Plasma THDOC levels measured by liquid chromatography-mass spectrometry were markedly increased 6 h after injection of both CYP11B1 inhibitors and this increase was attenuated by finasteride pretreatment. We conclude that inhibition of CYP11B1 causes delayed seizure protection due to slow build-up of neurosteroids. Early seizure protection is independent of neurosteroids. PMID:21458468

Associations of serum sex steroid hormones and 5α-androstane-3α,17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride

PubMed Central

Kristal, Alan R.; Till, Cathee; Tangen, Catherine M.; Goodman, Phyllis J.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Chu, Lisa W.; Patel, Sherfaraz K.; Thompson, Ian; Reichardt, Juergen K.; Hoque, Ashraful; Platz, Elizabeth A.; Figg, William D.; Van Bokhoven, Adrie; Lippman, Scott M.; Hsing, Ann W

2012-01-01

BACKGROUND Finasteride, an inhibitor of 5 α-reductase (Type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1) and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. METHODS In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin (SHBG) were measured at baseline and approximately 3-years post-treatment in 553 prostate cancer cases and 694 controls. RESULTS Median post-treatment changes in concentrations of 3α-dG, T, E1, and E2 were −73.8%, +10.1%, +11.2%, and +7.5% (all p<0.001), respectively. Neither the pre- nor post-treatment concentrations of 3α-dG, nor its change, were associated with risk. Pre-treatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk (Odds Ratio[95% CI] quartile 4 vs 1: 1.38[0.99–1.93] ptrend=0.03; 0.64 [0.43–0.93] ptrend=0.07, respectively). Post-treatment, high concentrations of both E1 and E2 and were associated with increased cancer risk (OR[95% CI] quartile 4 vs 1: 1.54[1.09–2.17] ptrend=0.03; 1.49[1.07–2.07] ptrend=0.02, respectively). CONCLUSIONS Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2–6, 7–10 or 8–10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. IMPACT Low post-treatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer. PMID:22879203

Inhibition of 5α-Reductase in Rat Prostate Reveals Differential Regulation of Androgen-Response Gene Expression by Testosterone and Dihydrotestosterone

PubMed Central

Dadras, Soheil S.; Cai, Xiaoyan; Abasolo, Ibane; Wang, Zhou

2001-01-01

The growth and development of some of the male sex accessory organs such as the prostate requires the conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase. To provide insights into the role of testosterone versus DHT in the prostate, we studied the impact of finasteride, a potent and specific inhibitor of 5α-reductase, on the expression of prostatic androgen-response genes in testis-intact rats and in 7-day castrated rats. Finasteride inhibition of the conversion of testosterone to DHT was confirmed by measuring serum and intraprostatic androgens. As expected, finasteride treatment caused a reduction in the wet weight of the prostate in the testis-intact rats and inhibited the testosterone-stimulated prostatic regrowth in the 7-day castrated rats. Although finasteride treatment had little or no effect on the expression of the surveyed androgen-response genes in testis-intact rats, its administration enhanced the expression of many androgen-response genes during the testosterone-stimulated regrowth of the regressed prostate in castrated rats. These observations suggest that testosterone is more potent than DHT in stimulating the expression of many androgen-response genes in the regressed prostate. The expression of androgen-response genes is mainly prostate specific and thus is likely to be associated with androgen-dependent prostatic differentiation. Therefore, testosterone is more potent than DHT in inducing differentiation and weaker in stimulating proliferation during prostate regrowth. The fact that testosterone is a strong inducer of prostatic differentiation has potential clinical implications. PMID:11444528

Hormonal Treatment of Transgender Women with Oral Estradiol.

PubMed

Leinung, Matthew C; Feustel, Paul J; Joseph, Jalaja

2018-01-01

Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve this. We investigated the effectiveness of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since 2008 treated with oral estradiol. We looked at the success of achieving serum levels of testosterone and 17-β estradiol in the normal range on various doses of estradiol (with and without antiandrogens spironolactone and finasteride). Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.

Quantitative evaluation of glandular and stromal compartments in hyperplastic dog prostates: effect of 5-alpha reductase inhibitors.

PubMed

Laroque, P A; Prahalada, S; Molon-Noblot, S; Cohen, S M; Soper, K; Duprat, P; Peter, C P; van Zwieten, M J

1995-09-01

The objective of this study was to determine the effects of 2 different 5-alpha reductase inhibitors (finasteride and MK-0434) on the glandular and stromal compartments of hyperplastic canine prostates. In this study, dogs received 1 of the 2 compounds orally, at a dose of 1 mg/kg/day for 16 weeks; control dogs received a placebo. The morphological changes in the glandular and stromal compartments in the prostate were quantitated by a point-counting method on Masson's trichrome-stained sections. Treatment with 5-alpha reductase inhibitors resulted in significant (P < or = 0.05) decreases in mean prostatic volumes, microscopic evidence of prostatic atrophy, and significant (P < or = 0.05) decreases in the absolute volumes of the prostatic glandular and stromal compartments compared to controls. In finasteride-treated dogs, the mean percent change from baseline was: epithelium, -52; lumens, -58; fibrovascular stroma, -41; and smooth muscle, -29. In MK-0434-treated dogs, the mean percent change from baseline was: epithelium, -77; lumens, -58; fibrovascular stroma, -38; and smooth muscle, -42. The effect on the glandular compartment in dogs treated with MK-0434 was slightly greater than in dogs treated with finasteride; however, the effect on the stroma was similar. These results clearly demonstrate that inhibition of 5-alpha reductase enzyme activity affects growth and maintenance of both glandular and stromal compartments of dog hyperplastic prostates. It is likely that the decrease in size of the prostate in finasteride-treated (Proscar) men is due to shrinkage of both glandular and stromal compartments.

Effects of flutamide and finasteride on rat testicular descent.

PubMed

Spencer, J R; Torrado, T; Sanchez, R S; Vaughan, E D; Imperato-McGinley, J

1991-08-01

The endocrine control of descent of the testis in mammalian species is poorly understood. The androgen dependency of testicular descent was studied in the rat using an antiandrogen (flutamide) and an inhibitor of the enzyme 5 alpha-reductase (finasteride). Androgen receptor blockade inhibited testicular descent more effectively than inhibition of 5 alpha-reductase activity. Moreover, its inhibitory effect was limited to the outgrowth phase of the gubernaculum testis, particularly the earliest stages of outgrowth. Gubernacular size was also significantly reduced in fetuses exposed to flutamide during the outgrowth period. In contrast, androgen receptor blockade or 5 alpha-reductase inhibition applied after the initiation of gubernacular outgrowth or during the regression phase did not affect testicular descent. Successful inhibition of the development of epididymis and vas by prenatal flutamide did not correlate with ipsilateral testicular maldescent, suggesting that an intact epididymis is not required for descent of the testis. Plasma androgen assays confirmed significant inhibition of dihydrotestosterone formation in finasteride-treated rats. These data suggest that androgens, primarily testosterone, are required during the early phases of gubernacular outgrowth for subsequent successful completion of testicular descent.

Imaging prostate cancer (PCa) with [99m Tc(CO)3 ]finasteride dithiocarbamate.

PubMed

Shah, Syed Qaiser; Gul-E-Raana; Uddin, Ghias

2018-06-15

This investigation aimed to modify finasteride (1) to finasteride dithiocarbamate (2) for subsequent synthesis of the rhenium analogue (3) and [ 99m Tc]tricarbonyl complexes (4), to assess its prostate cancer (PCa) targeting potential in a rat model. To validate the identity of (4), reference (3) has been synthesized by using fac-[Net 4 ] 2 [ReBr 3 (CO) 3 ] precursor and characterized by 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis. The analogue (4) was synthesized by using fac-[ 99m Tc(H 2 O) 3 (CO) 3 ] + precursor, and its structure was confirmed by comparative HPLC by using (3) as a reference. Further, the suitability of (4) as a PCa imaging agent was investigated in vitro and in vivo. At room temperature, (4) had ≥99% radiochemical purity and remained ≥84% stable in serum. In preclinical studies, biodistribution of (4) in histopathologically established rat model showed adequately high in vivo uptake in the prostate attracting the possibility of using it for noninvasive imaging of PCa. Copyright © 2018 John Wiley & Sons, Ltd.

Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome

PubMed Central

Fertig, Raymond; Shapiro, Jerry; Bergfeld, Wilma; Tosti, Antonella

2017-01-01

Postfinasteride syndrome (PFS) is a term recently coined to characterize a constellation of reported undesirable side effects described in postmarketing reports and small uncontrolled studies that developed during or after stopping finasteride treatment, and persisted after drug discontinuation. Symptoms included decreased libido, erectile dysfunction, sexual anhedonia, decreased sperm count, gynecomastia, skin changes, cognitive impairment, fatigue, anxiety, depression, and suicidal ideation. The aim of this study is to review the existing medical literature for evidence-based research of permanent sexual dysfunction and mood changes during treatment with 5-alpha-reductase inhibitors including finasteride and dutasteride. PMID:28232919

The use of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator in a Mexican referral population: a validation study.

PubMed

Liang, Yuanyuan; Ketchum, Norma S; Louden, Christopher; Jimenez-Rios, Miguel A; Thompson, Ian M; Camarena-Reynoso, Hector R

2012-01-01

To perform the first validation study of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (finPCPTRC) in a contemporary referral population in Mexico. 837 patients referred to the Instituto Nacional de Cancerología, Mexico City, Mexico, between 2005 and 2009 were used to validate the finPCPTRC by examining various measures of discrimination and calibration. Net benefit curve analysis was used to gain insight into the use of the finPCPTRC for clinical decisions. Prostate cancer (PCa) incidence (72.8%) was high in this Mexican referral cohort and 45.7% of men who were diagnosed with PCa had high-grade lesions (HGPCa, Gleason score >6). 1.3% of the patients were taking finasteride. The finPCPTRC was a superior diagnostic tool compared to prostate-specific antigen alone when discriminating patients with PCa from those without PCa (AUC = 0.784 vs. AUC = 0.687, p < 0.001) and when discriminating patients with HGPCa from those without HGPCa (AUC = 0.768 vs. AUC = 0.739, p < 0.001). The finPCPTRC underestimated the risk of PCa but overestimated the risk of HGPCa (both p < 0.001). Compared with other strategies to opt for biopsy, the net benefit would be larger with utilization of the finPCPTRC for patients accepting higher risks of HGPCa. Rates of biopsy-detectable PCa and HGPCa were high and 1.3% of this referral cohort in Mexico was taking finasteride. The risks of PCa or HGPCa calculated by the finPCPTRC were not well calibrated for this referral Mexican population and new clinical diagnostic tools are needed. Copyright © 2012 S. Karger AG, Basel.

[Establishment of an in vitro screening model for steroid 5 alpha-reductase inhibitors with the microplate reader].

PubMed

Wu, Jian-Hui; Sun, Zu-Yue

2013-06-01

To establish an in vitro screening model for steroid 5 alpha-reductase inhibitors using the microplate reader. Steroid 5 alpha-reductase was obtained from the liver of female rats, an in vitro screening model for steroid 5 alpha-reductase inhibitors established using the 96-well plate and microplate reader after determination of the enzymatic activity, and the reliability of the model verified with the known 5 alpha-reductase inhibitors epristeride and finasteride. Added to the 96-well plate were the final concentrations of testosterone (0-40 micromol/L), NADPH (22 micromol/L), epristeride (0-60 nmol/L) or finasteride (0-60 nmol/ L) and steroid 5 alpha-reductase (20 microl), the total volume of each well adjusted to 200 microl with Tris-Hcl buffer. The 96-well plate was placed in the microplate reader, mixed and incubated at 37 degrees C, followed by detection of the A340nm value at 0 and 10 min and analysis of the data. The Km value of steroid 5 alpha-reductase was 3.794 micromol/L, with a Vmax of 0.271 micromol/(L. min). The Ki of epristeride was 148.2 nmol/L, with an IC50 of 31.5 nmol/L, and the enzymatic reaction kinetic curve suggested that epristeride was an uncompetitive enzyme inhibitor. The Ki of finasteride was 158. 8 nmol/L, with an IC50 of 13.6 nmol/L. The enzymatic reaction kinetic curve showed that both epristeride and finasteride were competitive enzyme inhibitors, similar to those reported in the published literature. A screening model was successfully established, which could rapidly and effectively screen steroid 5 alpha-reductase inhibitors in vitro.

Evidence for the efficacy and safety of tadalafil and finasteride in combination for the treatment of lower urinary tract symptoms and erectile dysfunction in men with benign prostatic hyperplasia

PubMed Central

Olesovsky, Chris; Kapoor, Anil

2016-01-01

Benign prostatic hyperplasia (BPH) is an age-related phenomenon associated with prostatic enlargement and bladder outlet obstruction that can cause significant lower urinary tract symptoms (LUTS). These LUTS have a negative impact on an individual’s quality of life, which is why treatment of symptomatic BPH has become a major priority. Although surgical interventions exist for treating BPH, pharmacological therapies are often preferred due to their minimal invasiveness and high degree of effectiveness. The three classes of drugs approved for treating BPH include α-blockers, 5-α-reductase inhibitors (5-ARIs) and phosphodiesterase 5 (PDE-5) inhibitors. Individually, each class of drug has been studied and shown to improve symptom relief through a variety of different mechanisms. A more recent focus has been on the development of combinatorial therapies that combine classes of drugs in order to provide maximal benefit. The mTOPS and CombAT studies were the first of their kind to examine whether the combination of 5-ARIs and α-blockers was more effective than monotherapy alone. Both studies found similar results in that the combinatorial therapy was superior to monotherapy. Over the last decade other combinatorial therapies have been at the forefront of investigation. One in particular is the combination of tadalafil, a PDE-5 inhibitor, with finasteride, a 5-ARI. Studies have shown that the combination of tadalafil and finasteride is a safe, effective, and well tolerated treatment for BPH. Evidence suggests that this combination may be particularly effective in reducing treatment-related sexual adverse events associated with 5-ARI treatments. The following review will explore in detail the current evidence surrounding treatment of BPH LUTS using tadalafil and finasteride. PMID:27928428

Effects of Kangquan Recipe on sex steroids and cell proliferation in rats with benign prostatic hyperplasia.

PubMed

Huang, Yuan-peng; Du, Jian; Hong, Zhen-feng; Chen, Zhi-qing; Wu, Jin-fa; Zhao, Jin-yan

2009-08-01

To investigate the effects of Kangquan Recipe (KQR) on sex steroids and cell proliferation in an experimental benign prostatic hyperplasia (BPH) model in rats. Seventy-two SD rats were randomly divided into six groups: the normal group, the model group, the finasteride group, and the low-, middle-, and high-dose KQR groups, 12 in each group. Except those in the normal group, the rats were injected with testosterone after castration for the establishment of BPH model and then given respectively with normal saline, finasteride, and low-, middle-, and high-dose of KQR for 30 days. The levels of plasma testosterone (T) and estradiol (E(2)) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression ) of proliferating cell nuclear antigen (PCNA) in prostate tissue was detected by reverse transcription-polymerase chain reaction (RT-PCR) after administration. Compared with the model group, the prostate weight, the plasma T, and the mRNA expression of PCNA were significantly lower, and the plasma E(2) and the ratio of E(2)/T were higher in the three KQR groups (P<0.05 or P<0.01). There was no significant difference in the prostate weight, plasma T and E(2), and ratio of E(2)/T among the finasteride group and the three KQR groups (P>0.05). The mRNA expressions of PCNA were significantly higher in the middle- and low-dose of KQR groups than those in the finasteride group (P<0.05). KQR shows multitarget effects on experimental BPH rats, and the mechanism might be related with regulating the balance of plasma T and E(2) and decreasing the PCNAmRNA expression in prostate tissue to restrain cell proliferation in a dose-dependent manner.

Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial

PubMed Central

Tang, Li; Yao, Song; Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.; Wu, Yue; Kristal, Alan R.; Platz, Elizabeth A.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Reichardt, Juergen K.V.; Santella, Regina M.; Hsing, Ann; Hoque, Ashraful; Lippman, Scott M.; Thompson, Ian M.; Ambrosone, Christine B.

2011-01-01

The etiology of prostate cancer remains elusive, although steroid hormones probably play a role. Considering the carcinogenic potential of estrogen metabolites as well as altered intraprostatic estrogen biosynthesis during the development of prostate cancer, we investigated associations between repeat polymorphisms of three key estrogen-related genes (CYP11A1, CYP19A1, UGT1A1) and risk of prostate cancer in the Prostate Cancer Prevention Trial (PCPT), designed to test finasteride versus placebo as a chemoprevention agent. Using data and specimens from 1154 cases and 1351 controls who were frequency matched on age, family history of prostate cancer and PCPT treatment arm, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) separately in the placebo and finasteride arms. Among men in the placebo arm, CYP19A1 7/8 genotype carriers had a significantly higher risk of prostate cancer compared with those with the 7/7 genotype (OR = 1.70, 95% CI = 1.16–2.5), regardless of Gleason grade. This genotype was also associated with elevated serum estrogen levels. For the (TA)n repeat polymorphism in UGT1A1, the heterozygous short (<7 repeats)/long (≥7 repeats) genotype was significantly associated with the risk of low-grade prostate cancer (OR = 1.34, 95% CI = 1.05–1.70) compared with the short/short genotype. No significant association was found with CYP11A1. These associations were not observed among men in the finasteride arm. The results indicate that repeat polymorphisms in genes involved in estrogen biosynthesis and metabolism may influence risk of prostate cancer but that their effects may be modified by factors altering hormone metabolism, such as finasteride treatment. PMID:21771722

Pharmacokinetics of 2 Novel Formulations of Modified-Release Oral Testosterone Alone and With Finasteride in Normal Men With Experimental Hypogonadism

PubMed Central

Snyder, Christin N.; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Roth, Mara Y.; Page, Stephanie T.; Bremner, William J.; Amory, John K.

2011-01-01

Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current “immediate-release” formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiologic peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed 2 novel modified-release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in 16 normal young men enrolled in a 2-arm, open-label clinical trial. Three hundred-mg and 600-mg doses of immediate-release and modified fast-release or slow-release formulations were administered sequentially to 8 normal men rendered hypogonadal by the administration of the gonadotropin-releasing hormone antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of 8 men was studied with the coadministration of 1 mg of the 5α-reductase inhibitor finasteride daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the postdose peaks of serum testosterone and reduced peak concentrations of serum DHT compared with the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared with immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency. PMID:20378927

Fixed-dose combination PRO 160/120 of sabal and urtica extracts improves nocturia in men with LUTS suggestive of BPH: re-evaluation of four controlled clinical studies.

PubMed

Oelke, Matthias; Berges, Richard; Schläfke, Sandra; Burkart, Martin

2014-10-01

To determine the effects of the herbal fixed-dose combination PRO 160/120 (extracts from saw palmetto fruits and stinging nettle roots) on nocturnal voiding frequency, as measured by question 7 of the IPSS questionnaire, in patients with moderate-to-severe LUTS/BPH after 24 weeks of treatment compared to placebo, to the α-blocker tamsulosin, or to the 5α-reductase inhibitor finasteride. The study is about post hoc evaluation of four published randomized, double-blind clinical trials on PRO 160/120, two compared with placebo, one with finasteride and one with tamsulosin. In addition, a pooled data analysis of the two placebo-controlled trials was conducted. We analyzed data from a total of 922 patients with a mean age of 66 years and a mean baseline nocturnal voiding frequency of 2.1. In the pooled analysis of placebo-controlled trials, nocturnal voids improved by 0.8 (29 %) with PRO 160/120 compared to 0.6 (18 %) with placebo (p = 0.015, Wilcoxon test, one-tailed). The 69 % responder rate to PRO 160/120 was significantly superior to the placebo response (52 %; p = 0.003, χ (2)-test, two-tailed). The majority of responders improved by 1 void/night. Absolute improvements and response rates were consistently higher with PRO 160/120 than with placebo over a range of baseline nocturnal voiding frequencies. There were no differences between PRO 160/120 and finasteride or tamsulosin regarding absolute improvement of nocturnal voids or responds rates. PRO 160/120 significantly improved nocturnal voiding frequency compared to placebo and similar to tamsulosin or finasteride.

Use of low-level laser therapy as monotherapy or concomitant therapy for male and female androgenetic alopecia.

PubMed

Munck, Andréia; Gavazzoni, Maria Fernanda; Trüeb, Ralph M

2014-04-01

Androgenetic alopecia (AGA) is the most common form of hair loss in men and in women. Currently, minoxidil and finasteride are the treatments with the highest levels of medical evidence, but patients who exhibit intolerance or poor response to these treatments are in need of additional treatment modalities. The aim was to evaluate the efficacy and safety of low-level laser therapy (LLLT) for AGA, either as monotherapy or as concomitant therapy with minoxidil or finasteride, in an office-based setting. Retrospective observational study of male and female patients with AGA, treated with the 655 nm-HairMax Laser Comb(®), in an office-based setting. Efficacy was assessed with global photographic imaging. Of 32 patients (21 female, 11 male), 8 showed significant, 20 moderate, and 4 no improvement. Improvement was seen both with monotherapy and with concomitant therapy. Improvement was observed as early as 3 months and was sustained up to a maximum observation time of 24 months. No adverse reactions were reported. LLLT represents a potentially effective treatment for both male and female AGA, either as monotherapy or concomitant therapy. Combination treatments with minoxidil, finasteride, and LLLT may act synergistic to enhance hair growth.

Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin?

PubMed

Giatti, Silvia; Diviccaro, Silvia; Panzica, Giancarlo; Melcangi, Roberto Cosimo

2018-04-19

Sexual dysfunction is a clinical condition due to different causes including the iatrogenic origin. For instance, it is well known that sexual dysfunction may occur in patients treated with antidepressants like selective serotonin reuptake inhibitors (SSRI). A similar side effect has been also reported during treatment with finasteride, an inhibitor of the enzyme 5alpha-reductase, for androgenetic alopecia. Interestingly, sexual dysfunction persists in both cases after drug discontinuation. These conditions have been named post-SSRI sexual dysfunction (PSSD) and post-finasteride syndrome (PFS). In particular, feeling of a lack of connection between the brain and penis, loss of libido and sex drive, difficulty in achieving an erection and genital paresthesia have been reported by patients of both conditions. It is interesting to note that the incidence of these diseases is probably so far underestimated and their etiopathogenesis is not sufficiently explored. To this aim, the present review will report the state of art of these two different pathologies and discuss, on the basis of the role exerted by three different neuromodulators such as dopamine, serotonin and neuroactive steroids, whether the persistent sexual dysfunction observed could be determined by common mechanisms.

Null Mutation of 5α-Reductase Type I Gene Alters Ethanol Consumption Patterns in a Sex-Dependent Manner

PubMed Central

Nickel, Jeffrey D.; Kaufman, Moriah N.; Finn, Deborah A.

2014-01-01

The neuroactive steroid allopregnanolone (ALLO) is a positive modulator of GABAA receptors, and manipulation of neuroactive steroid levels via injection of ALLO or the 5α-reductase inhibitor finasteride alters ethanol self-administration patterns in male, but not female, mice. The Srd5a1 gene encodes the enzyme 5α-reductase-1, which is required for the synthesis of ALLO. The current studies investigated the influence of Srd5a1 deletion on voluntary ethanol consumption in male and female wildtype (WT) and knockout (KO) mice. Under a continuous access condition, 6 and 10 % ethanol intake was significantly greater in KO versus WT females, but significantly lower in KO versus WT males. In 2-h limited access sessions, Srd5a1 deletion retarded acquisition of 10 % ethanol intake in female mice, but facilitated it in males, versus respective WT mice. The present findings demonstrate that the Srd5a1 gene modulates ethanol consumption in a sex-dependent manner that is also contingent upon ethanol access condition and concentration. PMID:25416204

Null mutation of 5α-reductase type I gene alters ethanol consumption patterns in a sex-dependent manner.

PubMed

Ford, Matthew M; Nickel, Jeffrey D; Kaufman, Moriah N; Finn, Deborah A

2015-05-01

The neuroactive steroid allopregnanolone (ALLO) is a positive modulator of GABAA receptors, and manipulation of neuroactive steroid levels via injection of ALLO or the 5α-reductase inhibitor finasteride alters ethanol self-administration patterns in male, but not female, mice. The Srd5a1 gene encodes the enzyme 5α-reductase-1, which is required for the synthesis of ALLO. The current studies investigated the influence of Srd5a1 deletion on voluntary ethanol consumption in male and female wildtype (WT) and knockout (KO) mice. Under a continuous access condition, 6 and 10 % ethanol intake was significantly greater in KO versus WT females, but significantly lower in KO versus WT males. In 2-h limited access sessions, Srd5a1 deletion retarded acquisition of 10 % ethanol intake in female mice, but facilitated it in males, versus respective WT mice. The present findings demonstrate that the Srd5a1 gene modulates ethanol consumption in a sex-dependent manner that is also contingent upon ethanol access condition and concentration.

Use of Low-Level Laser Therapy as Monotherapy or Concomitant Therapy for Male and Female Androgenetic Alopecia

PubMed Central

Munck, Andréia; Gavazzoni, Maria Fernanda; Trüeb, Ralph M

2014-01-01

Background: Androgenetic alopecia (AGA) is the most common form of hair loss in men and in women. Currently, minoxidil and finasteride are the treatments with the highest levels of medical evidence, but patients who exhibit intolerance or poor response to these treatments are in need of additional treatment modalities. Objective: The aim was to evaluate the efficacy and safety of low-level laser therapy (LLLT) for AGA, either as monotherapy or as concomitant therapy with minoxidil or finasteride, in an office-based setting. Materials and Methods: Retrospective observational study of male and female patients with AGA, treated with the 655 nm-HairMax Laser Comb®, in an office-based setting. Efficacy was assessed with global photographic imaging. Results: Of 32 patients (21 female, 11 male), 8 showed significant, 20 moderate, and 4 no improvement. Improvement was seen both with monotherapy and with concomitant therapy. Improvement was observed as early as 3 months and was sustained up to a maximum observation time of 24 months. No adverse reactions were reported. Conclusions: LLLT represents a potentially effective treatment for both male and female AGA, either as monotherapy or concomitant therapy. Combination treatments with minoxidil, finasteride, and LLLT may act synergistic to enhance hair growth. PMID:25191036

Neonatal finasteride administration alters hippocampal α4 and δ GABAAR subunits expression and behavioural responses to progesterone in adult rats.

PubMed

Modol, Laura; Casas, Caty; Navarro, Xavier; Llidó, Anna; Vallée, Monique; Pallarès, Marc; Darbra, Sònia

2014-02-01

Allopregnanolone is a neurosteroid that has been reported to fluctuate during early developmental stages. Previous experiments reported the importance of neonatal endogenous allopregnanolone levels for the maturation of the central nervous system and particularly for the hippocampus. Changes in neonatal allopregnanolone levels have been related to altered adult behaviour and with psychopathological susceptibility, including anxiety disorders, schizophrenia and drug abuse. However, the mechanism underlying these changes remains to be elucidated. In the present study we assessed changes in hippocampal expression of α4 and δ GABAA receptor (GABAAR) subunits as a consequence of neonatal finasteride (a 5-α reductase inhibitor) administration during early development (PD6 to PD15) in male rats. We observed that the treatment altered the temporal window of the natural peak in the expression of these subunits during development. Additionally, the level of these subunits were higher than in non-handled and control animals in the adult hippocampus. We observed that in adulthood, neonatal finasteride-treated animals presented an anxiogenic-like profile in response to progesterone administration which was absent in the rest of the groups. In conclusion, these results corroborate the relevance of neonatal maintenance of neurosteroid levels for behavioural anxiety responses in the adult, and point to some of the mechanisms involved in this alterations.

Testosterone Conversion Blockade Increases Breathing Stability in Healthy Men during NREM Sleep

PubMed Central

Chowdhuri, Susmita; Bascom, Amy; Mohan, David; Diamond, Michael P.; Badr, M. Safwan

2013-01-01

Study Objectives: Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. Design: Randomization to oral finasteride vs. sham, single-center study. Setting: Sleep research laboratory. Participants: Fourteen healthy young males without sleep apnea Intervention: Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. Measurements and Results: The apnea threshold (AT) was defined as the end-tidal CO2 (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 between eupnea and AT. The apneic threshold and CO2 reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO2 reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. Conclusions: Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations. Citation: Chowdhuri S; Bascom A; Mohan D; Diamond MP; Badr MS. Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep. SLEEP 2013;36(12):1793-1798. PMID:24293753

The effects of dutasteride and finasteride on BPH-related hospitalization, surgery and prostate cancer diagnosis: a record-linkage analysis.

PubMed

Cindolo, Luca; Fanizza, Caterina; Romero, Marilena; Pirozzi, Luisella; Autorino, Riccardo; Berardinelli, Francesco; Schips, Luigi

2013-06-01

To investigate differences in the risk of benign prostatic hyperplasia (BPH)-related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients using finasteride or dutasteride. A retrospective cohort study was conducted using data from record linkage of administrative databases (pharmaceutical prescription data, hospital discharge records, Italian population registry). Men aged ≥ 40 years old who had received a prescription for at least 10 packs/year between January 1, 2004 and December 31, 2004 were included and followed for 5 years. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity score-matched analysis and a 5-1, greedy 1:1 matching algorithm were performed. 8,132 patients were identified. Overall incidence rates of BPH hospitalization and BPH-related surgery were 21.05 (95 % CI 19.52-22.71) and 20.97 (95 % CI 19.45-22.61) per 1,000 person-years, respectively. In the dutasteride group compared with finasteride group, the incidence rate of both events was statistically significant lower: 16.07 versus 21.76 for BPH hospitalization and 15.91 versus 21.69 for BPH-related surgery. The incidence rate of new PCa was also lower for the dutasteride group [8.34 (95 % CI 5.96-11.68) vs. 10.25 (95 % CI 9.15-11.49)]. Dutasteride was associated with a reduction in BPH-related hospitalizations (HR 0.75, 95 % CI 0.58-0.98 and 0.58-0.98 for surgical and non-surgical reasons). The matched analysis confirmed the risk reduction with dutasteride for BPH-related surgery. These findings suggest that the clinical effects of dutasteride and finasteride might be different. Patients treated with dutasteride seem to be less likely to experience BPH-related hospitalization. Comparative studies are needed to confirm these results.

Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.

PubMed

Gasco, M; Villegas, L; Yucra, S; Rubio, J; Gonzales, G F

2007-08-01

The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.

Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor.

PubMed

Clark, Richard V; Hermann, David J; Cunningham, Glenn R; Wilson, Timothy H; Morrill, Betsy B; Hobbs, Stuart

2004-05-01

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.

Hair loss

MedlinePlus

... that is applied to the scalp to stimulate hair growth. Other medicines, such as hormones, may be prescribed to decrease hair loss and promote hair growth. Drugs such as finasteride and dutasteride can be ...

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

PubMed Central

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B.; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-01-01

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis. PMID:27529214

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

PubMed

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-08-11

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

Testosterone Plus Finasteride Treatment After Spinal Cord Injury

ClinicalTrials.gov

2018-05-16

Spinal Cord Injury; Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male

Finasteride

MedlinePlus

... Propecia) is also used to treat male pattern hair loss (gradual thinning of the hair on the scalp, leading to a receding hairline ... Propecia) has not been shown to treat thinning hair at the temples and is not used to ...

Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man.

PubMed

Hazlehurst, Jonathan M; Oprescu, Andrei I; Nikolaou, Nikolaos; Di Guida, Riccardo; Grinbergs, Annabel E K; Davies, Nigel P; Flintham, Robert B; Armstrong, Matthew J; Taylor, Angela E; Hughes, Beverly A; Yu, Jinglei; Hodson, Leanne; Dunn, Warwick B; Tomlinson, Jeremy W

2016-01-01

5α-Reductase 1 and 2 (SRD5A1, SRD5A2) inactivate cortisol to 5α-dihydrocortisol in addition to their role in the generation of DHT. Dutasteride (dual SRD5A1 and SRD5A2 inhibitor) and finasteride (selective SRD5A2 inhibitor) are commonly prescribed, but their potential metabolic effects have only recently been identified. Our objective was to provide a detailed assessment of the metabolic effects of SRD5A inhibition and in particular the impact on hepatic lipid metabolism. We conducted a randomized study in 12 healthy male volunteers with detailed metabolic phenotyping performed before and after a 3-week treatment with finasteride (5 mg od) or dutasteride (0.5 mg od). Hepatic magnetic resonance spectroscopy (MRS) and two-step hyperinsulinemic euglycemic clamps incorporating stable isotopes with concomitant adipose tissue microdialysis were used to evaluate carbohydrate and lipid flux. Analysis of the serum metabolome was performed using ultra-HPLC-mass spectrometry. The study was performed in the Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, United Kingdom. Incorporation of hepatic lipid was measured with MRS. Dutasteride, not finasteride, increased hepatic insulin resistance. Intrahepatic lipid increased on MRS after dutasteride treatment and was associated with increased rates of de novo lipogenesis. Adipose tissue lipid mobilization was decreased by dutasteride. Analysis of the serum metabolome demonstrated that in the fasted state, dutasteride had a significant effect on lipid metabolism. Dual-SRD5A inhibition with dutasteride is associated with increased intrahepatic lipid accumulation.

[With alpha blockers, finasteride and nettle root against benign prostatic hyperplasia. Which patients are helped by conservative therapy?].

PubMed

Vahlensieck, W

2002-04-18

Symptomatic benign prostatic hyperplasia (BPH), which a man has a 50% chance of developing during the course of his lifetime, should receive stage-related treatment. While Vahlensieck stage I disease requires no therapy, stages II and III are indications for medication. Established medications for the treatment of BPH in current use are alpha-blockers, finasteride, and the phytotherapeutic agents pumpkin seed (cucurbitae semen), nettle root (urticae radix), the phytosterols contained in Hypoxis rooperi, rye pollen and the fruits of saw palmetto (sabalis serrulati fructus). If the patient responds, these medicaments can be given life-long, or intermittently. The hard criterion for the rational use of drug treatment of BPH is, over the long term, the reduction in the number of prostate operations. In stage IV disease surgical measures--after prior compensation of renal function--are to the fore.

Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia.

PubMed

Said, Mahmoud M; Hassan, Nahla S; Schlicht, Michael J; Bosland, Maarten C

2015-01-01

Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

Repetitive Prostatic Massage and Drug Therapy as an Alternative to Transurethral Resection of the Prostate

PubMed Central

Hennenfent, Bradley R.; Lazarte, Alfred R.; Feliciano, Antonio E.

2006-01-01

We describe 5 men with urinary retention and indwelling urethral catheters who were treated with repetitive prostatic massage, antimicrobials, alpha blockers, and – in 2 cases – finasteride. We retrospectively reviewed the charts of all patients presenting to the genitourinary clinic with indwelling urinary catheters during a 1-year period. Five men (mean age, 70 years; range, 64–76; SD 4.47) presented to the Manila Genitourinary Clinic (Cebu Branch), Cebu, Philippines, wearing indwelling urinary catheters placed for acute urinary retention. Urologists had told all 5 men that they needed to undergo transurethral resection of the prostate (TURP). The Cebu genitourinary physician removed the catheters, instituted repetitive prostatic massage, and diagnosed all 5 patients with prostatitis. All 5 patients received repetitive prostatic massage, alpha-blocker medication, and antibiotic therapy, whereas finasteride was given to 2 patients. During treatment, statistically significant improvements occurred in global symptom severity scores, urethral white blood cell (WBC) counts, WBC counts of the expressed prostatic secretions (EPS), EPS red blood cell (RBC) counts, urinary WBC counts, and urinary RBC counts. Fluorescing Chlamydia elementary bodies disappeared in 3 of the 4 positive patients by the end of treatment. (One patient was not available for retesting.) Repetitive prostatic massage, antimicrobial therapy, alpha-blocker therapy, and – in 2 cases – finasteride enabled catheter removal in all 5 men (100%) as well as successful urination in all 5 men (100%). TURP has been prevented for a mean of 2.53 years (range, 16–38 months). PMID:17415302

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.

Ultrasound image features of intravesical prostatic protrusion indicated failure of medication therapy of finasteride and doxazosin in patients with benign prostatic hyperplasia (LUTS/BPH).

PubMed

Liu, Qiang; Zhu, Yunkai; Liu, Jianping; Qi, Jun; Kang, Jian

2017-03-01

Intravesical prostatic protrusion (IPP) is a type of benign prostatic hyperplasia (BPH) adenoma, and it plays a critical role in the pathogenesis of bladder outlet obstruction in patients with lower urinary tract syndromes (LUTS/BPH). The goal of this study was to investigate the effect of a combination therapy with finasteride and doxazosin on IPP in BPU/LUTS patients. A total of 322 BPH patients with enlarged prostatic volume as well as moderate to severe symptom scores were enrolled and divided into four groups according to the degree of IPP (IPP > 10 mm, 5-10 mm, <5 mm and no IPP) in this study. Aggravated International Prostatic Symptom Score (IPSS), acute urinary retention or relevant urinary complications were considered as failure of the therapy. The degrees of IPP were recorded before and after 6 months of treatment. Student's t test and χ 2 were performed between the baseline and endpoint of the therapy. The results showed that the total prostate volume (TPV) and transition zone volume (TZV) of the prostate decreased significantly after 6-month combination therapy (P < 0.05), while no significant changes in IPP were observed at that point (P > 0.05). Failure rates of the medication differed significantly among the four groups. The study indicated that the combination therapy using finasteride and doxazosin could not reduce the degree of IPP. LUTS/BPH patients with IPP which contributes to the failure of medication tend to have a higher risk of progression.

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

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

MedlinePlus

... the researchers gathered using data from the Social Security Death Index (SSDI) from the time the trial ... Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department ...

The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis.

PubMed

Adil, Areej; Godwin, Marshall

2017-07-01

Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food and Drug Administration (FDA)-approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia. This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators. A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process. A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo (P < .00001) in the 5 meta-analyses. Other treatments were not included because the appropriate data were lacking. High heterogeneity in most studies. This meta-analysis strongly suggests that minoxidil, finasteride, and low-level laser light therapy are effective for promoting hair growth in men with androgenetic alopecia and that minoxidil is effective in women with androgenetic alopecia. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

PubMed Central

Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

2016-01-01

Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

Effects of neonatal allopregnanolone manipulations and early maternal separation on adult alcohol intake and monoamine levels in ventral striatum of male rats.

PubMed

Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc

2016-06-01

Changes in endogenous neonatal levels of the neurosteroid allopregnanolone (AlloP) as well as a single 24h period of early maternal separation (EMS) on postnatal day (PND) 9 affect the development of the central nervous system (CNS), causing adolescent/adult alterations including systems and behavioural traits that could be related to vulnerability to drug abuse. In rats, some behavioural alterations caused by EMS can be neutralised by previous administration of AlloP. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP could increase adult alcohol consumption, and if EMS could change these effects. We administered AlloP or finasteride, a 5α-reductase inhibitor, from PND5 to PND9, followed by 24h of EMS at PND9. At PND70 we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 15days. Ventral striatum samples were obtained to determine monoamine levels. Results revealed that neonatal finasteride increased both ethanol and glucose consumption, and AlloP increased alcohol intake compared with neonatal vehicle-injected animals. The differences between neonatal groups in alcohol consumption were not found in EMS animals. In accordance, both finasteride and AlloP animals that did not suffer EMS showed lower levels of dopamine and serotonin in ventral striatum. Taken together, these results reveal that neonatal neurosteroids alterations affect alcohol intake; an effect which can be modified by subsequent EMS. Thus, these data corroborate the importance of the relationship between neonatal neurosteroids and neonatal stress for the correct CNS development. Copyright © 2016 Elsevier Inc. All rights reserved.

Various treatment options for benign prostatic hyperplasia: A current update

PubMed Central

Shrivastava, Alankar; Gupta, Vipin B.

2012-01-01

In benign prostatic hyperplasia (BPH) there will be a sudden impact on overall quality of life of patient. This disease occurs normally at the age of 40 or above and also is associated with sexual dysfunction. Thus, there is a need of update on current medications of this disease. The presented review provides information on medications available for BPH. Phytotherapies with some improvements in BPH are also included. Relevant articles were identified through a search of the English-language literature indexed on MEDLINE, PUBMED, Sciencedirect and the proceedings of scientific meetings. The search terms were BPH, medications for BPH, drugs for BPH, combination therapies for BPH, Phytotherapies for BPH, Ayurveda and BPH, BPH treatments in Ayurveda. Medications including watchful waitings, Alpha one adrenoreceptor blockers, 5-alpha reductase inhibitors, combination therapies including tamsulosin-dutasteride, doxazosin-finasteride, terazosin-finasteride, tolterodine-tamsulosin and rofecoxib-finasteride were found. Herbal remedies such as Cernilton, Saxifraga stolonifera, Zi-Shen Pill (ZSP), Orbignya speciosa, Phellodendron amurense, Ganoderma lucidum, Serenoa Repens, pumpkin extract and Lepidium meyenii (Red Maca) have some improvements on BPH are included. Other than these discussions on Ayurvedic medications, TURP and minimally invasive therapies (MITs) are also included. Recent advancements in terms of newly synthesized molecules are also discussed. Specific alpha one adrenoreceptor blockers such as tamsulosin and alfuzosin will remain preferred choice of urologists for symptom relief. Medications with combination therapies are still needs more investigation to establish as preference in initial stage for fast symptom relief reduced prostate growth and obviously reduce need for BPH-related surgery. Due to lack of proper evidence Phytotherapies are not gaining much advantage. MITs and TURP are expensive and are rarely supported by healthcare systems. PMID:22923974

Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.

PubMed

Zhang, Hui; Ma, Li; Yin, Yan-Ling; Dong, Lian-Qiang; Cheng, Gang-Ge; Ma, Ya-Qun; Li, Yun-Feng; Xu, Bai-Nan

2016-09-01

The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular profiles of finasteride effects on prostate carcinogenesis.

PubMed

Li, Jin; Kim, Jeri

2009-06-01

Our inability to distinguish between low-grade prostate cancers that pose no threat and those that can kill compels newly diagnosed early prostate cancer patients to make decisions that may negatively affect their lives needlessly for years afterward. To reliably stratify patients into different risk categories and apply appropriate treatment, we need a better molecular understanding of prostate cancer progression. Androgen ablation therapy and 5-alpha reductase inhibitors reduce dihydrotestosterone levels and increase apoptosis. Because of the differing biological potentials of tumor cells, however, these treatments may, in some cases, worsen outcome by selecting for or inducing adaptation of stronger androgen receptor signaling pathways. Reduced dihydrotestosterone also may be associated with altered survival pathways. Complicating treatment effects further, molecular adaptation may be accelerated by interactions between epithelial and stromal cells. The hypothesis that early prostate cancer cells with differing biological potential may respond differently to finasteride treatment is worth testing. Ongoing studies using a systems biology approach in a preoperative prostate cancer setting are testing this hypothesis toward developing more-rational clinical interventions.

Epoxy Fatty Acids and Inhibition of the Soluble Epoxide Hydrolase Selectively Modulate GABA Mediated Neurotransmission to Delay Onset of Seizures

PubMed Central

Inceoglu, Bora; Zolkowska, Dorota; Yoo, Hyun Ju; Wagner, Karen M.; Yang, Jun; Hackett, Edward; Hwang, Sung Hee; Lee, Kin Sing Stephen; Rogawski, Michael A.; Morisseau, Christophe; Hammock, Bruce D.

2013-01-01

In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders. PMID:24349022

Biorepository for Prostate Cancer Prevention Trial (PCPT) | Division of Cancer Prevention

Cancer.gov

The PCPT biorepository and extended data was used to further explore the initial suggestion that some men taking finasteride were at risk of developing high-grade prostate cancers, and to look at the value of prostate-specific antigen (PSA) for early detection. Researchers showed that: |

The Impact of 5α-Reductase Inhibitor Use for Male Pattern Hair Loss on Men's Health.

PubMed

Said, Mohammed A; Mehta, Akanksha

2018-06-16

Male pattern hair loss, mediated by dihydrotestosterone, is a common hair loss disorder, affecting over 50% of men over the age of 50. The 5-α reductase inhibitors, finasteride and dutasteride, are Food and Drug Administration-approved drugs for the treatment of this disorder. Several recent studies have reported adverse sexual and spermatogenic events among young men using 5-α reductase inhibitors, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility. In this review, we summarize and analyze the literature regarding the efficacy and safety of these medications, with an overall focus on men's health. Finasteride for the treatment of male pattern hair loss was considered safe according to many previous clinical trials. However, these trials have been recently criticized for inadequate safety reporting. Comprehensive review of the current literature reveals that there is a disproportionately high number of men with 5-α reductase inhibitor-associated sexual dysfunction and infertility. Although uncommon, the use of 5-α reductase inhibitors is associated with serious and persistent sexual and reproductive side effects, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility.

Persistent escalation of alcohol consumption by mice exposed to brief episodes of social defeat stress: suppression by CRF-R1 antagonism.

PubMed

Newman, Emily L; Albrechet-Souza, Lucas; Andrew, Peter M; Auld, John G; Burk, Kelly C; Hwa, Lara S; Zhang, Eric Y; DeBold, Joseph F; Miczek, Klaus A

2018-06-01

Episodic bouts of social stress can precede the initiation, escalation, or relapse to disordered alcohol intake. Social stress may engender neuroadaptations in the hypothalamic-pituitary-adrenal (HPA) axis and in extrahypothalamic stress circuitry to promote the escalation of alcohol intake. We aimed to (1) confirm a pattern of escalated drinking in socially defeated mice and to (2) test drugs that target distinct aspects of the HPA axis and extrahypothalamic neural substrates for their effectiveness in reducing murine, stress-escalated drinking. Male C57BL/6J (B6) mice were socially defeated by resident Swiss-derived males for ten consecutive days receiving 30 bites/day. Ten days after the final defeat, cohorts of B6 mice received continuous or intermittent access to 20% EtOH (w/v) and water. After 4 weeks of drinking, mice were injected with weekly, systemic doses of the CRF-R1 antagonist, CP376395; the glucocorticoid receptor antagonist, mifepristone; the 11-beta-hydroxylase inhibitor, metyrapone; or the 5-alpha-reductase inhibitor, finasteride. Prior to drug treatments, defeated mice reliably consumed more EtOH than non-defeated controls, and mice given alcohol intermittently consumed more EtOH than those with continuous access. CP376395 (17-30 mg/kg) reduced continuous, but not intermittent EtOH intake (g/kg) in socially defeated mice. Mifepristone (100 mg/kg), however, increased drinking by defeated mice with intermittent access to alcohol while reducing drinking during continuous access. When administered finasteride (100 mg/kg) or metyrapone (50 mg/kg), all mice reduced their EtOH intake while increasing their water consumption. Mice with a history of episodic social defeat stress were selectively sensitive to the effects of CRF-R1 antagonism, suggesting that CRF-R1 may be a potential target for treating alcohol use disorders in individuals who escalate their drinking after exposure to repeated bouts of psychosocial stress. Future studies will clarify how social defeat stress may alter the expression of extrahypothalamic CRF-R1 and glucocorticoid receptors.

Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sayed, Rabab H., E-mail: rabab.sayed@pharma.cu.edu

Serotonin level plays a role in suppressing the pathological findings of benign prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor, dapoxetine was used to test its ability to ameliorate the pathological changes in the rat prostate. A dose response curve was constructed between the dose of dapoxetine and prostate weight as well as relative prostate weight, then a 5 mg/kg dose was used as a representative dose for dapoxetine administration. Rats were divided into four groups; the control group that received the vehicle; the BPH-induced group received daily s.c injection of 3 mg/kg testosterone propionate dissolved in olivemore » oil for four weeks; BPH-induced group treated with finasteride 5 mg/kg/day p.o and BPH-induced group treated with dapoxetine 5 mg/kg/day p.o. Injection of testosterone increased prostate weight and relative prostate weight which were both returned back to the normal value after treatment with dapoxetine as well as finasteride. Testosterone also upregulated androgen receptor (AR) and proliferating cell nuclear antigen gene expression. Furthermore, testosterone injection elevated cyclooxygenase-II (COX II), inducible nitric oxide synthase (iNOS), B-cell lymphoma-2 (Bcl2) expression and tumor necrosis factor alpha content and reduced caspase-3 activity, Bcl-2-associated X protein (Bax) expression and Bax/Bcl2 ratio. Dapoxetine and finasteride administration reverted most of the changes made by testosterone injection. In conclusion, the current study provides an evidence for the protective effects of dapoxetine against testosterone-induced BPH in rats. This can be attributed, at least in part, to decreasing AR expression, and the anti-proliferative, anti-inflammatory and pro-apoptotic activities of dapoxetine in BPH. - Highlights: • Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats. • Dapoxetine decreased androgen receptor gene expression in rat prostate. • Dapoxetine possess anti-proliferative, anti-inflammatory and pro-apoptotic activities.« less

Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

PubMed Central

Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

2014-01-01

Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around −30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds. PMID:24634584

Hair growth promoting effect of white wax and policosanol from white wax on the mouse model of testosterone-induced hair loss.

PubMed

Wang, Zhan-di; Feng, Ying; Ma, Li-Yi; Li, Xian; Ding, Wei-Feng; Chen, Xiao-Ming

2017-05-01

White wax (WW) has been traditionally used to treat hair loss in China. However there has been no reporter WW and its extract responsible for hair growth-promoting effect on androgenetic alopecia. In this paper, we examined the hair growth-promoting effects of WW and policosanol of white wax (WWP) on model animal of androgenetic alopecia and the potential target cell of WW and WWP. WW (1, 10 and 20%) and WWP (0.5, 1 and 2%) were applied topically to the backs of mice. Finasteride (2%) was applied topically as a positive control. MTS assays were performed to evaluate cell proliferation in culture human follicle dermal papilla cells (HFDPCs). The inhibition of WW and WWP for 5α- reductase were tested in Vitro. Results showed more lost hairs were clearly seen in mice treated with TP only and TP plus vehicle. Mice which received TP plus WW and WWP showed less hair loss. WW and WWP showed an outstanding hair growth-promoting activity as reflected by the follicular length, follicular density, A/T ratio, and hair bulb diameter. The optimal treatment effect was observed at 10% WW and 1% WWP, which were better than 2% finasteride treatment. MTS assay results suggested that WW and WWP remarkably increased the proliferation of HFDPCs. Inhibitor assay of 5α- reductase showed that WW and WWP inhibited significantly the conversion of testosterone to dihydrotesterone, and the IC 50 values of WW and WWP were higher than that of finasteride. In Conclusion, WW and WWP could act against testosterone-induced alopecia in mice, and they promoted hair growth by inhibiting 5α-reductase activity and HFDPCs proliferation. DPCs is the target cell of WW and WWP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Differential expression of steroid 5alpha-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer.

PubMed

Das, Kakoli; Lorena, Pia D N; Ng, Lai Kuan; Lim, Diana; Shen, Liang; Siow, Woei Yun; Teh, Ming; Reichardt, Juergen K V; Salto-Tellez, Manuel

2010-09-01

The biological role of steroid 5alpha-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor beta 1 (TGFB1), endothelin (EDN1), TGFalpha (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 muM). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors.

Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies.

PubMed

Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

2014-01-01

Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds.

A Multiscale, Mechanism-Driven, Dynamic Model for the Effects of 5α-Reductase Inhibition on Prostate Maintenance

PubMed Central

Zager, Michael G.; Barton, Hugh A.

2012-01-01

A systems-level mathematical model is presented that describes the effects of inhibiting the enzyme 5α-reductase (5aR) on the ventral prostate of the adult male rat under chronic administration of the 5aR inhibitor, finasteride. 5aR is essential for androgen regulation in males, both in normal conditions and disease states. The hormone kinetics and downstream effects on reproductive organs associated with perturbing androgen regulation are complex and not necessarily intuitive. Inhibition of 5aR decreases the metabolism of testosterone (T) to the potent androgen 5α-dihydrotestosterone (DHT). This results in decreased cell proliferation, fluid production and 5aR expression as well as increased apoptosis in the ventral prostate. These regulatory changes collectively result in decreased prostate size and function, which can be beneficial to men suffering from benign prostatic hyperplasia (BPH) and could play a role in prostate cancer. There are two distinct isoforms of 5aR in male humans and rats, and thus developing a 5aR inhibitor is a challenging pursuit. Several inhibitors are on the market for treatment of BPH, including finasteride and dutasteride. In this effort, comparisons of simulated vs. experimental T and DHT levels and prostate size are depicted, demonstrating the model accurately described an approximate 77% decrease in prostate size and nearly complete depletion of prostatic DHT following 21 days of daily finasteride dosing in rats. This implies T alone is not capable of maintaining a normal prostate size. Further model analysis suggests the possibility of alternative dosing strategies resulting in similar or greater effects on prostate size, due to complex kinetics between T, DHT and gene occupancy. With appropriate scaling and parameterization for humans, this model provides a multiscale modeling platform for drug discovery teams to test and generate hypotheses about drugging strategies for indications like BPH and prostate cancer, such as compound binding properties, dosing regimens, and target validation. PMID:22970204

Overexpression of Aldo-Keto Reductase 1C3 (AKR1C3) in LNCaP Cells Diverts Androgen Metabolism towards Testosterone Resulting in Resistance to the 5α-Reductase Inhibitor Finasteride

PubMed Central

Byrns, Michael C.; Mindnich, Rebekka; Duan, Ling; Penning, Trevor M.

2012-01-01

Type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) is the major enzyme in the prostate that reduces 4-androstene-3,17-dione (Δ4-Adione) to the androgen receptor (AR) ligand testosterone. AKR1C3 is upregulated in prostate cancer (PCa) and castrate resistant prostate cancer (CRPC) that develops after androgen deprivation therapy. PCa and CRPC often depend on intratumoral androgen biosynthesis and upregulation of AKR1C3 could contribute to intracellular synthesis of AR ligands and stimulation of proliferation through AR signalling. To test this hypothesis, we developed an LNCaP prostate cancer cell line overexpressing AKR1C3 (LNCaP-AKR1C3) and compared its metabolic and proliferative responses to Δ4-Adione treatment with that of the parental, AKR1C3 negative LNCaP cells. In LNCaP and LNCaP-AKR1C3 cells, metabolism proceeded via 5α-reduction to form 5α-androstane-3,17-dione and then (epi)androsterone-3-glucuronide. LNCaP-AKR1C3 cells made significantly higher amounts of testosterone-17β-glucuronide. When 5α-reductase was inhibited by finasteride, the production of testosterone-17β-glucuronide was further elevated in LNCaP-AKR1C3 cells. When AKR1C3 activity was inhibited with indomethacin the production of testosterone-17β-glucuronide was significantly decreased. Δ4-Adione treatment stimulated cell proliferation in both cell lines. Finasteride inhibited LNCaP cell proliferation, consistent with 5α-androstane-3,17-dione acting as the major metabolite that stimulates growth by binding to the mutated AR. However, LNCaP-AKR1C3 cells were resistant to the growth inhibitory properties of finasteride, consistent with the diversion of Δ4-Adione metabolism from 5α-reduced androgens to increased formation of testosterone. Indomethacin did not result in differences in Δ4-Adione induced proliferation since this treatment led to the same metabolic profile in LNCaP and LNCaP-AKR1C3 cells. We conclude that AKR1C3 overexpression diverts androgen metabolism to testosterone that results in proliferation in androgen sensitive prostate cancer. This effect is seen despite high levels of uridine glucuronosyl transferases suggesting that AKR1C3 activity can surmount the effects of this elimination pathway. Treatment options in prostate cancer that target 5α-reductase where AKR1C3 co-exists may be less effective due to the diversion of Δ4-Adione to testosterone. PMID:22265960

Synergistic Disruption of External Male Sex Organ Development by a Mixture of Four Antiandrogens

PubMed Central

Christiansen, Sofie; Scholze, Martin; Dalgaard, Majken; Vinggaard, Anne Marie; Axelstad, Marta; Kortenkamp, Andreas; Hass, Ulla

2009-01-01

Background By disrupting the action of androgens during gestation, certain chemicals present in food, consumer products, and the environment can induce irreversible demasculinization and malformations of sex organs among male offspring. However, the consequences of simultaneous exposure to such chemicals are not well described, especially when they exert their actions by differing molecular mechanisms. Objectives To fill this gap, we investigated the effects of mixtures of a widely used plasticizer, di(2-ethylhexyl) phthalate (DEHP); two fungicides present in food, vinclozolin and prochloraz; and a pharmaceutical, finasteride, on landmarks of male sexual development in the rat, including changes in anogenital distance (AGD), retained nipples, sex organ weights, and malformations of genitalia. These chemicals were chosen because they disrupt androgen action with differing mechanisms of action. Results Strikingly, the effect of combined exposure to the selected chemicals on malformations of external sex organs was synergistic, and the observed responses were greater than would be predicted from the toxicities of the individual chemicals. In relation to other hallmarks of disrupted male sexual development, including changes in AGD, retained nipples, and sex organ weights, the combined effects were dose additive. When the four chemicals were combined at doses equal to no observed adverse effect levels estimated for nipple retention, significant reductions in AGD were observed in male offspring. Conclusions Because unhindered androgen action is essential for human male development in fetal life, these findings are highly relevant to human risk assessment. Evaluations that ignore the possibility of combination effects may lead to considerable underestimations of risks associated with exposures to chemicals that disrupt male sexual differentiation. PMID:20049201

Methods for measurement of developmental reproductive ...

EPA Pesticide Factsheets

NR OP Abstract:The purpose of this SOP is to outline a procedure for the evaluation of the presence or absence of nipples/areola in the day 13 rodent pup. In the absence of androgens from the developing testes, female rats develop nipples/areola, while dihydrotestosterone induces regression or apoptosis of the nipple anlage in male rats. Thus, nipple development in male rats is a useful endpoint for evaluating the degree of demasculinization produced by in utero/lactational exposure to antiandrogenic compounds. AGD OP Abstract: As a sexually dimorphic secondary sex characteristic in mammals, anogenital distance may be used to measure the degree of demasculinization or feminization of males as a consequence of developmental exposure to androgen receptor (AR) antagonists (Vinclozolin, Procymidone and Flutamide), 5 alpha reductase inhibitors (finasteride) or compounds which inhibit steroidogenesis (some diester phthalates), (see Appendices 7.a). Likewise, AGD is useful in measuring the degree of masculinization or defeminization of females exposed during sexual differentiation to androgenic compounds such as the cattle growth stimulant Trenbolone (see Appendices 7.b). This OP should be used in all studies that include measurement of AGD in rats. NCEA, EPA scientists have requested a copy of two of our laboratory OPs used to measure Anogenital Distance in newborn rats and nipple retention/agenesis in infant male and female rats. These will be submitted to an up

A Case-Based Toxicology Module on Agricultural- and Mining-Related Occupational Exposures

PubMed Central

2012-01-01

Objective. To develop and assess a toxicology module to teach pharmacy students about farming- and mining-related occupational exposures in the context of an existing toxicology elective course. Design. A teaching unit that included lectures and case studies was developed to address the unique occupational exposures of patients working in agricultural and mining environments. Upon completion of this 4-hour (2 class periods) module, students were expected to recognize the clinical signs and symptoms associated with these occupational exposures and propose acceptable therapeutic plans. Assessment. After completing the module, students scored significantly higher on a patient case involving suicide resulting from pesticide consumption. Seventy-three percent of the students scored higher than 90% on a 33-item multiple-choice examination. Eighty-two percent of students were able to correctly read a product label to determine the type of pesticide involved in an occupational exposure. Conclusion. Pharmacy students who completed a module on occupation exposure demonstrated competence in distinguishing occupational exposures from each other and from exposure to prescription and nonprescription drugs. This module can be used to educate future pharmacists about occupational health issues, some of which may be more prevalent in a rural setting. PMID:23049108

Hand-arm vibration exposure monitoring with wearable sensor module.

PubMed

Austad, Hanne O; Røed, Morten H; Liverud, Anders E; Dalgard, Steffen; Seeberg, Trine M

2013-01-01

Vibration exposure is a serious risk within work physiology for several work groups. Combined with cold artic climate, the risk for permanent harm is even higher. Equipment that can monitor the vibration exposure and warn the user when at risk will provide a safer work environment for these work groups. This study evaluates whether data from a wearable wireless multi-parameter sensor module can be used to estimate vibration exposure and exposure time. This work has been focused on the characterization of the response from the accelerometer in the sensor module and the optimal location of the module in the hand-arm configuration.

Hair growth is promoted by BeauTop via expression of EGF and FGF-7

PubMed Central

Lee, Chien-Ying; Yang, Chi-Yu; Lin, Ching-Che; Yu, Min-Chien; Sheu, Shuenn-Jyi; Kuan, Yu-Hsiang

2018-01-01

Minoxidil and finasteride have been approved to treat hair loss by the Food and Drug Administration. However, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. BeauTop (BT) is a health food supplement which contains Ginseng radix, Astragali radix, Radix Angelicae sinensis, Ligustri fructus, Rehmannia glutinosa and Eclipta prostrata (Linn). Susbsequent to oral administration of BT at 0.6 g/kg/day to wax/rosin-induced alopecia in C57BL/6 mice, BT significantly induced hair growth at day 8 compared with control treatment (P<0.05). The expression levels of epidermal growth factor (EGF), and fibroblast growth factor (FGF)-7 were increased compared with control animals on day 8. In contrast, levels of FGF-5 of the BT group were reduced compared with the control on day 12. There were no effects on the expression of insulin-like growth factor 1. The results demonstrated that the mechanism of BT improving alopecia is potentially associated with modulation of EGF and FGF-7 levels. Taken together, it is suggested that BT may have a potential effect of the promotion of hair growth. PMID:29693180

Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to the finasteride Arm in the Prostate Cancer Prevention Trial*

PubMed Central

Winchester, Danyelle; Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.; Santella, Regina M.; Johnson-Pais, Teresa L.; Leach, Robin J.; Xu, Jianfeng; Zheng, S. Lilly; Thompson, Ian M.; Lucia, M. Scott; Lippman, Scott M.; Parnes, Howard L.; Isaacs, William B.; De Marzo, Angelo M.; Drake, Charles G.; Platz, Elizabeth A.

2017-01-01

BACKGROUND We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer, but not individually with the prevalence of intraprostatic inflammation in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk of lower- and higher-grade prostate cancer in men randomized to finasteride, and with prevalence of intraprostatic inflammation among controls. METHODS 16 candidate SNPs in IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and 7 tagSNPs in IL10 were genotyped in 625 white prostate cancer cases, and 532 white controls negative for cancer on an end-of-study biopsy nested in the PCPT finasteride arm. We used logistic regression to estimate log-additive odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history. RESULTS Minor alleles of rs2243250 (T) in IL4 (OR=1.46, 95% CI 1.03–2.08, P-trend=0.03), rs1800896 (G) in IL10 (OR=0.77, 95% CI 0.61–0.96, P-trend=0.02), rs2430561 (A) in IFNG (OR=1.33, 95% CI 1.02–1.74; P-trend=0.04), rs3747531 (C) in MSR1 (OR=0.55, 95% CI 0.32–0.95; P-trend=0.03), and possibly rs4073 (A) in IL8 (OR=0.81, 95% CI 0.64–1.01, P-trend=0.06) were associated with higher- (Gleason 7–10; N=222), but not lower- (Gleason 2–6; N=380) grade prostate cancer. In men with low PSA (<2 ng/mL), these higher-grade disease associations were attenuated and/or no longer significant, whereas associations with higher-grade disease were apparent for minor alleles of rs1800795 (C: OR=0.70, 95% CI 0.51–0.94, P-trend=0.02) and rs1800797 (A: OR=0.72, 95% CI 0.53–0.98, P-trend=0.04) in IL6. While some IL10 tagSNPs were associated with lower- and higher-grade prostate cancer, distributions of IL10 haplotypes did not differ, except possibly between higher-grade cases and controls among those with low PSA (P=0.07). We did not observe an association between the studied SNPs and intraprostatic inflammation in the controls. CONCLUSION In the PCPT finasteride arm, variation in genes involved in the immune response, including possibly IL8 and IL10 as in the placebo arm, may be associated with prostate cancer, especially higher-grade disease, but not with intraprostatic inflammation. We cannot rule out PSA-associated detection bias or chance due to multiple testing. PMID:28317149

Inhibition of 5α-reductase activity in late pregnancy decreases gestational length and fecundity and impairs object memory and central progestogen milieu of juvenile rat offspring

PubMed Central

Paris, Jason J.; Brunton, Paula J.; Russell, John A.; Walf, Alicia A.; Frye, Cheryl A.

2011-01-01

Psychological, physical, and/or immune stressors during pregnancy are associated with negative birth outcomes, such as preterm birth and developmental abnormalities. In rodents, prenatal stressors can alter the expression of 5α-reductase enzymes in the brain and may influence cognitive function and anxiety-type behaviour in the offspring. Progesterone plays a critical role in maintaining gestation. Here it was hypothesised that 5α-reduced progesterone metabolites influence birth outcomes and/or the cognitive and neuroendocrine function of the offspring. 5α-reduced steroids were manipulated in pregnant Long-Evans rats via administration of vehicle, the 5α-reduced, neuroactive metabolite of progesterone, 5α-pregnan-3α-ol-20-one (3α,5α-THP, allopregnanolone; 10 mg/kg/ml, SC), or the 5α-reductase inhibitor, finasteride (50 mg/kg/ml, SC), daily from gestational days 17–21. Compared to vehicle or 3α,5α-THP treatment, finasteride, significantly reduced the length of gestation and the number of pups per litter found in the dams’ nests after parturition. The behaviour of the offspring in hippocampus-dependent tasks (object recognition, open field) was examined on post-natal days 28–30. Compared to vehicle-exposed controls, prenatal 3α,5α-THP treatment significantly increased motor behaviour in females compared to males, decreased progesterone content in the medial prefrontal cortex (mPFC) and diencephalon, increased 3α,5α-THP and 17β-estradiol content in the hippocampus, mPFC, and diencephalon, and significantly increased serum corticosterone concentrations in males and females. Prenatal finasteride treatment significantly reduced object recognition, decreased hippocampal 3α,5α-THP content, increased progesterone concentration in the mPFC and diencephalon, and increased serum corticosterone concentration in female (but not male) juvenile offspring, compared with vehicle-exposed controls. Thus, inhibiting formation of 5α-reduced steroids during late gestation in rats reduces gestational length, the number of viable pups/litter, and impairs cognitive and neuroendocrine function in the juvenile offspring. PMID:21914008

Sexual dysfunction in subjects treated with inhibitors of 5α-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis.

PubMed

Corona, G; Tirabassi, G; Santi, D; Maseroli, E; Gacci, M; Dicuio, M; Sforza, A; Mannucci, E; Maggi, M

2017-07-01

Despite their efficacy in the treatment of benign prostatic hyperplasia, the popularity of inhibitors of 5α-reductase (5ARIs) is limited by their association with adverse sexual side effects. The aim of this study was to review and meta-analyze currently available randomized clinical trials evaluating the rate of sexual side effects in men treated with 5ARIs. An extensive Medline Embase and Cochrane search was performed including the following words: 'finasteride', 'dutasteride', 'benign prostatic hyperplasia'. Only placebo-controlled randomized clinical trials evaluating the effect of 5ARI in subjects with benign prostatic hyperplasia were considered. Of 383 retrieved articles, 17 were included in this study. Randomized clinical trials enrolled 24,463 in the active and 22,270 patients in the placebo arms, respectively, with a mean follow-up of 99 weeks and mean age of 64.0 years. No difference was observed between trials using finasteride or dutasteride as the active arm considering age, trial duration, prostate volume or International Prostatic Symptoms Score at enrollment. Overall, 5ARIs determined an increased risk of hypoactive sexual desire [OR = 1.54 (1.29; 1.82); p < 0.0001] and erectile dysfunction [OR = 1.47 (1.29; 1.68); p < 0.0001]. No difference between finasteride and dutasteride regarding the risk of hypoactive sexual desire and erectile dysfunction was observed. Meta-regression analysis showed that the risk of hypoactive sexual desire and erectile dysfunction was higher in subjects with lower Q max at enrollment and decreased as a function of trial follow-up. Conversely, no effect of age, low urinary tract symptom or prostate volume at enrollment as well as Q max at end-point was observed. In conclusion, present data show that the use of 5ARI significantly increases the risk of erectile dysfunction and hypoactive sexual desire in subjects with benign prostatic hyperplasia. Patients should be adequately informed before 5ARIs are prescribed. © 2017 American Society of Andrology and European Academy of Andrology.

Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II.

PubMed

Pais, Pilar

2010-08-01

The nicotinamide adenine dinucleotide phosphate (NADPH)-dependent membrane protein 5alpha-reductase irreversibly catalyses the conversion of testosterone to the most potent androgen, 5alpha-dihydrotestosterone (DHT). In humans, two 5alpha-reductase isoenyzmes are expressed: type I and type II. Type II is found primarily in prostate tissue. Saw palmetto extract (SPE) has been widely used for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The mechanisms of the pharmacological effects of SPE include the inhibition of 5alpha-reductase, among other actions. Clinical studies of SPE have been equivocal, with some showing significant results and others not. These inconsistent results may be due, in part, to varying bioactivities of the SPE used in the studies. The aim of the present study was to determine the in vitro potency of a novel saw palmetto ethanol extract (SPET-085), an inhibitor of the 5alpha-reductase isoenzyme type II, in a cell-free test system. On the basis of the enzymatic conversion of the substrate androstenedione to the 5alpha-reduced product 5alpha-androstanedione, the inhibitory potency was measured and compared to those of finasteride, an approved 5alpha-reductase inhibitor. SPET-085 concentration-dependently inhibited 5alpha-reductase type II in vitro (IC(50)=2.88+/-0.45 microg/mL). The approved 5alpha-reductase inhibitor, finasteride, tested as positive control, led to 61% inhibition of 5alpha-reductase type II. SPET-085 effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is very low compared to data reported for other extracts. It can be concluded from data in the literature that SPET-085 is as effective as a hexane extract of saw palmetto that exhibited the highest levels of bioactivity, and is more effective than other SPEs tested. This study confirmed that SPET-085 has prostate health-promoting bioactivity that also corresponds favorably to that reported for the established prescription drug standard of therapy, finasteride.

Comparison of two expert-based assessments of diesel exhaust exposure in a case-control study: programmable decision rules versus expert review of individual jobs.

PubMed

Pronk, Anjoeka; Stewart, Patricia A; Coble, Joseph B; Katki, Hormuzd A; Wheeler, David C; Colt, Joanne S; Baris, Dalsu; Schwenn, Molly; Karagas, Margaret R; Johnson, Alison; Waddell, Richard; Verrill, Castine; Cherala, Sai; Silverman, Debra T; Friesen, Melissa C

2012-10-01

Professional judgment is necessary to assess occupational exposure in population-based case-control studies; however, the assessments lack transparency and are time-consuming to perform. To improve transparency and efficiency, we systematically applied decision rules to questionnaire responses to assess diesel exhaust exposure in the population-based case-control New England Bladder Cancer Study. 2631 participants reported 14 983 jobs; 2749 jobs were administered questionnaires ('modules') with diesel-relevant questions. We applied decision rules to assign exposure metrics based either on the occupational history (OH) responses (OH estimates) or on the module responses (module estimates); we then combined the separate OH and module estimates (OH/module estimates). Each job was also reviewed individually to assign exposure (one-by-one review estimates). We evaluated the agreement between the OH, OH/module and one-by-one review estimates. The proportion of exposed jobs was 20-25% for all jobs, depending on approach, and 54-60% for jobs with diesel-relevant modules. The OH/module and one-by-one review estimates had moderately high agreement for all jobs (κ(w)=0.68-0.81) and for jobs with diesel-relevant modules (κ(w)=0.62-0.78) for the probability, intensity and frequency metrics. For exposed subjects, the Spearman correlation statistic was 0.72 between the cumulative OH/module and one-by-one review estimates. The agreement seen here may represent an upper level of agreement because the algorithm and one-by-one review estimates were not fully independent. This study shows that applying decision-based rules can reproduce a one-by-one review, increase transparency and efficiency, and provide a mechanism to replicate exposure decisions in other studies.

Low-level laser therapy for the treatment of androgenic alopecia: a review.

PubMed

Darwin, Evan; Heyes, Alexandra; Hirt, Penelope A; Wikramanayake, Tongyu Cao; Jimenez, Joaquin J

2018-02-01

There are many new low-level laser technologies that have been released commercially that claim to support hair regrowth. In this paper, we will examine the clinical trials to determine whether the body of evidence supports the use of low-level laser therapy (LLLT) to treat androgenic alopecia (AGA). A literature search was conducted through Pubmed, Embase, and Clinicaltrials.gov for clinical trials using LLLT to treat AGA. Thirteen clinical trials were assessed. Review articles were not included. Ten of 11 trials demonstrated significant improvement of androgenic alopecia in comparison to baseline or controls when treated with LLLT. In the remaining study, improvement in hair counts and hair diameter was recorded, but did not reach statistical significance. Two trials did not include statistical analysis, but showed marked improvement by hair count or by photographic evidence. Two trials showed efficacy for LLLT in combination with topical minoxidil. One trial showed efficacy when accompanying finasteride treatment. LLLT appears to be a safe, alternative treatment for patients with androgenic alopecia. Clinical trials have indicated efficacy for androgenic alopecia in both men and women. It may be used independently or as an adjuvant of minoxidil or finasteride. More research needs to be undertaken to determine the optimal power and wavelength to use in LLLT as well as LLLT's mechanism of action.

Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and lactating rats.

PubMed

Frye, Cheryl A; Walf, Alicia A

2004-07-01

The 5alpha-reduced metabolite of progesterone (P), 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), may mediate progestins' effects to reduce depressive behavior of female rats in part through actions in the hippocampus. To investigate, forced swim test behavior and plasma and hippocampal progestin levels were assessed in groups of rats expected to differ in their 3alpha,5alpha-THP levels due to endogenous differences (pregnant and postpartum), administration of a 5alpha-reductase inhibitor (finasteride; 50 mg/kg sc), and/or gestational stress [prenatal stress (PNS)], an animal model of depression. Pregnant rats had higher plasma and hippocampal 3alpha,5alpha-THP levels and less depressive behavior (decreased immobility, increased struggling and swimming) in the forced swim test than did postpartum rats. Finasteride, compared to vehicle-administration, reduced plasma and hippocampal 3alpha,5alpha-THP levels and increased depressive behavior (increased immobility, decreased struggling and swimming). PNS was associated with lower hippocampal, but not plasma, 3alpha,5alpha-THP levels and increased swimming compared to that observed in control rats. Together, these data suggest that 3alpha,5alpha-THP in the hippocampus may mediate antidepressive behavior of female rats.

Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to the finasteride arm in the Prostate Cancer Prevention Trial.

PubMed

Winchester, Danyelle A; Till, Cathee; Goodman, Phyllis J; Tangen, Catherine M; Santella, Regina M; Johnson-Pais, Teresa L; Leach, Robin J; Xu, Jianfeng; Zheng, S Lilly; Thompson, Ian M; Lucia, M Scott; Lippman, Scott M; Parnes, Howard L; Isaacs, William B; De Marzo, Angelo M; Drake, Charles G; Platz, Elizabeth A

2017-06-01

We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer, but not individually with the prevalence of intraprostatic inflammation in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk of lower- and higher-grade prostate cancer in men randomized to finasteride, and with prevalence of intraprostatic inflammation among controls. Methods A total of 16 candidate SNPs in IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and 7 tagSNPs in IL10 were genotyped in 625 white prostate cancer cases, and 532 white controls negative for cancer on an end-of-study biopsy nested in the PCPT finasteride arm. We used logistic regression to estimate log-additive odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history. Minor alleles of rs2243250 (T) in IL4 (OR = 1.46, 95% CI 1.03-2.08, P-trend = 0.03), rs1800896 (G) in IL10 (OR = 0.77, 95% CI 0.61-0.96, P-trend = 0.02), rs2430561 (A) in IFNG (OR = 1.33, 95% CI 1.02-1.74; P-trend = 0.04), rs3747531 (C) in MSR1 (OR = 0.55, 95% CI 0.32-0.95; P-trend = 0.03), and possibly rs4073 (A) in IL8 (OR = 0.81, 95% CI 0.64-1.01, P-trend = 0.06) were associated with higher- (Gleason 7-10; N = 222), but not lower- (Gleason 2-6; N = 380) grade prostate cancer. In men with low PSA (<2 ng/mL), these higher-grade disease associations were attenuated and/or no longer significant, whereas associations with higher-grade disease were apparent for minor alleles of rs1800795 (C: OR = 0.70, 95% CI 0.51-0.94, P-trend = 0.02) and rs1800797 (A: OR = 0.72, 95% CI 0.53-0.98, P-trend = 0.04) in IL6. While some IL10 tagSNPs were associated with lower- and higher-grade prostate cancer, distributions of IL10 haplotypes did not differ, except possibly between higher-grade cases and controls among those with low PSA (P = 0.07). We did not observe an association between the studied SNPs and intraprostatic inflammation in the controls. In the PCPT finasteride arm, variation in genes involved in the immune response, including possibly IL8 and IL10 as in the placebo arm, may be associated with prostate cancer, especially higher-grade disease, but not with intraprostatic inflammation. We cannot rule out PSA-associated detection bias or chance due to multiple testing. © 2017 Wiley Periodicals, Inc.

Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

DTIC Science & Technology

2005-02-01

40 E 250° U0 200- 0 150- 50- 01 Treament group (tumor volume in cm3 at time of randomization) Figure 2: a) Mean percent change in LNCaP tumor volume...40- S30- . 20- 10 CAA F T T+F c 350- 300- OM P 250- 2! ." Q. 0 200- 0 150- ~.100 ** ’ 50 Treament group (tumor volume in cm 3 at time of randomization

Hair growth is promoted by BeauTop via expression of EGF and FGF‑7.

PubMed

Lee, Chien-Ying; Yang, Chi-Yu; Lin, Ching-Che; Yu, Min-Chien; Sheu, Shuenn-Jyi; Kuan, Yu-Hsiang

2018-06-01

Minoxidil and finasteride have been approved to treat hair loss by the Food and Drug Administration. However, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. BeauTop (BT) is a health food supplement which contains Ginseng radix, Astragali radix, Radix Angelicae sinensis, Ligustri fructus, Rehmannia glutinosa and Eclipta prostrata (Linn). Susbsequent to oral administration of BT at 0.6 g/kg/day to wax/rosin‑induced alopecia in C57BL/6 mice, BT significantly induced hair growth at day 8 compared with control treatment (P<0.05). The expression levels of epidermal growth factor (EGF), and fibroblast growth factor (FGF)‑7 were increased compared with control animals on day 8. In contrast, levels of FGF‑5 of the BT group were reduced compared with the control on day 12. There were no effects on the expression of insulin‑like growth factor 1. The results demonstrated that the mechanism of BT improving alopecia is potentially associated with modulation of EGF and FGF‑7 levels. Taken together, it is suggested that BT may have a potential effect of the promotion of hair growth.

Multi-therapies in androgenetic alopecia: review and clinical experiences.

PubMed

Rossi, Alfredo; Anzalone, Alessia; Fortuna, Maria Caterina; Caro, Gemma; Garelli, Valentina; Pranteda, Giulia; Carlesimo, Marta

2016-11-01

Androgenetic alopecia (AGA) is a genetically determined progressive hair-loss condition which represents the most common cause of hair loss in men. The use of the medical term androgenetic alopecia reflects current knowledge about the important role of androgens and genetic factors in its etiology. In addition to androgen-dependent changes in the hair cycle, sustained microscopic follicular inflammation contributes to its onset. Furthermore, Prostaglandins have been demonstrated to have the ability in modulating hair follicle cycle; in particular, PGD2 inhibits hair growth while PGE2/F2a promote growth. Due to the progressive nature of AGA, the treatment should be started early and continued indefinitely, since the benefit will not be maintained upon ceasing therapy. To date, only two therapeutic agents have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of AGA: topical minoxidil and oral finasteride. Considering the many pathogenetic mechanisms involved in AGA, various treatment options are available: topical and systemic drugs may be used and the choice depends on various factors including grading of AGA, patients' pathological conditions, practicability, costs and risks. So, the treatment for AGA should be based on personalized therapy and targeted at the different pathophysiological aspects of AGA. © 2016 Wiley Periodicals, Inc.

The Effect of the Aqueous Extract of Bidens Pilosa L. on Androgen Deficiency Dry Eye in Rats.

PubMed

Zhang, Chuanwei; Li, Kai; Yang, Zichao; Wang, Yuliang; Si, Haipeng

2016-01-01

Bidens pilosa L. (Bp) is widely distributed in China and has been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of the extract of Bp on androgen deficiency dry eye and determine its possible mechanisms. Twenty-four rats were randomly divided into four groups: Group Con (control), Group Sal (physiological saline), Group Fin (oral finasteride), and Group Bp (oral finasteride and Bp). The dry eye model was established in group Fin and group Bp. Aqueous tear quantity was measured with phenol red-impregnated cotton threads with anesthesia. Tear film breakup time (BUT) and corneal epithelial damage were evaluated by fluorescein staining. Animals were sacrificed at 28 days, and ocular tissues (lacrimal gland and cornea) were evaluated with light microscopy; gene microarray analysis for inflammatory cytokines and Western blot were also performed. Finasteride administration effectively induced dry eye in rats by 14 days after administration. Group Fin rats had significantly higher fluorescein staining scores and lower aqueous tear quantity and BUT than the group Con rats, and notable inflammatory cell infiltrates were observed in the lacrimal gland of group Fin rats. The fluorescein staining score, aqueous tear quantity and BUT significantly improved with Bp treatment in the group Bp rats, and the structures of the lacrimal gland were well maintained without significant lymphocyte infiltration. Cytokine antibody array data identified the cytokines B7-2/Cd86, IL-1β, IL-4, IL-6, IL-10, MMP-8, FasL, TNF-α and TIMP-1 as candidates for validation by Western blot. Expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in group Fin were upregulated compared with group Con. Levels of anti-inflammatory cytokines, such as IL-4 and IL-10, in group Fin were also upregulated compared with those in group Con. Compared with group Fin, IL-1β, FasL, and TNF-α were significantly decreased in group Bp. The extract of Bp appears to be effective for the treatment of androgen deficiency dry eye in rats by improving aqueous tear quantity, maintaining tear film stability, and inhibiting the inflammation of the lacrimal gland. © 2016 The Author(s) Published by S. Karger AG, Basel.

Determination of the potency of a novel saw palmetto supercritical CO2 extract (SPSE) for 5α-reductase isoform II inhibition using a cell-free in vitro test system.

PubMed

Pais, Pilar; Villar, Agustí; Rull, Santiago

2016-01-01

The nicotinamide adenine dinucleotide phosphate-dependent membrane protein 5α-reductase catalyses the conversion of testosterone to the most potent androgen - 5α-dihydrotestosterone. Two 5α-reductase isoenzymes are expressed in humans: type I and type II. The latter is found primarily in prostate tissue. Saw palmetto extract (SPE) has been used extensively in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The pharmacological effects of SPE include the inhibition of 5α-reductase, as well as anti-inflammatory and antiproliferative effects. Clinical studies of SPE have been inconclusive - some have shown significant results, and others have not - possibly the result of varying bioactivities of the SPEs used in the studies. To determine the in vitro potency in a cell-free test system of a novel SP supercritical CO2 extract (SPSE), an inhibitor of the 5α-reductase isoenzyme type II. The inhibitory potency of SPSE was compared to that of finasteride, an approved 5α-reductase inhibitor, on the basis of the enzymatic conversion of the substrate androstenedione to the 5α-reduced product 5α-androstanedione. By concentration-dependent inhibition of 5α-reductase type II in vitro (half-maximal inhibitory concentration 3.58±0.05 μg/mL), SPSE demonstrated competitive binding toward the active site of the enzyme. Finasteride, the approved 5α-reductase inhibitor tested as positive control, led to 63%-75% inhibition of 5α-reductase type II. SPSE effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is comparatively low. It can be confirmed from the results of this study that SPSE has bioactivity that promotes prostate health at a level that is superior to that of many other phytotherapeutic extracts. The bioactivity of SPSE corresponds favorably to that reported for the hexane extract used in a large number of positive BPH clinical trials, as well as to finasteride, the established standard of therapy among prescription drugs. Future in vitro and clinical trials involving SPEs would be useful for elucidating their comparative differences, as well as appropriate patient selection for their use.

Characterization of 5α-reductase activity and isoenzymes in human abdominal adipose tissues.

PubMed

Fouad Mansour, Mohamed; Pelletier, Mélissa; Tchernof, André

2016-07-01

The substrate for the generation of 5α-dihydrotestosterone (DHT) is either androstenedione (4-dione) which is first converted to androstanedione and then to DHT through 17-oxoreductase activity, or testosterone, which is directly converted to DHT. Three 5α-reductase isoenzymes have been characterized and designated as types 1, 2 and 3 (SRD5A1, 2 and 3). To define the predominant source of local DHT production in human adipose tissues, identify 5α-reductase isoenzymes and test their impact on preadipocyte differentiation. Cultures of omental (OM) and subcutaneous (SC) preadipocytes were treated for 0, 6 or 24h with 30nM (14)C-4-dione or (14)C-testosterone, with and without 500nM 5α-reductase inhibitors 17-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androstan-3-one (4-MA) or finasteride. Protein level and mRNA abundance of 5α-reductase isoenzymes/transcripts were examined in whole SC and OM adipose tissue. HEK-293 cells stably transfected with 5α-reductase type 1, 2 or 3 were used to test 5α-reductase inhibitors. We also assessed the impact of 5α-reductase inhibitors on preadipocyte differentiation. Over 24h, DHT formation from 4-dione increased gradually (p<0.05) and was significantly higher compared to that generated from testosterone (p<0.001). DHT formation from both 4-dione and testosterone was blocked by both 5α-reductase inhibitors. In whole adipose tissue from both fat compartments, SRD5A3 was the most highly expressed isoenzyme followed by SRD5A1 (p<0.001). SRD5A2 was not expressed. In HEK-293 cells, 4-MA and finasteride inhibited activity of 5α-reductases types 2 and 3 but not type 1. In preadipocyte cultures where differentiation was inhibited by 4-dione (p<0.05, n=7) or testosterone (p<0.05, n=5), the inhibitors 4-MA and finasteride abolished these effects. Although 4-dione is the main source of DHT in human preadipocytes, production of this steroid by 5α-reductase isoenzymes mediates the inhibitory effect of both 4-dione and testosterone on preadipocyte differentiation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers.

PubMed

Xu, Yi; Dalrymple, Susan L; Becker, Robyn E; Denmeade, Samuel R; Isaacs, John T

2006-07-01

Prostatic dihydrotestosterone (DHT) concentration is regulated by precursors from systemic circulation and prostatic enzymes of androgen metabolism, particularly 5alpha-reductases (i.e., SRD5A1 and SRD5A2). Therefore, the levels of expression SRD5A1 and SRD5A2 and the antiprostatic cancer growth response to finasteride, a selective SRD5A2 inhibitor, versus the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, were compared. Real-time PCR and enzymatic assays were used to determine the levels of SRD5A1 and SRD5A2 in normal versus malignant rat and human prostatic tissues. Rats bearing the Dunning R-3327H rat prostate cancer and nude mice bearing LNCaP or PC-3 human prostate cancer xenografts were used as model systems. Tissue levels of testosterone and DHT were determined using liquid chromatography-mass spectrometry. Prostate cancer cells express undetectable to low levels of SRD5A2 but elevated levels of SRD5A1 activity compared with nonmalignant prostatic tissue. Daily oral treatment of rats with the SRD5A2 selective inhibitor, finasteride, reduces prostate weight and DHT content but did not inhibit R-3327H rat prostate cancer growth or DHT content in intact (i.e., noncastrated) male rats. In contrast, daily oral treatment with even a low 1 mg/kg/d dose of the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, reduces both normal prostate and H tumor DHT content and weight in intact rats while elevating tissue testosterone. Daily oral treatment with finasteride significantly (P < 0.05) inhibits growth of LNCaP human prostate cancer xenografts in intact male nude mice, but this inhibition is not as great as that by equimolar oral dosing with dutasteride. This anticancer efficacy is not equivalent, however, to that produced by castration. Only combination of dutasteride and castration produces a greater tumor inhibition (P < 0.05) than castration monotherapy against androgen-responsive LNCaP cancers. In contrast, no response was induced by dutasteride in nude mice bearing androgen-independent PC-3 human prostatic cancer xenografts. These results document that testosterone is not as potent as DHT but does stimulate prostate cancer growth, thus combining castration with dutasteride enhances therapeutic efficacy.

Determination of the potency of a novel saw palmetto supercritical CO2 extract (SPSE) for 5α-reductase isoform II inhibition using a cell-free in vitro test system

PubMed Central

Pais, Pilar; Villar, Agustí; Rull, Santiago

2016-01-01

Background The nicotinamide adenine dinucleotide phosphate-dependent membrane protein 5α-reductase catalyses the conversion of testosterone to the most potent androgen – 5α-dihydrotestosterone. Two 5α-reductase isoenzymes are expressed in humans: type I and type II. The latter is found primarily in prostate tissue. Saw palmetto extract (SPE) has been used extensively in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The pharmacological effects of SPE include the inhibition of 5α-reductase, as well as anti-inflammatory and antiproliferative effects. Clinical studies of SPE have been inconclusive – some have shown significant results, and others have not – possibly the result of varying bioactivities of the SPEs used in the studies. Purpose To determine the in vitro potency in a cell-free test system of a novel SP supercritical CO2 extract (SPSE), an inhibitor of the 5α-reductase isoenzyme type II. Materials and methods The inhibitory potency of SPSE was compared to that of finasteride, an approved 5α-reductase inhibitor, on the basis of the enzymatic conversion of the substrate androstenedione to the 5α-reduced product 5α-androstanedione. Results By concentration-dependent inhibition of 5α-reductase type II in vitro (half-maximal inhibitory concentration 3.58±0.05 μg/mL), SPSE demonstrated competitive binding toward the active site of the enzyme. Finasteride, the approved 5α-reductase inhibitor tested as positive control, led to 63%–75% inhibition of 5α-reductase type II. Conclusion SPSE effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is comparatively low. It can be confirmed from the results of this study that SPSE has bioactivity that promotes prostate health at a level that is superior to that of many other phytotherapeutic extracts. The bioactivity of SPSE corresponds favorably to that reported for the hexane extract used in a large number of positive BPH clinical trials, as well as to finasteride, the established standard of therapy among prescription drugs. Future in vitro and clinical trials involving SPEs would be useful for elucidating their comparative differences, as well as appropriate patient selection for their use. PMID:27186566

Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats

PubMed Central

Nagaya, Naomi; Acca, Gillian M.; Maren, Stephen

2015-01-01

Trauma- and stress-related disorders are among the most common types of mental illness affecting the U.S. population. For many of these disorders, there is a striking sex difference in lifetime prevalence; for instance, women are twice as likely as men to be affected by posttraumatic stress disorder (PTSD). Gonadal steroids and their metabolites have been implicated in sex differences in fear and anxiety. One example, allopregnanolone (ALLO), is a neuroactive metabolite of progesterone that allosterically enhances GABAA receptor activity and has anxiolytic effects. Like other ovarian hormones, it not only occurs at different levels in males and females but also fluctuates over the female reproductive cycle. One brain structure that may be involved in neuroactive steroid regulation of fear and anxiety is the bed nucleus of the stria terminalis (BNST). To explore this question, we examined the consequences of augmenting or reducing ALLO activity in the BNST on the expression of Pavlovian fear conditioning in rats. In Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing behavior (a fear response) to the conditioned context, but did not influence freezing to a discrete tone conditioned stimulus (CS). In Experiment 2, intra-BNST infusion of either finasteride (FIN), an inhibitor of ALLO synthesis, or 17-phenyl-(3α,5α)-androst-16-en-3-ol, an ALLO antagonist, in female rats enhanced contextual freezing; neither treatment affected freezing to the tone CS. These findings support a role for ALLO in modulating contextual fear via the BNST and suggest that sex differences in fear and anxiety could arise from differential steroid regulation of BNST function. The susceptibility of women to disorders such as PTSD may be linked to cyclic declines in neuroactive steroid activity within fear circuitry. PMID:26300750

Allopregnanolone in the bed nucleus of the stria terminalis modulates contextual fear in rats.

PubMed

Nagaya, Naomi; Acca, Gillian M; Maren, Stephen

2015-01-01

Trauma- and stress-related disorders are among the most common types of mental illness affecting the U.S. population. For many of these disorders, there is a striking sex difference in lifetime prevalence; for instance, women are twice as likely as men to be affected by posttraumatic stress disorder (PTSD). Gonadal steroids and their metabolites have been implicated in sex differences in fear and anxiety. One example, allopregnanolone (ALLO), is a neuroactive metabolite of progesterone that allosterically enhances GABAA receptor activity and has anxiolytic effects. Like other ovarian hormones, it not only occurs at different levels in males and females but also fluctuates over the female reproductive cycle. One brain structure that may be involved in neuroactive steroid regulation of fear and anxiety is the bed nucleus of the stria terminalis (BNST). To explore this question, we examined the consequences of augmenting or reducing ALLO activity in the BNST on the expression of Pavlovian fear conditioning in rats. In Experiment 1, intra-BNST infusions of ALLO in male rats suppressed freezing behavior (a fear response) to the conditioned context, but did not influence freezing to a discrete tone conditioned stimulus (CS). In Experiment 2, intra-BNST infusion of either finasteride (FIN), an inhibitor of ALLO synthesis, or 17-phenyl-(3α,5α)-androst-16-en-3-ol, an ALLO antagonist, in female rats enhanced contextual freezing; neither treatment affected freezing to the tone CS. These findings support a role for ALLO in modulating contextual fear via the BNST and suggest that sex differences in fear and anxiety could arise from differential steroid regulation of BNST function. The susceptibility of women to disorders such as PTSD may be linked to cyclic declines in neuroactive steroid activity within fear circuitry.

Protective Effects of Lepidium meyenii (Maca) Aqueous Extract and Lycopene on Testosterone Propionate-Induced Prostatic Hyperplasia in Mice.

PubMed

Zou, Ying; Aboshora, Waleed; Li, Jing; Xiao, Tiancun; Zhang, Lianfu

2017-08-01

The inhibitory effect of maca extractant, lycopene, and their combination was evaluated in benign prostatic hyperplasia (BPH) mice induced by testosterone propionate. Mice were divided into a saline group, solvent control group and testosterone propionate-induced BPH mice [BPH model group, solvent BPH model group, benzyl glucosinolate group (1.44 mg/kg), maca group (60 mg/kg), lycopene treated (15, 5, and 2.5 mg/kg), maca (30 mg/kg) combine lycopene treated (7.5, 2.5, and 1.25 mg/kg), and finasteride treated]. Benzyl glucosinolate was used in order to evaluate its pharmacological activity on BPH to find out whether it is the major active component of maca aqueous extract. Finasteride was used as positive control. The compounds were administered once for 30 successive days. Compared with solvent BPH model group, BPH mice fed with maca (30 mg/kg) and lycopene (7.5 mg/kg) combination exhibited significant reductions in the prostatic index, prostatic acid phospatase, estradiol, testosterone, and dihydrotestosterone levels in serum. They also had similar histological compared with those aspects observed in the mice in the solvent control group. The results indicated that combination of maca and lycopene synergistically inhibits BPH in mice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Skin deposition and permeation of finasteride in vitro: effects of propylene glycol, ethanol and sodium lauryl sulfate.

PubMed

Limpongsa, Ekapol; Jaipakdee, Napaphak; Pongjanyakul, Thaned

2014-08-27

Abstract The objective of this study was to investigate the effects of propylene glycol (PG), ethanol (EtOH) and sodium lauryl sulfate (SLS) on the in vitro deposition and permeation of finasteride (FNS). A side-by-side diffusion cell mounted with a pig ear skin and a saturated solution of FNS in PG (10, 20% v/v), EtOH (10, 20% v/v) or SLS (0.5, 1% w/v) vehicles were used. Incorporation of PG, EtOH or SLS caused a significant increase in FNS solubility both in the solution and on the skin with SLS > EtOH > PG. The results obtained from skin deposition studies showed that the FNS deposition rate and time increased in the same order as that of the solubility. The deposition kinetics of FNS solubilized in PG, EtOH and SLS vehicles followed either zero-order, square-root-of-time or pseudo-first-order kinetic models depending on the type and concentration of the enhancer. The permeation studies demonstrated that FNS permeation fluxes were enhanced only by EtOH vehicles. These results suggest that PG and SLS could be used as deposition enhancers, while EtOH could be the effective permeation enhancer of FNS. The obtained results can be used as the considerable insights for formulating the topical and transdermal products of FNS.

Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor β (ERβ) Response to 5α-Reductase Inhibition in Prostate Epithelial Cells*

PubMed Central

Liu, Teresa T.; Grubisha, Melanie J.; Frahm, Krystle A.; Wendell, Stacy G.; Liu, Jiayan; Ricke, William A.; Auchus, Richard J.; DeFranco, Donald B.

2016-01-01

Current pharmacotherapies for symptomatic benign prostatic hyperplasia (BPH), an androgen receptor-driven, inflammatory disorder affecting elderly men, include 5α-reductase (5AR) inhibitors (i.e. dutasteride and finasteride) to block the conversion of testosterone to the more potent androgen receptor ligand dihydrotestosterone. Because dihydrotestosterone is the precursor for estrogen receptor β (ERβ) ligands, 5AR inhibitors could potentially limit ERβ activation, which maintains prostate tissue homeostasis. We have uncovered signaling pathways in BPH-derived prostate epithelial cells (BPH-1) that are impacted by 5AR inhibition. The induction of apoptosis and repression of the cell adhesion protein E-cadherin by the 5AR inhibitor dutasteride requires both ERβ and TGFβ. Dutasteride also induces cyclooxygenase type 2 (COX-2), which functions in a negative feedback loop in TGFβ and ERβ signaling pathways as evidenced by the potentiation of apoptosis induced by dutasteride or finasteride upon pharmacological inhibition or shRNA-mediated ablation of COX-2. Concurrently, COX-2 positively impacts ERβ action through its effect on the expression of a number of steroidogenic enzymes in the ERβ ligand metabolic pathway. Therefore, effective combination pharmacotherapies, which have included non-steroidal anti-inflammatory drugs, must take into account biochemical pathways affected by 5AR inhibition and opposing effects of COX-2 on the tissue-protective action of ERβ. PMID:27226548

Homologous recombination induced by doxazosin mesylate and saw palmetto in the Drosophila wing-spot test.

PubMed

Gabriel, Katiane Cella; Dihl, Rafael Rodrigues; Lehmann, Mauricio; Reguly, Maria Luiza; Richter, Marc François; Andrade, Heloisa Helena Rodrigues de

2013-03-01

Benign prostatic hyperplasia (BPH) is the most common tumor in men over 40 years of age. Acute urinary retention (AUR) is regarded as the most serious hazard of untreated BPH. α-Blockers, such as doxazosin mesylate, and 5-α reductase inhibitors, such as finasteride, are frequently used because they decrease both AUR and the need for BPH-related surgery. An extract of the fruit from American saw palmetto plant has also been used as an alternative treatment for BPH. The paucity of information available concerning the genotoxic action of these compounds led us to assess their activity as inducers of different types of DNA lesions using the somatic mutation and recombination test in Drosophila melanogaster. Finasteride did not induce gene mutation, chromosomal mutation or mitotic recombination, which means it was nongenotoxic in our experimental conditions. On the other hand, doxazosin mesylate and saw palmetto induced significant increases in spot frequencies in trans-heterozygous flies. In order to establish the actual role played by mitotic recombination and by mutation in the genotoxicity observed, the balancer-heterozygous flies were also analyzed, showing no increment in the total spot frequencies in relation to the negative control, for both drugs. Doxazosin mesylate and saw palmetto were classified as specific inducers of homologous recombination in Drosophila proliferative cells, an event linked to the loss of heterozygosity. Copyright © 2011 John Wiley & Sons, Ltd.

Enhanced topical delivery of finasteride using glyceryl monooleate-based liquid crystalline nanoparticles stabilized by cremophor surfactants.

PubMed

Madheswaran, Thiagarajan; Baskaran, Rengarajan; Yong, Chul Soon; Yoo, Bong Kyu

2014-02-01

The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1-208.6 and 153.7-243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 ± 0.005 μgcm(-2)h(-1)) compared with lower concentration (0.029 ± 0.007 μgcm(-2)h(-1)). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS.

Open-field exposure facilitates consummatory extinction.

PubMed

Justel, Nadia; Psyrdellis, Mariana; Pautassi, Ricardo M

2016-12-07

During extinction, the organism learns that a conditioned stimulus or a conditioned response is no longer associated with an unconditioned stimulus, and as a consequence, a decrement in the response is presented. The exposure to novel situations (e.g. exploration of a novel open field) has been used widely to modulate (i.e. either enhance or deteriorate) learning and memory. The aim of the present study was to test whether open-field exposure could modulate consummatory extinction. The results indicated that open-field exposure accelerated the extinction response (i.e. experimental animals provided novelty exposure had lower consummatory behavior than control animals) when applied before - but not after - the first extinction trial, or when applied before the second extinction trial. The results suggest that environmental treatments such as novelty exposure provide a valuable, nonpharmacological alternative to potentially modulate extinction processes.

Comparison of two expert-based assessments of diesel exhaust exposure in a case-control study: Programmable decision rules versus expert review of individual jobs

PubMed Central

Pronk, Anjoeka; Stewart, Patricia A.; Coble, Joseph B.; Katki, Hormuzd A.; Wheeler, David C.; Colt, Joanne S.; Baris, Dalsu; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Waddell, Richard; Verrill, Castine; Cherala, Sai; Silverman, Debra T.; Friesen, Melissa C.

2012-01-01

Objectives Professional judgment is necessary to assess occupational exposure in population-based case-control studies; however, the assessments lack transparency and are time-consuming to perform. To improve transparency and efficiency, we systematically applied decision rules to the questionnaire responses to assess diesel exhaust exposure in the New England Bladder Cancer Study, a population-based case-control study. Methods 2,631 participants reported 14,983 jobs; 2,749 jobs were administered questionnaires (‘modules’) with diesel-relevant questions. We applied decision rules to assign exposure metrics based solely on the occupational history responses (OH estimates) and based on the module responses (module estimates); we combined the separate OH and module estimates (OH/module estimates). Each job was also reviewed one at a time to assign exposure (one-by-one review estimates). We evaluated the agreement between the OH, OH/module, and one-by-one review estimates. Results The proportion of exposed jobs was 20–25% for all jobs, depending on approach, and 54–60% for jobs with diesel-relevant modules. The OH/module and one-by-one review had moderately high agreement for all jobs (κw=0.68–0.81) and for jobs with diesel-relevant modules (κw=0.62–0.78) for the probability, intensity, and frequency metrics. For exposed subjects, the Spearman correlation statistic was 0.72 between the cumulative OH/module and one-by-one review estimates. Conclusions The agreement seen here may represent an upper level of agreement because the algorithm and one-by-one review estimates were not fully independent. This study shows that applying decision-based rules can reproduce a one-by-one review, increase transparency and efficiency, and provide a mechanism to replicate exposure decisions in other studies. PMID:22843440

Occupational exposure to magnetic fields and the risk of brain tumors

PubMed Central

Coble, Joseph B.; Dosemeci, Mustafa; Stewart, Patricia A.; Blair, Aaron; Bowman, Joseph; Fine, Howard A.; Shapiro, William R.; Selker, Robert G.; Loeffler, Jay S.; Black, Peter M.; Linet, Martha S.; Inskip, Peter D.

2009-01-01

We investigated the association between occupational exposure to extremely low-frequency magnetic fields (MFs) and the risk of glioma and meningioma. Occupational exposure to MF was assessed for 489 glioma cases, 197 meningioma cases, and 799 controls enrolled in a hospital-based case–control study. Lifetime occupational history questionnaires were administered to all subjects; for 24% of jobs, these were supplemented with job-specific questionnaires, or “job modules,” to obtain information on the use of electrically powered tools or equipment at work. Job-specific quantitative estimates for exposure to MF in milligauss were assigned using a previously published job exposure matrix (JEM) with modification based on the job modules. Jobs were categorized as ≤1.5 mG, >1.5 to <3.0 mG, and ≥3.0 mG. Four exposure metrics were evaluated: (1) maximum exposed job; (2) total years of exposure >1.5 mG; (3) cumulative lifetime exposure; and (4) average lifetime exposure. Odds ratios (ORs) were calculated using unconditional logistic regression with adjustment for the age, gender, and hospital site. The job modules increased the number of jobs with exposure ≥3.0 mG from 4% to 7% relative to the JEM. No statistically significant elevation in ORs or trends in ORs across exposure categories was observed using four different exposure metrics for the three tumor types analyzed. Occupational exposure to MFs assessed using job modules was not associated with an increase in the risk for glioma, glioblastoma, or meningioma among the subjects evaluated in this study. PMID:19234232

Simultaneous exposure to concentrated ambient particles and acrolein causes cardiac effects mediated by parasympathetic modulation in mice

EPA Science Inventory

This study shows that exposure to CAPs and acrolein causes an increase in HRV that is mediated by the parasympathetic nervous system. Numerous studies show that short-term air pollution exposure modulates heart rate variability (HRV), which is an indicator of autonomic influence...

Characterizing use-phase chemical releases, fate, and disposal for modeling longitudinal human exposures to consumer products

EPA Science Inventory

The US EPA’s Human Exposure Model (HEM) is an integrated modeling system to estimate human exposure to chemicals in household consumer products. HEM consists of multiple modules, which may be run either together, or independently. The Source-to-Dose (S2D) module in HEM use...

Systems toxicology of chemically induced liver and kidney injuries: histopathology‐associated gene co‐expression modules

PubMed Central

Te, Jerez A.; AbdulHameed, Mohamed Diwan M.

2016-01-01

Abstract Organ injuries caused by environmental chemical exposures or use of pharmaceutical drugs pose a serious health risk that may be difficult to assess because of a lack of non‐invasive diagnostic tests. Mapping chemical injuries to organ‐specific histopathology outcomes via biomarkers will provide a foundation for designing precise and robust diagnostic tests. We identified co‐expressed genes (modules) specific to injury endpoints using the Open Toxicogenomics Project‐Genomics Assisted Toxicity Evaluation System (TG‐GATEs) – a toxicogenomics database containing organ‐specific gene expression data matched to dose‐ and time‐dependent chemical exposures and adverse histopathology assessments in Sprague–Dawley rats. We proposed a protocol for selecting gene modules associated with chemical‐induced injuries that classify 11 liver and eight kidney histopathology endpoints based on dose‐dependent activation of the identified modules. We showed that the activation of the modules for a particular chemical exposure condition, i.e., chemical‐time‐dose combination, correlated with the severity of histopathological damage in a dose‐dependent manner. Furthermore, the modules could distinguish different types of injuries caused by chemical exposures as well as determine whether the injury module activation was specific to the tissue of origin (liver and kidney). The generated modules provide a link between toxic chemical exposures, different molecular initiating events among underlying molecular pathways and resultant organ damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons, Ltd. PMID:26725466

Performance losses in rooftop-mounted PV modules from long-term environmental exposure at Las Cruces, New Mexico

NASA Astrophysics Data System (ADS)

Rosenthal, Andrew L.; Czanderna, A. W.; Pern, F. J.

1999-03-01

Forty-eight PV modules of four different types were instrumented and tested monthly for 3 years to measure and record the performance effects of environmental exposure. Two modules were removed from each set of 12 as a control and for "initial" characterization. As a secondary goal, the effects of mounting topology (open rack, integrated roof, conventional standoff mount) were also closely monitored. Current-voltage (I-V) curve data were archived and normalized according to accepted methods. The EVA pottant in all modules monitored was discolored to a deep yellow-to-brown color from prior exposures before the monitoring was begun. Modules showing observable performance degradation were removed from their mounts and prepared for in-depth analysis. During the 3-year monitoring period, 4 of the 10 Solarex a-Si modules stopped producing, 3 of the 10 Solarex MIT pc-Si modules lost from 5% to 10% efficiency, and 1 Mobil Ra-180 pc-Si module lost about 10% efficiency. For all of the other modules, a loss of less than 1% per year was recorded, which included all 10 of the Sovonics P-101 a-Si modules.

Dose Response Data for Hormonally Active Chemicals ...

EPA Pesticide Factsheets

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

Preliminary results of accelerated exposure testing of solar cell system components

NASA Technical Reports Server (NTRS)

Anagnostou, E.; Forestieri, A. F.

1977-01-01

Plastic samples and solar cell sub modules were exposed to an accelerated outdoor environment in Arizona and an accelerated simulated environment in a cyclic ultraviolet exposure tester which included humidity exposure. These tests were for preliminary screening of materials suitable for use in the manufacture of solar cell modules which are to have a 20-year lifetime. The samples were exposed for various times up to six months, equivalent to a real time exposure of four years. Suitable materials were found to be FEP-A, FEP-C, PFA, acrylic, silicone compounds and adhesives and possibly parylene. The method of packaging the sub modules was also found to be important to their performance.

[What is the value of low-energie lasers in the treatment of androgenetic alopecia ?

PubMed

Paquet, Ph; Orduz, M; Franchimont, C; Nikkels, A F

2017-12-01

Male and female androgenetic alopecia is a common, chronic, psychologically stressful disorder affecting more than 50 % of the individuals by 50 years of age. Despite the current topical (minoxidil) or oral (the inhibitors of 5-? reductase finasteride or dutasteride) treatments, there is a need for more effective management options. The current clinical evidence, the possible mechanisms of action and the rare adverse events of the low level laser therapy in the treatment of androgenetic alopecia are presented.

Saw palmetto and finasteride in the treatment of category-III prostatitis/chronic pelvic pain syndrome.

PubMed

Yang, Jennifer; Te, Alexis E

2005-07-01

Chronic nonbacterial prostatitis/chronic pelvic pain syndrome is a common entity for which a standardized management has not been established. Patients often have a significant symptom complex and impact on quality of life, but very little is known about the efficacy of second- and third-line treatments, such as the use of herbal supplements. Many treatments studied in recent literature include antibiotics, alpha-blockade, anti-inflammatory agents, and cognitive behavioral interventions such as biofeedback and psychotherapy.

Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia

PubMed Central

Hagberg, Katrina Wilcox; Divan, Hozefa A; Fang, Shona C; Nickel, J Curtis; Jick, Susan S

2017-01-01

Background Clinical trial results suggest that 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) may increase the risk of gynecomastia and male breast cancer, but epidemiological studies have been limited. Patients and methods We conducted a cohort study with nested case–control analyses using the UK Clinical Practice Research Datalink. We identified men diagnosed with BPH who were free from Klinefelter syndrome, prostate, genital or urinary cancer, prostatectomy or orchiectomy, or evidence of gynecomastia or breast cancer. Patients entered the cohort at age ≥40 years and at least 3 years after the start of their electronic medical record. We classified exposure as 5ARIs (alone or in combination with alpha blockers [ABs]), AB only, or unexposed to 5ARIs and ABs. Cases were men who had a first-time diagnosis of gynecomastia or breast cancer. Incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) in the gynecomastia analysis and crude and adjusted odds ratios (ORs) with 95% CIs in both analyses were calculated. Results Compared to no exposure, gynecomastia risk was elevated for users of 5ARIs (alone or in combination with ABs) in both the cohort (IRR=3.55, 95% CI 3.05–4.14) and case–control analyses (OR=3.31, 95% CI 2.66–4.10), whereas the risk was null for users of AB only. The increased risk of gynecomastia with the use of 5ARIs persisted regardless of the number of prescriptions, exposure timing, and presence or absence of concomitant prescriptions for drugs known to be associated with gynecomastia. The risk was higher for dutasteride than for finasteride. 5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61–3.80). Conclusion In men with BPH, 5ARIs significantly increased the risk of gynecomastia, but not breast cancer, compared to AB use and no exposure. PMID:28228662

Amplitude modulation detection by human listeners in reverberant sound fields: Effects of prior listening exposure.

PubMed

Zahorik, Pavel; Anderson, Paul W

2013-01-01

Previous work [Zahorik et al., POMA, 15, 050002 (2012)] has reported that for both broadband and narrowband noise carrier signals in a simulated reverberant sound field, human sensitivity to amplitude modulation (AM) is higher than would be predicted based on the acoustical modulation transfer function (MTF) of the listening environment. These results may be suggestive of mechanisms that functionally enhance modulation in reverberant listening, although many details of this enhancement effect are unknown. Given recent findings that demonstrate improvements in speech understanding with prior exposure to reverberant listening environments, it is of interest to determine whether listening exposure to a reverberant room might also influence AM detection in the room, and perhaps contribute to the AM enhancement effect. Here, AM detection thresholds were estimated (using an adaptive 2-alternative forced-choice procedure) in each of two listening conditions: one in which consistent listening exposure to a particular room was provided, and a second that intentionally disrupted listening exposure by varying the room from trial-to-trial. Results suggest that consistent prior listening exposure contributes to enhanced AM sensitivity in rooms. [Work supported by the NIH/NIDCD.].

Determination of illegal adulteration of dietary supplements with synthetic hair-growth compounds by UPLC and LC-Q-TOF/MS.

PubMed

Lee, Ji Hyun; Kang, Gihaeng; Park, Han Na; Kim, Jihee; Kim, Nam Sook; Park, Seongsoo; Park, Sung-Kwan; Baek, Sun Young; Kang, Hoil

2018-02-01

In this study, we developed a UPLC-PDA and LC-Q-TOF/MS method to identify and measure the following prohibited substances that may be found in dietary supplements:triaminodil, minoxidil, bimatoprost, alimemazine, diphenylcyclopropenone, α-tradiol, finasteride, methyltestosterone, spironolatone, flutamide, cyproterone, dutasteride, and testosterone 17-propionate.The method was validated according to International Conference on Harmonization guidelines in terms of specificity, linearity, accuracy, precision, LOD, LOQ, recovery, and stability. The method was completely validated showing satisfactory data for all method validation parameters. The linearity was good (R 2  > 0.999) with intra- and inter-day precision values of 0.2-3.4% and 0.3-2.9%, respectively. Moreover, the intra- and inter-day accuracies were 87-102% and 86-103%, respectively, and the precision was better than 9.4% (relative standard deviation).Hence, the proposed method is precise and has high quality,and can be utilised to comprehensively and continually monitor illegal drug adulteration in various forms of dietary supplements. Furthermore, to evaluate the applicability of the proposed method, we analysed 13 hair-growth compounds in 78 samples including food and dietary supplements. Minoxidil and triaminodil were detected in capsules at concentrations of 4.69 mg/g and 6.54 mg/g. In addition, finasteride was detected in a tablet at 13.45 mg/g. In addition, the major characteristic fragment ions were confirmed once again using LC-Q-TOF/MS for higher accuracy.

Selective and rapid determination of tadalafil and finasteride using solid phase extraction by high performance liquid chromatography and tandem mass spectrometry.

PubMed

Pappula, Nagaraju; Kodali, Balaji; Datla, Peda Varma

2018-04-15

Highly selective and fast liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for simultaneous determination of tadalafil (TDL) and finasteride (FNS) in human plasma. The method was successfully applied for analysis of TDL and FNS samples in clinical study. The method was validated as per USFDA (United States Food and Drug Administration), EMA (European Medicines Agency), and ANVISA (Agência Nacional de Vigilância Sanitária-Brazil) bio analytical method validation guidelines. Glyburide (GLB) was used as common internal standard (ISTD) for both analytes. The selected multiple reaction monitoring (MRM) transitions for mass spectrometric analysis were m/z 390.2/268.2, m/z 373.3/305.4 and m/z 494.2/369.1 for TDL, FNS and ISTD respectively. The extraction of analytes and ISTD was accomplished by a simple solid phase extraction (SPE) procedure. Rapid analysis time was achieved on Zorbax Eclipse C18 column (50 × 4.6 mm, 5 μm). The calibration ranges for TDL and FNS were 5-800 ng/ml and 0.2-30 ng/ml respectively. The results of precision and accuracy, linearity, recovery and matrix effect of the method are acceptable. The accuracy was in the range of 92.9%-106.4% and method precision was also good; %CV was less than 8.1%. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of neurosteroids in the anticonvulsant activity of midazolam.

PubMed

Dhir, Ashish; Rogawski, Michael A

2012-04-01

Midazolam is a short-acting benzodiazepine that is widely used as an i.v. sedative and anticonvulsant. Besides interacting with the benzodiazepine site associated with GABA(A) receptors, some benzodiazepines act as agonists of translocator protein (18 kDa) (TSPO) to enhance the synthesis of steroids, including neurosteroids with positive modulatory actions on GABA(A) receptors. We sought to determine if neurosteroidogenesis induced by midazolam contributes to its anticonvulsant action. Mice were pretreated with neurosteroid synthesis inhibitors and potentiators followed by midazolam or clonazepam, a weak TSPO ligand. Anticonvulsant activity was assessed with the i.v. pentylenetetrazol (PTZ) threshold test. Midazolam (500-5000 µg·kg(-1) , i.p.) caused a dose-dependent increase in seizure threshold. Pretreatment with the neurosteroid synthesis inhibitors finasteride, a 5α-reductase inhibitor, and a functional TSPO antagonist PK 11195, reduced the anticonvulsant action of midazolam. The anticonvulsant action of midazolam was enhanced by the neurosteroidogenic drug metyrapone, an 11β-hydroxylase inhibitor. In contrast, the anticonvulsant action of clonazepam (100 µg·kg(-1) ) was reduced by finasteride but not by PK 11195, indicating a possible contribution of neurosteroids unrelated to TSPO. Enhanced endogenous neurosteroid synthesis, possibly mediated by an interaction with TSPO, contributed to the anticonvulsant action of midazolam. Enhanced neurosteroidogenesis may also be a factor in the actions of other benzodiazepines, even those that only weakly interact with TSPO. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis.

PubMed

Tokuda, Kazuhiro; O'Dell, Kazuko A; Izumi, Yukitoshi; Zorumski, Charles F

2010-12-15

Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.

Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis

PubMed Central

Tokuda, Kazuhiro; O’Dell, Kazuko A.; Izumi, Yukitoshi; Zorumski, Charles F.

2010-01-01

Benzodiazepines (BDZs) enhance γ-aminobutyric acid-A (GABAA) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors (translocator protein 18kDa, TSPO) and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition following stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA (17-phenyl-(3α, 5α)-androst-16-en-3-ol), a blocker of neurosteroid effects on GABAA receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN, a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated one day prior to midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically-important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity. PMID:21159950

Role of neurosteroids in the anticonvulsant activity of midazolam

PubMed Central

Dhir, Ashish; Rogawski, Michael A

2012-01-01

BACKGROUND AND PURPOSE Midazolam is a short-acting benzodiazepine that is widely used as an i.v. sedative and anticonvulsant. Besides interacting with the benzodiazepine site associated with GABAA receptors, some benzodiazepines act as agonists of translocator protein (18 kDa) (TSPO) to enhance the synthesis of steroids, including neurosteroids with positive modulatory actions on GABAA receptors. We sought to determine if neurosteroidogenesis induced by midazolam contributes to its anticonvulsant action. EXPERIMENTAL APPROACH Mice were pretreated with neurosteroid synthesis inhibitors and potentiators followed by midazolam or clonazepam, a weak TSPO ligand. Anticonvulsant activity was assessed with the i.v. pentylenetetrazol (PTZ) threshold test. KEY RESULTS Midazolam (500–5000 µg·kg−1, i.p.) caused a dose-dependent increase in seizure threshold. Pretreatment with the neurosteroid synthesis inhibitors finasteride, a 5α-reductase inhibitor, and a functional TSPO antagonist PK 11195, reduced the anticonvulsant action of midazolam. The anticonvulsant action of midazolam was enhanced by the neurosteroidogenic drug metyrapone, an 11β-hydroxylase inhibitor. In contrast, the anticonvulsant action of clonazepam (100 µg·kg−1) was reduced by finasteride but not by PK 11195, indicating a possible contribution of neurosteroids unrelated to TSPO. CONCLUSION AND IMPLICATIONS Enhanced endogenous neurosteroid synthesis, possibly mediated by an interaction with TSPO, contributed to the anticonvulsant action of midazolam. Enhanced neurosteroidogenesis may also be a factor in the actions of other benzodiazepines, even those that only weakly interact with TSPO. PMID:22014182

Oral Finasteride Presents With Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia in Men.

PubMed

Perez-Mora, Nicolas; Velasco, Carlos; Bermüdez, Fernando

2015-01-01

Side effects associated with oral finasteride (FT) (1 mg/d) and topical 5% minoxidil (M5) have been previously described. The authors have evaluated long-term adverse effects and causes of long-term therapy withdrawal in patients with androgenic alopecia (AGA) treated with M5+FT vs M5 without FT. A total of 130 AGA patients with a minimum 2-year follow-up volunteered to complete a questionnaire on side effects. Patients' responses were classified as "never," "rarely," "sometimes," "often," and "all the time." An adverse effect was considered in the presence of an "often" or "all the time" response. A total of 100 patients received combined M5+FT and were compared with 30 patients receiving single-therapy M5 according to the physician's clinical criteria. Erectile dysfunction (3%), diminished libido (4%), and reduced ejaculation (7%) were present in patients taking M5+FT but were absent in patients taking M5. Only 1 of 100 patients taking M5+FT quit long-term therapy due to sexual adverse effects (diminished libido). The main causes for therapy withdrawal in the FT group were lack of positive results in 11% and in the M5 group side effects in 4% (P < .02). Increased body hair was different between groups: with 6.6% in the M5 group and 4% in the M5+FT group (P < .03). FT demonstrates sexual-unrelated reasons as the main cause of therapy withdrawal in long-term treated AGA patients.

Bioactives in Chinese Proprietary Medicine Modulates 5α-Reductase Activity and Gene Expression Associated with Androgenetic Alopecia

PubMed Central

Tan, Justin J. Y.; Pan, Jing; Sun, Lihan; Zhang, Junying; Wu, Chunyong; Kang, Lifeng

2017-01-01

Androgenetic alopecia (AGA) is characterized by a progressive and patterned transformation of thick, pigmented terminal scalp hairs into short, hypo-pigmented vellus-like hairs. The use of Minoxidil and Finasteride to treat AGA are often associated with complications in safety and efficacy. However, herbal remedies are deemed to have lesser side effects in many societies. This study aims to identify potential hair growth properties of individual compounds from a Chinese proprietary medicine known as Yangxue Shengfa capsule (YSC), used in China for many years for improving AGA. Six marker compounds, including 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), Chlorogenic acid, Emodin, Ferulic acid, Isoimperatorin, and Paeoniflorin were used for simultaneous HPLC quantification and anti-AGA in-vitro screening. Simultaneous quantification of these components was performed on 75% (v/v) methanol extracts of YSC, using a Welch Ultimate XB-C18 column and gradient elution. Five compounds significantly promoted cell proliferation in cultured immortalized human Dermal Papilla Cells (DPC). Multiple genes associated with the progression of AGA, including IGF-1, DKK-1, and TGF-β1, were found to be regulated by some of these compounds. Interestingly, Ferulic acid and Emodin demonstrated good pharmacological properties against AGA, thereby concluding the potential of these bioactives to be used in the treatment against AGA. PMID:28450835

High definition video teaching module for learning neck dissection.

PubMed

Mendez, Adrian; Seikaly, Hadi; Ansari, Kal; Murphy, Russell; Cote, David

2014-03-25

Video teaching modules are proven effective tools for enhancing student competencies and technical skills in the operating room. Integration into post-graduate surgical curricula, however, continues to pose a challenge in modern surgical education. To date, video teaching modules for neck dissection have yet to be described in the literature. To develop and validate an HD video-based teaching module (HDVM) to help instruct post-graduate otolaryngology trainees in performing neck dissection. This prospective study included 6 intermediate to senior otolaryngology residents. All consented subjects first performed a control selective neck dissection. Subjects were then exposed to the video teaching module. Following a washout period, a repeat procedure was performed. Recordings of the both sets of neck dissections were de-identified and reviewed by an independent evaluator and scored using the Observational Clinical Human Reliability Assessment (OCHRA) system. In total 91 surgical errors were made prior to the HDVM and 41 after exposure, representing a 55% decrease in error occurrence. The two groups were found to be significantly different. Similarly, 66 and 24 staff takeover events occurred pre and post HDVM exposure, respectively, representing a statistically significant 64% decrease. HDVM is a useful adjunct to classical surgical training. Residents performed significantly less errors following exposure to the HD-video module. Similarly, significantly less staff takeover events occurred following exposure to the HDVM.

Transplacental exposure to environmental carcinogens: Association with childhood cancer risks and the role of modulating factors.

PubMed

Fucic, A; Guszak, V; Mantovani, A

2017-09-01

Biological responses to carcinogens from environmental exposure during adulthood are modulated over years or decades. Conversely, during transplacental exposure, the effects on the human foetus change within weeks, intertwining with developmental mechanisms: even short periods of transplacental exposure may be imprinted in the organism for a lifetime. The pathways leading to childhood and juvenile cancers, such as leukaemias, neuroblastoma/brain tumours, hepatoblastoma, and Willm's tumour involve prenatally-induced genomic, epigenomic and/or non-genomic effects caused by xenobiotics. Pregnant women most often live in complex environmental settings that cause transplacental exposure of the foetus to xenobiotic mixtures. Mother-child biomonitoring should integrate the analysis of chemicals/radiation present in the living and workplace environment with relevant risk modulators related to life style. The interdisciplinary approach for transplacental cancer risk assessment in high-pressure areas should be based on an integrated model for mother-child exposure estimation via profiling the exposure level by water quality analysis, usage of emission grids, and land use maps. Copyright © 2017. Published by Elsevier Inc.

Microwave influence on the isolated heart function. 1: Effect of modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pakhomov, A.G.; Dubovick, B.V.; Degtyariov, I.G.

1995-09-01

Dependence of the microwave effect on modulation parameters (pulse width, duty ratio, and peak intensity) was studied in an isolated frog auricle preparation. The rate and amplitude of spontaneous auricle twitches were measured during and after a 2 min exposure to 915 or 885 MHz microwaves and were compared to preexposure values. The studied ranges of modulation parameters were: pulse width, 10{sup {minus}6}--10{sup {minus}2} s; duty ratio, 7:100000, and peak specific absorption rate, 100--3,000 W/kg. Combinations of the parameters were chosen by chance, and about 400 various exposure regimes were tested. The experiments established that no regime was effective unlessmore » the average microwave power was high enough to induce preparation heating (0.1--0.4 C). The twitch rate instantly increased, and the amplitude decreased, as the temperature rose; similar changes could be induced by equivalent conventional heating. the data provide evidence that the effect of short-term microwave exposure on the isolated heart pacemaker and contractile functions depends on pulse modulation just as much as modulation determines the average absorbed power. These functions demonstrated no specific dependence on exposure parameters such as frequency or power windows.« less

[Management of androgenetic alopecia in postmenopausal women].

PubMed

Rivera, R; Guerra-Tapia, A

2008-05-01

Female androgenetic alopecia or female-pattern alopecia is one of the most common causes of hair loss, affecting 50 % of women over their lifetime. The appearance of this condition is the cause of significant stress and psychological problems, making appropriate management important. Cases exist in which it is associated with hyperandrogenism. Here, we review the different clinical forms (diffuse, male-pattern, and Christmas-tree pattern), discuss the most appropriate laboratory tests (complete blood count, thyroid stimulating hormone, ferritin, prolactin, free and/or total testosterone, and dehydroepiandrosterone sulfate), and the different treatments, including finasteride.

CT dose modulation using automatic exposure control in whole-body PET/CT: effects of scout imaging direction and arm positioning.

PubMed

Inoue, Yusuke; Nagahara, Kazunori; Kudo, Hiroko; Itoh, Hiroyasu

2018-01-01

Automatic exposure control (AEC) modulates tube current and consequently X-ray exposure in CT. We investigated the behavior of AEC systems in whole-body PET/CT. CT images of a whole-body phantom were acquired using AEC on two scanners from different manufactures. The effects of scout imaging direction and arm positioning on dose modulation were evaluated. Image noise was assessed in the chest and upper abdomen. On one scanner, AEC using two scout images in the posteroanterior (PA) and lateral (Lat) directions provided relatively constant image noise along the z-axis with the arms at the sides. Raising the arms increased tube current in the head and neck and decreased it in the body trunk. Image noise increased in the upper abdomen, suggesting excessive reduction in radiation exposure. AEC using the PA scout alone strikingly increased tube current and reduced image noise in the shoulder. Raising the arms did not substantially influence dose modulation and decreased noise in the abdomen. On the other scanner, AEC using the PA scout alone or Lat scout alone resulted in similar dose modulation. Raising the arms increased tube current in the head and neck and decreased it in the trunk. Image noise was higher in the upper abdomen than in the middle and lower chest, and was not influenced by arm positioning. CT dose modulation using AEC may vary greatly depending on scout direction. Raising the arms tended to decrease radiation exposure; however, the effect depends on scout direction and the AEC system.

Medical student knowledge regarding radiology before and after a radiological anatomy module: implications for vertical integration and self-directed learning.

PubMed

Murphy, Kevin P; Crush, Lee; O'Malley, Eoin; Daly, Fergus E; O'Tuathaigh, Colm M P; O'Connor, Owen J; Cryan, John F; Maher, Michael M

2014-10-01

To examine the impact that anatomy-focused radiology teaching has on non-examined knowledge regarding radiation safety and radiology as a specialty. First-year undergraduate medical students completed surveys prior to and after undertaking the first-year anatomy programme that incorporates radiological anatomy. Students were asked opinions on preferred learning methodology and tested on understanding of radiology as a specialty and radiation safety. Pre-module and post-module response rates were 93 % (157/168) and 85 % (136/160), respectively. Pre-module and post-module, self-directed learning (SDL) ranked eighth (of 11) for preferred gross-anatomy teaching formats. Correct responses regarding radiologist/radiographer roles varied from 28-94 % on 16 questions with 4/16 significantly improving post-module. Identification of modalities that utilise radiation significantly improved for five of eight modalities post-module but knowledge regarding relative amount of modality-specific radiation use was variable pre-module and post-module. SDL is not favoured as an anatomy teaching method. Exposure of students to a radiological anatomy module delivered by senior clinical radiologists improved basic knowledge regarding ionising radiation use, but there was no improvement in knowledge regarding radiation exposure relative per modality. A possible explanation is that students recall knowledge imparted in didactic lectures but do little reading around the subject when the content is not examined. • Self-directed learning is not favoured as a gross anatomy teaching format amongst medical students. • An imaging anatomy-focused module improved basic knowledge regarding ionising radiation use. • Detailed knowledge of modality-specific radiation exposure remained suboptimal post-module. • Knowledge of roles within a clinical radiology department showed little change post-module.

Subcortical amplitude modulation encoding deficits suggest evidence of cochlear synaptopathy in normal-hearing 18-19 year olds with higher lifetime noise exposure.

PubMed

Paul, Brandon T; Waheed, Sajal; Bruce, Ian C; Roberts, Larry E

2017-11-01

Noise exposure and aging can damage cochlear synapses required for suprathreshold listening, even when cochlear structures needed for hearing at threshold remain unaffected. To control for effects of aging, behavioral amplitude modulation (AM) detection and subcortical envelope following responses (EFRs) to AM tones in 25 age-restricted (18-19 years) participants with normal thresholds, but different self-reported noise exposure histories were studied. Participants with more noise exposure had smaller EFRs and tended to have poorer AM detection than less-exposed individuals. Simulations of the EFR using a well-established cochlear model were consistent with more synaptopathy in participants reporting greater noise exposure.

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia.

PubMed

Fano, Diego; Vásquez-Velásquez, Cinthya; Gonzales-Castañeda, Cynthia; Guajardo-Correa, Emanuel; Orihuela, Pedro A; Gonzales, Gustavo F

2017-01-01

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ER β , but only the aqueous fraction increased androgen receptors and ER α . In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ER β without affecting androgen receptors and ER α . This effect was not observed with aqueous fraction of methanolic extract of red maca.

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia

PubMed Central

Vásquez-Velásquez, Cinthya

2017-01-01

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ERβ, but only the aqueous fraction increased androgen receptors and ERα. In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ERβ without affecting androgen receptors and ERα. This effect was not observed with aqueous fraction of methanolic extract of red maca. PMID:29375645

Effect of two different extracts of red maca in male rats with testosterone-induced prostatic hyperplasia.

PubMed

Gonzales, Gustavo F; Vasquez, Vanessa; Rodriguez, Daniella; Maldonado, Carmen; Mormontoy, Juliet; Portella, Jimmy; Pajuelo, Monica; Villegas, León; Gasco, Manuel

2007-03-01

To determine the effect of two different extracts of red maca in male rats. Prostatic hyperplasia was induced in male rats with testosterone enanthate (TE). The study comprised six groups: one control group (group 1), one group treated with TE (group 2), two groups treated with TE and aqueous extract of red maca (groups 3 and 4), one group treated with hydroalcoholic extract of red maca (group 5) and one group treated with finasteride (0.1 mg, group 6). Differences in the aqueous extract dependent on the length of time of boiling, whether for 2 or 3 hours, for groups 3 and 4 was assessed. Extracts of red maca contained 0.1 mg of benzylglucosinolate. Thereafter, a dose-response effect of different doses of benzylglucosinolates (0.02-0.08 mg) in red maca extracts was assessed. Prostate weight was similar in rats treated with freeze-dried aqueous extract of red maca prepared after 2 and 3 hours of boiling. Freeze-dried aqueous extract of red maca, hydroalcoholic extract of red maca and finasteride reduced prostate weight in rats with prostatic hyperplasia. No difference was observed between the data obtained from aqueous extract or hydroalcoholic extract of red maca. A dose dependent reduction of prostate weight was observed with the increase of the dose of benzylglucosinolates in red maca extracts. The present study showed that hydroalcoholic or aqueous extract of red maca containing 0.1 mg of benzylglucosinolate can reduce prostate size in male rats in which prostatic hyperplasia had been induced by TE.

Inhibition of 5-alpha-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate.

PubMed

Corradi, Lara S; Góes, Rejane M; Carvalho, Hernandes F; Taboga, Sebastião R

2004-06-01

Prostatic differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Dihydrotestosterone, which is synthesized from testosterone by 5 alpha-reductase (5 alpha-r), is the active molecule triggering androgen action within the prostate. In the present work, we examined the effects of 5 alpha-reductase inhibition by finasteride in the ventral prostate (VP) of the adult gerbil, employing histochemical and electron microscopy techniques to demonstrate the morphological and organizational changes of the organ. After 10 days of finasteride treatment at a dose of 100 mg/kg/day, the prostatic complex (VP and dorsolateral prostate) absolute weight was reduced to about 18%. The epithelial cells became short and cuboidal, with less secretory blebs and reduced acid phosphatase activity. The luminal sectional area diminished, suggestive of decreased secretory activity. The stromal/epithelial ratio increased, the stroma becoming thicker but less cellular. There was a striking accumulation of collagen fibrils, which was accompanied by an increase in deposits of amorphous granular material adjacent to the basal lamina and in the clefts between smooth muscle cells (SMC). Additionally, the periacinar smooth muscle became loosely packed. Some SMC were atrophic and showed a denser array of the cytoskeleton, whereas other SMC had a highly irregular outline with numerous spine-like projections. The present data indicate that 5 alpha-r inhibition causes epithelial and stromal changes by affecting intra-prostatic hormone levels. These alterations are probably the result of an imbalance of the homeostatic interaction between the epithelium and the underlying stroma.

Measurement of tamsulosin in human serum by liquid chromatography-tandem mass spectrometry.

PubMed

Upreti, Rita; Homer, Natalie Z M; Naredo, Gregorio; Cobice, Diego F; Hughes, Katherine A; Stewart, Laurence H; Walker, Brian R; Andrew, Ruth

2013-07-01

A simple, sensitive and robust method to extract tamsulosin from human serum, and quantify by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated and is applicable as a measure of compliance in clinical research. Tamsulosin was extracted from human serum (100μL) via liquid-liquid extraction with methyl tert-butyl ether (2mL) following dilution with 0.1M ammonium hydroxide (100μL), achieving 99.9% analyte recovery. Internal standard, d9-finasteride, was synthesised in-house. Analyte and internal standard were separated on an Ascentis(®) Express C18 (100mm×3mm, 2.7μm) column using a gradient elution with mobile phases methanol and 2mM aqueous ammonium acetate (5:95, v/v). Total run-time was 6min. Tamsulosin was quantified using a triple quadrupole mass spectrometer operated in multi-reaction-monitoring (MRM) mode using positive electrospray ionisation. Mass transitions monitored for quantitation were: tamsulosin m/z 409→228 and d9-finasteride m/z 382→318, with the structural formulae of ions confirmed by Fourier transform ion cyclotron resonance mass spectrometry (within 10ppm). The limit of quantitation was 0.2ng/mL, and the method was validated in the linear range 0.2-50ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers in a clinical study of benign prostatic hyperplasia. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Ovine placental steroid synthesis and metabolism in late gestation.

PubMed

Reynolds, Lawrence P; Legacki, Erin L; Corbin, C Jo; Caton, Joel S; Vonnahme, Kimberly A; Stanley, Scott; Conley, Alan J

2018-04-14

Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude 1) that diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and 2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.

Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation

PubMed Central

Ahmed, Tarek A

2016-01-01

In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom–up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability. PMID:26893559

Guidelines for the diagnosis and treatment of male-pattern and female-pattern hair loss, 2017 version.

PubMed

Manabe, Motomu; Tsuboi, Ryoji; Itami, Satoshi; Osada, Shin-Ichi; Amoh, Yasuyuki; Ito, Taisuke; Inui, Shigeki; Ueki, Rie; Ohyama, Manabu; Kurata, Sotaro; Kono, Takeshi; Saito, Norimitsu; Sato, Akio; Shimomura, Yutaka; Nakamura, Motonobu; Narusawa, Hiroshi; Yamazaki, Masashi

2018-06-04

Male-pattern hair loss (MPHL, androgenetic alopecia) is a slowly progressive form of alopecia which begins after puberty. In 2010, we published the first Japanese edition of guidelines for the diagnosis and treatment of MPHL. It achieved the original goal of providing physicians and patients in Japan with evidence-based information for choosing efficacious and safe therapy for MPHL. Subsequently, new therapeutic drugs and treatment methods have been developed, and women's perception of MPHL has undergone change and the term "female-pattern hair loss (FPHL)" is becoming more common internationally. Thus, here we report a revised version of the 2010 guidelines aimed at both MPHL and FPHL. In these guidelines, finasteride 1 mg daily, dutasteride 0.5 mg daily and topical 5% minoxidil twice daily for MPHL, and topical 1% minoxidil twice daily for FPHL, are recommended as the first-line treatments. Self-hair transplantation, irradiation by light-emitting diodes and low-level lasers, and topical application of adenosine for MPHL are recommended, whereas prosthetic hair transplantation and oral administration of minoxidil should not be performed. Oral administration of finasteride or dutasteride are contraindicated for FPHL. In addition, we have evaluated the effectiveness of topical application of carpronium chloride, t-flavanone, cytopurine, pentadecane and ketoconazole, and wearing a wig. Unapproved topical application of bimatoprost and latanoprost, and emerging hair regeneration treatments have also been addressed. We believe that the revised guidelines will improve further the diagnostic and treatment standards for MPHL add FPHL in Japan. © 2018 Japanese Dermatological Association.

Improvement of the CULTEX® exposure technology by radial distribution of the test aerosol.

PubMed

Aufderheide, Michaela; Heller, Wolf-Dieter; Krischenowski, Olaf; Möhle, Niklas; Hochrainer, Dieter

2017-07-05

The exposure of cellular based systems cultivated on microporous membranes at the air-liquid interface (ALI) has been accepted as an appropriate approach to simulate the exposure of cells of the respiratory tract to native airborne substances. The efficiency of such an exposure procedure with regard to stability and reproducibility depends on the optimal design at the interface between the cellular test system and the exposure technique. The actual exposure systems favor the dynamic guidance of the airborne substances to the surface of the cells in specially designed exposure devices. Two module types, based on a linear or radial feed of the test atmosphere to the test system, were used for these studies. In our technical history, the development started with the linear designed version, the CULTEX ® glass modules, fulfilling basic requirements for running ALI exposure studies (Mohr and Durst, 2005). The instability in the distribution of different atmospheres to the cells caused us to create a new exposure module, characterized by a stable and reproducible radial guidance of the aerosol to the cells. The outcome was the CULTEX ® RFS (Mohr et al., 2010). In this study, we describe the differences between the two systems with regard to particle distribution and deposition clarifying the advantages and disadvantages of a radial to a linear aerosol distribution concept. Copyright © 2017 Elsevier GmbH. All rights reserved.

Attentional modulation of the mere exposure effect.

PubMed

Yagi, Yoshihiko; Ikoma, Shinobu; Kikuchi, Tadashi

2009-11-01

The mere exposure effect refers to the phenomenon where previous exposures to stimuli increase participants' subsequent affective preference for those stimuli. This study explored the effect of selective attention on the mere exposure effect. The experiments manipulated the to-be-attended drawings in the exposure period (either red or green polygons in Experiments 1 and 2; both red and green polygons in Experiments 3 and 4) and black to-be-evaluated drawings in the affective judgment period (morphologically identical to the red or green polygons in Experiments 1 and 4; morphologically identical to the composite drawings in Experiments 2 and 3). The results showed a significant mere exposure effect only for the target shapes involved in attentional selection, even when the participants could recognize the nontarget shapes. This indicates that selective attention modulated the mere exposure effect.

Steroid withdrawal in the mouse results in anxiogenic effects of 3alpha,5beta-THP: a possible model of premenstrual dysphoric disorder.

PubMed

Smith, Sheryl S; Ruderman, Yevgeniy; Frye, Cheryl; Homanics, Gregg; Yuan, Maoli

2006-06-01

3alpha-OH-5alpha[beta]-pregnan-20-one (THP) is a positive modulator of the GABAA receptor (GABAR), which underlies its reported anxiolytic effect. However, there are conditions such as premenstrual dysphoric disorder (PMDD) where increases in THP levels can be associated with adverse mood. In order to test for conditions where THP might be anxiogenic, we developed a mouse model of THP withdrawal. Because delta-containing GABAR are highly sensitive to THP modulation, results were compared in wild-type and delta knockout mice. Finasteride, a 5alpha-reductase blocker, was administered for 3 days to female wild-type or delta knockout mice. Then, animals were tested in the elevated plus maze, following acute administration of THP, lorazepam, flumazenil, or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), and results compared to vehicle-injected controls. CA1 hippocampal GABAR alpha4 subunit levels were assessed by Western blot. After THP withdrawal, THP produced anxiogenic effects, decreasing open arm entries on the elevated plus maze, following a brief shock, in contrast to its expected anxiolytic effects. As we have shown in rats, THP withdrawal also resulted in increased expression of the alpha4 subunit in mouse CA1 hippocampus. As expected for increases in alpha4-containing GABAR, THP withdrawn mice were relatively insensitive to the benzodiazepine (BDZ) lorazepam and had atypical responses to the BDZ antagonist flumazenil when tested on the plus maze. In contrast, they showed a greater anxiolytic response to THIP, which has greater efficacy at alpha4betadelta than other GABAR. Although THP withdrawal in delta knockout mice also increased the alpha4 GABAR subunit, the anxiogenic effects of THP and the anxiolytic effects of THIP were not observed, implicating alpha4betadelta GABAR in these effects. Based on these behavioral and pharmacological findings, we suggest that THP withdrawal in the mouse may serve as a rodent model of PMDD.

Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

PubMed Central

Xu, Joella; Huang, Guannan; Guo, Tai L.

2016-01-01

Bisphenol A (BPA), used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors), epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg) cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS), have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases. PMID:29051427

Developmental Bisphenol A Exposure Modulates Immune-Related Diseases.

PubMed

Xu, Joella; Huang, Guannan; Guo, Tai L

2016-09-26

Bisphenol A (BPA), used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors), epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg) cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS), have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases.

Modulation of human alveolar macrophage properties by ozone exposure in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becker, S.; Madden, M.C.; Newman, S.L.

The study investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3)(0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2(PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, the authors found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2) production in response to phorbol ester was reduced aftermore » exposure of HAM to O3 while the basal O2 release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3-exposed HAM produced significantly lower levels of these cytokines when simulated with bacterial lipopolysaccharide (LPS).« less

Dual hologram design study

NASA Technical Reports Server (NTRS)

Liu, H. K.

1978-01-01

A phase modulated triple exposure technique was incorporated into a holographic nondestructive test (HNDT) system. The technique was able to achieve a goal of simultaneously identifying the zero-order fringe and determining the direction of motion (or displacement). Basically, the technique involves the addition of one more exposure, during the loading of the tested object, to the conventional double-exposure hologram. A phase shifter is added to either the object beam or the reference beam during the second and third exposure. Theoretical analysis with the assistance of computer simulation illustrated the feasibility of implementing the phase modulation and triple-exposure in the HNDT systems. Main advantages of the technique are the enhancement of accuracy in data interpretation and a better determination of the nature of the flaws in the tested object.

Attentional Modulation of the Mere Exposure Effect

ERIC Educational Resources Information Center

Yagi, Yoshihiko; Ikoma, Shinobu; Kikuchi, Tadashi

2009-01-01

The "mere exposure effect" refers to the phenomenon where previous exposures to stimuli increase participants' subsequent affective preference for those stimuli. This study explored the effect of selective attention on the mere exposure effect. The experiments manipulated the to-be-attended drawings in the exposure period (either red or green…

Hair loss in women.

PubMed

Camacho-Martínez, Francisco M

2009-03-01

Female pattern hair loss (FPHL) is a clinical problem that is becoming more common in women. Female alopecia with androgen increase is called female androgenetic alopecia (FAGA) and without androgen increase is called female pattern hair loss. The clinical picture of typical FAGA begins with a specific "diffuse loss of hair from the parietal or frontovertical areas with an intact frontal hairline." Ludwig called this process "rarefaction." In Ludwig's classification of hair loss in women, progressive type of FAGA, 3 patterns were described: grade I or minimal, grade II or moderate, and grade III or severe. Ludwig also described female androgenetic alopecia with male pattern (FAGA.M) that should be subclassified according to Ebling's or Hamilton-Norwood's classification. FAGA.M may be present in 4 conditions: persistent adrenarche syndrome, alopecia caused by an adrenal or an ovarian tumor, posthysterectomy, and as an involutive alopecia. A more recent classification (Olsen's classification of FPHL) proposes 2 types: early- and late-onset with or without excess of androgens in each. The diagnosis of FPHL is made by clinical history, clinical examination, wash test, dermoscopy, trichoscan, trichograms and laboratory test, especially androgenic determinations. Topical treatment of FPHL is with minoxidil, 2-5% twice daily. When FPHL is associated with high levels of androgens, systemic antiandrogenic therapy is needed. Persistent adrenarche syndrome (adrenal SAHA) and alopecia of adrenal hyperandrogenism is treated with adrenal suppression and antiandrogens. Adrenal suppression is achieved with glucocorticosteroids. Antiandrogens therapy includes cyproterone acetate, drospirenone, spironolactone, flutamide, and finasteride. Excess release of ovarian androgens (ovarian SAHA) and alopecia of ovarian hyperandrogenism is treated with ovarian suppression and antiandrogens. Ovarian suppression includes the use of contraceptives containing an estrogen, ethinylestradiol, and a progestogen. Antiandrogens such as cyproterone acetate, always accompanied by tricyclic contraceptives, are the best choice of antiandrogens to use in patients with FPHL. Gonadotropin-releasing hormone agonists such as leuprolide acetate suppress pituitary and gonadal function through a reduction in luteinizing hormone and follicle-stimulating hormone levels. Subsequently, ovarian steroid levels also will be reduced, especially in patients with polycystic ovary syndrome. When polycystic ovary syndrome is associated with insulin resistance, metformin must be considered as treatment. Hyperprolactinemic SAHA and alopecia of pituitary hyperandrogenism should be treated with bromocriptine or cabergoline. Postmenopausal alopecia, with previous high levels of androgens or with prostatic-specific antigen greater than 0.04 ng/mL, improves with finasteride or dutasteride. Although we do not know the reason, postmenopausal alopecia in normoandrogenic women also improves with finasteride or dutasteride at a dose of 2.5 mg per day. Dermatocosmetic concealment with a hairpiece, hair prosthesis as extensions, or partial hairpieces can be useful. Lastly, weight loss undoubtedly improves hair loss in hyperandrogenic women.

Total Risk Integrated Methodology (TRIM) - TRIM.Expo

EPA Pesticide Factsheets

The Exposure Event module of TRIM (TRIM.Expo), similar to most human exposure models, provides an analysis of the relationships between various chemical concentrations in the environment and exposure levels of humans.

IN VITRO LUNG ALVEOLAR EPITHELIAL CELL INJURY AND INFLAMMATORY RESPONSE TO PARTICULATE MATTER-ASSOCIATED METALS - MODULATION BY EXPOSURE TO TNF-ALPHA, IL-BETA, OR IFN-GAMMA

EPA Science Inventory

IN VITRO LUNG ALVEOLAR EPITHELIAL CELL INJURY AND INFLAMMATORY RESPONSE TO PARTICULATE MATTER-ASSOCIATED METALS - MODULATION BY EXPOSURE TO TNF , IL-1 , OR IFN .

JA Dye, KE Peoples*, CL Hayes?. US EPA, ORD, Pulmonary Toxicology Branch, RTP, NC, *HHMI-SRI, NCSU, Raleigh, NC...

Epigenetic modulations in early endothelial cells and DNA hypermethylation in human skin after sulfur mustard exposure.

PubMed

Steinritz, Dirk; Schmidt, Annette; Balszuweit, Frank; Thiermann, Horst; Simons, Thilo; Striepling, Enno; Bölck, Birgit; Bloch, Wilhelm

2016-02-26

Victims that were exposed to the chemical warfare agent sulfur mustard (SM) suffer from chronic dermal and ocular lesions, severe pulmonary problems and cancer development. It has been proposed that epigenetic perturbations might be involved in that process but this has not been investigated so far. In this study, we investigated epigenetic modulations in vitro using early endothelial cells (EEC) that were exposed to different SM concentrations (0.5, 1.0, 23.5 and 50μM). A comprehensive analysis of 78 genes related to epigenetic pathways (i.e., DNA-methylation and post-translational histone modifications) was performed. Moreover, we analyzed global DNA methylation in vitro in EEC after SM exposure as a maker for epigenetic modulations and in vivo using human skin samples that were obtained from a patient 1 year after an accidently exposure to pure SM. SM exposure resulted in a complex regulation pattern of epigenetic modulators which was accompanied by a global increase of DNA methylation in vitro. Examination of the SM exposed human skin samples also revealed a significant increase of global DNA methylation in vivo, underlining the biological relevance of our findings. Thus, we demonstrated for the first time that SM affects epigenetic pathways and causes epigenetic modulations both in vivo and in vitro. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Real time outdoor exposure testing of solar cell modules and component materials

NASA Technical Reports Server (NTRS)

Anagnostou, E.; Forestieri, A. F.

1977-01-01

Plastic samples, solar cell modules, and sub-modules were exposed at test sites in Florida, Arizona, Puerto Rico, and Cleveland, Ohio, in order to determine materials suitable for use in solar cell modules with a proposed 20-year lifetime. Various environments were encountered including subtropical, subtropical with a sea air atmosphere, desert, rain forest, normal urban, and urban-polluted. The samples were exposed for periods up to six months. Materials found not suitable were polyurethane, polyester, Kapton, Mylar, and UV-stabilized Lexan. Suitable materials were acrylic, FEP-A, and glass. The results of exposure of polyvinylidene fluoride were dependent on the specific formulation, but several types appear suitable. RTV silicone rubber (clear) appears to pick up and hold dirt both as a free film and as a potting medium for modules. The results indicate that dirt accumulation and cleanability are important factors in the selection of solar cell module covers and encapsulants.

Apoptotic cell death during Drosophila oogenesis is differentially increased by electromagnetic radiation depending on modulation, intensity and duration of exposure.

PubMed

Sagioglou, Niki E; Manta, Areti K; Giannarakis, Ioannis K; Skouroliakou, Aikaterini S; Margaritis, Lukas H

2016-01-01

Present generations are being repeatedly exposed to different types and doses of non-ionizing radiation (NIR) from wireless technologies (FM radio, TETRA and TV stations, GSM and UMTS phones/base stations, Wi-Fi networks, DECT phones). Although there is controversy on the published data regarding the non-thermal effects of NIR, studies have convincingly demonstrated bioeffects. Their results indicate that modulation, intensity, exposure duration and model system are important factors determining the biological response to irradiation. Attempting to address the dependence of NIR bioeffectiveness on these factors, apoptosis in the model biological system Drosophila melanogaster was studied under different exposure protocols. A signal generator was used operating alternatively under Continuous Wave (CW) or Frequency Modulation (FM) emission modes, at three power output values (10 dB, 0, -10 dB), under four carrier frequencies (100, 395, 682, 900 MHz). Newly emerged flies were exposed either acutely (6 min or 60 min on the 6th day), or repeatedly (6 min or 60 min daily for the first 6 days of their life). All exposure protocols resulted in an increase of apoptotic cell death (ACD) observed in egg chambers, even at very low electric field strengths. FM waves seem to have a stronger effect in ACD than continuous waves. Regarding intensity and temporal exposure pattern, EMF-biological tissue interaction is not linear in response. Intensity threshold for the induction of biological effects depends on frequency, modulation and temporal exposure pattern with unknown so far mechanisms. Given this complexity, translating such experimental data into possible human exposure guidelines is yet arbitrary.

Results from the first five years of radiation exposure monitoring aboard the ISS

NASA Astrophysics Data System (ADS)

Golightly, M.; Semones, E.; Shelfer, T.; Johnson, S.; Zapp, N.; Weyland, M.

NASA uses a variety of radiation monitoring devices aboard the International Space Station as part of its space flight radiation health program. This operational monitoring system consists of passive dosimeters, internal and external charged particle telescopes, and a tissue equivalent proportional counter (TEPC). Sixteen passive dosimeters, each consisting of TLD-100, TLD-300, TLD-600, and TLD-700 chips in a small acrylic holder, are placed throughout the habitable volume of the ISS. The TEPC and internal charged particle telescopes are portable and can be relocated to multiple locations in the Lab Module or Service Module. The external charged particle telescopes are mounted to a fixed boom attached to the starboard truss. Passive dosimeters were used in eleven monitoring periods over the period 20 May 1999 to 04 May 2003. Over this period exposure rates from TLD-100 measurements ranged from 0.120-0.300 mGy/d. Exposure rates inside the habitable volume are non-uniform: exposures vary by a factor of ˜ 1.7 from minimum to maximum, with the greatest non-uniformity occurring in the Lab Module. Highest daily exposure rates are near the window in the Lab Module, inside the Joint Airlock, and the sleep stations inside the Service Module, while the lowest rates occur inside the polyethylene-lined Temporary Sleep Station in the Lab Module, adjacent to the port ``arm'' of Node 1, and the aft end of the Service Module. The minimum exposure rates as measured by the passive dosimeters occurred in the spring of 2002, very close to the solar F10.7 emission maximum (Feb 2002), and two years after the sunspot maximum (Apr 2000). Exposure rates have since gradually increased as the sun's activity transitions towards solar minimum conditions. Since 01 Jun 2002, dose rates measured by the IV-CPDS, estimated from the count rate in first detector of the telescope's stack, ranged from ˜ 0.170-0.390 mGy/d. The maximum measured dose rate occurred 28 Oct 2003 during the ``Halloween'' space weather event. Interestingly, the minimum dose rate occurred 31 Oct 2003, near the end of the same remarkable space weather event, when the Earth was experiencing a significant Forbush decrease. The average IV-CPDS-measured dose rate increased from 0.194 to 0.234 mGy/d since 01 Jun 2002--an increase of ˜ 21% and a further indication that the low-Earth radiation environment is transitioning from solar maximum conditions towards solar minimum.

THE CONTRIBUTION OF AMBIENT PM2.5 TO TOTAL PERSONAL EXPOSURES: RESULTS FROM A POPULATION EXPOSURE MODEL FOR PHILADELPHIA, PA

EPA Science Inventory

The US EPA National Exposure Research Laboratory (NERL) is currently developing an integrated human exposure source-to-dose modeling system (HES2D). This modeling system will incorporate population exposure modules that use a probabilistic approach to predict population exposu...

CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

EPA Science Inventory

Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

Cell line specific modulation of connexin43 expression after exposure to ionizing radiation.

PubMed

Banaz-Yaşar, Ferya; Tischka, Rabea; Iliakis, George; Winterhager, Elke; Gellhaus, Alexandra

2005-01-01

Gap junctional intercellular communication plays a significant role in mediating radiation-induced bystander effects. However, the level of Cx43 itself is influenced by ionizing radiation, which could modify the bystander effect. Here we have investigated several cell lines for the modulation of Cx43 expression 24 h after irradiation with 5 Gy X-rays. The mouse endothelial cell line bEnd3 revealed a significantly elevated level of Cx43 already 15 min after exposure to X-rays, whereas human hybrid endothelial cells (EA.hy926) exhibited a transient downregulation of Cx43 mRNA. No obvious changes in the communication properties of the different cell lines could be observed after irradiation. The communication-deficient malignant human trophoblast cell line Jeg3 stably transfected with Cx43 did not reveal any induction of endogenous nor alteration in the exogenous Cx43 transcript level upon exposure to 5 Gy. Taken together, our data show a cell line specific modulation of Cx43 expression after exposure to X-rays.

Waveband specific transcriptional control of select genetic pathways in vertebrate skin (Xiphophorus maculatus).

PubMed

Walter, Ronald B; Boswell, Mikki; Chang, Jordan; Boswell, William T; Lu, Yuan; Navarro, Kaela; Walter, Sean M; Walter, Dylan J; Salinas, Raquel; Savage, Markita

2018-05-10

Evolution occurred exclusively under the full spectrum of sunlight. Conscription of narrow regions of the solar spectrum by specific photoreceptors suggests a common strategy for regulation of genetic pathways. Fluorescent light (FL) does not possess the complexity of the solar spectrum and has only been in service for about 60 years. If vertebrates evolved specific genetic responses regulated by light wavelengths representing the entire solar spectrum, there may be genetic consequences to reducing the spectral complexity of light. We utilized RNA-Seq to assess changes in the transcriptional profiles of Xiphophorus maculatus skin after exposure to FL ("cool white"), or narrow wavelength regions of light between 350 and 600 nm (i.e., 50 nm or 10 nm regions, herein termed "wavebands"). Exposure to each 50 nm waveband identified sets of genes representing discrete pathways that showed waveband specific transcriptional modulation. For example, 350-400 or 450-500 nm waveband exposures resulted in opposite regulation of gene sets marking necrosis and apoptosis (i.e., 350-400 nm; necrosis suppression, apoptosis activation, while 450-500 nm; apoptosis suppression, necrosis activation). Further investigation of specific transcriptional modulation employing successive 10 nm waveband exposures between 500 and 550 nm showed; (a) greater numbers of genes may be transcriptionally modulated after 10 nm exposures, than observed for 50 nm or FL exposures, (b) the 10 nm wavebands induced gene sets showing greater functional specificity than 50 nm or FL exposures, and (c) the genetic effects of FL are primarily due to 30 nm between 500 and 530 nm. Interestingly, many genetic pathways exhibited completely opposite transcriptional effects after different waveband exposures. For example, the epidermal growth factor (EGF) pathway exhibits transcriptional suppression after FL exposure, becomes highly active after 450-500 nm waveband exposure, and again, exhibits strong transcriptional suppression after exposure to the 520-530 nm waveband. Collectively, these results suggest one may manipulate transcription of specific genetic pathways in skin by exposure of the intact animal to specific wavebands of light. In addition, we identify genes transcriptionally modulated in a predictable manner by specific waveband exposures. Such genes, and their regulatory elements, may represent valuable tools for genetic engineering and gene therapy protocols.

Colour changes of orthodontic elastomeric module materials exposed to in vitro dietary media.

PubMed

Ardeshna, Anil P; Vaidyanathan, Tritala K

2009-09-01

To evaluate the colour stability of orthodontic elastomeric module material exposed to dietary media. An in vitro laboratory study. Coloured and clear orthodontic elastomeric modules from four companies were exposed to coffee, cola, tea and spices for 72 h. The difference in colour components was measured with a Minolta chromameter before and after exposure. Significant changes in colour, including grey level and chromaticity, both as a function of colour and company of elastomeric ligature module were found following exposure to beverages and spices. Colour change was most affected by Deltab* (yellowness) and most significant in clear modules. Modules made using injection mouldings were more resistant to colour change than those by extrusion. Spice mix had the most effect and cola beverage the least. Clinically, these changes compromised both colour stability and esthetics of the elastomeric module. Clinicians should make patients aware of the effect of consuming beverages and spices on the colour stability of their selected ligature modules. Clinicians should favour modules made with injection moulding. Darker colour modules may be preferred to clear modules to avoid excessive colour degradation through dietary media such as beverages and food spices. Patients consuming large amounts of spices or coffee should avoid clear modules made by extrusion processing because of their tendency to discolour.

Apparatus configured for identification of a material and method of identifying a material

DOEpatents

Slater, John M.; Crawford, Thomas M.; Frickey, Dean A.

2001-01-01

The present invention relates to an apparatus configured for identification of a material and method of identifying a material. One embodiment of the present invention provides an apparatus configured for identification of a material including a first region configured to receive a first sample and output a first spectrum responsive to exposure of the first sample to radiation; a signal generator configured to provide a reference signal having a reference frequency and a modulation signal having a modulation frequency; a modulator configured to selectively modulate the first spectrum using the modulation signal according to the reference frequency; a second region configured to receive a second sample and output a second spectrum responsive to exposure of the second sample to the first spectrum; and a detector configured to detect the second spectrum.

Hedonic sensitivity to natural rewards is affected by prenatal stress in a sex-dependent manner.

PubMed

Reynaert, Marie-Line; Marrocco, Jordan; Mairesse, Jérôme; Lionetto, Luana; Simmaco, Maurizio; Deruyter, Lucie; Allorge, Delphine; Moles, Anna; Pittaluga, Anna; Maccari, Stefania; Morley-Fletcher, Sara; Van Camp, Gilles; Nicoletti, Ferdinando

2016-11-01

Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-like behavior. Some of the hallmarks of PRS rats are known to be sex-dependent. We report that PRS enhanced and reduced milk chocolate-induced conditioned place preference in males and females, respectively. Male PRS rats also show increases in plasma dihydrotestosterone (DHT) levels and dopamine (DA) levels in the nucleus accumbens (NAc), and reductions in 5-hydroxytryptamine (5-HT) levels in the NAc and prefrontal cortex (PFC). In male rats, systemic treatment with the DHT-lowering drug finasteride reduced both milk chocolate preference and NAc DA levels. Female PRS rats showed lower plasma estradiol (E 2 ) levels and lower DA levels in the NAc, and 5-HT levels in the NAc and PFC. E 2 supplementation reversed the reduction in milk chocolate preference and PFC 5-HT levels. In the hypothalamus, PRS increased ERα and ERβ estrogen receptor and CARTP (cocaine-and-amphetamine receptor transcript peptide) mRNA levels in males, and 5-HT 2 C receptor mRNA levels in females. Changes were corrected by treatments with finasteride and E 2 , respectively. These new findings show that early life stress has a profound impact on hedonic sensitivity to high-palatable food via long-lasting changes in gonadal hormones. This paves the way to the development of hormonal strategies aimed at correcting abnormalities in the response to natural rewards. © 2015 Society for the Study of Addiction.

Transdermal film-loaded finasteride microplates to enhance drug skin permeation: Two-step optimization study.

PubMed

Ahmed, Tarek A; El-Say, Khalid M

2016-06-10

The goal was to develop an optimized transdermal finasteride (FNS) film loaded with drug microplates (MIC), utilizing two-step optimization, to decrease the dosing schedule and inconsistency in gastrointestinal absorption. First; 3-level factorial design was implemented to prepare optimized FNS-MIC of minimum particle size. Second; Box-Behnken design matrix was used to develop optimized transdermal FNS-MIC film. Interaction among MIC components was studied using physicochemical characterization tools. Film components namely; hydroxypropyl methyl cellulose (X1), dimethyl sulfoxide (X2) and propylene glycol (X3) were optimized for their effects on the film thickness (Y1) and elongation percent (Y2), and for FNS steady state flux (Y3), permeability coefficient (Y4), and diffusion coefficient (Y5) following ex-vivo permeation through the rat skin. Morphological study of the optimized MIC and transdermal film was also investigated. Results revealed that stabilizer concentration and anti-solvent percent were significantly affecting MIC formulation. Optimized FNS-MIC of particle size 0.93μm was successfully prepared in which there was no interaction observed among their components. An enhancement in the aqueous solubility of FNS-MIC by more than 23% was achieved. All the studied variables, most of their interaction and quadratic effects were significantly affecting the studied variables (Y1-Y5). Morphological observation illustrated non-spherical, short rods, flakes like small plates that were homogeneously distributed in the optimized transdermal film. Ex-vivo study showed enhanced FNS permeation from film loaded MIC when compared to that contains pure drug. So, MIC is a successful technique to enhance aqueous solubility and skin permeation of poor water soluble drug especially when loaded into transdermal films. Copyright © 2016 Elsevier B.V. All rights reserved.

Sex-dependent effect of a low neurosteroid environment and intrauterine growth restriction on foetal guinea pig brain development.

PubMed

Kelleher, Meredith A; Palliser, Hannah K; Walker, David W; Hirst, Jonathan J

2011-03-01

Progesterone and its neuroactive metabolite, allopregnanolone, are present in high concentrations during pregnancy, but drop significantly following birth. Allopregnanolone influences foetal arousal and enhances cognitive and behavioural recovery following traumatic brain injury. Inhibition of allopregnanolone synthesis increases cell death in foetal animal brains with experimental hypoxia. We hypothesised that complications during pregnancy, such as early or preterm loss of placental steroids and intrauterine growth restriction (IUGR), would disrupt the foetal neurosteroid system, contributing to poor neurodevelopmental outcomes. This study aimed to investigate the effects of chronic inhibition of allopregnanolone synthesis before term and IUGR on developmental processes in the foetal brain. Guinea pig foetuses were experimentally growth restricted at mid-gestation and treated with finasteride, an inhibitor of allopregnanolone synthesis. Finasteride treatment reduced foetal brain allopregnanolone concentrations by up to 75% and was associated with a reduction in myelin basic protein (MBP) (P = 0.001) and an increase in glial fibrillary acidic protein expression in the subcortical white matter brain region (P < 0.001). IUGR resulted in decreased MBP expression (P < 0.01) and was associated with a reduction in the expression of steroidogenic enzyme 5α-reductase (5αR) type 2 in the foetal brain (P = 0.061). Brain levels of 5αR1 were higher in male foetuses (P = 0.008). Both IUGR and reduced foetal brain concentrations of allopregnanolone were associated with altered expression of myelination and glial cell markers within the developing foetal brain. The potential role of neurosteroids in protecting and regulating neurodevelopmental processes in the foetal brain may provide new directions for treatment of neurodevelopmental disorders in infants who are exposed to perinatal insults and pathologies.

Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014).

PubMed

Oelke, Matthias; Becher, Klaus; Castro-Diaz, David; Chartier-Kastler, Emmanuel; Kirby, Mike; Wagg, Adrian; Wehling, Martin

2015-09-01

we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification. to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process. for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin. dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D). © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells.

PubMed

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

2017-10-20

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

Measurement of tamsulosin in human serum by liquid chromatography–tandem mass spectrometry☆

PubMed Central

Upreti, Rita; Homer, Natalie Z.M.; Naredo, Gregorio; Cobice, Diego F.; Hughes, Katherine A.; Stewart, Laurence H.; Walker, Brian R.; Andrew, Ruth

2013-01-01

A simple, sensitive and robust method to extract tamsulosin from human serum, and quantify by liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed and validated and is applicable as a measure of compliance in clinical research. Tamsulosin was extracted from human serum (100 μL) via liquid–liquid extraction with methyl tert-butyl ether (2 mL) following dilution with 0.1 M ammonium hydroxide (100 μL), achieving 99.9% analyte recovery. Internal standard, d9-finasteride, was synthesised in-house. Analyte and internal standard were separated on an Ascentis® Express C18 (100 mm × 3 mm, 2.7 μm) column using a gradient elution with mobile phases methanol and 2 mM aqueous ammonium acetate (5:95, v/v). Total run-time was 6 min. Tamsulosin was quantified using a triple quadrupole mass spectrometer operated in multi-reaction-monitoring (MRM) mode using positive electrospray ionisation. Mass transitions monitored for quantitation were: tamsulosin m/z 409 → 228 and d9-finasteride m/z 382 → 318, with the structural formulae of ions confirmed by Fourier transform ion cyclotron resonance mass spectrometry (within 10 ppm). The limit of quantitation was 0.2 ng/mL, and the method was validated in the linear range 0.2–50 ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers in a clinical study of benign prostatic hyperplasia. PMID:23743242

Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.

PubMed

Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc

2016-08-01

Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of Saw Palmetto (extract and whole berry) and Cernitin on prostate growth in rats.

PubMed

Talpur, Nadeem; Echard, Bobby; Bagchi, Debasis; Bagchi, Manashi; Preuss, Harry G

2003-08-01

Pharmaceuticals such as finasteride and alpha blockers are used to treat symptoms of benign prostatic hyperplasia (BPH) and are known to cause severe adverse reactions. Accordingly, a search for safer, natural products has been undertaken. Two natural agents (nutraceuticals) have come under recent scrutiny; because natural products, in general, often have evidence of long-term safety. The present study compares the in vivo effects on androgen-induced prostatic enlargement in rats of two nutraceuticals--the widely recognized Saw Palmetto (Serenoa repens) and the less well-known Cernitin (defined pollen extract). Non-castrated rats, had a mean prostate weight of 124 mg +/- 8.8 (S.E.M.) compared to the 24.5 mg +/- 1.9 (S.E.M.) of the castrated rat followed under the same regimen (p < 0.01). When castrated rats were given testosterone, the mass increased significantly to 250.0 mg +/- 31.7 (S.E.M.) (p < 0.01). In the five remaining groups, castrated rats receiving testosterone were given finasteride, an extract of Saw Palmetto, crushed whole berry derived from Saw Palmetto fruit, a water soluble and fat soluble extract of Cernitin or a combination of the Saw Palmetto extract and Cernitin. All treatments decreased the size of the prostate to roughly the same size as in the non-castrated rats, a size that was significantly smaller than castrated rats treated with testosterone in the same manner (p < 0.01). A second study examining non-castrated rats treated with very high doses of testosterone showed similar results. In both studies, the nutraceuticals generally decreased body weight. In conclusion, these studies show the ability of Saw Palmetto (whole berry and extract) and Cernitin to influence prostatic hyperplasia via effects on androgen metabolism.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells

PubMed Central

Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH. PMID:29152074

Print exposure modulates the effects of repetition priming during sentence reading.

PubMed

Lowder, Matthew W; Gordon, Peter C

2017-12-01

Individual readers vary greatly in the quality of their lexical representations, and consequently in how quickly and efficiently they can access orthographic and lexical knowledge. This variability may be explained, at least in part, by individual differences in exposure to printed language, because practice at reading promotes the development of stronger reading skills. In the present eyetracking experiment, we tested the hypothesis that the efficiency of word recognition during reading improves with increases in print exposure, by determining whether the magnitude of the repetition-priming effect is modulated by individual differences in scores on the author recognition test (ART). Lexical repetition of target words was manipulated across pairs of unrelated sentences that were presented on consecutive trials. The magnitude of the repetition effect was modulated by print exposure in early measures of processing, such that the magnitude of the effect was inversely related to scores on the ART. The results showed that low levels of print exposure, and thus lower-quality lexical representations, are associated with high levels of difficulty recognizing words, and thus with the greatest room to benefit from repetition. Furthermore, the interaction between scores on the ART and repetition suggests that print exposure is not simply an index of general reading speed, but rather that higher levels of print exposure are associated with an enhanced ability to access lexical knowledge and recognize words during reading.

Response of cardiac autonomic modulation after a single exposure to musical auditory stimulation

PubMed Central

Ferreira, Lucas L.; Vanderlei, Luiz Carlos M.; Guida, Heraldo L.; de Abreu, Luiz Carlos; Garner, David M.; Vanderlei, Franciele M.; Ferreira, Celso; Valenti, Vitor E.

2015-01-01

The acute effects after exposure to different styles of music on cardiac autonomic modulation assessed through heart rate variability (HRV) analysis have not yet been well elucidated. We aimed to investigate the recovery response of cardiac autonomic modulation in women after exposure to musical auditory stimulation of different styles. The study was conducted on 30 healthy women aged between 18 years and 30 years. We did not include subjects having previous experience with musical instruments and those who had an affinity for music styles. The volunteers remained at rest for 10 min and were exposed to classical baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was evaluated for 30 min after music cessation. We analyzed the following HRV indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean square of successive differences (RMSSD), percentage of normal-to-normal 50 (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in absolute units (ms2) and normalized (nu), and LF/HF ratio increased while HF index (nu) decreased after exposure to classical baroque music. Regarding the heavy metal music style, it was observed that there were increases in SDNN, RMSSD, pNN50, and LF (ms2) after the musical stimulation. In conclusion, the recovery response of cardiac autonomic modulation after exposure to auditory stimulation with music featured an increased global activity of both systems for the two musical styles, with a cardiac sympathetic modulation for classical baroque music and a cardiac vagal tone for the heavy metal style. PMID:25774614

Exposure to 4100K fluorescent light elicits sex specific transcriptional responses in Xiphophorus maculatus skin.

PubMed

Boswell, William T; Boswell, Mikki; Walter, Dylan J; Navarro, Kaela L; Chang, Jordan; Lu, Yuan; Savage, Markita G; Shen, Jianjun; Walter, Ronald B

2018-06-01

It has been reported that exposure to artificial light may affect oxygen intake, heart rate, absorption of vitamins and minerals, and behavioral responses in humans. We have reported specific gene expression responses in the skin of Xiphophorus fish after exposure to ultraviolet light (UV), as well as, both broad spectrum and narrow waveband visible light. In regard to fluorescent light (FL), we have shown that male X. maculatus exposed to 4100K FL (i.e. "cool white") rapidly suppress transcription of many genes involved with DNA replication and repair, chromosomal segregation, and cell cycle progression in skin. We have also detailed sex specific transcriptional responses of Xiphophorus skin after exposure to UVB. However, investigation of gender differences in global gene expression response after exposure to 4100K FL has not been reported, despite common use of this FL source for residential, commercial, and animal facility illumination. Here, we compare RNA-Seq results analyzed to assess changes in the global transcription profiles of female and male X. maculatus skin in response to 4100K FL exposure. Our results suggest 4100K FL exposure incites a sex-biased genetic response including up-modulation of inflammation in females and down modulation of DNA repair/replication in males. In addition, we identify clusters of genes that become oppositely modulated in males and females after FL exposure that are principally involved in cell death and cell proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Providing Experiential Business and Management Training for Biomedical Research Trainees

PubMed Central

Petrie, Kimberly A.; Carnahan, Robert H.; Brown, Abigail M.; Gould, Kathleen L.

2017-01-01

Many biomedical PhD trainees lack exposure to business principles, which limits their competitiveness and effectiveness in academic and industry careers. To fill this training gap, we developed Business and Management Principles for Scientists, a semester-long program that combined didactic exposure to business fundamentals with practical team-based projects aimed at solving real business problems encountered by institutional shared-­resource core facilities. The program also included a retreat featuring presentations by and networking with local life science entrepreneurs and final team presentations to expert judges. Quantitative and qualitative metrics were used to evaluate the program’s impact on trainees. A pretest–posttest approach was used to assess trainees’ baseline knowledge and mastery of module concepts, and each individual’s pretest and posttest responses were compared. The mean score improved by more than 17 percentage points. Trainees also took an online survey to provide feedback about the module. Nearly all participants agreed or strongly agreed that the module was a valuable use of their time and will help guide their career decisions and that project work helped drive home module concepts. More than 75% of trainees reported discussing the module with their research advisors, and all of these participants reported supportive or neutral responses. Collectively, the trainee feedback about the module, improvement in test scores, and trainee perception of advisor support suggest that this short module is an effective method of providing scientists with efficient and meaningful exposure to business concepts. PMID:28798213

Hypoxia-Related Hormonal Appetite Modulation in Humans during Rest and Exercise: Mini Review

PubMed Central

Debevec, Tadej

2017-01-01

Obesity is associated with numerous chronic ailments and represents one of the major health and economic issues in the modernized societies. Accordingly, there is an obvious need for novel treatment approaches. Recently, based on the reports of reduced appetite and subsequent weight loss following high-altitude sojourns, exposure to hypoxia has been proposed as a viable weight-reduction strategy. While altitude-related appetite modulation is complex and not entirely clear, hypoxia-induced alterations in hormonal appetite modulation might be among the key underlying mechanisms. The present paper summarizes the up-to-date research on hypoxia/altitude-induced changes in the gut and adipose tissue derived peptides related to appetite regulation. Orexigenic hormone ghrelin and anorexigenic peptides leptin, glucagon-like peptide-1, peptide YY, and cholecystokinin have to-date been investigated as potential modulators of hypoxia-driven appetite alterations. Current evidence suggests that hypoxia can, especially acutely, lead to decreased appetite, most probably via reduction of acylated ghrelin concentration. Hypoxia-related short and long-term changes in other hormonal markers are more unclear although hypoxia seems to importantly modulate leptin levels, especially following prolonged hypoxic exposures. Limited evidence also suggests that different activity levels during exposures to hypoxia do not additively affect hormonal appetite markers. Although very few studies have been performed in obese/overweight individuals, the available data indicate that hypoxia/altitude exposures do not seem to differentially affect appetite regulation via hormonal pathways in this cohort. Given the lack of experimental data, future well-controlled acute and prolonged studies are warranted to expand our understanding of hypoxia-induced hormonal appetite modulation and its kinetics in health and disease. PMID:28611686

Identifying gender differences in reported occupational information from three US population-based case-control studies.

PubMed

Locke, Sarah J; Colt, Joanne S; Stewart, Patricia A; Armenti, Karla R; Baris, Dalsu; Blair, Aaron; Cerhan, James R; Chow, Wong-Ho; Cozen, Wendy; Davis, Faith; De Roos, Anneclaire J; Hartge, Patricia; Karagas, Margaret R; Johnson, Alison; Purdue, Mark P; Rothman, Nathaniel; Schwartz, Kendra; Schwenn, Molly; Severson, Richard; Silverman, Debra T; Friesen, Melissa C

2014-12-01

Growing evidence suggests that gender-blind assessment of exposure may introduce exposure misclassification, but few studies have characterised gender differences across occupations and industries. We pooled control responses to job-specific, industry-specific and exposure-specific questionnaires (modules) that asked detailed questions about work activities from three US population-based case-control studies to examine gender differences in work tasks and their frequencies. We calculated the ratio of female-to-male controls that completed each module. For four job modules (assembly worker, machinist, health professional, janitor/cleaner) and for subgroups of jobs that completed those modules, we evaluated gender differences in task prevalence and frequency using χ(2) and Mann-Whitney U tests, respectively. The 1360 female and 2245 male controls reported 6033 and 12 083 jobs, respectively. Gender differences in female:male module completion ratios were observed for 39 of 45 modules completed by ≥20 controls. Gender differences in task prevalence varied in direction and magnitude. For example, female janitors were significantly more likely to polish furniture (79% vs 44%), while male janitors were more likely to strip floors (73% vs 50%). Women usually reported more time spent on tasks than men. For example, the median hours per week spent degreasing for production workers in product manufacturing industries was 6.3 for women and 3.0 for men. Observed gender differences may reflect actual differences in tasks performed or differences in recall, reporting or perception, all of which contribute to exposure misclassification and impact relative risk estimates. Our findings reinforce the need to capture subject-specific information on work tasks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Identifying gender differences in reported occupational information from three U.S. population-based case-control studies

PubMed Central

Locke, Sarah J.; Colt, Joanne S.; Stewart, Patricia A.; Armenti, Karla R.; Baris, Dalsu; Blair, Aaron; Cerhan, James R.; Chow, Wong-Ho; Cozen, Wendy; Davis, Faith; De Roos, Anneclaire J.; Hartge, Patricia; Karagas, Margaret R.; Johnson, Alison; Purdue, Mark P.; Rothman, Nathaniel; Schwartz, Kendra; Schwenn, Molly; Severson, Richard; Silverman, Debra T.; Friesen, Melissa C.

2014-01-01

Objectives Growing evidence suggests that gender-blind assessment of exposure may introduce exposure misclassification, but few studies have characterized gender differences across occupations and industries. We pooled control responses to job-, industry-, and exposure-specific questionnaires (modules) that asked detailed questions about work activities from three US population-based case-control studies to examine gender differences in work tasks and their frequencies. Methods We calculated the ratio of female to male controls that completed each module. For four job modules (assembly worker, machinist, health professional, janitor/cleaner) and for subgroups of jobs that completed those modules, we evaluated gender differences in task prevalence and frequency using Chi-square and Mann-Whitney U-tests, respectively. Results The 1,360 female and 2,245 male controls reported 6,033 and 12,083 jobs, respectively. Gender differences in female:male module completion ratios were observed for 39 of 45 modules completed by ≥20 controls. Gender differences in task prevalence varied in direction and magnitude. For example, female janitors were significantly more likely to polish furniture (79% vs. 44%), while male janitors were more likely to strip floors (73% vs. 50%). Women usually reported more time spent on tasks than men. For example, the median hours per week spent degreasing for production workers in product manufacturing industries was 6.3 for women and 3.0 for men. Conclusions Observed gender differences may reflect actual differences in tasks performed or differences in recall, reporting, or perception, all of which contribute to exposure misclassification and impact relative risk estimates. Our findings reinforce the need to capture subject-specific information on work tasks. PMID:24683012

[Pulse-modulated Electromagnetic Radiation of Extremely High Frequencies Protects Cellular DNA against Damaging Effect of Physico-Chemical Factors in vitro].

PubMed

Gapeyev, A B; Lukyanova, N A

2015-01-01

Using a comet assay technique, we investigated protective effects of. extremely high frequency electromagnetic radiation in combination with the damaging effect of X-ray irradiation, the effect of damaging agents hydrogen peroxide and methyl methanesulfonate on DNA in mouse whole blood leukocytes. It was shown that the preliminary exposure of the cells to low intensity pulse-modulated electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20-min exposure, modulation frequencies of 1 and 16 Hz) caused protective effects decreasing the DNA damage by 20-45%. The efficacy of pulse-modulated electromagnetic radiation depended on the type of genotoxic agent and increased in a row methyl methanesulfonate--X-rays--hydrogen peroxide. Continuous electromagnetic radiation was ineffective. The mechanisms of protective effects may be connected with an induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated electromagnetic radiation.

Effects of outdoor exposure on solar cell modules in the ERDA/NASA Lewis Research Center Systems Test Facility

NASA Technical Reports Server (NTRS)

Weinberg, I.; Curtis, H. B.; Forestieri, A. F.

1977-01-01

The effects of outdoor exposure were determined by comparing standard I-V data obtained for the as-received modules with similar data obtained after removal from the field and cleaning with detergent solution. All modules measured in this way exhibited nonrecoverable degradation in P sub maximum varying from 4 to 7 percent. One module exposed for 41 days exhibited partial cell discoloration, loss of front surface metallization over the discolored portion, and a decrease in P sub maximum of 7 percent, tentatively attributed to cell damage. Measurements before and after cleaning showed a recoverable degradation due to dirt accumulation. This recoverable loss in power was 11 percent after 245 days in the field for one brand of module, 6 percent after 48 days for another brand, and 4 1/2 percent for the third brand.

Post-Flight Test Results of Seed Laser Module Subjected to Space Exposure. Paper No. 8876-9

NASA Technical Reports Server (NTRS)

Prasad, Narasimha S.

2013-01-01

The objective of the Materials International Space Station Experiment (MISSE) is to study the performance of novel materials when subjected to the synergistic effects of the harsh space environment for several months. MISSE missions provide an opportunity for developing space qualifiable materials. Several laser and lidar components were sent by NASA Langley Research Center (LaRC) as a part of the MISSE 7 mission. The MISSE 7 module was transported to the international space station (ISS) via STS 129 mission that was launched on Nov 16, 2009. Later, the MISSE 7 module was brought back to the earth via the STS 134 that landed on June 1, 2011. The MISSE 7 module that was subjected to exposure in space environment for more than one and a half year included fiber laser, solid-state laser gain materials, detectors, and semiconductor laser diode. Performance testing of these components is now progressing. In this paper, the results of performance testing of a laser diode module sent by NASA Langley Research Center on MISSE 7 mission will be discussed. This paper will present the comparison of pre-flight and post-flight performance curves and discuss the effect of space exposure on the laser diode module. Preliminary findings on output power measurements show that the COTS laser diode characteristics did not undergo any significant performance degradation.

Saw palmetto for prostate disorders.

PubMed

Gordon, Andrea E; Shaughnessy, Allen F

2003-03-15

Saw palmetto is an herbal product used in the treatment of symptoms related to benign prostatic hyperplasia. The active component is found in the fruit of the American dwarf palm tree. Studies have demonstrated the effectiveness of saw palmetto in reducing symptoms associated with benign prostatic hyperplasia. Saw palmetto appears to have efficacy similar to that of medications like finasteride, but it is better tolerated and less expensive. There are no known drug interactions with saw palmetto, and reported side effects are minor and rare. No data on its long-term usage are available. The herbal product also has been used to treat chronic prostatitis, but currently there is no evidence of its efficacy.

Virtual patient instruction for dental students: can it improve dental care access for persons with special needs?

PubMed

Sanders, Carla; Kleinert, Harold L; Boyd, Sara E; Herren, Chris; Theiss, Lynn; Mink, John

2008-01-01

An interactive, virtual-patient module was produced on compact disc (CD-ROM) in response to the critical need to increase dental students' clinical exposure to patients with developmental disabilities. A content development team consisting of dental faculty members, parents of children with developmental disabilities, an individual with a developmental disability, and educational specialists developed the interactive, virtual-patient module. The module focused on a young man with congenital deafblindness presenting as a new patient with a painful molar. Students were required to make decisions regarding clinical interactions throughout the module. Differences in both comfort and knowledge level were measured pre- and post-module completion, as well as the dental students' overall satisfaction with the learning experience. Significant results were obtained in students' perceived comfort and knowledge base. Participants reported overall satisfaction using the modules. This study demonstrated that an interactive, multi-media (CD-ROM), virtual patient learning module for dental students could be an effective tool in providing students needed clinical exposure to patients with developmental disabilities.

Non-thermal continuous and modulated electromagnetic radiation fields effects on sleep EEG of rats☆

PubMed Central

Mohammed, Haitham S.; Fahmy, Heba M.; Radwan, Nasr M.; Elsayed, Anwar A.

2012-01-01

In the present study, the alteration in the sleep EEG in rats due to chronic exposure to low-level non-thermal electromagnetic radiation was investigated. Two types of radiation fields were used; 900 MHz unmodulated wave and 900 MHz modulated at 8 and 16 Hz waves. Animals has exposed to radiation fields for 1 month (1 h/day). EEG power spectral analyses of exposed and control animals during slow wave sleep (SWS) and rapid eye movement sleep (REM sleep) revealed that the REM sleep is more susceptible to modulated radiofrequency radiation fields (RFR) than the SWS. The latency of REM sleep increased due to radiation exposure indicating a change in the ultradian rhythm of normal sleep cycles. The cumulative and irreversible effect of radiation exposure was proposed and the interaction of the extremely low frequency radiation with the similar EEG frequencies was suggested. PMID:25685416

Modulated grayscale UV pattern for uniform photopolymerization based on a digital micromirror device system

NASA Astrophysics Data System (ADS)

Yoon, Jinsik; Kim, Kibeom; Park, Wook

2017-07-01

We present an essential method for generating microparticles uniformly in a single ultraviolet (UV) light exposure area for optofluidic maskless lithography. In the optofluidic maskless lithography process, the productivity of monodisperse microparticles depends on the size of the UV exposure area. An effective fabrication area is determined by the size of the UV intensity profile map, satisfying the required uniformity of UV intensity. To increase the productivity of monodisperse microparticles in optofluidic maskless lithography, we expanded the effective UV exposure area by modulating the intensity of the desired UV light pattern based on the premeasured UV intensity profile map. We verified the improvement of the uniformity of the microparticles generated by the proposed modulation technique, providing histogram analyses of the conjugated fluorescent intensities and the sizes of the microparticles. Additionally, we demonstrated the generation of DNA uniformly encapsulated in microparticles.

Digital micromirror device camera with per-pixel coded exposure for high dynamic range imaging.

PubMed

Feng, Wei; Zhang, Fumin; Wang, Weijing; Xing, Wei; Qu, Xinghua

2017-05-01

In this paper, we overcome the limited dynamic range of the conventional digital camera, and propose a method of realizing high dynamic range imaging (HDRI) from a novel programmable imaging system called a digital micromirror device (DMD) camera. The unique feature of the proposed new method is that the spatial and temporal information of incident light in our DMD camera can be flexibly modulated, and it enables the camera pixels always to have reasonable exposure intensity by DMD pixel-level modulation. More importantly, it allows different light intensity control algorithms used in our programmable imaging system to achieve HDRI. We implement the optical system prototype, analyze the theory of per-pixel coded exposure for HDRI, and put forward an adaptive light intensity control algorithm to effectively modulate the different light intensity to recover high dynamic range images. Via experiments, we demonstrate the effectiveness of our method and implement the HDRI on different objects.

Poverty, household chaos, and interparental aggression predict children’s ability to recognize and modulate negative emotions

PubMed Central

Raver, C. Cybele; Blair, Clancy; Garrett-Peters, Patricia

2015-01-01

The following prospective longitudinal study considers the ways that protracted exposure to verbal and physical aggression between parents may take a substantial toll on emotional adjustment for 1,025 children followed from 6 to 58 months of age. Exposure to chronic poverty from infancy to early childhood as well as multiple measures of household chaos were also included as predictors of children’s ability to recognize and modulate negative emotions in order to disentangle the role of interparental conflict from the socioeconomic forces that sometimes accompany it. Analyses revealed that exposure to greater levels of interparental conflict, more chaos in the household, and a higher number of years in poverty can be empirically distinguished as key contributors to 58-month-olds’ ability to recognize and modulate negative emotion. Implications for models of experiential canalization of emotional processes within the context of adversity are discussed. PMID:25215541

Poverty, household chaos, and interparental aggression predict children's ability to recognize and modulate negative emotions.

PubMed

Raver, C Cybele; Blair, Clancy; Garrett-Peters, Patricia

2015-08-01

The following prospective longitudinal study considers the ways that protracted exposure to verbal and physical aggression between parents may take a substantial toll on emotional adjustment for 1,025 children followed from 6 to 58 months of age. Exposure to chronic poverty from infancy to early childhood as well as multiple measures of household chaos were also included as predictors of children's ability to recognize and modulate negative emotions in order to disentangle the role of interparental conflict from the socioeconomic forces that sometimes accompany it. Analyses revealed that exposure to greater levels of interparental conflict, more chaos in the household, and a higher number of years in poverty can be empirically distinguished as key contributors to 58-month-olds' ability to recognize and modulate negative emotion. Implications for models of experiential canalization of emotional processes within the context of adversity are discussed.

EFFECTS OF CONTINUOUS-WAVE, PULSED, AND SINUSOIDAL-AMPLITUDE-MODULATED MICROWAVES ON BRAIN ENERGY METABOLISM

EPA Science Inventory

A comparison of the effects of continuous wave, sinusoidal-amplitude modulated, and pulsed square-wave-modulated 591-MHz microwave exposures on brain energy metabolism was made in male Sprague Dawley rats (175-225g). Brain NADH fluorescence, adensine triphosphate (ATP) concentrat...

Modelling of aircrew radiation exposure from galactic cosmic rays and solar particle events.

PubMed

Takada, M; Lewis, B J; Boudreau, M; Al Anid, H; Bennett, L G I

2007-01-01

Correlations have been developed for implementation into the semi-empirical Predictive Code for Aircrew Radiation Exposure (PCAIRE) to account for effects of extremum conditions of solar modulation and low altitude based on transport code calculations. An improved solar modulation model, as proposed by NASA, has been further adopted to interpolate between the bounding correlations for solar modulation. The conversion ratio of effective dose to ambient dose equivalent, as applied to the PCAIRE calculation (based on measurements) for the legal regulation of aircrew exposure, was re-evaluated in this work to take into consideration new ICRP-92 radiation-weighting factors and different possible irradiation geometries of the source cosmic-radiation field. A computational analysis with Monte Carlo N-Particle eXtended Code was further used to estimate additional aircrew exposure that may result from sporadic solar energetic particle events considering real-time monitoring by the Geosynchronous Operational Environmental Satellite. These predictions were compared with the ambient dose equivalent rates measured on-board an aircraft and to count rate data observed at various ground-level neutron monitors.

Low-Temperature Ozone Exposure Technique to Modulate the Stoichiometry of WO(x) Nanorods and Optimize the Electrochromic Performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, F.; Li, C. P.; Chen, G.

A low-temperature ozone exposure technique was employed for the post-treatment of WO{sub x} nanorod thin films fabricated from hot-wire chemical vapor deposition (HWCVD) and ultrasonic spray deposition (USD) techniques. The resulting films were characterized with x-ray diffraction (XRD), transmission electron microscopy (TEM), Raman spectroscopy, UV-vis-NIR spectroscopy and x-ray photoelectron spectroscopy (XPS). The stoichiometry and surface crystallinity of the WO{sub x} thin films were subsequently modulated upon ozone exposure and thermal annealing without particle growth. The electrochromic performance was studied in a LiClO{sub 4}-propylene carbonate electrolyte, and the results suggest that the low-temperature ozone exposure technique is superior to the traditionalmore » high-temperature thermal annealing (employed to more fully oxidize the WO{sub x}). The optical modulation at 670 nm was improved from 35% for the as-deposited film to 57% for the film after ozone exposure at 150 C. The coloration efficiency was improved and the switching speed to the darkened state was significantly accelerated from 18.0 s for the as-deposited film to 11.8 s for the film after the ozone exposure. The process opens an avenue for low-temperature and cost-effective manufacturing of electrochromic films, especially on flexible polymer substrates.« less

CPV cell characterization following one-year exposure in Golden Colorado

NASA Astrophysics Data System (ADS)

Bosco, Nick; Kurtz, Sarah

2014-09-01

A CPV module containing 30 III-V multijunction cells was operated on-sun for one year in Golden, Colorado. Each cell was characterized prior to and following exposure. A module power degradation of 10% was observed and found to be a result as an overall decrease in cell short circuit current and the presence of at least one shunted cell. A positive correlation between initial shunt current and an increase in shunt current following exposure was also found. Cell exfoliation was also observed and found to be coincident with the presence of water and/or charring of the cell package due to an off-sun event.

Degradation Analysis of Field-Exposed Photovoltaic Modules with Non-Fluoropolymer-Based Backsheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kempe, Michael D; Fairbrother, Andrew; Julien, Scott

The selection of polymeric materials utilized in photovoltaic (PV) modules has changed relatively little since the inception of the PV industry, with ethylene-vinyl acetate (EVA), polyethylene terephthalate (PET), and fluoropolymer-based laminates being the most widely adopted primary components of the encapsulant and backsheet materials. The backsheet must serve to electrically insulate the solar cells and protect them from the effects of weathering. Due to continued downward pressure on cost, other polymeric materials are being formulated to withstand outdoor exposure for use in backsheets to replace either the PET film, the fluoropoymer film, or both. Because of their relatively recent deployment,more » less is known about their reliability and if they are durable enough to fulfill the greater than or equal to 25 year warranties of current PV modules. This work presents a degradation analysis of field-exposed modules with polyamide- and polyester-based backsheets. Modules were exposed for up to five years in different geographic locations: USA (Maryland, Ohio), China, and Italy. Surface and cross-sectional analysis included visual inspection, colorimetry, glossimetry, and Fourier-transform infrared spectroscopy. Each module experienced different types of degradation depending on the exposure site, even for the same material and module brand. For instance, the polyamide-based backsheet experienced hairline cracking and greater yellowing and chemical changes in China (Changsu, humid subtropical climate), while in Italy (Rome, hot-summer Mediterranean climate) it underwent macroscopic cracking and greater losses in gloss. Spectroscopic studies have permitted identification of degradation products and changes in polymer structure over time. Comparisons are made to fielded modules with fluoropolymer-based backsheets, as well as backsheet materials in accelerated laboratory exposures. Implications for qualification testing and service life prediction of the non-fluoropolymer-based backsheets are discussed.« less

Degradation analysis of field-exposed photovoltaic modules with non-fluoropolymer-based backsheets

NASA Astrophysics Data System (ADS)

Fairbrother, Andrew; Julien, Scott; Wan, Kai-Tak; Ji, Liang; Boyce, Kenneth; Merzlic, Sebastien; Lefebvre, Amy; O'Brien, Greg; Wang, Yu; Bruckman, Laura; French, Roger; Kempe, Michael; Gu, Xiaohong

2017-08-01

The selection of polymeric materials utilized in photovoltaic (PV) modules has changed relatively little since the inception of the PV industry, with ethylene-vinyl acetate (EVA), polyethylene terephthalate (PET), and fluoropolymer-based laminates being the most widely adopted primary components of the encapsulant and backsheet materials. The backsheet must serve to electrically insulate the solar cells and protect them from the effects of weathering. Due to continued downward pressure on cost, other polymeric materials are being formulated to withstand outdoor exposure for use in backsheets to replace either the PET film, the fluoropoymer film, or both. Because of their relatively recent deployment, less is known about their reliability and if they are durable enough to fulfill the >=25 year warranties of current PV modules. This work presents a degradation analysis of field-exposed modules with polyamide- and polyester-based backsheets. Modules were exposed for up to five years in different geographic locations: USA (Maryland, Ohio), China, and Italy. Surface and cross-sectional analysis included visual inspection, colorimetry, glossimetry, and Fourier-transform infrared spectroscopy. Each module experienced different types of degradation depending on the exposure site, even for the same material and module brand. For instance, the polyamide-based backsheet experienced hairline cracking and greater yellowing and chemical changes in China (Changsu, humid subtropical climate), while in Italy (Rome, hot-summer Mediterranean climate) it underwent macroscopic cracking and greater losses in gloss. Spectroscopic studies have permitted identification of degradation products and changes in polymer structure over time. Comparisons are made to fielded modules with fluoropolymer-based backsheets, as well as backsheet materials in accelerated laboratory exposures. Implications for qualification testing and service life prediction of the non-fluoropolymer-based backsheets are discussed.

Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se.

PubMed

Haussmann, Hans-Juergen; Fariss, Marc W

2016-09-01

The effects of long-term use of nicotine per se on cancer risk, in the absence of tobacco extract or smoke, are not clearly understood. This review evaluates the strength of published scientific evidence, in both epidemiological and animal studies, for the potential carcinogenic effects of nicotine per se; that is to act as a complete carcinogen or as a modulator of carcinogenesis. For human studies, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a carcinogenic effect due to the limited information available. In animal studies, limited evidence suggests an association between long-term nicotine exposure and a lack of a complete carcinogenic effect. Conclusive studies using current bioassay guidelines, however, are missing. In studies using chemical/physical carcinogens or transgenic models, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a modulating (stimulating) effect on carcinogenesis. This is primarily due to the large number of conflicting studies. In contrast, a majority of studies provides sufficient evidence for an association between nicotine exposure and enhanced carcinogenesis of cancer cells inoculated in mice. This modulating effect was especially prominent in immunocompromized mice. Overall, taking the human and animal studies into consideration, there appears to be inadequate evidence to conclude that nicotine per se does or does not cause or modulate carcinogenesis in humans. This conclusion is in agreement with the recent US Surgeon General's 2014 report on the health consequences of nicotine exposure.

Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se

PubMed Central

Haussmann, Hans-Juergen; Fariss, Marc W.

2016-01-01

Abstract The effects of long-term use of nicotine per se on cancer risk, in the absence of tobacco extract or smoke, are not clearly understood. This review evaluates the strength of published scientific evidence, in both epidemiological and animal studies, for the potential carcinogenic effects of nicotine per se; that is to act as a complete carcinogen or as a modulator of carcinogenesis. For human studies, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a carcinogenic effect due to the limited information available. In animal studies, limited evidence suggests an association between long-term nicotine exposure and a lack of a complete carcinogenic effect. Conclusive studies using current bioassay guidelines, however, are missing. In studies using chemical/physical carcinogens or transgenic models, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a modulating (stimulating) effect on carcinogenesis. This is primarily due to the large number of conflicting studies. In contrast, a majority of studies provides sufficient evidence for an association between nicotine exposure and enhanced carcinogenesis of cancer cells inoculated in mice. This modulating effect was especially prominent in immunocompromized mice. Overall, taking the human and animal studies into consideration, there appears to be inadequate evidence to conclude that nicotine per se does or does not cause or modulate carcinogenesis in humans. This conclusion is in agreement with the recent US Surgeon General’s 2014 report on the health consequences of nicotine exposure. PMID:27278157

The design and development of a rectangular, shingle-type photovoltaic module

NASA Astrophysics Data System (ADS)

Shepard, N. F., Jr.

A shingle-type photovoltaic module has been designed and developed to meet the requirements of specifications for residential applications. The module is ideally suited for installation directly to the sheathing of a sloping, south-facing roof of a residential, industrial, or commercial building. The design requirements are examined, taking into account also module safety requirements. Aspects of module design and analysis are discussed, giving attention to installation details, solar cells and electrical circuit design, the encapsulation system, substrate lamination, and the module-to-module interconnecting cable. Details of module assembly experience and test and outdoor exposure experience are also considered.

The design and development of a rectangular, shingle-type photovoltaic module

NASA Technical Reports Server (NTRS)

Shepard, N. F., Jr.

1982-01-01

A shingle-type photovoltaic module has been designed and developed to meet the requirements of specifications for residential applications. The module is ideally suited for installation directly to the sheathing of a sloping, south-facing roof of a residential, industrial, or commercial building. The design requirements are examined, taking into account also module safety requirements. Aspects of module design and analysis are discussed, giving attention to installation details, solar cells and electrical circuit design, the encapsulation system, substrate lamination, and the module-to-module interconnecting cable. Details of module assembly experience and test and outdoor exposure experience are also considered.

Quantitative risk assessment of human campylobacteriosis associated with thermophilic Campylobacter species in chickens.

PubMed

Rosenquist, Hanne; Nielsen, Niels L; Sommer, Helle M; Nørrung, Birgit; Christensen, Bjarke B

2003-05-25

A quantitative risk assessment comprising the elements hazard identification, hazard characterization, exposure assessment, and risk characterization has been prepared to assess the effect of different mitigation strategies on the number of human cases in Denmark associated with thermophilic Campylobacter spp. in chickens. To estimate the human exposure to Campylobacter from a chicken meal and the number of human cases associated with this exposure, a mathematical risk model was developed. The model details the spread and transfer of Campylobacter in chickens from slaughter to consumption and the relationship between ingested dose and the probability of developing campylobacteriosis. Human exposure was estimated in two successive mathematical modules. Module 1 addresses changes in prevalence and numbers of Campylobacter on chicken carcasses throughout the processing steps of a slaughterhouse. Module 2 covers the transfer of Campylobacter during food handling in private kitchens. The age and sex of consumers were included in this module to introduce variable hygiene levels during food preparation and variable sizes and compositions of meals. Finally, the outcome of the exposure assessment modules was integrated with a Beta-Poisson dose-response model to provide a risk estimate. Simulations designed to predict the effect of different mitigation strategies showed that the incidence of campylobacteriosis associated with consumption of chicken meals could be reduced 30 times by introducing a 2 log reduction of the number of Campylobacter on the chicken carcasses. To obtain a similar reduction of the incidence, the flock prevalence should be reduced approximately 30 times or the kitchen hygiene improved approximately 30 times. Cross-contamination from positive to negative flocks during slaughter had almost no effect on the human Campylobacter incidence, which indicates that implementation of logistic slaughter will only have a minor influence on the risk. Finally, the simulations showed that people in the age of 18-29 years had the highest risk of developing campylobacteriosis.

Navy Occupational Health Information Management System (NOHIMS). Environmental Exposure Module. Users’ Manual

DTIC Science & Technology

1987-01-16

menus , controls user and device access to the system, manages the security features associated with menus , devices, and users, provides...in the files, or the number of files in the system. 2-2 3.0 MODULE INPUT PROCESSES 3.1 Summary of Input Processes The EE module contains many menu ...Output Processes The EE module contains many menu options which enable the user to obtain needed information from the module. These options can be

Exposure-driven macroalgal phase shift following catastrophic disturbance on coral reefs

NASA Astrophysics Data System (ADS)

Roff, George; Chollett, Iliana; Doropoulos, Christopher; Golbuu, Yimnang; Steneck, Robert S.; Isechal, Adelle L.; van Woesik, Robert; Mumby, Peter J.

2015-09-01

Environmental conditions play an important role in post-disturbance dynamics of ecosystems by modulating recovery of surviving communities and influencing patterns of succession. Here, we document the effects of wave exposure following a catastrophic disturbance on coral reefs in driving a phase shift to macroalgal dominance. In December 2012, a Category 5 super typhoon (`Typhoon Bopha') passed 50 km to the south of Palau (Micronesia), causing a major loss of reef corals. Immediately post-disturbance, a rapid and extensive phase shift of the macroalgae Liagora sp. (Rhodophyta) was observed at sites exposed to chronic wave exposure. To quantify the influence of biotic and abiotic drivers in modulating the extent of post-disturbance Liagora blooms, we compared benthic substrates and herbivore assemblages at sites surveyed pre- and post-disturbance across a gradient of wave exposure. Relative changes in herbivore biomass and coral cover before and after disturbance did not significantly predict the extent of Liagora cover, indicating that changes in herbivore biomass or reductions in grazing pressure were not directly responsible for driving the Liagora blooms. By contrast, the degree of wave exposure experienced at sites post-disturbance explained >90 % of model variance ( p < 0.001, R 2 = 0.69), in that Liagora was absent at low exposure sites, while most extensive blooms were observed at highly exposed sites. At regional scales, spatial maps of wave exposure accurately predicted the presence of Liagora at impacted sites throughout the Palau archipelago (>150 km distance), highlighting the predictive capacity of wave exposure as an explanatory variable and the deterministic nature of post-disturbance macroalgal blooms. Understanding how physical conditions modulate recovery of ecosystems after disturbance allows insight into post-disturbance dynamics and succession of communities, ultimately allowing management strategies to prioritise restoration efforts in regions that are most effective.

Extremely Low Frequency-Magnetic Field (ELF-MF) Exposure Characteristics among Semiconductor Workers

PubMed Central

Choi, Sangjun; Cha, Wonseok; Kim, Won; Yoon, Chungsik; Park, Ju-Hyun; Ha, Kwonchul; Park, Donguk

2018-01-01

We assessed the exposure of semiconductor workers to extremely low frequency-magnetic fields (ELF-MF) and identified job characteristics affecting ELF-MF exposure. These were demonstrated by assessing the exposure of 117 workers involved in wafer fabrication (fab) and chip packaging wearing personal dosimeters for a full shift. A portable device was used to monitor ELF-MF in high temporal resolution. All measurements were categorized by operation, job and working activity during working time. ELF-MF exposure of workers were classified based on the quartiles of ELF-MF distribution. The average levels of ELF-MF exposure were 0.56 µT for fab workers, 0.59 µT for chip packaging workers and 0.89 µT for electrical engineers, respectively. Exposure to ELF-MF differed among types of factory, operation, job and activity. Workers engaged in the diffusion and chip testing activities showed the highest ELF-MF exposure. The ELF-MF exposures of process operators were found to be higher than those of maintenance engineers, although peak exposure and/or patterns varied. The groups with the highest quartile ELF-MF exposure level are operators in diffusion, ion implantation, module and testing operations, and maintenance engineers in diffusion, module and testing operations. In conclusion, ELF-MF exposure among workers can be substantially affected by the type of operation and job, and the activity or location. PMID:29614730

Product Use Scheduler: A Scheduling Module used in EPA’s Human Exposure Model

EPA Science Inventory

The scheduling model (SM) was developed for scheduling the use of consumer products in the U.S. EPA’s Human Exposure Model (HEM), an integrated modeling system to estimate human exposure to chemicals in household consumer products. The SM begins with year-long daily activit...

Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Beckham, Jean C; Vujanovic, Anka A; Schmidt, Norman B

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association.

Trauma Exposure and Cigarette Smoking: The Impact of Negative Affect and Affect-Regulatory Smoking Motives

PubMed Central

Farris, Samantha G.; Zvolensky, Michael J.; Beckham, Jean C.; Vujanovic, Anka A.; Schmidt, Norman B.

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association. PMID:25299617

CPV Cell Characterization Following One-Year Exposure in Golden, Colorado

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosco, Nick; Kurtz, Sarah

2014-09-26

A CPV module containing 30 III-V multijunction cells was operated on--sun for one year in Golden, Colorado. Each cell was characterized prior to and following exposure. A module power degradation of 10% was observed and found to be a result as an overall decrease in cell short circuit current and the presence of at least one shunted cell. A positive correlation between initial shunt current and an increase in shunt current following exposure was also found. Cell exfoliation was also observed and found to be coincident with the presence of water and/or charring of the cell package due to anmore » off-sun event.« less

CPV Cell Characterization Following One-Year Exposure in Golden, Colorado: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosco, N.; Kurtz, S.

2014-08-01

A CPV module containing 30 III-V multijunction cells was operated on?sun for one year in Golden, Colorado. Each cell was characterized prior to and following exposure. A module power degradation of 10% was observed and found to be a result as an overall decrease in cell short circuit current and the presence of at least one shunted cell. A positive correlation between initial shunt current and an increase in shunt current following exposure was also found. Cell exfoliation was also observed and found to be coincident with the presence of water and/or charring of the cell package due to anmore » off-sun event.« less

Modulation of elevated plus maze behavior after chronic exposure to the anabolic steroid 17alpha-methyltestosterone in adult mice.

PubMed

Rojas-Ortiz, Yoel Antonio; Rundle-González, Valerie; Rivera-Ramos, Isamar; Jorge, Juan Carlos

2006-01-01

Exposure to supraphysiological doses of androgens may disrupt affective components of behavior. In this study, behavior of adult C57Bl/6 male mice was studied after exposure to the anabolic androgenic steroid (AAS) 17alpha-methyltestosterone (17alpha-meT; 7.5 mg/kg) via a subcutaneous osmotic pump for 17 days. Controls received vehicle implants (0.9% NaCl + 30% cyclodextrine). On day 15, experimental animals were challenged with an ethanol (EtOH) injection (i.p.; 1 g/kg) while controls received saline injections. Five minutes after the injection, animals were tested in an automated elevated plus maze (EPM) or in automated activity chambers. In addition, injection-free animals were tested for ethanol consumption on day 16 after an overnight water deprivation period. Whereas chronic exposure to 17alpha-meT did not modulate open arm behavior, EtOH-exposed animals made more entries into the open arms than controls (P < 0.05). A significant reduction of risk assessment behaviors (rearing, flat approach behavior, and stretch attended posture) over the EPM was noted for EtOH-exposed animals whereas a reduction in stretch attended postures was observed among 17alpha-meT-exposed animals. Locomotor activity, and light-dark transitions in activity chambers remained unaltered. Exposure to AAS did not modulate EtOH consumption. Our data suggest that exposure to a supraphysiological dose of 17alpha-meT has minimal effects on exploratory-based anxiety.

Hair loss and regeneration performed on animal models

PubMed Central

ORASAN, MEDA SANDRA; ROMAN, IULIA IOANA; CONEAC, ANDREI; MURESAN, ADRIANA; ORASAN, REMUS IOAN

2016-01-01

Research in the field of reversal hair loss remains a challenging subject. As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical treatments for inducing hair regrowth, research is necessary in order to improve therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell type - dermal papilla or organ culture of isolated cell follicles. In vivo research on this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking into consideration the advantages and disadvantages of each animal model and the depilation options. Further studies are required not only to compare the efficiency of different therapies but more importantly to establish their long term safety. PMID:27547051

Medicolegal aspects of doping in football

PubMed Central

Graf‐Baumann, T

2006-01-01

This article describes the historical background of the medicolegal aspects of doping in sports and especially in football. The definitions of legal terms are explained and the procedure of individual case management as part of FIFA's approach to doping is presented. Finally, three medicolegal problems awaiting urgent solution are outlined: firstly, the difficulties in decision making arising from the decrease of the T/E ratio from 6 to 4; secondly, the therapeutic application of α‐reductase inhibitors for male pattern baldness in the face of the classification of finasteride as a forbidden masking agent; and lastly, the increasing use of recreational drugs and its social and legal implications in positive cases. PMID:16799105

Exposure calculation code module for reactor core analysis: BURNER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vondy, D.R.; Cunningham, G.W.

1979-02-01

The code module BURNER for nuclear reactor exposure calculations is presented. The computer requirements are shown, as are the reference data and interface data file requirements, and the programmed equations and procedure of calculation are described. The operating history of a reactor is followed over the period between solutions of the space, energy neutronics problem. The end-of-period nuclide concentrations are determined given the necessary information. A steady state, continuous fueling model is treated in addition to the usual fixed fuel model. The control options provide flexibility to select among an unusually wide variety of programmed procedures. The code also providesmore » user option to make a number of auxiliary calculations and print such information as the local gamma source, cumulative exposure, and a fine scale power density distribution in a selected zone. The code is used locally in a system for computation which contains the VENTURE diffusion theory neutronics code and other modules.« less

Mercury exposure induces cytoskeleton disruption and loss of renal function through epigenetic modulation of MMP9 expression.

PubMed

Khan, Hafizurrahman; Singh, Radha Dutt; Tiwari, Ratnakar; Gangopadhyay, Siddhartha; Roy, Somendu Kumar; Singh, Dhirendra; Srivastava, Vikas

2017-07-01

Mercury is one of the major heavy metal pollutants occurring in elemental, inorganic and organic forms. Due to ban on most inorganic mercury containing products, human exposure to mercury generally occurs as methylmercury (MeHg) by consumption of contaminated fish and other sea food. Animal and epidemiological studies indicate that MeHg affects neural and renal function. Our study is focused on nephrotoxic potential of MeHg. In this study, we have shown for the first time how MeHg could epigenetically modulate matrix metalloproteinase 9(MMP9) to promote nephrotoxicity using an animal model of sub chronic MeHg exposure. MeHg caused renal toxicity as was seen by increased levels of serum creatinine and expression of early nephrotoxicity markers (KIM-1, Clusterin, IP-10, and TIMP). MeHg exposure also correlated strongly with induction of MMP9 mRNA and protein in a dose dependent manner. Further, while induction of MMP9 promoted cytoskeleton disruption and loss of cell-cell adhesion (loss of F-actin, Vimentin and Fibronectin), inhibition of MMP9 was found to reduce these disruptions. Mechanistic studies by ChIP analysis showed that MeHg modulated MMP9 by promoting demethylation of its regulatory region to increase its expression. Bisulfite sequencing identified critical CpGs in the first exon of MMP9 which were demethylated following MeHg exposure. ChIP studies also showed loss of methyl binding protein, MeCP2 and transcription factor PEA3 at the demethylated site confirming decreased CpG methylation. Our studies thus show how MeHg could epigenetically modulate MMP9 to promote cytoskeleton disruption leading to loss of renal function. Copyright © 2017 Elsevier B.V. All rights reserved.

PARTNERSHIPS TO IMPROVE IMMUNOTOXICITY TESTING

EPA Science Inventory

Research in ITB is focused on the effects that chemicals/environmental contaminants have on modulation of the immune system. Immune modulation may result in suppressed immune function, while exposure to certain contaminants may result in hypersensitivity reactions (e.g., asthma ...

Behavioral data of thin-film single junction amorphous silicon (a-Si) photovoltaic modules under outdoor long term exposure

PubMed Central

Kichou, Sofiane; Silvestre, Santiago; Nofuentes, Gustavo; Torres-Ramírez, Miguel; Chouder, Aissa; Guasch, Daniel

2016-01-01

Four years׳ behavioral data of thin-film single junction amorphous silicon (a-Si) photovoltaic (PV) modules installed in a relatively dry and sunny inland site with a Continental-Mediterranean climate (in the city of Jaén, Spain) are presented in this article. The shared data contributes to clarify how the Light Induced Degradation (LID) impacts the output power generated by the PV array, especially in the first days of exposure under outdoor conditions. Furthermore, a valuable methodology is provided in this data article permitting the assessment of the degradation rate and the stabilization period of the PV modules. Further discussions and interpretations concerning the data shared in this article can be found in the research paper “Characterization of degradation and evaluation of model parameters of amorphous silicon photovoltaic modules under outdoor long term exposure” (Kichou et al., 2016) [1]. PMID:26977439

Second LDEF Post-Retrieval Symposium interim results of experiment A0034

NASA Technical Reports Server (NTRS)

Linton, Roger C.; Kamenetzky, Rachel R.

1993-01-01

Thermal control coatings and contaminant collector mirrors were exposed on the leading and trailing edge modules of Long Duration Exposure Facility (LDEF) experiment A0034 to provide a basis of comparison for investigating the role of atomic oxygen in the stimulation of volatile outgassing products. The exposure of identical thermal coatings on both the leading and trailing edges of the LDEF and the additional modified exposure of identical coatings under glass windows and metallic covers in each of the flight modules provided multiple combinations of space environmental exposure to the coatings and the contaminant collector mirrors. Investigations were made to evaluate the effects of the natural space and the induced environments on the thermal coatings and the collector mirrors to differentiate the sources of observed material degradation. Two identical flight units were fabricated for the LDEF mission, each of which included twenty-five thermal control coatings mounted in isolated compartments, each with an adjacent contaminant collector mirror mounted on the wall. The covers of the flight units included apertures for each compartment, exposing the thermal coatings directly to the space environment. Six of these compartments were sealed with ultraviolet-grade transmitting quartz windows and four other compartments were sealed with aluminum covers. One module of this passive LDEF experiment, occupying one-sixth of a full tray, was mounted in Tray C9 (leading edge), while the other identical module was mounted in Tray C3 (trailing edge).

Does Temperature and UV Exposure History Modulate the Effects of Temperature and UV Stress on Symbiodinium Growth Rates?

EPA Science Inventory

Temperature and ultraviolet radiation (UV) alone or in combination are known to inhibit the growth of Symbiodinium isolates. This conclusion was drawn from a number of studies having widely different exposure scenarios. Here we have examined the effects of pre-exposure acclimat...

Light exposure before learning improves memory consolidation at night

PubMed Central

Shan, Li-Li; Guo, Hao; Song, Ning-Ning; Jia, Zheng-Ping; Hu, Xin-Tian; Huang, Jing-Fei; Ding, Yu-Qiang; Richter-Levine, Gal; Zhou, Qi-Xin; Xu, Lin

2015-01-01

Light is recently recognized as a modulator able to activate the hippocampus and modulate memory processing, but little is known about the molecular mechanisms. Here, we report that in mice, a short pulse of white light before learning dramatically improves consolidation of contextual fear memory during the night. The light exposure increases hippocampal active p21-activated kinase 1 (PAK1) and CA1 long-term potentiation (LTP). These light effects are abolished in PAK1 knockout and dominant-negative transgenic mice, but preserved by expression of constitutively active PAK1 in the hippocampus. Our results indicate that light can act as a switch of PAK1 activity that modulate CA1 LTP and thereby memory consolidation without affecting learning and short-term memory. PMID:26493375

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Dietary Module Version 1: Technical Manual

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

RATE Exposure Assessment Modules - EXA 408, EXA 409

EPA Science Inventory

EXA 408 – Interpreting Biomonitoring Data and Using Pharmacokinetic Modeling in Exposure Assessment Widespread acceptance and use of the CDC's National Health and Nutritional Examination Survey (NHANES) database, which, among other things, reports measured concentrations of...

Modulation of lipopolysaccharide-induced chorioamnionitis in fetal sheep by maternal betamethasone.

PubMed

Wolfe, Katherine B; Snyder, Candice C; Gisslen, Tate; Kemp, Matthew W; Newnham, John P; Kramer, Boris W; Jobe, Alan H; Kallapur, Suhas

2013-12-01

We tested the hypothesis that the order of exposure to maternal betamethasone and intra-amniotic (IA) lipopolysaccharide (LPS) will differentially modulate inflammation in the chorioamnion. Time-mated Merino ewes with singleton fetuses received saline alone, IA LPS alone, maternal betamethasone before LPS, or betamethasone after LPS. We assessed inflammatory markers in the chorioamnion and the amniotic fluid. Inflammatory cell infiltration, expression of myeloperoxidase, serum amyloid A3 (acute phase reactant) in the chorioamnion, and levels of interleukin (IL)-8 in the amniotic fluid increased 7 days after LPS exposure. Betamethasone prior to LPS decreased infiltration of the inflammatory cells, CD3+ T cells, and decreased the levels of IL-1β and IL-8 in the amniotic fluid. Betamethasone 7 days prior to LPS exposure suppressed LPS-induced inflammation. The markers of inflammation largely had returned to the baseline 14 days after LPS exposure.

School-to-Work and Inclusion in General Education Teacher Preparation Programs: Instructional Modules for Middle Childhood Subject Area Methods Courses.

ERIC Educational Resources Information Center

Hamill, Lee B.; Geer, Cindy H.

Six instructional modules for middle childhood subject area methods courses are designed to target students in preservice middle childhood general education programs. The modules have been developed for each of the content area methods courses to ensure all preservice teachers have ample exposure to the school-to-work (STW) philosophy and…

Adrenal-derived stress hormones modulate ozone-induced lung injury and inflammation

EPA Science Inventory

Ozone-induced systemic effects are modulated through activation of the neuro-hormonal stress response pathway. Adrenal demedullation (DEMED)or bilateral total adrenalectomy (ADREX) inhibits systemic and pulmonary effect of acute ozone exposure. To understand the influence of adre...

Impact of traffic-related air pollution on acute changes in cardiac autonomic modulation during rest and physical activity: a cross-over study.

PubMed

Cole-Hunter, Tom; Weichenthal, Scott; Kubesch, Nadine; Foraster, Maria; Carrasco-Turigas, Glòria; Bouso, Laura; Martínez, David; Westerdahl, Dane; de Nazelle, Audrey; Nieuwenhuijsen, Mark

2016-01-01

People are often exposed to traffic-related air pollution (TRAP) during physical activity (PA), but it is not clear if PA modifies the impact of TRAP on cardiac autonomic modulation. We conducted a panel study among 28 healthy adults in Barcelona, Spain to examine how PA may modify the impact of TRAP on cardiac autonomic regulation. Participants completed four 2-h exposure scenarios that included either rest or intermittent exercise in high- and low-traffic environments. Time- and frequency-domain measures of heart rate variability (HRV) were monitored during each exposure period along with continuous measures of TRAP. Linear mixed-effects models were used to estimate the impact of TRAP on HRV as well as potential effect modification by PA. Exposure to TRAP was associated with consistent decreases in HRV; however, exposure-response relationships were not always linear over the broad range of exposures. For example, each 10 μg/m(3) increase in black carbon was associated with a 23% (95% CI: -31, -13) decrease in high frequency power at the low-traffic site, whereas no association was observed at the high-traffic site. PA modified the impact of TRAP on HRV at the high-traffic site and tended to weaken inverse associations with measures reflecting parasympathetic modulation (P ≤ 0.001). Evidence of effect modification at the low-traffic site was less consistent. The strength and direction of the relationship between TRAP and HRV may vary across exposure gradients. PA may modify the impact of TRAP on HRV, particularly at higher concentrations.

Radiation safety in the cardiac catheterization lab: A time series quality improvement initiative.

PubMed

Abuzeid, Wael; Abunassar, Joseph; Leis, Jerome A; Tang, Vicky; Wong, Brian; Ko, Dennis T; Wijeysundera, Harindra C

Interventional cardiologists have one of the highest annual radiation exposures yet systems of care that promote radiation safety in cardiac catheterization labs are lacking. This study sought to reduce the frequency of radiation exposure, for PCI procedures, above 1.5Gy in labs utilizing a Phillips system at our local institution by 40%, over a 12-month period. We performed a time series study to assess the impact of different interventions on the frequency of radiation exposure above 1.5Gy. Process measures were percent of procedures where collimation and magnification were used and percent of completion of online educational modules. Balancing measures were the mean number of cases performed and mean fluoroscopy time. Information sessions, online modules, policies and posters were implemented followed by the introduction of a new lab with a novel software (AlluraClarity©) to reduce radiation dose. There was a significant reduction (91%, p<0.05) in the frequency of radiation exposure above 1.5Gy after utilizing a novel software (AlluraClarity©) in a new Phillips lab. Process measures of use of collimation (95.0% to 98.0%), use of magnification (20.0% to 14.0%) and completion of online modules (62%) helped track implementation. The mean number of cases performed and mean fluoroscopy time did not change significantly. While educational strategies had limited impact on reducing radiation exposure, implementing a novel software system provided the most effective means of reducing radiation exposure. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Search for an Annual Modulation in a p-Type Point Contact Germanium Dark Matter Detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbeau, P.S.; Collar, J.I.; Fields, N.

2011-01-01

Fifteen months of cumulative CoGeNT data are examined for indications of an annual modulation, a predicted signature of weakly interacting massive particle (WIMP) interactions. Presently available data support the presence of a modulated component of unknown origin, with parameters prima facie compatible with a galactic halo composed of light-mass WIMPs. Unoptimized estimators yield a statistical significance for a modulation of {approx}2.8{sigma}, limited by the short exposure.

Search for an Annual Modulation in a p-Type Point Contact Germanium Dark Matter Detector

NASA Astrophysics Data System (ADS)

Aalseth, C. E.; Barbeau, P. S.; Colaresi, J.; Collar, J. I.; Diaz Leon, J.; Fast, J. E.; Fields, N.; Hossbach, T. W.; Keillor, M. E.; Kephart, J. D.; Knecht, A.; Marino, M. G.; Miley, H. S.; Miller, M. L.; Orrell, J. L.; Radford, D. C.; Wilkerson, J. F.; Yocum, K. M.

2011-09-01

Fifteen months of cumulative CoGeNT data are examined for indications of an annual modulation, a predicted signature of weakly interacting massive particle (WIMP) interactions. Presently available data support the presence of a modulated component of unknown origin, with parameters prima facie compatible with a galactic halo composed of light-mass WIMPs. Unoptimized estimators yield a statistical significance for a modulation of ˜2.8σ, limited by the short exposure.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Residential Module Version 4: User Guide, June 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Residential Module Version 4: Technical Manual, May 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Dietary Module Version 1: User Guide, June 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

Serum cation profile of broilers at various stages of exposure to deoxynivalenol.

PubMed

Yunus, Agha Waqar; Böhm, Josef

2013-05-01

The present experiment was carried out to investigate if levels of serum cations in broilers are modulated differently at various stages of exposure to deoxynivalenol (DON). Male broiler chicks at 7 days of age were fed a basal diet (0.27 mg of DON; 0.01 mg of zearalenone/kg), or either a low DON diet (1.68 mg of DON; 0.15 mg of zearalenone/kg) or a high DON diet (12.21 mg of DON; 1.09 mg of zearalenone/kg) produced using extracts from Fusarium graminearum cultures. Blood samples from the birds were collected during weeks 2, 4, and 5 of exposure. The high DON diet resulted in lower serum calcium levels compared to the basal diet at all the 3 sampling stages, while the low DON diet resulted in lower serum calcium levels only during weeks 2 and 5. Serum potassium levels were reduced under both the DON diets during weeks 2 and 5, while no diet-associated changes were found for serum levels of magnesium, sodium, and zinc. Under the present experimental conditions, the serum levels of calcium were consistently modulated in the broilers exposed to the DON-contaminated diets. The modulation of serum levels of potassium was, however, dependent upon the stage of exposure to DON.

Repeated Gestational Exposure of Mice to Chlorpyrifos Oxon Is Associated with Paraoxonase 1 (PON1) Modulated Effects in Maternal and Fetal Tissues

PubMed Central

Co, Aila L.; Hay, Ariel M.; MacDonald, James W.; Bammler, Theo K.; Farin, Federico M.; Costa, Lucio G.; Furlong, Clement E.

2014-01-01

Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured enzyme inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1−/−), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), red blood cell acylpeptide hydrolase (APH), and plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1−/− and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1−/− mice, but not in other genotypes. Weighted gene co-expression network analysis identified five gene modules based on clustering of the correlations among their fetal-brain expression values, allowing for correlation of module membership with the phenotypic data on enzyme inhibition. One module that correlated highly with maternal brain AChE activity had a large representation of homeobox genes. Gene set enrichment analysis revealed multiple gene sets affected by gestational CPO exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved in protein export, lipid metabolism, and neurotransmission. These data indicate that maternal PON1 status modulates the effects of repeated gestational CPO exposure on fetal-brain gene expression and on inhibition of both maternal and fetal biomarker enzymes. PMID:25070982

SIMULATING INTEGRATED MULTIMEDIA CHEMICAL FATE AND TRANSPORT FOR NATIONAL RISK ASSESSMENTS

EPA Science Inventory

The site-based multimedia, multipathway and multireceptor risk assessment (3MRA) approach is comprised of source, fate and transport, exposure and risk modules. The main interconnected multimedia fate and transport modules are: watershed, air, surface water, vadose zone and sat...

Application of 265-nm UVC LED Lighting to Sterilization of Typical Gram Negative and Positive Bacteria

NASA Astrophysics Data System (ADS)

Lee, Yong Wook; Yoon, Hyung Do; Park, Jae-Hyoun; Ryu, Uh-Chan

2018-05-01

UV LED lightings have been displacing conventional UV lamps due to their high efficiency, long lifetime, etc. A sterilizing lighting was prepared by assembling a UV LED module composed of 265-nm UVC LEDs and a silica lens array with a driver module comprised of a driver IC controlling pulse width modulation and constant current. The silica lens array was designed and fabricated to focus UV beam and simultaneously to give a uniform light distribution over specimens. Then pasteurizing effect of the lighting was analyzed for four kinds of bacteria and one yeast which are dangerous to people with low immunity. Sterilizing tests on these germs were carried out at the both exposure distances of 10 and 100 mm for various exposure durations up to 600 s.

Method and apparatus configured for identification of a material

DOEpatents

Slater, John M.; Crawford, Thomas M.

2000-01-01

The present invention includes an apparatus configured for identification of a material, and methods of identifying a material. One embodiment of the invention provides an apparatus including a first region configured to receive a first sample, the first region being configured to output a first spectrum corresponding to the first sample and responsive to exposure of the first sample to radiation; a modulator configured to modulate the first spectrum according to a first frequency; a second region configured to receive a second sample, the second region being configured to output a second spectrum corresponding to the second sample and responsive to exposure of the second sample to the modulated first spectrum; and a detector configured to detect the second spectrum having a second frequency greater than the first frequency.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Dietary Module Version 1: Quick Start Guide, May 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals: Residential Module Version 4: Quick Start Guide, April 2012

EPA Pesticide Factsheets

SHEDS - Multimedia is EPA's premier physically-based, probabilistic model, that can simulate cumulative or aggregate exposures for a population across a variety of multimedia, multipathway environmental chemicals.

Real-time and accelerated outdoor endurance testing of solar cells

NASA Technical Reports Server (NTRS)

Forestieri, A. F.; Anagnostou, E.

1978-01-01

Materials for solar-cell module construction have been studied on the basis of limited real-time outdoor exposure evaluations. The materials tested included transmission samples, sub-modules, and actual solar cells. The results suggest that glass, fluorinated ethylene propylene, and perfluoroalkoxy are good materials for the covering or encapsulation of solar-cell modules. In all cases, dirt accumulation and cleanability are important factors.

Modulation of human alveolar macrophage properties by ozone exposure in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becker, S.; Madden, M.C.; Newman, S.L.

The authors have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAMmore » to O3 while the basal O2- release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual.« less

A decision support framework for characterizing and managing dermal exposures to chemicals during Emergency Management and Operations.

PubMed

Dotson, G Scott; Hudson, Naomi L; Maier, Andrew

2015-01-01

Emergency Management and Operations (EMO) personnel are in need of resources and tools to assist in understanding the health risks associated with dermal exposures during chemical incidents. This article reviews available resources and presents a conceptual framework for a decision support system (DSS) that assists in characterizing and managing risk during chemical emergencies involving dermal exposures. The framework merges principles of three decision-making techniques: 1) scenario planning, 2) risk analysis, and 3) multicriteria decision analysis (MCDA). This DSS facilitates dynamic decision making during each of the distinct life cycle phases of an emergency incident (ie, preparedness, response, or recovery) and identifies EMO needs. A checklist tool provides key questions intended to guide users through the complexities of conducting a dermal risk assessment. The questions define the scope of the framework for resource identification and application to support decision-making needs. The framework consists of three primary modules: 1) resource compilation, 2) prioritization, and 3) decision. The modules systematically identify, organize, and rank relevant information resources relating to the hazards of dermal exposures to chemicals and risk management strategies. Each module is subdivided into critical elements designed to further delineate the resources based on relevant incident phase and type of information. The DSS framework provides a much needed structure based on contemporary decision analysis principles for 1) documenting key questions for EMO problem formulation and 2) a method for systematically organizing, screening, and prioritizing information resources on dermal hazards, exposures, risk characterization, and management.

Biophysical control of the growth of Agrobacterium tumefaciens using extremely low frequency electromagnetic waves at resonance frequency.

PubMed

Fadel, M Ali; El-Gebaly, Reem H; Mohamed, Shaimaa A; Abdelbacki, Ashraf M M

2017-12-09

Isolated Agrobacterium tumefaciens was exposed to different extremely low frequencies of square amplitude modulated waves (QAMW) from two generators to determine the resonance frequency that causes growth inhibition. The carrier was 10 MHz sine wave with amplitude ±10 Vpp which was modulated by a second wave generator with a modulation depth of ± 2Vpp and constant field strength of 200 V/m at 28 °C. The exposure of A. tumefaciens to 1.0 Hz QAMW for 90 min inhibited the bacterial growth by 49.2%. In addition, the tested antibiotics became more effective against A. tumefaciens after the exposure. Furthermore, results of DNA, dielectric relaxation and TEM showed highly significant molecular and morphological changes due to the exposure to 1.0 Hz QAMW for 90 min. An in-vivo study has been carried out on healthy tomato plants to test the pathogenicity of A. tumefaciens before and after the exposure to QAMW at the inhibiting frequency. Symptoms of crown gall and all pathological symptoms were more aggressive in tomato plants treated with non-exposed bacteria, comparing with those treated with exposed bacteria. We concluded that, the exposure of A. tumefaciens to 1.0 Hz QAMW for 90 min modified its cellular activity and DNA structure, which inhibited the growth and affected the microbe pathogenicity. Copyright © 2017 Elsevier Inc. All rights reserved.

A decision support framework for characterizing and managing dermal exposures to chemicals during Emergency Management and Operations

PubMed Central

Dotson, G. Scott; Hudson, Naomi L.; Maier, Andrew

2016-01-01

Emergency Management and Operations (EMO) personnel are in need of resources and tools to assist in understanding the health risks associated with dermal exposures during chemical incidents. This article reviews available resources and presents a conceptual framework for a decision support system (DSS) that assists in characterizing and managing risk during chemical emergencies involving dermal exposures. The framework merges principles of three decision-making techniques: 1) scenario planning, 2) risk analysis, and 3) multicriteria decision analysis (MCDA). This DSS facilitates dynamic decision making during each of the distinct life cycle phases of an emergency incident (ie, preparedness, response, or recovery) and identifies EMO needs. A checklist tool provides key questions intended to guide users through the complexities of conducting a dermal risk assessment. The questions define the scope of the framework for resource identification and application to support decision-making needs. The framework consists of three primary modules: 1) resource compilation, 2) prioritization, and 3) decision. The modules systematically identify, organize, and rank relevant information resources relating to the hazards of dermal exposures to chemicals and risk management strategies. Each module is subdivided into critical elements designed to further delineate the resources based on relevant incident phase and type of information. The DSS framework provides a much needed structure based on contemporary decision analysis principles for 1) documenting key questions for EMO problem formulation and 2) a method for systematically organizing, screening, and prioritizing information resources on dermal hazards, exposures, risk characterization, and management. PMID:26312660

Chronic varied stress modulates experimental autoimmune encephalomyelitis in Wistar rats.

PubMed

Correa, S G; Rodriguez-Galán, M C; Rivero, V E; Riera, C M

1998-06-01

Stress disturbs homeostasis by altering the equilibrium of various hormones which have a significant impact on immune responses. Few studies have examined the influence of stressors on autoimmune disease in animal models. In our work, we studied the effects of long-term exposure (14 days) to chronic varied stress (CVS) in a model of experimental autoimmune encephalomyelitis (EAE) in Wistar rats. We studied whether the exposure to CVS before or after the immune challenge would correlate with differences in the clinical course of the disease. We also examined whether the CVS would modulate the magnitude of the cellular or the humoral immune response. We observed opposite effects on the clinical signs in animals stressed before or after the immune challenge. The clinical signs of the disease were attenuated in animals stressed before but not after the immune challenge. Relationships were found in the modulation of the clinical severity related to the time of exposure to the CVS, the histological alterations and the proliferative results. Stressed animals with milder clinical signs presented an exacerbated humoral response against myelin antigens while stressed animals with more severe clinical symptoms exhibited a significantly diminished one. Besides, we detected the presence of specific IgG1 associated with the exposure to CVS before the induction of EAE. Our results show that, depending on the timing of the exposure of Wistar rats to the CVS, the neuroendocrine disbalance favors a more pronounced humoral or cellular profile of the response.

Opposite effects of dihydrotestosterone and estradiol on apoptosis in the anterior pituitary gland from male rats.

PubMed

Magri, María Laura; Gottardo, María Florencia; Zárate, Sandra; Eijo, Guadalupe; Ferraris, Jimena; Jaita, Gabriela; Ayala, Mariela Moreno; Candolfi, Marianela; Pisera, Daniel; Seilicovich, Adriana

2016-03-01

Hormones locally synthesized in the anterior pituitary gland are involved in regulation of pituitary cell renewal. In the pituitary, testosterone (T) may exert its actions per se or by conversion to dihydrotestosterone (DHT) or 17β-estradiol (E2) by 5α-reductase and aromatase activity, which are expressed in this gland. Previous reports from our laboratory showed that estrogens modulate apoptosis of lactotropes and somatotropes from female rats. Now, we examined the in vitro and in vivo effects of gonadal steroids on apoptosis of anterior pituitary cells from adult male rats. T in vitro did not modify apoptosis in anterior pituitary cells from gonadectomized (GNX) male rats. DHT, a non-aromatizable androgen, exerted direct antiapoptotic action on total anterior pituitary cells and folliculo-stellate cells, but not on lactotropes, somatotropes, or gonadotropes. On the contrary, E2 exerted a rapid apoptotic effect on total cells as well as on lactotropes and somatotropes. Incubation of anterior pituitary cells with T in presence of Finasteride, an inhibitor of 5α-reductase, increased the percentage of TUNEL-positive cells. In vivo administration of DHT to GNX rats reduced apoptosis in the anterior pituitary whereas E2 exerted proapoptotic action and reduced cells in G2/M-phase of the cell cycle. In summary, our results indicate that DHT and E2 have opposite effects on apoptosis in the anterior pituitary gland suggesting that local metabolization of T to these steroids could be involved in pituitary cell turnover in males. Changes in expression and/or activity of 5α-reductase and aromatase may play a role in the development of anterior pituitary tumors.

Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat.

PubMed

Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

2015-01-01

Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

Astronaut Vance Brand practices operating Docking Module hatch for ASTP

NASA Technical Reports Server (NTRS)

1975-01-01

Astronaut Vance D. Brand, command module pilot of the American Apollo Soyuz Test Project (ASTP) prime crew, practices operating a Docking Module hatch during ASTP pre-flight training at JSC. The Docking Module is designed to link the Apollo and Soyuz spacecraft during their docking in Earth orbit mission. Gary L. Doerre of JSC's Crew Training and Procedures Division is working with Brand. Doerre is wearing a face mask to help prevent possible exposure to Brand of disease prior to the ASTP launch.

Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism

PubMed Central

San Martín, Alejandro; Arce-Molina, Robinson; Galaz, Alex; Pérez-Guerra, Gustavo; Barros, L. Felipe

2017-01-01

Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling. PMID:28341740

Alopecia secondary to mesotherapy.

PubMed

Duque-Estrada, Bruna; Vincenzi, Colombina; Misciali, Cosimo; Tosti, Antonella

2009-10-01

Mesotherapy has recently become an advertised method for the treatment of different types of alopecia despite the lack of any data regarding its efficacy and possible side effects. The substances injected into the scalp include "cocktails" of natural plant extracts, homoeopathic agents, vitamins, vasodilators, and drugs that may stimulate hair growth, such as finasteride and minoxidil. We report two cases of patchy alopecia that developed after mesotherapy for the treatment of androgenetic alopecia. In the first patient, alopecia developed after injections of the heparinoid vasodilator mesoglycan; the 3-month follow-up examination revealed a small residual area of cicatricial alopecia. The second patient developed reversible alopecia after multiple scalp injections of homeopathic agents. These cases underline the possible risks of mesotherapy as a therapeutic technique for hair loss.

Laying the foundation to use Raspberry Pi 3 V2 camera module imagery for scientific and engineering purposes

NASA Astrophysics Data System (ADS)

Pagnutti, Mary; Ryan, Robert E.; Cazenavette, George; Gold, Maxwell; Harlan, Ryan; Leggett, Edward; Pagnutti, James

2017-01-01

A comprehensive radiometric characterization of raw-data format imagery acquired with the Raspberry Pi 3 and V2.1 camera module is presented. The Raspberry Pi is a high-performance single-board computer designed to educate and solve real-world problems. This small computer supports a camera module that uses a Sony IMX219 8 megapixel CMOS sensor. This paper shows that scientific and engineering-grade imagery can be produced with the Raspberry Pi 3 and its V2.1 camera module. Raw imagery is shown to be linear with exposure and gain (ISO), which is essential for scientific and engineering applications. Dark frame, noise, and exposure stability assessments along with flat fielding results, spectral response measurements, and absolute radiometric calibration results are described. This low-cost imaging sensor, when calibrated to produce scientific quality data, can be used in computer vision, biophotonics, remote sensing, astronomy, high dynamic range imaging, and security applications, to name a few.

Impact of electromagnetic fields on human vestibular system and standing balance: pilot results and future developments

NASA Astrophysics Data System (ADS)

Allen, A.; Villard, S.; Corbacio, M.; Goulet, D.; Plante, M.; Souques, M.; Deschamps, F.; Ostiguy, G.; Lambrozo, J.; Thomas, A. W.; Legros, A.

2016-03-01

Although studies have found that extremely low-frequency (ELF, < 300 Hz) magnetic fields (MF) can modulate human standing balance, the acute effects of electromagnetic fields on standing balance have not been systematically investigated. This work aims to establish the threshold for acute standing balance modulation during ELFMF exposure. One hundred volunteers will be exposed to transcranial electric stimulations (Direct Current - DC and Alternating Current - AC, 1 mA) and ELFMF (0 to 160 Hz, 0 to 100 mT). The displacement of their center of pressure will be collected and analyzed as an indicator of vestibular performance. During pilot testing (n=6), we found increased lateral sway with DC, and to a lesser extent, AC exposure. The ELFMF exposure system still needs to be adapted to allow meaningful results. Future protocol design will test for possible effects due to exposures in the radiofrequency range (i.e. above 3 kHz). These results will contribute to the literature documenting exposure guidelines aiming to protect workers and the general public.

Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.

PubMed

Rager, Julia E; Auerbach, Scott S; Chappell, Grace A; Martin, Elizabeth; Thompson, Chad M; Fry, Rebecca C

2017-10-16

Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling. Genome-wide DNA methylation, microRNA expression, mRNA expression, and protein expression levels in cord blood were modeled against total urinary arsenic (U-tAs) levels from pregnant women exposed to varying levels of iAs. Dose-response relationships were modeled in BMDExpress, and BMDs representing 10% response levels were estimated. Overall, DNA methylation changes were estimated to occur at lower exposure concentrations in comparison to other molecular endpoints. Multi-omic module eigengenes were derived through weighted gene co-expression network analysis, representing co-modulated signatures across transcriptomic, proteomic, and epigenomic profiles. One module eigengene was associated with decreased gestational age occurring alongside increased iAs exposure. Genes/proteins within this module eigengene showed enrichment for organismal development, including potassium voltage-gated channel subfamily Q member 1 (KCNQ1), an imprinted gene showing differential methylation and expression in response to iAs. Modeling of this prioritized multi-omic module eigengene resulted in a BMD(BMDL) of 58(45) μg/L U-tAs, which was estimated to correspond to drinking water arsenic concentrations of 51(40) μg/L. Results are in line with epidemiological evidence supporting effects of prenatal iAs occurring at levels <100 μg As/L urine. Together, findings present a variety of BMD measures to estimate doses at which prenatal iAs exposure influences neonatal outcome-relevant transcriptomic, proteomic, and epigenomic profiles.

Providing Experiential Business and Management Training for Biomedical Research Trainees.

PubMed

Petrie, Kimberly A; Carnahan, Robert H; Brown, Abigail M; Gould, Kathleen L

2017-01-01

Many biomedical PhD trainees lack exposure to business principles, which limits their competitiveness and effectiveness in academic and industry careers. To fill this training gap, we developed Business and Management Principles for Scientists, a semester-long program that combined didactic exposure to business fundamentals with practical team-based projects aimed at solving real business problems encountered by institutional shared--resource core facilities. The program also included a retreat featuring presentations by and networking with local life science entrepreneurs and final team presentations to expert judges. Quantitative and qualitative metrics were used to evaluate the program's impact on trainees. A pretest-posttest approach was used to assess trainees' baseline knowledge and mastery of module concepts, and each individual's pretest and posttest responses were compared. The mean score improved by more than 17 percentage points. Trainees also took an online survey to provide feedback about the module. Nearly all participants agreed or strongly agreed that the module was a valuable use of their time and will help guide their career decisions and that project work helped drive home module concepts. More than 75% of trainees reported discussing the module with their research advisors, and all of these participants reported supportive or neutral responses. Collectively, the trainee feedback about the module, improvement in test scores, and trainee perception of advisor support suggest that this short module is an effective method of providing scientists with efficient and meaningful exposure to business concepts. © 2017 K. A. Petrie et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Modulation of redox regulatory molecules and electron transport chain activity in muscle of air breathing fish Heteropneustes fossilis under air exposure stress.

PubMed

Paital, Biswaranjan

2014-01-01

Responses of redox regulatory system to long-term survival (>18 h) of the catfish Heteropneustes fossilis in air are not yet understood. Lipid and protein oxidation level, oxidant (H2O2) generation, antioxidative status (levels of superoxide dismutase, catalase, glutathione peroxidase and reductase, ascorbic acid and non-protein sulfhydryl) and activities of respiratory complexes (I, II, III and IV) in mitochondria were investigated in muscle of H. fossilis under air exposure condition (0, 3, 6, 12 and 18 h at 25 °C). The increased levels of both H2O2 and tissue oxidation were observed due to the decreased activities of antioxidant enzymes in muscle under water deprivation condition. However, ascorbic acid and non-protein thiol groups were the highest at 18 h air exposure time. A linear increase in complex II activity with air exposure time and an increase up to 12 h followed by a decrease in activity of complex I at 18 h were observed. Negative correlation was observed for complex III and V activity with exposure time. Critical time to modulate the above parameters was found to be 3 h air exposure. Dehydration induced oxidative stress due to modulation of electron transport chain and redox metabolizing enzymes in muscle of H. fossilis was clearly observed. Possible contribution of redox regulatory system in muscle tissue of the fish for long-term survival in air is elucidated. Results of the present study may be useful to understand the redox metabolism in muscle of fishes those are exposed to air in general and air breathing fishes in particular.

Indoor and outdoor weathering of PV-modules

NASA Astrophysics Data System (ADS)

Koehl, Michael; Heck, Markus; Philipp, Daniel; Weiss, Karl-Anders; Ferrara, Claudio; Herrmann, Werner

2008-08-01

Manufacturers of PV-modules usually give a warranty for at least 20 years. There is still only little knowledge about the lifetime of newly developed modules, however. How do they cope with snow, desert-climate or tropical humidity? In order to answer this question the Fraunhofer-Institute for Solar Energy Systems and TUV Rheinland have installed different outdoor exposure sites where modules have to stand extreme climates: high temperatures with high differences between day and night in the Negev desert at Israel, snow, wind and changing irradiation in the German Alps, and high humidity at warm temperatures at Indonesia. Commercial modules from industrial partners as well as innovative modules with different combinations of encapsulants and back-sheets were exposed. UV-irradiation, solar-irradiation, ambient- and module temperatures, ambient humidity and wind speed is measured and collected at a central server in Germany. These data are the basis for the calculation of integral loads for the comparison of different climatic regions and for an estimation of the service life, an exciting field of work since decades. Results from the evaluation of the monitoring during the fist 12 months of exposure are compared. Fluorescent lamps are chosen for accelerated UV-testing, since they simulate the UV-irradiation of the sun well while emitting less thermal radiation than Xenon-lamps. The UV-source is designed for use in climatic cabinets for damp-heat testing with UV.

Post-Flight Test Results of Acousto-Optic Modulator Devices Subjected to Space Exposure

NASA Technical Reports Server (NTRS)

Prasad, Narasimha S.; Trivedi, Sudhir; Rosemeier, Jolanta; Diestler, Mark

2014-01-01

The objective of the Materials International Space Station Experiment (MISSE) is to study the performance of novel materials when subjected to the synergistic effects of the harsh space environment for several months. MISSE missions provide an opportunity for developing space qualifiable materials. Several laser and lidar components were sent by NASA Langley Research Center (LaRC) as a part of the MISSE 7 mission. The MISSE 7 module was transported to the international space station (ISS) via STS 129 mission that was launched on Nov 16, 2009. Later, the MISSE 7 module was brought back to the earth via the STS 134 that landed on June 1, 2011. The MISSE 7 module that was subjected to exposure in a space environment for more than one and a half years included fiber laser, solid-state laser gain materials, detectors, and semiconductor laser diode. Performance testing of these components is now progressing. In this paper, the results of performance testing of a laser diode module sent by NASA Langley Research Center on MISSE 7 mission will be discussed. This paper will present the comparison of pre-flight and post-flight performance of two different COTS acousto-optic modulator (AOM) devices. Post-flight measurements indicate that these two devices did not undergo any significant performance degradation.

Sex Amphibian, Xenopus tropicalis, following Larval Exposure to an Aromatase Inhibitor

EPA Science Inventory

Aromatase is a steroidogenic enzyme that catalyzes the conversion of androgens to estrogens in vertebrates. Modulation of this enzyme’s activity by xenobiotic exposure has been shown to adversely affect gonadal differentiation in a number of diverse species. We hypothesized tha...

Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

EPA Science Inventory

Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

Dietary Intervention to Mitigate the Health Effects of PM Exposure in Humans

EPA Science Inventory

Exposure to ambient air pollution is a major cause of global morbidity and mortality. This presentation will highlight previously published, ongoing and planned studies conducted at the Human Studies Facility that have examined the efficacy of nutritional supplementation in modul...

Nicotine-induced plasticity during development: modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing.

PubMed

Heath, Christopher J; Picciotto, Marina R

2009-01-01

Despite a great deal of progress, more than 10% of pregnant women in the USA smoke. Epidemiological studies have demonstrated correlations between developmental tobacco smoke exposure and sensory processing deficits, as well as a number of neuropsychiatric conditions, including attention deficit hyperactivity disorder. Significantly, data from animal models of developmental nicotine exposure have suggested that the nicotine in tobacco contributes significantly to the effects of developmental smoke exposure. Consequently, we hypothesize that nicotinic acetylcholine receptors (nAChRs) are important for setting and refining the strength of corticothalamic-thalamocortical loops during critical periods of development and that disruption of this process by developmental nicotine exposure can result in long-lasting dysregulation of sensory processing. The ability of nAChR activation to modulate synaptic plasticity is likely to underlie the effects of both endogenous cholinergic signaling and pharmacologically administered nicotine to alter cellular, physiological and behavioral processes during critical periods of development.

Protective influence of healthful nutrition on mechanisms of environmental pollutant toxicity and disease risks.

PubMed

Hoffman, Jessie B; Hennig, Bernhard

2017-06-01

Human exposures to environmental contaminants around the world contribute to the global burden of disease and thus require urgent attention. Exploring preventive measures against environmental exposure and disease risk is essential. While a sedentary lifestyle and/or poor dietary habits can exacerbate the deleterious effects resulting from exposure to toxic chemicals, much emerging evidence suggests that positive lifestyle changes (e.g., healthful nutrition) can modulate and/or reduce the toxicity of environmental pollutants. Our work has shown that diets high in anti-inflammatory bioactive food components (e.g., phytochemicals or polyphenols) are possible strategies for modulating and reducing the disease risks associated with exposure to toxic pollutants in the environment. Thus, consuming healthy diets rich in plant-derived bioactive nutrients may reduce the vulnerability to diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationships between nutrition and other lifestyle modifications and toxicant-induced diseases. © 2017 New York Academy of Sciences.

Electromagnetic interference in the permeability of saquinavir across the blood-brain barrier using nanoparticulate carriers.

PubMed

Kuo, Yung-Chih; Kuo, Chan-Ying

2008-03-03

Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN>PBCA>MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases.

Spatial atomic layer deposition for coating flexible porous Li-ion battery electrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yersak, Alexander S.; Sharma, Kashish; Wallas, Jasmine M.

Ultrathin atomic layer deposition (ALD) coatings on the electrodes of Li-ion batteries can enhance the capacity stability of the Li-ion batteries. To commercialize ALD for Li-ion battery production, spatial ALD is needed to decrease coating times and provide a coating process compatible with continuous roll-to-roll (R2R) processing. The porous electrodes of Li-ion batteries provide a special challenge because higher reactant exposures are needed for spatial ALD in porous substrates. This work utilized a modular rotating cylinder spatial ALD reactor operating at rotation speeds up to 200 revolutions/min (RPM) and substrate speeds up to 200 m/min. The conditions for spatial ALDmore » were adjusted to coat flexible porous substrates. The reactor was initially used to characterize spatial Al2O3 and ZnO ALD on flat, flexible metalized polyethylene terephthalate foils. These studies showed that slower rotation speeds and spacers between the precursor module and the two adjacent pumping modules could significantly increase the reactant exposure. The modular rotating cylinder reactor was then used to coat flexible, model porous anodic aluminum oxide (AAO) membranes. The uniformity of the ZnO ALD coatings on the porous AAO membranes was dependent on the aspect ratio of the pores and the reactant exposures. Larger reactant exposures led to better uniformity in the pores with higher aspect ratios. The reactant exposures were increased by adding spacers between the precursor module and the two adjacent pumping modules. The modular rotating cylinder reactor was also employed for Al2O3 ALD on porous LiCoO2 (LCO) battery electrodes. Uniform Al coverages were obtained using spacers between the precursor module and the two adjacent pumping modules at rotation speeds of 25 and 50 RPM. The LCO electrodes had a thickness of ~49 um and pores with aspect ratios of ~12-25. Coin cells were then constructed using the ALD-coated LCO electrodes and were tested to determine their battery performance. The capacity of the Al2O3 ALD-coated LCO battery electrodes was measured versus the number of charge-discharge cycles. Both temporal and spatial ALD processing methods led to higher capacity stability compared with uncoated LCO battery electrodes. The results for improved battery performance were comparable for temporal and spatial ALD-coated electrodes. The next steps are also presented for scale-up to R2R spatial ALD using the modular rotating cylinder reactor.« less

Effect of acute alarm odor exposure and biological sex on generalized avoidance and glutamatergic signaling in the hippocampus of Wistar rats.

PubMed

Homiack, Damek; O'Cinneide, Emma; Hajmurad, Sema; Dohanich, Gary P; Schrader, Laura A

2018-06-19

Post-traumatic stress disorder (PTSD) is characterized by the development of paradoxical memory disturbances including intrusive memories and amnesia for specific details of the traumatic experience. Despite evidence that women are at higher risk to develop PTSD, most animal research has focused on the processes by which male rodents develop adaptive fear memory. As such, the mechanisms contributing to sex differences in the development of PTSD-like memory disturbances are poorly understood. In this investigation, we exposed adult male and female Wistar rats to the synthetic alarm odor 2,4,5-trimethylthiazole (TMT) to assess development of generalized fear behavior and rapid modulation of glutamate uptake and signaling cascades associated with hippocampus-dependent long-term memory. We report that female Wistar rats exposed to alarm odor exhibit context discrimination impairments relative to TMT-exposed male rats, suggesting the intriguing possibility that females are at greater risk in developing generalized fear memories. Mechanistically, alarm odor exposure rapidly modulated signaling cascades consistent with activation of the CREB shut-off cascade in the male, but not the female hippocampus. Moreover, TMT exposure dampened glutamate uptake and affected expression of the glutamate transporter, GLT-1 in the hippocampus. Taken together, these results provide evidence for rapid sex-dependent modulation of CREB signaling in the hippocampus by alarm odor exposure which may contribute to the development of generalized fear.

Adrenal-derived stress hormones modulate ozone-induced ...

EPA Pesticide Factsheets

Ozone-induced systemic effects are modulated through activation of the neuro-hormonal stress response pathway. Adrenal demedullation (DEMED)or bilateral total adrenalectomy (ADREX) inhibits systemic and pulmonary effect of acute ozone exposure. To understand the influence of adrenal-derived stress hormones in mediating ozone-induced lung injury/inflammation, we assessed global gene expression (mRNA sequencing) and selected proteins in lung tissues from male Wistar-Kyoto rats that underwent DEMED, ADREX, or sham surgery (SHAM)prior to their exposure to air or ozone (1 ppm),4 h/day for 1 or 2days. Ozone exposure significantly changed the expression of over 2300 genes in lungs of SHAM rats, and these changes were markedly reduced in DEMED and ADREX rats. SHAM surgery but not DEMED or ADREX resulted in activation of multiple ozone-responsive pathways, including glucocorticoid, acute phase response, NRF2, and Pl3K-AKT.Predicted targets from sequencing data showed a similarity between transcriptional changes induced by ozone and adrenergic and steroidal modulation of effects in SHAM but not ADREX rats. Ozone-induced Increases in lung 116 in SHAM rats coincided with neutrophilic Inflammation, but were diminished in DEMED and ADREX rats. Although ozone exposure in SHAM rats did not significantly alter mRNA expression of lfny and 11-4, the IL-4 protein and ratio of IL-4 to IFNy (IL-4/IFNy) proteins increased suggesting a tendency for a Th2 response. This did not occur

Environmental exposure to lead induces oxidative stress and modulates the function of the antioxidant defense system and the immune system in the semen of males with normal semen profile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kasperczyk, Aleksandra; Dobrakowski, Michał; Czuba, Zenon P.

We investigated the associations between environmental exposure to lead and a repertoire of cytokines in seminal plasma of males with normal semen profile according to the WHO criteria. Based on the median lead concentration in seminal plasma, 65 samples were divided into two groups: low (LE) and high exposure to lead (HE). Differences in semen volume and the pH, count, motility and morphology of sperm cells were not observed between the examined groups. The total oxidant status value and the level of protein sulfhydryl groups as well as the activities of manganese superoxide dismutase and catalase were significantly higher inmore » the HE group, whereas the total antioxidant capacity value and the activities of glutathione reductase and glutathione-S-transferase were depressed. IL-7, IL-10, IL-12, and TNF-α levels were significantly higher in the HE group compared with the LE group. Environmental exposure to lead is sufficient to induce oxidative stress in seminal plasma and to modulate antioxidant defense system. - Highlights: • Lead induces oxidative stress in seminal plasma in human. • Lead modulates antioxidant defense system in seminal plasma in human. • Lead does not change a Th1/Th2 imbalance in seminal plasma in human.« less

Environmental testing of CIS based modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willett, D.

1995-11-01

This report describes environmental testing of Siemen`s CIS modules. Charts and diagrams are presented on data concerning: temporary power loss of laminated mini-modules; the 50 thermal cycle test; the 10 humidity freeze cycle test; results after 1000 hours of exposure to damp heat; and interconnect test structures in damp heat testing. It is concluded that moisture ingress causes permanent increases in the series resistance of modules, and that improved packaging is needed for better high humidity reliability. Also, dry dark heat caused temporary power losses which were recovered in sunlight.

Comparative assessment of endocrine modulators with oestrogenic activity: I. Definition of a hygiene-based margin of safety (HBMOS) for xeno-oestrogens against the background of European developments.

PubMed

Bolt, H M; Janning, P; Michna, H; Degen, G H

2001-01-01

A novel concept - the hygiene-based margin of safety (HBMOS) - is suggested for the assessment of the impact of potential endocrine modulators. It integrates exposure scenarios and potency data for industrial chemicals and naturally occurring dietary compounds with oestrogenic activity. An HBMOS is defined as a quotient of estimated daily intakes weighted by the relative in vivo potencies of these compounds. The Existing Chemicals Programme of the European Union provides Human and Environmental Risk Assessments of Existing Chemicals which include human exposure scenarios. Such exposure scenarios, along with potency estimates for endocrine activities, may provide a basis for a quantitative comparison of the potential endocrine-modulating effects of industrial chemicals with endocrine modulators as natural constituents of human diet. Natural phyto-oestrogens exhibit oestrogenic activity in vitro and in vivo. Important phyto-oestrogens for humans are isoflavones (daidzein, genistein) and lignans, with the highest quantities found in soybeans and flaxseed, respectively. Daily isoflavone exposures calculated for infants on soy-based formulae were in the ranges of 4.5-8 mg/kg body wt.; estimates for adults range up to 1 mg/kg body wt. The Senate Commission on the Evaluation of Food Safety (SKLM) of the Deutsche Forschungsgemeinschaft has also indicated a wide range of dietary exposures. For matters of risk assessment, the SKLM has based recommendations on dietary exposure scenarios, implying a daily intake of phyto-oestrogens in the order of 1 mg/kg body wt. On the basis of information compiled within the Existing Chemicals Programme of the EU, it appears that a daily human exposure to nonylphenol of 2 microg/kg body wt. may be a worst-case assumption, but which is based on valid scenarios. The intake of octylphenol is much lower, due to a different use pattern and applications, and may be neglected. Data from migration studies led to estimations of the daily human uptake of bisphenol A of maximally 1 microg/kg body wt. On the basis of comparative data from uterotrophic assays in rats, with three consecutive days of oral applications involved, and taking the natural phyto-oestrogen daidzein as reference (= 1), relative uterotrophic activities in DA/Han rats follow the sequence: daidzein = 1; bisphenol A = 1; p-tertoctylphenol = 2; o, p'-DDT = 4; ethinyl oestradiol = 40,000. The derived values from exposure scenarios, as well as these relative potency values and bridging assumptions, led to calculations of HBMOS as a quantitative comparison of potential endocrine-modulating effects of industrial chemicals with those of natural constituents of human diet. HBMOS estimates for nonylphenol ranged between 250 and 500, dependent on bridging assumptions, and around 1000 for bisphenol A. The derivations of HBMOS were in full support of the conclusions reached by the SKLM of the Deutsche Forschungsgemeinschaft. The estimated HBMOS values for the industrial chemicals (nonylphenol, bisphenol A) appear sufficiently high to ensure the absence of a practical risk to human health under the present exposure conditions.

Agmatine Reduces Balance Deficits In a Rat Model Of Third Trimester Binge-Like Ethanol Exposure

PubMed Central

Lewis, B.; Wellman, K.A.; Barron, S.

2007-01-01

This study examined the effects of binge-like ethanol (ETOH) exposure in neonatal rats on a cerebellar-mediated balance task, and the ability of agmatine, an n-methyl-d-aspartate receptor (NMDAR) modulator, to reverse such effects. Five neonatal treatments groups were used, including ETOH (6.0 g/kg/day), AG (20 mg/kg), ETOH plus AG (6.0 g/kg/day and 20 mg/kg), a maltose control, and a non-treated control. Ethanol was administered via oral intubation twice daily for eight days, (AG was administered with the last ETOH intubation only). Two exposure periods were used; PND 1–8 or PND 8–15. On PND 31–33, balance performance on a single dowel was tested. Treatment with AG during withdrawal in ETOH exposed animals improved performance relative to ETOH alone among the PND 1–8 exposure period. ETOH exposure during the 2nd postnatal week did not impair balance. These findings provide further support that exposure to ETOH during critical developmental periods can impair performance on a cerebellar-dependent balance task. Of perhaps greater significance, co-administration of agmatine reduced these deficits suggesting that NMDA modulation via polyamine blockade may provide a novel approach to attenuating damage associated with binge-like ETOH consumption. PMID:17714770

Redox-Dependent Modulation of Anthocyanin Biosynthesis by the TCP Transcription Factor TCP15 during Exposure to High Light Intensity Conditions in Arabidopsis1[OPEN

PubMed Central

Viola, Ivana L.; Gonzalez, Daniel H.

2016-01-01

TCP proteins integrate a family of transcription factors involved in the regulation of developmental processes and hormone responses. It has been shown that most members of class I, one of the two classes in which the TCP family is divided, contain a conserved Cys that leads to inhibition of DNA binding when oxidized. In this work, we describe that the class-I TCP protein TCP15 inhibits anthocyanin accumulation during exposure of plants to high light intensity by modulating the expression of transcription factors involved in the induction of anthocyanin biosynthesis genes, as suggested by the study of plants that express TCP15 from the 35SCaMV promoter and mutants in TCP15 and the related gene TCP14. In addition, the effect of TCP15 on anthocyanin accumulation is lost after prolonged incubation under high light intensity conditions. We provide evidence that this is due to inactivation of TCP15 by oxidation of Cys-20 of the TCP domain. Thus, redox modulation of TCP15 activity in vivo by high light intensity may serve to adjust anthocyanin accumulation to the duration of exposure to high irradiation conditions. PMID:26574599

Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism.

PubMed

San Martín, Alejandro; Arce-Molina, Robinson; Galaz, Alex; Pérez-Guerra, Gustavo; Barros, L Felipe

2017-06-02

Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection

EPA Science Inventory

Exposure to oxidant air pollution is associated with Increased respiratory morbiditses and susceptibility to Infections Ozone is a commonly encountered oxidant air pollutant, yet Its effects on influenza infections in humans are not known ‘the greater Mexico City area was the pri...

Assessment of general public exposure to LTE and RF sources present in an urban environment.

PubMed

Joseph, Wout; Verloock, Leen; Goeminne, Francis; Vermeeren, Günter; Martens, Luc

2010-10-01

For the first time, in situ electromagnetic field exposure of the general public to fields from long term evolution (LTE) cellular base stations is assessed. Exposure contributions due to different radiofrequency (RF) sources are compared with LTE exposure at 30 locations in Stockholm, Sweden. Total exposures (0.2-2.6 V/m) satisfy the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference levels (from 28 V/m for frequency modulation (FM), up to 61 V/m for LTE) at all locations. LTE exposure levels up to 0.8 V/m were measured, and the average contribution of the LTE signal to the total RF exposure equals 4%.

Reaction of photochemical resists used in screen printing under the influence of digitally modulated ultra violet light

NASA Astrophysics Data System (ADS)

Gmuender, T.

2017-02-01

Different chemical photo-reactive emulsions are used in screen printing for stencil production. Depending on the bandwidth, optical power and depth of field from the optical system, the reaction / exposure speed has a diverse value. In this paper, the emulsions get categorized and validated in a first step. After that a mathematical model gets developed and adapted due to heuristic experience to estimate the exposure speed under the influence of digitally modulated ultra violet (UV) light. The main intention is to use the technical specifications (intended wavelength, exposure time, distance to the stencil, electrical power, stencil configuration) in the emulsion data sheet primary written down with an uncertainty factor for the end user operating with large projector arc lamps and photo films. These five parameters are the inputs for a mathematical formula which gives as an output the exposure speed for the Computer to Screen (CTS) machine calculated for each emulsion / stencil setup. The importance of this work relies in the possibility to rate with just a few boundaries the performance and capacity of an exposure system used in screen printing instead of processing a long test series for each emulsion / stencil configuration.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

NASA Astrophysics Data System (ADS)

Ghita, Mihaela; Coffey, Caroline B.; Butterworth, Karl T.; McMahon, Stephen J.; Schettino, Giuseppe; Prise, Kevin M.

2016-01-01

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module X. Medical Emergencies.

ERIC Educational Resources Information Center

National Highway Traffic Safety Administration (DOT), Washington, DC.

This instructor's lesson plan guide on medical emergencies is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Ten units of study are presented: (1) diabetic emergencies; (2) anaphylactic reactions; (3) exposure to environmental extremes; (4) alcoholism and drug abuse; (5) poisoning and…

The glutathione-S-transferase mu 1 (GSTM1) null genotype and increased neutrophil response to low-level ozone (0.06 ppm).

EPA Science Inventory

Background: Exposure of healthy young adults to 03 modulates immune cell biology in the airways and causes a significant increase in neutrophilic inflammation which can vary considerably in magnitude across individuals. The GSTM1null genotype modulates Oj-induced inflammation, bu...

Attenuation and image noise level based online z-axis tube current modulation for CT scans independent with localizer radiograph: simulation study and results

NASA Astrophysics Data System (ADS)

Tian, Yi; Chen, Mahao; Kong, Jun

2009-02-01

With the online z-axis tube current modulation (OZTCM) technique proposed by this work, full automatic exposure control (AEC) for CT systems could be realized with online feedback not only for angular tube current modulation (TCM) but also for z-axis TCM either. Then the localizer radiograph was not required for TCM any more. OZTCM could be implemented with 2 schemes as attenuation based μ-OZTCM and image noise level based μ-OZTCM. Respectively the maximum attenuation of projection readings and standard deviation of reconstructed images can be used to modulate the tube current level in z-axis adaptively for each half (180 degree) or full (360 degree) rotation. Simulation results showed that OZTCM achieved better noise level than constant tube current scan case by using same total dose in mAs. The OZTCM can provide optimized base tube current level for angular TCM to realize an effective auto exposure control when localizer radiograph is not available or need to be skipped for simplified scan protocol in case of emergency procedure or children scan, etc.

Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge*

PubMed Central

Mulinari-Brenner, Fabiane Andrade; Guilherme, Marina Riedi; Peretti, Murilo Calvo; Werner, Betina

2017-01-01

Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation. PMID:29267454

Frontal fibrosing alopecia treatment options.

PubMed

Fertig, Raymond; Tosti, Antonella

2016-11-01

Frontal fibrosing alopecia (FFA) is a rare dermatologic disease that causes scarring and hair loss and is increasing in prevalence worldwide. FFA patients typically present with hair loss in the frontal scalp region and eyebrows which may be associated with sensations of itching or burning. FFA is a clinically distinct variant of lichen planopilaris (LPP) that affects predominantly postmenopausal women, although men and premenopausal women may also be affected. Early diagnosis and prompt treatment are necessary to prevent definitive scarring and permanent hair loss. Data from retrospective studies indicate that 5-alpha-reductase inhibitors (5aRIs) are effective in stabilizing the disease. In our clinical experience, we have seen optimal results treating FFA patients with oral finasteride in conjunction with hydroxychloroquine, topical calcineurin inhibitors (tacrolimus) and excimer laser in patients with signs of active inflammation.

Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge.

PubMed

Mulinari-Brenner, Fabiane Andrade; Guilherme, Marina Riedi; Peretti, Murilo Calvo; Werner, Betina

2017-01-01

Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation.

Management of transgenderism.

PubMed

Spack, Norman P

2013-02-06

Gender identity disorder (transgenderism) is poorly understood from both mechanistic and clinical standpoints. Awareness of the condition appears to be increasing, probably because of greater societal acceptance and available hormonal treatment. Therapeutic options include hormone and surgical treatments but may be limited by insurance coverage because costs are high. For patients seeking male-to-female (MTF) change, hormone treatment includes estrogens, finasteride, spironolactone, and gonadotropin-releasing hormone (GnRH) analogs. Surgical options include feminizing genital and facial surgery, breast augmentation, and various fat transplantations. For patients seeking a female-to-male (FTM) gender change, medical therapy includes testosterone and GnRH analogs and surgical therapy includes mammoplasty and phalloplasty. Medical therapy for both FTM and MTF can be started in early puberty, although long-term effects are not known. All patients considering treatment need counseling and medical monitoring.

Effects of acoustic radiation force and shear waves for absorption and stiffness sensing in ultrasound modulated optical tomography.

PubMed

Li, Rui; Elson, Daniel S; Dunsby, Chris; Eckersley, Robert; Tang, Meng-Xing

2011-04-11

Ultrasound-modulated optical tomography (UOT) combines optical contrast with ultrasound spatial resolution and has great potential for soft tissue functional imaging. One current problem with this technique is the weak optical modulation signal, primarily due to strong optical scattering in diffuse media and minimal acoustically induced modulation. The acoustic radiation force (ARF) can create large particle displacements in tissue and has been shown to be able to improve optical modulation signals. However, shear wave propagation induced by the ARF can be a significant source of nonlocal optical modulation which may reduce UOT spatial resolution and contrast. In this paper, the time evolution of shear waves was examined on tissue mimicking-phantoms exposed to 5 MHz ultrasound and 532 nm optical radiation and measured with a CCD camera. It has been demonstrated that by generating an ARF with an acoustic burst and adjusting both the timing and the exposure time of the CCD measurement, optical contrast and spatial resolution can be improved by ~110% and ~40% respectively when using the ARF rather than 5 MHz ultrasound alone. Furthermore, it has been demonstrated that this technique simultaneously detects both optical and mechanical contrast in the medium and the optical and mechanical contrast can be distinguished by adjusting the CCD exposure time. © 2011 Optical Society of America

GABAB Receptor Positive Modulation Decreases Selective Molecular and Behavioral Effects of Cocaine

PubMed Central

Lhuillier, Loic; Mombereau, Cedric; Cryan, John F.; Kaupmann, Klemens

2006-01-01

Exposure to cocaine induces selective behavioral and molecular adaptations. In rodents, acute cocaine induces increased locomotor activity whereas prolonged drug exposure results in behavioral locomotor sensitization, which is thought to be a consequence of drug–induced neuroadaptive changes. Recent attention has been given to compounds activating GABAB receptors as potential anti-addictive therapies. In particular the principle of allosteric positive GABAB receptor modulators is very promising in this respect, as positive modulators lack the sedative and muscle relaxant properties of full GABAB receptor agonists such as baclofen. Here we investigated the effects of systemic application of the GABAB receptor positive modulator GS39783 in animals treated with acute and chronic cocaine administration. Both GS39783 and baclofen dose-dependently attenuated acute cocaine-induced hyperlocomotion. Furthermore, both compounds also efficiently blocked cocaine-induced Fos induction in the striatal complex. In chronic studies GS39783 induced a modest attenuation of cocaine-induced locomotor sensitization. Chronic cocaine induces the accumulation of the transcription factor ΔFosB and up regulates cAMP-response-element-binding-protein (CREB) and dopamine-and-cAMP-regulated-phosphoprotein of 32 kd (DARPP-32). GS39783 blocked the induction/activation of DARPP-32 and CREB in the nucleus accumbens and dorsal striatum and partially inhibited ΔFosB accumulation in the dorsal striatum. In summary our data provide evidence that GS39783 attenuates the acute behavioral effects of cocaine exposure in rodents and in addition prevents the induction of selective long-term adaptive changes in dopaminergic signaling pathways. Further investigation of GABAB receptor positive modulation as a novel therapeutic strategy for the treatment of cocaine dependence and possibly other drugs of abuse is therefore warranted. PMID:16710312

Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection.

PubMed

Roy, Anirban; Bauer, Stephen M; Lawrence, B Paige

2012-01-01

Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.

An HF exposure system for mice with improved efficiency.

PubMed

Capstick, Myles; Gong, Yijian; Pasche, Boris; Kuster, Niels

2016-05-01

An exposure system that addresses difficulties that arise for exposure of small animals at low frequencies with a high exposure level is presented. The system, intended to operate at 27 MHz, consists of two identical transverse electro-magnetic (TEM) cells for exposure and sham exposure of groups of 16 free-running mice housed in pairs within standard cages, capable of exposure over extended daily periods while being provided food and water. Inclusion of the exposure cell in a half-wavelength resonator has been developed as a new paradigm to enhance field strength for an increase of >50-fold in available specific absorption rate (SAR) levels compared to traditional TEM cell configurations. The system described allows both daily and weekly exposure schedules and supports blinded protocols with continuous wave (CW) and amplitude modulation (AM) signals with programmable modulation depths and frequencies. Electric field (E-field) homogeneity across the TEM cell along a vertical plane (orthogonal to the axis of the TEM line) was within 3.3%, and 3.1% along the horizontal plane. Accurate and comprehensive dosimetric assessments based on whole-body and organ-specific SAR essential for in vivo bioelectromagnetic experiments are presented, which takes into account various factors (e.g., mouse activities, close proximity, and field homogeneity). Average SAR levels are controllable in the range of 1 mW/kg to 2 W/kg, with expanded uncertainty (k = 2) of 1 dB and instantaneous variation (k = 1) of 4 dB. © 2016 Wiley Periodicals, Inc.

Functional and molecular alterations in T Cells induced by CCL5.

PubMed

Cridge, T J; Horowitz, K M; Marinucci, M N; Rose, K M; Wells, M; Werner, M T; Kurt, Robert A

2006-01-01

To delineate whether, and the extent to which, CCL5 could impact T cell function we examined cytokine production and proliferative ability following CCL5 treatment in vitro. We report a decreased ability of splenic T cells to produce IFN-? and TNF-a as well as proliferate in response to crosslinking with antibody to CD3 after 72, but not 24 hours of CCL5 exposure. To identify a mechanism by which CCL5 modulated T cell function, we examined T cell receptor translocation and lipid raft clustering. After exposure to CCL5, T cells were less efficient at translocating the TCR and clustering lipid rafts. Since TCR translocation and lipid raft clustering are required for creation of an immunological synapse, these data suggest that extended exposure to CCL5 may impact T cell effector function by modulating the ability to create a functional immunological synapse.

Amorphous-silicon module intercell corrosion

NASA Astrophysics Data System (ADS)

Mon, G. R.; Ross, R. G.

1987-06-01

Three non-electrochemical, moisture-induced a-Si module degradation modes have been observed and their mechanisms studied: (1) the formation and growth of pinholes in the thin-film layers; (2) the directional interfusion of pinholes along process scribe lines to form metallization-free regions that tend to open-circuit the module; and (3) worm-like filiform corrosion in the aluminum layer. The dependency on time-of-exposure to moist environments of the amount of material erosion in the module intercell zone has been quantified by two methods—directly by EDS analysis, and indirectly by sheet resistivity measurements on fully aluminized back surface modules. In addition, changes in maximum power output, series resistance, and open circuit voltage have been documented. Consequences for fielded modules are discussed.

Stimulation of the brain with radiofrequency electromagnetic field pulses affects sleep-dependent performance improvement.

PubMed

Lustenberger, Caroline; Murbach, Manuel; Dürr, Roland; Schmid, Marc Ralph; Kuster, Niels; Achermann, Peter; Huber, Reto

2013-09-01

Sleep-dependent performance improvements seem to be closely related to sleep spindles (12-15 Hz) and sleep slow-wave activity (SWA, 0.75-4.5 Hz). Pulse-modulated radiofrequency electromagnetic fields (RF EMF, carrier frequency 900 MHz) are capable to modulate these electroencephalographic (EEG) characteristics of sleep. The aim of our study was to explore possible mechanisms how RF EMF affect cortical activity during sleep and to test whether such effects on cortical activity during sleep interact with sleep-dependent performance changes. Sixteen male subjects underwent 2 experimental nights, one of them with all-night 0.25-0.8 Hz pulsed RF EMF exposure. All-night EEG was recorded. To investigate RF EMF induced changes in overnight performance improvement, subjects were trained for both nights on a motor task in the evening and the morning. We obtained good sleep quality in all subjects under both conditions (mean sleep efficiency > 90%). After pulsed RF EMF we found increased SWA during exposure to pulse-modulated RF EMF compared to sham exposure (P < 0.05) toward the end of the sleep period. Spindle activity was not affected. Moreover, subjects showed an increased RF EMF burst-related response in the SWA range, indicated by an increase in event-related EEG spectral power and phase changes in the SWA range. Notably, during exposure, sleep-dependent performance improvement in the motor sequence task was reduced compared to the sham condition (-20.1%, P = 0.03). The changes in the time course of SWA during the exposure night may reflect an interaction of RF EMF with the renormalization of cortical excitability during sleep, with a negative impact on sleep-dependent performance improvement. Copyright © 2013 Elsevier Inc. All rights reserved.

Termination of pseudopregnancy in the rat alters the response to progesterone, chlordiazepoxide, and MK-801 in the elevated plus-maze.

PubMed

Bitran, Daniel; Solano, Steven M

2005-07-01

Allopregnanolone, a neurosteroid-reduced metabolite of progesterone, is a well-documented positive modulator of the gamma-aminobutyric type A (GABA(A)) receptor. As has been reported for other positive modulators of the GABA(A) receptor, chronic exposure to neurosteroids is hypothesized to decrease GABA(A) receptor function. Drawing from the literature on chronic exposure to benzodiazepines or alcohol, putative changes in N-methyl-D-aspartate (NMDA) receptor function are also expected after chronic neurosteroid exposure. To assess the sensitivity of the GABA(A) and NMDA receptors after chronic elevation of neurosteroid produced by termination of pseudopregnancy in behavioral tests of anxiety and sensorimotor coordination. Female rats ovariectomized on day 10 of pseudopregnancy were tested in the elevated plus-maze and on the rotor rod after an acute injection of progesterone (4 mg/0.2 ml, s.c.), chlordiazepoxide (5 or 15 mg/kg, i.p.), or MK-801 (0.025, 0.05, or 0.1 mg/kg, i.p.). Pseudopregnancy termination produced an anxiogenic-like response in the plus-maze; an acute injection of progesterone restored baseline levels of behavior in this test. Pseudopregnancy termination eliminated the anxiolytic-like, sedative, and ataxic effects of chlordiazepoxide. In contrast, pseudopregnancy termination produced an increased sensitivity to the anxiolytic-like and ataxic effects of MK-801. The effects of pseudopregnancy termination on the behavioral response to positive modulators of the GABA(A) receptor are consistent with results from studies in which chronic exposure to neurosteroids decreases the response to acute neurosteroid and benzodiazepine administration. However, unlike the enhanced glutamatergic tone resulting from discontinuation of chronic benzodiazepine or alcohol exposure, the termination of pseudopregnancy apparently decreases NMDA receptor function.

Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

EPA Science Inventory

Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

August 2007 FIFRA Scientific Advisory Panel Recommendations for SHEDS-Dietary and SHEDS-Residential Modules (Summarized) and EPA Responses

EPA Science Inventory

Over the past ten years, the Agency has requested the Panel to review several probabilistic dietary exposure software models. These have included DEEM-FCID™, Calendex-FCID, CARES™, LifeLine™, and an earlier (specialized) version of SHEDS (SHEDS-Wood) designed to assess exposure...

75 FR 22779 - FIFRA Scientific Advisory Panel; Notice of Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... exposure factors to generate time series of exposure for simulated individuals. One-stage or two-stage...., built-in simple source-to- concentration module, user-entered time series from other models or field... FOR FURTHER INFORMATION CONTACT at least 10 days prior to the meeting to give EPA as much time as...

Post-flight test results of acousto-optic modulator devices subjected to space exposure

NASA Astrophysics Data System (ADS)

Prasad, Narasimha S.; Trivedi, Sudhir; Rosemeier, Jolanta; Diestler, Mark

2014-09-01

The objective of the Materials International Space Station Experiment (MISSE) is to study the performance of novel materials when subjected to the synergistic effects of the harsh space environment for several months. MISSE missions provide an opportunity for developing space qualifiable materials. Several laser and lidar components were sent by NASA Langley Research Center (LaRC) as a part of the MISSE 7 mission. The MISSE 7 module was transported to the international space station (ISS) via STS 129 mission that was launched on Nov 16, 2009. Later, the MISSE 7 modulewas brought back to the earth via the STS 134 that landed on June 1, 2011. The MISSE 7 module that was subjected to exposure in space environment for more than one and a half year included fiber laser, solid-state laser gain materials, detectors, and semiconductor laser diode. Performance testing of these components is now progressing. In this paper, the results of performance testing of a laser diode module sent by NASA Langley Research Center on MISSE 7 mission will be discussed. This paper will present the comparison of pre-flight and post-flight performance of two different COTS acousto-optic modulator devices. Post-flight measurements indicate that these two devices did not undergo any significant performance degradation.

Stress modulation of cognitive and affective processes

PubMed Central

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Impact of nutrition on pollutant toxicity: an update with new insights into epigenetic regulation

PubMed Central

Hoffman, Jessie B; Petriello, Michael C; Hennig, Bernhard

2017-01-01

Exposure to environmental pollutants is a global health problem and is associated with the development of many chronic diseases including cardiovascular disease, diabetes, and metabolic syndrome. There is a growing body of evidence that nutrition can both positively and negatively modulate the toxic effects of pollutant exposure. Diets high in pro-inflammatory fats, such as linoleic acid, can exacerbate pollutant toxicity while diets rich in bioactive and anti-inflammatory food components, including omega-3 fatty acids and polyphenols, can attenuate toxicant-associated inflammation. Previously, researchers have elucidated direct mechanisms of nutritional modulation including alteration of NF-κB signaling, but recently increased focus has been given to the ways in which nutrition and pollutants affect epigenetics. Nutrition has been demonstrated to modulate epigenetic markers that have been linked either to increased disease risks or to protection against diseases. Overnutrition (i.e. obesity) and undernutrition (i.e. famine) have been observed to alter prenatal epigenetic tags that may increase the risk of offspring developing disease later in life. Conversely, bioactive food components, including curcumin, have been shown to alter epigenetic markers that suppress activation of NF-κB, thus reducing inflammatory responses. Exposure to pollutants also alters epigenetic markers and may contribute to inflammation and disease. It has been demonstrated that pollutants, via epigenetic modulations, can increase activation of NF-κB and upregulate miRNAs associated with inflammation, cardiac injury, and oxidative damage. Importantly, recent evidence suggests that nutritional components, including EGCG, can protect against pollutant-induced inflammation through epigenetic regulation of pro-inflammatory target genes of NF-κB. Further research is needed to better understand how nutrition can modulate pollutant toxicity through epigenetic regulation. Further research is needed to better understand how nutrition can modulate pollutant toxicity through epigenetic regulation. Therefore, the objective of this review is to elucidate the current evidence linking epigenetic changes to pollutant-induced diseases and how this regulation may be modulated by nutrients allowing for the development of future personalized lifestyle interventions. PMID:28076319

Solar Electric System

NASA Technical Reports Server (NTRS)

1987-01-01

Heat Pipe Technology, Inc. undertook the development of a PV system that could bring solar electricity to the individual home at reasonable cost. His system employs high efficiency PV modules plus a set of polished reflectors that concentrate the solar energy and enhance the output of the modules. Dinh incorporated a sun tracking system derived from space tracking technology. It automatically follows the sun throughout the day and turns the modules so that they get maximum exposure to the solar radiation, further enhancing the system efficiency.

Preliminary Failure Modes and Effects Analysis of the US DCLL Test Blanket Module

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee C. Cadwallader

2010-06-01

This report presents the results of a preliminary failure modes and effects analysis (FMEA) of a small tritium-breeding test blanket module design for the International Thermonuclear Experimental Reactor. The FMEA was quantified with “generic” component failure rate data, and the failure events are binned into postulated initiating event families and frequency categories for safety assessment. An appendix to this report contains repair time data to support an occupational radiation exposure assessment for test blanket module maintenance.

Preliminary Failure Modes and Effects Analysis of the US DCLL Test Blanket Module

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee C. Cadwallader

2007-08-01

This report presents the results of a preliminary failure modes and effects analysis (FMEA) of a small tritium-breeding test blanket module design for the International Thermonuclear Experimental Reactor. The FMEA was quantified with “generic” component failure rate data, and the failure events are binned into postulated initiating event families and frequency categories for safety assessment. An appendix to this report contains repair time data to support an occupational radiation exposure assessment for test blanket module maintenance.

Evolutionary and Cognitive Motivations for Fractal Art in Art and Design Education

ERIC Educational Resources Information Center

Joye, Yannick

2005-01-01

Humans are endowed with cognitive modules specialised in processing information about the class of natural things. Due to their naturalness, fractal art and design can contribute to developing these modules, and trigger affective responses that are associated with certain natural objects. It is argued that exposure to fractals in an art and design…

Scaffolding Linguistic and Intercultural Goals in EFL with Simplified Novels and Their Film Adaptations

ERIC Educational Resources Information Center

Zoreda, Margaret Lee; Vivaldo-Lima, Javier

2008-01-01

This article argues that exposure to culture will help students develop complex linguistic and cultural skills. The authors discuss the use of graded literary readers, audio resources, and films. They present a detailed description of the implementation and results of two simplified novel modules in an EFL program. One module was taught to…

Frontal fibrosing alopecia in postmenopausal women.

PubMed

Tosti, Antonella; Piraccini, Bianca Maria; Iorizzo, Matilde; Misciali, Cosimo

2005-01-01

Frontal fibrosing alopecia is a variety of cicatricial alopecia characterized by a band of frontal/frontoparietal hair recession and marked decrease or a complete loss of the eyebrows, typically observed in women who are postmenopausal. The purpose of this study was to report clinical and histopathologic findings and results of treatment in a group of women affected by the disease. A total of 14 women with alopecia of the frontal hairline were evaluated from June 2000 through July 2003 in our outpatient consultation for hair disorders. Clinical examination revealed a band of symmetric recession of the frontoparietal hairline extending to the preauricular areas associated with loss of follicular orifices, mild skin atrophy, and perifollicular erythema at the scalp margin. In all, 9 patients also had partial or total loss of the eyebrows. The histologic features of the scalp specimens were similar in all our patients with a reduction of the number of hair follicles, and a high number of intermediate and velluslike follicles. Intemediate and velluslike follicles were more commonly affected than terminal follicles by the lymphocytic inflammatory infiltrate and perifollicular fibrosis. Frontal fibrosing alopecia is a cicatricial alopecia that follows destruction of hair follicles by an inflammatory lymphocytic infiltrate that is localized around the upper portion of the hair follicle. It differs from lichen planopilaris because the lymphocytic infiltrate and fibrosis affect selectively the intermediate and the velluslike follicles of the frontal margin and eyebrows. The reason for this selective involvement is still unknown. Frontal fibrosing alopecia may represent a variety of lichen planopilaris with selective involvement of certain androgen-dependent areas. The affected follicles may have typical biologic markers that could explain the clinical and histologic features found in the disease. It is interesting to note that some of the patients treated with finasteride (2.5 mg/d) showed an arrest in the progression of the disease. Even if there is no proof for a hormonal basis of the disease, the effectiveness of finasteride in some patients may indicate that androgens might be partially responsible of the pathogenesis of the disease.

Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

PubMed Central

Sutcliffe, Siobhan; Grubb, Robert L.; Platz, Elizabeth A.; Ragard, Lawrence R.; Riley, Thomas L.; Kazin, Sally S.; Hayes, Richard B.; Hsing, Ann W.; Andriole, Gerald L.

2011-01-01

Objectives To investigate the relationship between non-steroidal anti-inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)-related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development. Patients and methods At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate-specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n = 4771). During follow-up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia. Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self-reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥ 30 mL on any follow-up DRE) and elevation in PSA level (> 1.4 ng/mL on any follow-up PSA test). Results Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P = 0.043–0.91) and frequency of use (risk ratio for one category increase in NSAID use = 0.98–1.11, P-trends = 0.10–0.99) with incident BPH/LUTS. Conclusions The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development. PMID:22429766

Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice

NASA Astrophysics Data System (ADS)

Hu, Wei

Background: The medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol exposure is unknown. Here we explored the effects of acamprosate on an attentional set-shifting task, and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons. Methods: We induced alcohol dependence in mice via chronic intermittent ethanol (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2-bottle choice paradigm. Impairments of executive function were assessed in an attentional set-shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol-induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices. Results: Chronic ethanol exposure impaired cognitive flexibility in the attentional set-shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic ethanol exposure increased use-dependent presynaptic transmitter release and enhanced postsynaptic N-methyl-D-aspartate receptor (NMDAR) function. Moreover, CIE-treatment lowered input resistance, and decreased the threshold and the afterhyperpolarization (AHP) of action potentials, suggesting chronic ethanol exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these ethanol-induced changes cellular function. Conclusion: Acamprosate improved attentional control of ethanol exposed animals, but did not alter the concurrent changes in synaptic transmission or membrane excitability of mPFC neurons, indicating that these changes are not the pharmacological targets of acamprosate in the recovery of mPFC functions affected by chronic ethanol exposure.

The 2100MHz radiofrequency radiation of a 3G-mobile phone and the DNA oxidative damage in brain.

PubMed

Sahin, Duygu; Ozgur, Elcin; Guler, Goknur; Tomruk, Arın; Unlu, Ilhan; Sepici-Dinçel, Aylin; Seyhan, Nesrin

2016-09-01

We aimed to evaluate the effect of 2100MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone on the brain of rats during 10 and 40 days of exposure. The female rats were randomly divided into four groups. Group I; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 2 weeks, group II; control 10 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 2 weeks, group III; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 8 weeks and group IV; control 40 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 8 weeks. After the genomic DNA content of brain was extracted, oxidative DNA damage (8-hydroxy-2'deoxyguanosine, pg/mL) and malondialdehyde (MDA, nmoL/g tissue) levels were determined. Our main finding was the increased oxidative DNA damage to brain after 10 days of exposure with the decreased oxidative DNA damage following 40 days of exposure compared to their control groups. Besides decreased lipid peroxidation end product, MDA, was observed after 40 days of exposure. The measured decreased quantities of damage during the 40 days of exposure could be the means of adapted and increased DNA repair mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Exposure to chorioamnionitis alters the monocyte transcriptional response to the neonatal pathogen Staphylococcus epidermidis.

PubMed

de Jong, Emma; Hancock, David G; Wells, Christine; Richmond, Peter; Simmer, Karen; Burgner, David; Strunk, Tobias; Currie, Andrew J

2018-03-13

Preterm infants are uniquely susceptible to late-onset sepsis that is frequently caused by the skin commensal Staphylococcus epidermidis. Innate immune responses, particularly from monocytes, are a key protective mechanism. Impaired cytokine production by preterm infant monocytes is well described, but few studies have comprehensively assessed the corresponding monocyte transcriptional response. Innate immune responses in preterm infants may be modulated by inflammation such as prenatal exposure to histologic chorioamnionitis which complicates 40-70% of preterm pregnancies. Chorioamnionitis alters the risk of late-onset sepsis, but its effect on monocyte function is largely unknown. Here, we aimed to determine the impact of exposure to chorioamnionitis on the proportions and phenotype of cord blood monocytes using flow cytometry, as well as their transcriptional response to live S. epidermidis. RNA-seq was performed on purified cord blood monocytes from very preterm infants (<32 weeks gestation, with and without chorioamnionitis-exposure) and term infants (37-40 weeks), pre- and postchallenge with live S. epidermidis. Preterm monocytes from infants without chorioamnionitis-exposure did not exhibit an intrinsically deficient transcriptional response to S. epidermidis compared to term infants. In contrast, chorioamnionitis-exposure was associated with hypo-responsive transcriptional phenotype regarding a subset of genes involved in antigen presentation and adaptive immunity. Overall, our findings suggest that prenatal exposure to inflammation may alter the risk of sepsis in preterm infants partly by modulation of monocyte responses to pathogens. © 2018 Australasian Society for Immunology Inc.

Exposure fluctuations of astronauts due to orientation

NASA Technical Reports Server (NTRS)

Wilson, John W.; Nealy, John E.; Wood, James S.; Qualls, Gary; Atwell, William; Shinn, Judy L.; Simonsen, Lisa C.

1993-01-01

The dose incurred in an anisotropic environment depends on the orientation of the astronaut's body relative to the direction of the radiation field. The fluctuations in exposure of specific organs due to astronaut orientation are found to be a factor of 2 or more in a typical space habitation module and typical space radiations. An approximation function is found that overestimates astronaut exposure in most cases studied and is recommended as a shield design guide for future space missions.

Relationship between Telomere Length, Genetic Traits and Environmental/Occupational Exposures in Bladder Cancer Risk by Structural Equation Modelling.

PubMed

Pavanello, Sofia; Carta, Angela; Mastrangelo, Giuseppe; Campisi, Manuela; Arici, Cecilia; Porru, Stefano

2017-12-21

Background : Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods : Within the framework of a hospital-based case ( n = 96)/control ( n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results : The SEM analysis indicates negative direct links ( p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk ( p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects ( p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link). Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention.

Relationship between Telomere Length, Genetic Traits and Environmental/Occupational Exposures in Bladder Cancer Risk by Structural Equation Modelling

PubMed Central

Pavanello, Sofia; Carta, Angela; Mastrangelo, Giuseppe; Campisi, Manuela; Porru, Stefano

2017-01-01

Background: Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods: Within the framework of a hospital-based case (n = 96)/control (n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results: The SEM analysis indicates negative direct links (p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk (p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects (p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link). Conclusions: Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention. PMID:29267235

No Effects of Acute Exposure to Wi-Fi Electromagnetic Fields on Spontaneous EEG Activity and Psychomotor Vigilance in Healthy Human Volunteers.

PubMed

Zentai, Norbert; Csathó, Árpád; Trunk, Attila; Fiocchi, Serena; Parazzini, Marta; Ravazzani, Paolo; Thuróczy, György; Hernádi, István

2015-12-01

Mobile equipment use of wireless fidelity (Wi-Fi) signal modulation has increased exponentially in the past few decades. However, there is inconclusive scientific evidence concerning the potential risks associated with the energy deposition in the brain from Wi-Fi and whether Wi-Fi electromagnetism interacts with cognitive function. In this study we investigated possible neurocognitive effects caused by Wi-Fi exposure. First, we constructed a Wi-Fi exposure system from commercial parts. Dosimetry was first assessed by free space radiofrequency field measurements. The experimental exposure system was then modeled based on real geometry and physical characteristics. Specific absorption rate (SAR) calculations were performed using a whole-body, realistic human voxel model with values corresponding to conventional everyday Wi-Fi exposure (peak SAR10g level was 99.22 mW/kg with 1 W output power and 100% duty cycle). Then, in two provocation experiments involving healthy human volunteers we tested for two hypotheses: 1. Whether a 60 min long 2.4 GHz Wi-Fi exposure affects the spectral power of spontaneous awake electroencephalographic (sEEG) activity (N = 25); and 2. Whether similar Wi-Fi exposure modulates the sustained attention measured by reaction time in a computerized psychomotor vigilance test (PVT) (N = 19). EEG data were recorded at midline electrode sites while volunteers watched a silent documentary. In the PVT task, button press reaction time was recorded. No measurable effects of acute Wi-Fi exposure were found on spectral power of sEEG or reaction time in the psychomotor vigilance test. These results indicate that a single, 60 min Wi-Fi exposure does not alter human oscillatory brain function or objective measures of sustained attention.

Redox-Dependent Modulation of Anthocyanin Biosynthesis by the TCP Transcription Factor TCP15 during Exposure to High Light Intensity Conditions in Arabidopsis.

PubMed

Viola, Ivana L; Camoirano, Alejandra; Gonzalez, Daniel H

2016-01-01

TCP proteins integrate a family of transcription factors involved in the regulation of developmental processes and hormone responses. It has been shown that most members of class I, one of the two classes in which the TCP family is divided, contain a conserved Cys that leads to inhibition of DNA binding when oxidized. In this work, we describe that the class-I TCP protein TCP15 inhibits anthocyanin accumulation during exposure of plants to high light intensity by modulating the expression of transcription factors involved in the induction of anthocyanin biosynthesis genes, as suggested by the study of plants that express TCP15 from the 35SCaMV promoter and mutants in TCP15 and the related gene TCP14. In addition, the effect of TCP15 on anthocyanin accumulation is lost after prolonged incubation under high light intensity conditions. We provide evidence that this is due to inactivation of TCP15 by oxidation of Cys-20 of the TCP domain. Thus, redox modulation of TCP15 activity in vivo by high light intensity may serve to adjust anthocyanin accumulation to the duration of exposure to high irradiation conditions. © 2016 American Society of Plant Biologists. All Rights Reserved.

Impact of ionizing radiation exposure on in vitro differentiation of preosteoblastic cell lines

NASA Astrophysics Data System (ADS)

Hu, Yueyuan; Lau, Patrick; Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther

Bone demineralization of astronauts during residence in microgravity is a well known phe-nomenon during space travel. Besides altered gravity conditions, radiation risk is considered to be one of the major health hazards for astronauts in both orbital and interplanetary space. Un-til know, little is known about the effects of space radiation on the skeletal system especially on the bone forming osteoblasts. Accelerator facilities are used to simulate parts of the radiation environment in space. We examined the effects of heavy ion exposure on osteoblastic differ-entiation of murine preosteoblastic cell lines to gain insight into potential cellular mechanisms involved in bone cellular response after exposure to heavy ions. Therefore, we examined gene expression modulation of bone specific transcription factors, osteoblast specific marker genes as well as genes function as coupling factors that link bone resorption to bone formation. mRNA levels were determined using quantitative real time reverse transcriptase PCR (qRT-PCR). Expression of a target gene was standardized to unregulated reference genes. We investigated the transcriptional regulation of Osteocalcin (OCN) as well as TGF-β1, p21(CDKN1A) and the bone specific transcription factor Runx2 (cbfa1). We investigated gene expression modula-tions after exposure to energetic carbon ions (35 MeV/u, 73 keV/µm), iron ions (1000 MeV/u, 150 keV/µm) and lead ions (29 MeV/u, 9600 keV/µm) versus low LET X-rays. X-irradiation dose-dependently increased the mRNA levels of p21(CDKN1A) and Runx2 (cbfa1) whereas expression of OCN and TGF-β1 were elevated at later time points. Exposure to heavy ions provoked a more pronounced effect on osteoblastic specific gene expression within the dif-ferentiation process. Collectively, our results indicate that heavy ions facilitate osteoblastic differentiation more effectively than X-ray. Using the proposed in vitro model we confirmed that exposure to ionizing radiation significantly modulates gene expression levels of marker genes involved in the differentiation of osteoblasts. The data presented allow us to suggest that exposure to ionizing radiation interferes with bone formation at the level of cell differentiation.

Modulation of estrogenic exposure effects via alterations in salinity and dissolved oxygen in male fathead minnows, Pimephales promelas

USDA-ARS?s Scientific Manuscript database

Laboratory exposure data indicate that estrogens and estrogen mimics can cause endocrine disruption in male fathead minnows (Pimephales promelas). In the wild, conditions are not static as is often the case in the laboratory. Changes in water quality parameters, such as salinity influx due to road s...

Chronic Ethanol Exposure Produces Time- and Brain Region-Dependent Changes in Gene Coexpression Networks

PubMed Central

Osterndorff-Kahanek, Elizabeth A.; Becker, Howard C.; Lopez, Marcelo F.; Farris, Sean P.; Tiwari, Gayatri R.; Nunez, Yury O.; Harris, R. Adron; Mayfield, R. Dayne

2015-01-01

Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each region, there was little gene overlap across time (~20%). All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global ‘rewiring‘ of coexpression systems involving glial and immune signaling as well as neuronal genes. PMID:25803291

Lunar Dust Separation for Toxicology Studies

NASA Technical Reports Server (NTRS)

Cooper, Bonnie L.; McKay, D. S.; Riofrio, L. M.; Taylor, L. A.; Gonzalex, C. P.

2010-01-01

During the Apollo missions, crewmembers were briefly exposed to dust in the lunar module, brought in after extravehicular activity. When the lunar ascent module returned to micro-gravity, the dust that had settled on the floor now floated into the air, causing eye discomfort and occasional respiratory symptoms. Because our goal is to set an exposure standard for 6 months of episodic exposure to lunar dust for crew on the lunar surface, these brief exposures of a few days are not conclusive. Based on experience with industrial minerals such as sandblasting quartz, an exposure of several months may cause serious damage, while a short exposure may cause none. The detailed characteristics of sub-micrometer lunar dust are only poorly known, and this is the size range of particles that are of greatest concern. We have developed a method for extracting respirable dust (<2.5 micron) from Apollo lunar soils. This method meets stringent requirements that the soil must be kept dry, exposed only to pure nitrogen, and must conserve and recover the maximum amount of both respirable dust and coarser soil. In addition, we have developed a method for grinding coarser lunar soil to produce sufficient respirable soil for animal toxicity testing while preserving the freshly exposed grain surfaces in a pristine state.

Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

PubMed Central

Ming, Xin; Feng, Yuanming; Liu, Huan; Zhang, Ying; Zhou, Li; Deng, Jun

2015-01-01

Purpose To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years. Methods and Materials A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated. Results The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance. Conclusions Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy. PMID:26630566

Navy Occupational Health Information Management System (NOHIMS). Environmental Exposure Module. Operators’ Guide

DTIC Science & Technology

1987-01-01

be recorded. Obviously, without the close transaction the module cannot maintain the current status of each boundary. 4-1 0% Sle.t SOUNDARY tD NUMBER...HOp: 134 (MIMS) ... 0KI YES//-.. (YES) ARE YOU ADDING A NEW EMPLOYEE (THE 11TH FOR THIS IOUNDARY)9 Y (YES) RESPIRATOR TYPE: 1r~PF HALF FACE, DUST FUME

Direct dark matter search by annual modulation in XMASS-I

NASA Astrophysics Data System (ADS)

Abe, K.; Hiraide, K.; Ichimura, K.; Kishimoto, Y.; Kobayashi, K.; Kobayashi, M.; Moriyama, S.; Nakahata, M.; Norita, T.; Ogawa, H.; Sekiya, H.; Takachio, O.; Takeda, A.; Yamashita, M.; Yang, B. S.; Kim, N. Y.; Kim, Y. D.; Tasaka, S.; Fushimi, K.; Liu, J.; Martens, K.; Suzuki, Y.; Xu, B. D.; Fujita, R.; Hosokawa, K.; Miuchi, K.; Onishi, Y.; Oka, N.; Takeuchi, Y.; Kim, Y. H.; Lee, J. S.; Lee, K. B.; Lee, M. K.; Fukuda, Y.; Itow, Y.; Kegasa, R.; Kobayashi, K.; Masuda, K.; Takiya, H.; Nishijima, K.; Nakamura, S.; Xmass Collaboration

2016-08-01

A search for dark matter was conducted by looking for an annual modulation signal due to the Earth's rotation around the Sun using XMASS, a single phase liquid xenon detector. The data used for this analysis was 359.2 live days times 832 kg of exposure accumulated between November 2013 and March 2015. When we assume Weakly Interacting Massive Particle (WIMP) dark matter elastically scattering on the target nuclei, the exclusion upper limit of the WIMP-nucleon cross section 4.3 ×10-41 cm2 at 8 GeV/c2 was obtained and we exclude almost all the DAMA/LIBRA allowed region in the 6 to 16 GeV/c2 range at ∼10-40 cm2. The result of a simple modulation analysis, without assuming any specific dark matter model but including electron/γ events, showed a slight negative amplitude. The p-values obtained with two independent analyses are 0.014 and 0.068 for null hypothesis, respectively. We obtained 90% C.L. upper bounds that can be used to test various models. This is the first extensive annual modulation search probing this region with an exposure comparable to DAMA/LIBRA.

Effects of 900 MHz radiofrequency radiation on skin hydroxyproline contents.

PubMed

Çam, Semra Tepe; Seyhan, Nesrin; Kavaklı, Cengiz; Çelikbıçak, Ömür

2014-09-01

The present study aimed to investigate the possible effect of pulse-modulated radiofrequency radiation (RFR) on rat skin hydroxyproline content, since skin is the first target of external electromagnetic fields. Skin hydroxyproline content was measured using liquid chromatography mass spectrometer method. Two months old male wistar rats were exposed to a 900 MHz pulse-modulated RFR at an average whole body specific absorption rate (SAR) of 1.35 W/kg for 20 min/day for 3 weeks. The radiofrequency (RF) signals were pulse modulated by rectangular pulses with a repetition frequency of 217 Hz and a duty cycle of 1:8 (pulse width 0.576 ms). A skin biopsy was taken at the upper part of the abdominal costa after the exposure. The data indicated that whole body exposure to a pulse-modulated RF radiation that is similar to that emitted by the global system for mobile communications (GSM) mobile phones caused a statistically significant increase in the skin hydroxyproline level (p = 0.049, Mann-Whitney U test). Under our experimental conditions, at a SAR less than the International Commission on Non-Ionizing Radiation Protection safety limit recommendation, there was evidence that GSM signals could alter hydroxyproline concentration in the rat skin.

Instruction manual, Optical Effects Module, Model OEM

NASA Technical Reports Server (NTRS)

1975-01-01

The Optical Effects Module Model OEM-1, a laboratory prototype instrument designed for the automated measurement of radiation transmission and scattering through optical samples, is described. The system comprises two main components: the Optical Effects Module Enclosure (OEME) and the Optical Effects Module Electronic Controller and Processor (OEMCP). The OEM is designed for operation in the near UV at approximately 2540A, corresponding to the most intense spectral line activated by the mercury discharge lamp used for illumination. The radiation from this source is detected in transmission and reflection through a number of selectable samples. The basic objective of this operation is to monitor in real time the accretion of possible contamination on the surface of these samples. The optical samples are exposed outside of the OEME proper to define exposure conditions and to separate exposure and measurement environments. Changes in the transmissivity of the sample are attributable to surface contamination or to bulk effects due to radiation. Surface contamination will increase radiation scattering due to Rayleigh-Gans effect or to other phenomena, depending on the characteristics size of the particulate contaminants. Thus, also scattering from the samples becomes a part of the measurement program.

New Treatments for Hair Loss.

PubMed

Vañó-Galván, S; Camacho, F

2017-04-01

The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients' quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of topical application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Develop Silicone Encapsulation Systems for Terrestrial Silicon Solar Arrays

NASA Technical Reports Server (NTRS)

1979-01-01

The results of a study for Task 3 of the Low Cost Solar Array Project, directed toward the development of a cost effective encapsulation system for photovoltaic modules using silicon based materials, are reported. Results of the following are discussed: (1) weather-ometer stressing vs. weathering history of silicon and silicon modified materials; (2) humidity/temperature cycling exposure; (3) exposure at high humidity/high temperature; (4) outdoor exposure stress; (5) thermal cycling stress; and (6) UV screening agents. The plans for the next quarter are outlined.

[The interactive neuroanatomical simulation and practical application of frontotemporal transsylvian exposure in neurosurgery].

PubMed

Balogh, Attila; Czigléczki, Gábor; Papal, Zsolt; Preul, Mark C; Banczerowski, Péter

2014-11-30

There is an increased need for new digital education tools in neurosurgical training. Illustrated textbooks offer anatomic and technical reference but do not substitute hands-on experience provided by surgery or cadaver dissection. Due to limited availability of cadaver dissections the need for development of simulation tools has been augmented. We explored simulation technology for producing virtual reality-like reconstructions of simulated surgical approaches on cadaver. Practical application of the simulation tool has been presented through frontotemporal transsylvian exposure. The dissections were performed on two cadaveric heads. Arteries and veins were prepared and injected with colorful silicon rubber. The heads were rigidly fixed in Mayfield headholder. A robotic microscope with two digital cameras in inverted cone method of image acquisition was used to capture images around a pivot point in several phases of dissections. Multilayered, high-resolution images have been built into interactive 4D environment by custom developed software. We have developed the simulation module of the frontotemporal transsylvian approach. The virtual specimens can be rotated or tilted to any selected angles and examined from different surgical perspectives at any stage of dissections. Important surgical issues such as appropriate head positioning or surgical maneuvers to expose deep situated neuroanatomic structures can be simulated and studied by using the module. The simulation module of the frontotemporal transsylvian exposure helps to examine effect of head positioning on the visibility of deep situated neuroanatomic structures and study surgical maneuvers required to achieve optimal exposure of deep situated anatomic structures. The simulation program is a powerful tool to study issues of preoperative planning and well suited for neurosurgical training.

Response of Cultured Neuronal Network Activity After High-Intensity Power Frequency Magnetic Field Exposure

PubMed Central

Saito, Atsushi; Takahashi, Masayuki; Makino, Kei; Suzuki, Yukihisa; Jimbo, Yasuhiko; Nakasono, Satoshi

2018-01-01

High-intensity and low frequency (1–100 kHz) time-varying electromagnetic fields stimulate the human body through excitation of the nervous system. In power frequency range (50/60 Hz), a frequency-dependent threshold of the external electric field-induced neuronal modulation in cultured neuronal networks was used as one of the biological indicator in international guidelines; however, the threshold of the magnetic field-induced neuronal modulation has not been elucidated. In this study, we exposed rat brain-derived neuronal networks to a high-intensity power frequency magnetic field (hPF-MF), and evaluated the modulation of synchronized bursting activity using a multi-electrode array (MEA)-based extracellular recording technique. As a result of short-term hPF-MF exposure (50–400 mT root-mean-square (rms), 50 Hz, sinusoidal wave, 6 s), the synchronized bursting activity was increased in the 400 mT-exposed group. On the other hand, no change was observed in the 50–200 mT-exposed groups. In order to clarify the mechanisms of the 400 mT hPF-MF exposure-induced neuronal response, we evaluated it after blocking inhibitory synapses using bicuculline methiodide (BMI); subsequently, increase in bursting activity was observed with BMI application, and the response of 400 mT hPF-MF exposure disappeared. Therefore, it was suggested that the response of hPF-MF exposure was involved in the inhibitory input. Next, we screened the inhibitory pacemaker-like neuronal activity which showed autonomous 4–10 Hz firing with CNQX and D-AP5 application, and it was confirmed that the activity was reduced after 400 mT hPF-MF exposure. Comparison of these experimental results with estimated values of the induced electric field (E-field) in the culture medium revealed that the change in synchronized bursting activity occurred over 0.3 V/m, which was equivalent to the findings of a previous study that used the external electric fields. In addition, the results suggested that the potentiation of neuronal activity after 400 mT hPF-MF exposure was related to the depression of autonomous activity of pacemaker-like neurons. Our results indicated that the synchronized bursting activity was increased by hPF-MF exposure (E-field: >0.3 V/m), and the response was due to reduced inhibitory pacemaker-like neuronal activity. PMID:29662453

Interventions for female pattern hair loss.

PubMed

van Zuuren, Esther J; Fedorowicz, Zbys; Schoones, Jan

2016-05-26

Female pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). The frontal hair line may or may not be preserved. Hair loss can have a serious psychological impact on women. To determine the efficacy and safety of the available options for the treatment of female pattern hair loss in women. We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (2015, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1872), AMED (from 1985), LILACS (from 1982), PubMed (from 1947), and Web of Science (from 1945). We also searched five trial registries and checked the reference lists of included and excluded studies. We included randomised controlled trials that assessed the efficacy of interventions for FPHL in women. Two review authors independently assessed trial quality, extracted data and carried out analyses. We included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.The included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil. Pooled data from six studies indicated that a greater proportion of participants (157/593) treated with minoxidil (2% and one study with 1%) reported a moderate to marked increase in their hair regrowth when compared with placebo (77/555) (risk ratio (RR) = 1.93, 95% confidence interval (CI) 1.51 to 2.47; moderate quality evidence). These results were confirmed by the investigator-rated assessments in seven studies with 1181 participants (RR 2.35, 95% CI 1.68 to 3.28; moderate quality evidence). Only one study reported on quality of life (QoL) (260 participants), albeit inadequately (low quality evidence). There was an important increase of 13.18 in total hair count per cm² in the minoxidil group compared to the placebo group (95% CI 10.92 to 15.44; low quality evidence) in eight studies (1242 participants). There were 40/407 adverse events in the twice daily minoxidil 2% group versus 28/320 in the placebo group (RR 1.24, 95% CI 0.82 to 1.87; low quality evidence). There was also no statistically significant difference in adverse events between any of the individual concentrations against placebo.Four studies (1006 participants) evaluated minoxidil 2% versus 5%. In one study, 25/57 participants in the minoxidil 2% group experienced moderate to greatly increased hair regrowth versus 22/56 in the 5% group (RR 1.12, 95% CI 0.72 to 1.73). In another study, 209 participants experienced no difference based on a visual analogue scale (P = 0.062; low quality evidence). The assessments of the investigators based on three studies (586 participants) were in agreement with these findings (moderate quality evidence). One study assessed QoL (209 participants) and reported limited data (low quality evidence). Four trials (1006 participants) did not show a difference in number of adverse events between the two concentrations (RR 1.02, 95% CI 0.91 to 1.20; low quality evidence). Both concentrations did not show a difference in increase in total hair count at end of study in three trials with 631 participants (mean difference (MD) -2.12, 95% CI -5.47 to 1.23; low quality evidence).Three studies investigated finasteride 1 mg compared to placebo. In the finasteride group 30/67 participants experienced improvement compared to 33/70 in the placebo group (RR 0.95, 95% CI 0.66 to 1.37; low quality evidence). This was consistent with the investigators' assessments (RR 0.77, 95% CI 0.31 to 1.90; low quality evidence). QoL was not assessed. Only one study addressed adverse events (137 participants) (RR 1.03, 95% CI 0.45 to 2.34; low quality evidence). In two studies (219 participants) there was no clinically meaningful difference in change of hair count, whilst one study (12 participants) favoured finasteride (low quality evidence).Two studies (141 participants) evaluated low-level laser comb therapy compared to a sham device. According to the participants, the low-level laser comb was not more effective than the sham device (RR 1.54, 95% CI 0.96 to 2.49; and RR 1.18, 95% CI 0.74 to 1.89; moderate quality evidence). However, there was a difference in favour of low-level laser comb for change from baseline in hair count (MD 17.40, 95% CI 9.74 to 25.06; and MD 17.60, 95% CI 11.97 to 23.23; low quality evidence). These studies did not assess QoL and did not report adverse events per treatment arm and only in a generic way (low quality evidence). Low-level laser therapy against sham comparisons in two separate studies also showed an increase in total hair count but with limited further data.Single studies addressed the other comparisons and provided limited evidence of either the efficacy or safety of these interventions, or were unlikely to be examined in future trials. Although there was a predominance of included studies at unclear to high risk of bias, there was evidence to support the efficacy and safety of topical minoxidil in the treatment of FPHL (mainly moderate to low quality evidence). Furthermore, there was no difference in effect between the minoxidil 2% and 5% with the quality of evidence rated moderate to low for most outcomes. Finasteride was no more effective than placebo (low quality evidence). There were inconsistent results in the studies that evaluated laser devices (moderate to low quality evidence), but there was an improvement in total hair count measured from baseline.Further randomised controlled trials of other widely-used treatments, such as spironolactone, finasteride (different dosages), dutasteride, cyproterone acetate, and laser-based therapy are needed.

Training - Apollo-Soyuz Test Project (ASTP) - JSC

NASA Image and Video Library

1975-07-12

S75-28485 (12 July 1975) --- Astronaut Vance D. Brand, command module pilot of the American ASTP prime crew, practices operating a Docking Module hatch during Apollo-Soyuz Test Project preflight training at NASA's Johnson Space Center. The Docking Module is designed to link the Apollo and Soyuz spacecraft during their docking mission in Earth orbit. Gary L. Doerre of JSC?s Crew Training and Procedures Division is working with Brand. Doerre is wearing a face mask to help prevent possible exposure to Brand of disease prior to the ASTP launch.

A role for the serotonin reuptake transporter in the brain and intestinal features of autism spectrum disorders and developmental antidepressant exposure.

PubMed

Margolis, Kara Gross

2017-10-01

Many disease conditions considered CNS-predominant harbor significant intestinal comorbidities. Serotonin (5-HT) and the serotonin reuptake transporter (SERT) have increasingly been shown to play important roles in both brain and intestinal development and long-term function. 5-HT and SERT may thus modulate critical functions in the development and perpetuation of brain-gut axis disease. We discuss the potential roles of 5-HT and SERT in the brain and intestinal manifestations of autism spectrum disorders and developmental antidepressant exposure. The potential therapeutic value of 5-HT 4 modulation in the subsequent treatment of these conditions is also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Mir Environmental Effects Payload and Returned Mir Solar Panel Cleanliness

NASA Technical Reports Server (NTRS)

Harvey, Gale A.; Humes, Donald H.; Kinard, William H.

2000-01-01

The MIR Environmental Effects Payload (MEEP) was attached to the Docking Module of the MIR space station for 18 months during calendar years 1996 and 1997 (March 1996, STS 76 to October 1997, STS 86). A solar panel array with more than 10 years space exposure was removed from the MIR core module in November 1997, and returned to Earth in January, 1998, STS 89. MEEP and the returned solar array are part of the International Space Station (ISS) Risk Mitigation Program. This space flight hardware has been inspected and studied by teams of space environmental effects (SEE) investigators for micrometeoroid and space debris effects, space exposure effects on materials, and electrical performance. This paper reports changes in cleanliness of parts of MEEP and the solar array due to the space exposures. Special attention is given to the extensive water soluble residues deposited on some of the flight hardware surfaces. Directionality of deposition and chemistry of these residues are discussed.

November 2013 Analysis of High Energy Electrons on the Japan Experimental Module (JEM: Kibo)

NASA Technical Reports Server (NTRS)

Badavi, Francis F.; Matsumoto, Haruhisa; Koga, Kiyokazu; Mertens, Christopher J.; Slaba, Tony C.; Norbury, John W.

2015-01-01

Albedo (precipitating/splash) electrons, created by galactic cosmic rays (GCR) interaction with the upper atmosphere move upwards away from the surface of the earth. In the past validation work these particles were often considered to have negligible contribution to astronaut radiation exposure on the International Space Station (ISS). Estimates of astronaut exposure based on the available Computer Aided Design (CAD) models of ISS consistently underestimated measurements onboard ISS when the contribution of albedo particles to exposure were neglected. Recent measurements of high energy electrons outside ISS Japan Experimental Module (JEM) using Exposed Facility (EF), Space Environment Data Acquisition Equipment - Attached Payload (SEDA-AP) and Standard DOse Monitor (SDOM), indicates the presence of high energy electrons at ISS altitude. In this presentation the status of these energetic electrons is reviewed and mechanism for the creation of these particles inside/outside South Atlantic Anomaly (SAA) region explained. In addition, limited dosimetric evaluation of these electrons at 600 MeV and 10 GeV is presented.

Damage/Danger Associated Molecular Patterns (DAMPs) Modulate Chlamydia pecorum and C. trachomatis Serovar E Inclusion Development In Vitro.

PubMed

Leonard, Cory Ann; Schoborg, Robert V; Borel, Nicole

2015-01-01

Persistence, more recently termed the chlamydial stress response, is a viable but non-infectious state constituting a divergence from the characteristic chlamydial biphasic developmental cycle. Damage/danger associated molecular patterns (DAMPs) are normal intracellular components or metabolites that, when released from cells, signal cellular damage/lysis. Purine metabolite DAMPs, including extracellular ATP and adenosine, inhibit chlamydial development in a species-specific manner. Viral co-infection has been shown to reversibly abrogate Chlamydia inclusion development, suggesting persistence/chlamydial stress. Because viral infection can cause host cell DAMP release, we hypothesized DAMPs may influence chlamydial development. Therefore, we examined the effect of extracellular ATP, adenosine, and cyclic AMP exposure, at 0 and 14 hours post infection, on C. pecorum and C. trachomatis serovar E development. In the absence of de novo host protein synthesis, exposure to DAMPs immediately post or at 14 hours post infection reduced inclusion size; however, the effect was less robust upon 14 hours post infection exposure. Additionally, upon exposure to DAMPs immediately post infection, bacteria per inclusion and subsequent infectivity were reduced in both Chlamydia species. These effects were reversible, and C. pecorum exhibited more pronounced recovery from DAMP exposure. Aberrant bodies, typical in virus-induced chlamydial persistence, were absent upon DAMP exposure. In the presence of de novo host protein synthesis, exposure to DAMPs immediately post infection reduced inclusion size, but only variably modulated chlamydial infectivity. Because chlamydial infection and other infections may increase local DAMP concentrations, DAMPs may influence Chlamydia infection in vivo, particularly in the context of poly-microbial infections.

The modulation role of serotonin in Pacific oyster Crassostrea gigas in response to air exposure.

PubMed

Dong, Wenjing; Liu, Zhaoqun; Qiu, Limei; Wang, Weilin; Song, Xiaorui; Wang, Xiudan; Li, Yiqun; Xin, Lusheng; Wang, Lingling; Song, Linsheng

2017-03-01

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a critical neurotransmitter in the neuroendocrine-immune regulatory network and involved in regulation of the stress response in vertebrates and invertebrates. In the present study, serotonin was found to be widely distributed in the tissues of Pacific oyster Crassostrea gigas, including haemolymph, gonad, visceral ganglion, mantle, gill, labial palps and hepatopancreas, and its concentration increased significantly in haemolymph and mantle after the oysters were exposed to air for 1 d. The apoptosis rate of haemocytes was significantly declined after the oysters received an injection of extra serotonin, while the activity of superoxide dismutase (SOD) in haemolymph increased significantly. After the stimulation of serotonin during air exposure, the apoptosis rate of oyster haemocytes and the concentration of H 2 O 2 in haemolymph were significantly decreased, while the SOD activity was significantly elevated. Furthermore, the survival rate of oysters from 4 th to 6 th d after injection of serotonin was higher than that of FSSW group and air exposure group. The results clearly indicated that serotonin could modulate apoptotic effect and redox during air exposure to protect oysters from stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of UV/ozone treatment on polystyrene dielectric and its application on organic field-effect transistors

PubMed Central

2014-01-01

The influence of UV/ozone treatment on the property of polystyrene (PS) dielectric surface was investigated, and pentacene organic field-effect transistors (OFETs) based on the treated dielectric was fabricated. The dielectric and pentacene active layers were characterized by atomic force microscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy. The results showed that, at short UVO exposure time (<10 s), the chemical composition of PS dielectric surface remained the same. While at long UVO exposure time (>60 s), new chemical groups, including alcohol/ether, carbonyl, and carboxyl/ester groups, were formed. By adjusting the UVO exposure time to 5 s, the hole mobility of the OFETs increased to 0.52 cm2/Vs, and the threshold voltage was positively shifted to -12 V. While the time of UVO treatment exceeded 30 s, the mobility started to shrink, and the off-current was enlarged. These results indicate that, as a simple surface treatment method, UVO treatment could quantitatively modulate the property of PS dielectric surface by controlling the exposure time, and thus, pioneered a new way to modulate the characteristics of organic electronic devices. PMID:25258603

The heart as an extravascular target of endothelin-1 in ...

EPA Pesticide Factsheets

Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction have been explored, though linkage with specific factors or genes remains limited. Given evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction, the present review highlights the emerging role of endothelins as mediators of cardiac dysfunction following particulate matter exposure. Endothelin-1 is a small multifunctional protein expressed in the pulmonary and cardiovascular system, known for its ability to constrict blood vessels. Although endothelin-1 can also directly and indirectly (via secondary signaling events) modulate cardiac contractility, heart rate, and rhythm, research on the role of endothelins in the context of air pollution has tended to focus on the vascular effects. The plausibility of endothelin as a mechanism underlying particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. Extravascular effects of endothelin on the heart could better explain one mechanism by which particulate matter exposure may lead to cardiac dysfunction. We propose and support the novel hypothesis that autocrine/paracrine signaling systems, such as endothelins, mediate cardiac

Role of Autonomic Reflex Arcs in Cardiovascular Responses to Air Pollution Exposure

PubMed Central

Hazari, Mehdi S.; Farraj, Aimen K.

2016-01-01

The body responds to environmental stressors by triggering autonomic reflexes in the pulmonary receptors, baroreceptors, and chemoreceptors to maintain homeostasis. Numerous studies have shown that exposure to various gases and airborne particles can alter the functional outcome of these reflexes, particularly with respect to the cardiovascular system. Modulation of autonomic neural input to the heart and vasculature following direct activation of sensory nerves in the respiratory system, elicitation of oxidative stress and inflammation, or through other mechanisms is one of the primary ways that exposure to air pollution affects normal cardiovascular function. Any homeostatic process that utilizes the autonomic nervous system to regulate organ function might be affected. Thus, air pollution and other inhaled environmental irritants have the potential to alter both local airway function and baro-and chemoreflex responses, which modulate autonomic control of blood pressure and detect concentrations of key gases in the body. While each of these reflex pathways causes distinct responses, the systems are heavily integrated and communicate through overlapping regions of the brainstem to cause global effects. This short review summarizes the function of major pulmonary sensory receptors, baroreceptors, and carotid body chemoreceptors and discusses the impacts of air pollution exposure on these systems. PMID:25123706

Automatic exposure control in CT: the effect of patient size, anatomical region and prescribed modulation strength on tube current and image quality.

PubMed

Papadakis, Antonios E; Perisinakis, Kostas; Damilakis, John

2014-10-01

To study the effect of patient size, body region and modulation strength on tube current and image quality on CT examinations that use automatic tube current modulation (ATCM). Ten physical anthropomorphic phantoms that simulate an individual as neonate, 1-, 5-, 10-year-old and adult at various body habitus were employed. CT acquisition of head, neck, thorax and abdomen/pelvis was performed with ATCM activated at weak, average and strong modulation strength. The mean modulated mAs (mAsmod) values were recorded. Image noise was measured at selected anatomical sites. The mAsmod recorded for neonate compared to 10-year-old increased by 30 %, 14 %, 6 % and 53 % for head, neck, thorax and abdomen/pelvis, respectively, (P < 0.05). The mAsmod was lower than the preselected mAs with the exception of the 10-year-old phantom. In paediatric and adult phantoms, the mAsmod ranged from 44 and 53 for weak to 117 and 93 for strong modulation strength, respectively. At the same exposure parameters image noise increased with body size (P < 0.05). The ATCM system studied here may affect dose differently for different patient habitus. Dose may decrease for overweight adults but increase for children older than 5 years old. Care should be taken when implementing ATCM protocols to ensure that image quality is maintained. • ATCM efficiency is related to the size of the patient's body. • ATCM should be activated without caution in overweight adult individuals. • ATCM may increase radiation dose in children older than 5 years old. • ATCM efficiency depends on the protocol selected for a specific anatomical region. • Modulation strength may be appropriately tuned to enhance ATCM efficiency.

Analysis of twelve-month degradation in three polycrystalline photovoltaic modules

NASA Astrophysics Data System (ADS)

Lai, T.; Potter, B. G.; Simmons-Potter, K.

2016-09-01

Polycrystalline silicon photovoltaic (PV) modules have the advantage of lower manufacturing cost as compared to their monocrystalline counterparts, but generally exhibit both lower initial module efficiencies and more significant early-stage efficiency degradation than do similar monocrystalline PV modules. For both technologies, noticeable deterioration in power conversion efficiency typically occurs over the first two years of usage. Estimating PV lifetime by examining the performance degradation behavior under given environmental conditions is, therefore, one of continual goals for experimental research and economic analysis. In the present work, accelerated lifecycle testing (ALT) on three polycrystalline PV technologies was performed in a full-scale, industrial-standard environmental chamber equipped with single-sun irradiance capability, providing an illumination uniformity of 98% over a 2 x 1.6m area. In order to investigate environmental aging effects, timedependent PV performance (I-V characteristic) was evaluated over a recurring, compressed day-night cycle, which simulated local daily solar insolation for the southwestern United States, followed by dark (night) periods. During a total test time of just under 4 months that corresponded to a year equivalent exposure on a fielded module, the temperature and humidity varied in ranges from 3°C to 40°C and 5% to 85% based on annual weather profiles for Tucson, AZ. Removing the temperature de-rating effect that was clearly seen in the data enabled the computation of normalized efficiency degradation with time and environmental exposure. Results confirm the impact of environmental conditions on the module long-term performance. Overall, more than 2% efficiency degradation in the first year of usage was observed for all thee polycrystalline Si solar modules. The average 5-year degradation of each PV technology was estimated based on their determined degradation rates.

Testing flat plate photovoltaic modules for terrestrial environment

NASA Technical Reports Server (NTRS)

Hoffman, A. R.; Arnett, J. C.; Ross, R. G., Jr.

1979-01-01

New qualification tests have been developed for flat plate photovoltaic modules. Temperature cycling, cyclic pressure load, and humidity exposure are especially useful for detecting design and fabrication deficiencies. There is positive correlation between many of the observed field effects, such as power loss, and qualification test induced degradation. The status of research efforts for the development of test methodology for field-related problems is reviewed.

Space Environment Effects on Materials at Different Positions and Operational Periods of ISS

NASA Astrophysics Data System (ADS)

Kimoto, Yugo; Ichikawa, Shoichi; Miyazaki, Eiji; Matsumoto, Koji; Ishizawa, Junichiro; Shimamura, Hiroyuki; Yamanaka, Riyo; Suzuki, Mineo

2009-01-01

A space materials exposure experiment was condcuted on the exterior of the Russian Service Module (SM) of the International Space Station (ISS) using the Micro-Particles Capturer and Space Environment Exposure Device (MPAC&SEED) of the Japan Aerospace Exploration Agency (JAXA). Results reveal artificial environment effects such as sample contamination, attitude change effects on AO fluence, and shading effects of UV on ISS. The sample contamination was coming from ISS components. The particles attributed to micrometeoroids and/or debris captured by MPAC might originate from the ISS solar array. Another MPAC&SEED will be aboard the Exposure Facility of the Japanese Experiment Module, KIBO Exposure Facility (EF) on ISS. The JEM/MPAC&SEED is attached to the Space Environment Data Acquisition Equipment-Attached Payload (SEDA-AP) and is exposed to space. Actually, SEDA-AP is a payload on EF to be launched by Space Shuttle flight 2J/A. In fact, SEDA-AP has space environment monitors such as a high-energy particle monitor, atomic oxygen monitor, and plasma monitor to measure in-situ natural space environment data during JEM/MPAC&SEED exposure. Some exposure samples for JEM/MPAC&SEED are identical to SM/MPAC&SEED samples. Consequently, effects on identical materials at different positions and operation periods of ISS will be evaluated. This report summarizes results from space environment monitoring samples for atomic oxygen analysis on SM/MPAC&SEED, along with experimental plans for JEM/MPAC&SEED.

Effect of space relevant radiation exposure on differentiation and mineralization of murine osteoprogenitor cells

NASA Astrophysics Data System (ADS)

Lau, Patrick; Hu, Yueyuan; Hellweg, Christine; Baumstark-Khan, Christa; Reitz, Guenther

Extended exposure to altered gravity conditions like during long-term space flight results in significant bone loss. Exposure to ionizing radiation for cancer therapy causes bone damage and may increase the risk of fractures. Similarly, besides altered gravity conditions, astronauts on exploratory missions beyond low-Earth orbit will be exposed to high-energy heavy ions in addition to proton and photon radiation, although for prolonged periods and at lower doses and dose rates compared with therapy. Space conditions may place astronauts at a greater risk for mission-critical fractures. Until now, little is known about the effects of space radiation on the skeletal system especially on osteoprogenitor cells. Accelerator facilities are used to simulate parts of the radiation environment in space. Heavy ion accelerators therefore could be used to assess radiation risks for astronauts who will be exposed to higher radiation doses e.g. on a Mars mission. The aim of the present study was to determine the biological effects of spaceflight-relevant radiation exposure on the cellular level using murine osteoprogenitor cell lines compared to nonirradiated controls. To gain a deeper understanding of bone cell differenti-ation and mineralization after exposure to heavy ions, we examined gene expression modulation of bone specific transcription factors, osteoblast specific marker genes as well as genes function as coupling factors that link bone resorption to bone formation. We investigated the transcrip-tional modulation of type I collagen (Col I), osteocalcin (Ocn), Transforming growth factor-β1 (TGF-β1), interleukin-6 (IL-6) and the bone specific transcription factor Runx2 (Cbfa1). To gain deeper insight into potential cellular mechanisms involved in cellular response after ex-posure to heavy ions, we investigated gene expression modulations after exposure to energetic carbon ions (35 MeV/u, 73.2 keV/µm), iron ions (1000 MeV/u, 150 keV/µm) and lead ions (29 MeV/u, 9600 keV/µm) versus low LET X-rays. Exposure to X-irradiation dose-dependently increased the mRNA levels of Runx2 (cbfa1) whereas expression values of OCN and TGF-β1 were elevated at later time points. Exposure to heavy ions provoked a more marked effect on bone specific gene expression within the differentiation process. Collectively, our results indi-cate that heavy ions facilitate differentiation more effectively than X-rays as a major response in the progeny of irradiated osteoprogenitor cells. The data presented allow us to suggest that exposure to ionizing radiation interferes with bone formation at the level of cellular differenti-ation. In this regard, further experiments are needed to investigate gene expression patterns in mammalian cells that respond to differentiation after exposure to ionizing radiation.

Ursolic acid differentially modulates apoptosis in skin melanoma and retinal pigment epithelial cells exposed to UV-VIS broadband radiation.

PubMed

Lee, Yuan-Hao; Wang, Exing; Kumar, Neeru; Glickman, Randolph D

2014-05-01

The signaling pathways via mTOR (mammalian target of rapamycin) and AMPK (AMP-activated protein kinase) play key roles in transcription, translation and carcinogenesis, and may be activated by light exposure. These pathways can be modulated by naturally occurring compounds, such as the triterpenoid, ursolic acid (UA). Previously, the transcription factors p53 and NF-κB, which transactivate mitochondrial apoptosis-related genes, were shown to be differentially modulated by UA. UA-modulated apoptosis, following exposure to UV-VIS radiation (ultraviolet to visible light broadband radiation, hereafter abbreviated to UVR), is observed to correspond to differential levels of oxidative stress in retinal pigment epithelial (RPE) and skin melanoma (SM) cells. The cellular response to this phytochemical was characterized using western blot, flow cytometry, microscopy with reactive oxidative species probes MitoTracker and dihydroethidium, and membrane permeability assay. UA pretreatment potentiated cell cycle arrest and UVR-induced apoptosis selectively in SM cells while reducing photo-oxidative stress in the DNA of RPE cells presumably by antioxidant activity of UA. Mechanistically, the nuclear transportation of p65 and p53 was reduced by UA administration prior to UVR exposure while the levels of p65 and p53 nuclear transportation in SM cells were sustained at a substantially higher level. Finally, the mitochondrial functional assay showed that UVR induced the collapse of the mitochondrial membrane potential, and this effect was exacerbated by rapamycin or UA pretreatment in SM preferentially. These results were consistent with reduced proliferation observed in the clonogenic assay, indicating that UA treatment enhanced the phototoxicity of UVR, by modulating the activation of p53 and NF-κB and initiating a mitogenic response to optical radiation that triggered mitochondria-dependent apoptosis, particularly in skin melanoma cells. The study indicates that this compound has multiple actions with the potential for protecting normal cells while sensitizing skin melanoma cells to UV irradiation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osterwald, C. R.; Anderberg, A.; Rummel, S.

We present an analysis of the results of a solar weathering program that found a linear relationship between maximum power degradation and the total UV exposure dose for four different types of commercial crystalline Si modules. The average degradation rate for the four modules types was 0.71% per year. The analysis showed that losses of short-circuit current were responsible for the maximum power degradation. Judging by the appearance of the undegraded control modules, it is very doubtful that the short-circuit current losses were caused by encapsulation browning or obscuration. When we compared the quantum efficiency of a single cell inmore » a degraded module to one from an unexposed control module, it appears that most of the degradation has occurred in the 800 - 1100 nm wave-length region, and not the short wavelength region.« less

Effects of GSM modulated radio-frequency electromagnetic radiation on permeability of blood-brain barrier in male & female rats.

PubMed

Sırav, Bahriye; Seyhan, Nesrin

2016-09-01

With the increased use of mobile phones, their biological and health effects have become more important. Usage of mobile phones near the head increases the possibility of effects on brain tissue. This study was designed to investigate the possible effects of pulse modulated 900MHz and 1800MHz radio-frequency radiation on the permeability of blood-brain barrier of rats. Study was performed with 6 groups of young adult male and female wistar albino rats. The permeability of blood-brain barrier to intravenously injected evans blue dye was quantitatively examined for both control and radio-frequency radiarion exposed groups. For male groups; Evans blue content in the whole brain was found to be 0.08±0.01mg% in the control, 0.13±0.03mg% in 900MHz exposed and 0.26±0.05mg% in 1800MHz exposed animals. In both male radio-frequency radiation exposed groups, the permeability of blood-brain barrier found to be increased with respect to the controls (p<0.01). 1800MHz pulse modulated radio-frequency radiation exposure was found more effective on the male animals (p<0.01). For female groups; dye contents in the whole brains were 0.14±0.01mg% in the control, 0.24±0.03mg% in 900MHz exposed and 0.14±0.02mg% in 1800MHz exposed animals. No statistical variance found between the control and 1800MHz exposed animals (p>0.01). However 900MHz pulse modulated radio-frequency exposure was found effective on the permeability of blood-brain barrier of female animals. Results have shown that 20min pulse modulated radio-frequency radiation exposure of 900MHz and 1800MHz induces an effect and increases the permeability of blood-brain barrier of male rats. For females, 900MHz was found effective and it could be concluded that this result may due to the physiological differences between female and male animals. The results of this study suggest that mobile phone radation could lead to increase the permeability of blood-brain barrier under non-thermal exposure levels. More studies are needed to demonstrate the mechanisms of that breakdown. Copyright © 2015 Elsevier B.V. All rights reserved.

Leadership, cohesion, morale, and the mental health of UK Armed Forces in Afghanistan.

PubMed

Jones, Norman; Seddon, Rachel; Fear, Nicola T; McAllister, Pete; Wessely, Simon; Greenberg, Neil

2012-01-01

UK Armed Forces (AF) personnel deployed to Afghanistan are frequently exposed to intense combat and yet little is known about the short-term mental health consequences of this exposure and the potential mitigating effects of military factors such as cohesion, morale, and leadership. To assess the possible modulating influence of cohesion, morale, and leadership on post-traumatic stress disorder (PTSD) symptoms and common mental disorders resulting from combat exposure among UK AF personnel deployed to Afghanistan, UK AF personnel, during their deployment to Afghanistan in 2010, completed a self-report survey about aspects of their current deployment, including perceived levels of cohesion, morale, leadership, combat exposure, and their mental health status. Outcomes were symptoms of common mental disorder and symptoms of PTSD. Combat exposure was associated with both PTSD symptoms and symptoms of common mental disorder. Of the 1,431 participants, 17.1% reported caseness levels of common mental disorder, and 2.7% were classified as probable PTSD cases. Greater self-reported levels of unit cohesion, morale, and perceived good leadership were all associated with lower levels of common mental disorder and PTSD. Greater levels of unit cohesion, morale, and good leadership may help to modulate the effects of combat exposure and the subsequent development of mental health problems among UK Armed Forces personnel deployed to Afghanistan. © 2012 Guilford Publications, Inc.

In hamsters the D1 receptor antagonist SCH23390 depresses ventilation during hypoxia.

PubMed

Schlenker, Evelyn H

2008-01-02

During exposure of animals to hypoxia, brain and blood dopamine levels increase stimulating dopaminergic receptors which influence the integrated ventilatory response to low oxygen. The purpose of the present study is to test the hypothesis that in conscious hamsters, systemic antagonism of D(1) receptors would depress their breathing in air and in response to hypoxic and hypercapnic challenges. Nine male hamsters were treated with saline or 0.25 mg/kg SCH-23390 (SCH), a D(1) receptor antagonist that crosses the blood-brain barrier. Ventilation was determined using the barometric method, and oxygen consumption and CO(2) production were evaluated utilizing the flow-through method. During exposure to air, SCH decreased frequency of breathing. During exposure to hypoxia (10% oxygen in nitrogen), relative to saline, SCH-treated hamsters decreased minute ventilation by decreasing tidal volume and oxygen consumption but not CO(2) production. During exposure to hypercapnia (5% CO(2) in 95% O(2)), frequency of breathing was decreased with SCH, but there was no significant effect on minute ventilation. Relative to saline treatment body temperature was lower in SCH-treated hamsters by 0.6 degrees C. These results demonstrate that in hamsters D(1) receptors can modulate control of ventilation in air and during hypoxia and hypercapnic exposures. Whether D(1) receptors located centrally or on carotid bodies modulate these effects is not clear from this study.

Modulation of the antioxidative response of Spartina densiflora against iron exposure.

PubMed

Martínez Domínguez, David; Torronteras Santiago, Rafael; Córdoba García, Francisco

2009-06-01

Spartina densiflora, an invader cordgrass living in polluted salt marshes of the Odiel estuary (SW Spain), was collected and cultured under controlled laboratory conditions. After acclimation to non-polluted soils for 28 days, both metabolites and enzymes activities used as indicators of oxidative stress were reduced significantly. Then, plants were exposed to 500 and 1000 ppm Fe-ethylenediamine-N,N'-2-hydroxyphenyl acetic acid (EDDHA) for 28 days. Our data demonstrate that iron content in leaves was enhanced by iron exposure. This iron increase caused an enhancement in the concentration of H2O2, hydroperoxides and lipid peroxidation, and a decrease in chlorophyll levels. Thus, iron exposure led to oxidative stress conditions. However, oxidative indicators stabilised after first 2 weeks of exposure, although the highest iron levels in leaves were reached at the end of treatments. Iron exposure induced an enhancement of catalase, ascorbate peroxidase and guaiacol peroxidase activities, together with an increase in total and oxidised ascorbate. This response may be defensive against oxidative stress and thus help to explain why cell oxidative damages were stabilised. Thus, by using a sensitive long-time protocol, iron-dependent oxidative damages may be controlled and even reverted successfully by the activation of the antioxidative defences of S. densiflora. This efficient antioxidative system, rapidly modulated in response to excess iron and other environmental stressors, may account for S. densiflora's successful adaptation to stress conditions in its habitat.

Effects of methamphetamine exposure on anxiety-like behavior in the open field test, corticosterone, and hippocampal tyrosine hydroxylase in adolescent and adult mice.

PubMed

Struntz, Katelyn H; Siegel, Jessica A

2018-08-01

Methamphetamine (MA) is a psychomotor stimulant drug that can alter behavior, the stress response system, and the dopaminergic system. The effects of MA can be modulated by age, however relatively little research has examined the acute effects of MA in adolescents and how the effects compare to those found in adults. The hippocampal dopamine system is altered by MA exposure and can modulate anxiety-like behavior, but the effects of MA on the hippocampal dopamine system have not been well studied, especially in adolescent animals. In order to assess potential age differences in the effects of MA exposure, this research examined the effects of acute MA exposure on locomotor and anxiety-like behavior in the open field test, plasma corticosterone levels, and hippocampal total tyrosine hydroxylase and phosphorylated tyrosine hydroxylase levels in adolescent and adult male C57BL/6 J mice. Tyrosine hydroxylase is the rate limiting enzyme in the synthesis of dopamine and was used as a marker of the hippocampal dopaminergic system. Mice were exposed to saline or 4 mg/kg MA and locomotor and anxiety-like behavior were measured in the open field test. Serum and brains were collected immediately after testing and plasma corticosterone and hippocampal total tyrosine hydroxylase and phosphorylated tyrosine hydroxylase levels measured. MA-exposed mice showed increased locomotor activity and anxiety-like behavior in the open field test compared with saline controls, regardless of age. There was no effect of MA on plasma corticosterone levels or hippocampal total tyrosine hydroxylase or phosphorylated tyrosine hydroxylase levels in either adolescent or adult mice. These data suggest that acute MA exposure during adolescence and adulthood increases locomotor activity and anxiety-like behavior but does not alter plasma corticosterone levels or hippocampal total tyrosine hydroxylase or phosphorylated tyrosine hydroxylase levels, and that these effects are not modulated by age. Copyright © 2018 Elsevier B.V. All rights reserved.

Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit.

PubMed

Ganon-Elazar, Eti; Akirav, Irit

2013-09-01

Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis (Ganon-Elazar and Akirav, 2012). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). Here we examined whether cannabinoid receptor activation in a putative brain circuit that includes the BLA, hippocampus and prefrontal cortex (PFC), could prevent the effects of traumatic stress on contextual fear extinction and alterations in glucocorticoid receptor (GR) protein levels. We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

PubMed Central

Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

2015-01-01

Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects. PMID:26483631

Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

PubMed

Scarduzio, Mariangela; Panichi, Roberto; Pettorossi, Vito Enrico; Grassi, Silvarosa

2013-01-01

Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

STRESS RESPONSE STUDIES USING ANIMAL MODELS

EPA Science Inventory

This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

James Webb Space Telescope (JWST) Integrated Sciene Instrument Module (ISIM) Cryo-Vac 3 (CV3) Thermal Vacuum Test

NASA Technical Reports Server (NTRS)

Packard, Ed

2016-01-01

This presentation describes the test objectives, test summary, test configuration and test performance of the James Webb Space Telescope Integrated Science Instrument Module CryoVac 3 Thermal Vacuum Test. Verify the ISIM System in its final configuration after environmental exposure and provide a post-environmental performance baseline, including critical ground calibrations needed for science data processing in flight.

Ketoconazole and the modulation of multidrug resistance-mediated transport in Caco-2 and MDCKII-MDR1 drug transport models.

PubMed

Fan, Y; Rodriguez-Proteau, R

2008-02-01

The hypothesis tested was that ketoconazole can modulate P-glycoprotein, thereby altering cellular uptake and apparent permeability (P(app)) of multidrug-resistant substrates, such as cyclosporin A (CSA) and digoxin, across Caco-2, MDCKII-MDR1, and MDCKII wild-type cell transport models. (3)H-CSA/(3)H-digoxin transport experiments were performed with and without co-exposure to ketoconazole, and (3)H-ketoconzole transport experiments were performed with and without co-exposure to dietary flavonoids, epigallocatechin-3-gallate, and xanthohumol. Ketoconazole (3 microM) reduced the P(app) efflux of CSA and digoxin from 5.07 x 10(-6) to 2.91 x 10(-6) cm s(-1) and from 2.60 x 10(-6) to 1.41 x 10(-6) cm s(-1), respectively, in Caco-2 cells. In the MDCKII-MDR1 cells, ketoconazole reduced the P(app) efflux of CSA and increased the P(app) absorption of digoxin. Cellular uptake of ketoconazole in the Caco-2 cells was significantly inhibited by CSA and digoxin, whereas epigallocatechin-3-gallate and xanthohumol exhibited biphasic responses. In conclusion, ketoconazole modulates the P(app) of P-glycoprotein substrates by interacting with MDR1 protein. Epigallocatechin-3-gallate and xanthohumol modulate the transport and uptake of ketoconazole.

Cell oxidation-reduction imbalance after modulated radiofrequency radiation.

PubMed

Marjanovic, Ana Marija; Pavicic, Ivan; Trosic, Ivancica

2015-01-01

Aim of this study was to evaluate an influence of modulated radiofrequency field (RF) of 1800 MHz, strength of 30 V/m on oxidation-reduction processes within the cell. The assigned RF field was generated within Gigahertz Transversal Electromagnetic Mode cell equipped by signal generator, modulator, and amplifier. Cell line V79, was irradiated for 10, 30, and 60 min, specific absorption rate was calculated to be 1.6 W/kg. Cell metabolic activity and viability was determined by MTT assay. In order to define total protein content, colorimetric method was used. Concentration of oxidised proteins was evaluated by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) marked with fluorescent probe 2',7'-dichlorofluorescin diacetate were measured by means of plate reader device. In comparison with control cell samples, metabolic activity and total protein content in exposed cells did not differ significantly. Concentrations of carbonyl derivates, a product of protein oxidation, insignificantly but continuously increase with duration of exposure. In exposed samples, ROS level significantly (p < 0.05) increased after 10 min of exposure. Decrease in ROS level was observed after 30-min treatment indicating antioxidant defence mechanism activation. In conclusion, under the given laboratory conditions, modulated RF radiation might cause impairment in cell oxidation-reduction equilibrium within the growing cells.

Development and Assessment of Modules to Integrate Quantitative Skills in Introductory Biology Courses

PubMed Central

Hoffman, Kathleen; Leupen, Sarah; Dowell, Kathy; Kephart, Kerrie; Leips, Jeff

2016-01-01

Redesigning undergraduate biology courses to integrate quantitative reasoning and skill development is critical to prepare students for careers in modern medicine and scientific research. In this paper, we report on the development, implementation, and assessment of stand-alone modules that integrate quantitative reasoning into introductory biology courses. Modules are designed to improve skills in quantitative numeracy, interpreting data sets using visual tools, and making inferences about biological phenomena using mathematical/statistical models. We also examine demographic/background data that predict student improvement in these skills through exposure to these modules. We carried out pre/postassessment tests across four semesters and used student interviews in one semester to examine how students at different levels approached quantitative problems. We found that students improved in all skills in most semesters, although there was variation in the degree of improvement among skills from semester to semester. One demographic variable, transfer status, stood out as a major predictor of the degree to which students improved (transfer students achieved much lower gains every semester, despite the fact that pretest scores in each focus area were similar between transfer and nontransfer students). We propose that increased exposure to quantitative skill development in biology courses is effective at building competency in quantitative reasoning. PMID:27146161

Preclinical to Human Translational Pharmacology of the Novel M1 Positive Allosteric Modulator MK-7622.

PubMed

Uslaner, Jason M; Kuduk, Scott D; Wittmann, Marion; Lange, Henry S; Fox, Steve V; Min, Chris; Pajkovic, Natasa; Harris, Dawn; Cilissen, Caroline; Mahon, Chantal; Mostoller, Kate; Warrington, Steve; Beshore, Douglas C

2018-06-01

The current standard of care for treating Alzheimer's disease is acetylcholinesterase inhibitors, which nonselectively increase cholinergic signaling by indirectly enhancing activity of nicotinic and muscarinic receptors. These drugs improve cognitive function in patients, but also produce unwanted side effects that limit their efficacy. In an effort to selectively improve cognition and avoid the cholinergic side effects associated with the standard of care, various efforts have been aimed at developing selective M 1 muscarinic receptor activators. In this work, we describe the preclinical and clinical pharmacodynamic effects of the M 1 muscarinic receptor-positive allosteric modulator, MK-7622. MK-7622 attenuated the cognitive-impairing effects of the muscarinic receptor antagonist scopolamine and altered quantitative electroencephalography (qEEG) in both rhesus macaque and human. For both scopolamine reversal and qEEG, the effective exposures were similar between species. However, across species the minimum effective exposures to attenuate the scopolamine impairment were lower than for qEEG. Additionally, there were differences in the spectral power changes produced by MK-7622 in rhesus versus human. In sum, these results are the first to demonstrate translation of preclinical cognition and target modulation to clinical effects in humans for a selective M 1 muscarinic receptor-positive allosteric modulator. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Long Exposure Photos of Mobile Launcher

NASA Image and Video Library

2017-03-14

A long-exposure view of the mobile launcher at NASA's Kennedy Space Center in Florida. Cranes and rigging are being used to lift the bracket for the Orion Service Module Umbilical (OSMU) up for installation on the mobile launcher tower. The tower will be equipped with a number of lines, called umbilicals, that will connect to the Space Launch System rocket and Orion spacecraft for Exploration Mission-1 (EM-1). The OSMU will be located high on the mobile launcher tower and, prior to launch, will transfer liquid coolant for the electronics and air for the Environmental Control System to the Orion service module that houses these critical systems to support the spacecraft. EM-1 is scheduled to launch in 2018. The Ground Systems Development and Operations Program is overseeing installation of the umbilicals.

The potential of ultrasound in cardiac pacing and rhythm modulation.

PubMed

Kohut, Andrew R; Vecchio, Christopher; Adam, Dan; Lewin, Peter A

2016-09-01

This review examines the potential for ultrasound to induce or otherwise influence cardiac pacing and rhythm modulation. Of particular interest is the possibility of developing new, truly non-invasive, nonpharmacological, acute and chronic, ultrasound-based arrhythmia treatments. Such approaches would not depend upon implanted or indwelling devices of any kind and would use ultrasound at diagnostic exposure levels (so as not to harm the heart or surrounding tissues). It is known that ultrasound can cause cardiomyocyte depolarization and a variety of underlying mechanisms have been proposed. Expert commentary: Questions still remain regarding the effect of exposure parameters and work will also be necessary to identify the optimal target regions within the heart if ultrasound energy is to be used to induce safe and reliable pacing in a clinical setting.

Linking Light Exposure and Subsequent Sleep: A Field Polysomnography Study in Humans

PubMed Central

Woelders, Tom; Marring, Irene; van Rosmalen, Laura; Beersma, Domien G M; Gordijn, Marijke C M; Hut, Roelof A

2017-01-01

Abstract Study objectives To determine the effect of light exposure on subsequent sleep characteristics under ambulatory field conditions. Methods Twenty healthy participants were fitted with ambulatory polysomnography (PSG) and wrist-actigraphs to assess light exposure, rest–activity, sleep quality, timing, and architecture. Laboratory salivary dim-light melatonin onset was analyzed to determine endogenous circadian phase. Results Later circadian clock phase was associated with lower intensity (R2 = 0.34, χ2(1) = 7.19, p < .01), later light exposure (quadratic, controlling for daylength, R2 = 0.47, χ2(3) = 32.38, p < .0001), and to later sleep timing (R2 = 0.71, χ2(1) = 20.39, p < .0001). Those with later first exposure to more than 10 lux of light had more awakenings during subsequent sleep (controlled for daylength, R2 = 0.36, χ2(2) = 8.66, p < .05). Those with later light exposure subsequently had a shorter latency to first rapid eye movement (REM) sleep episode (R2 = 0.21, χ2(1) = 5.77, p < .05). Those with less light exposure subsequently had a higher percentage of REM sleep (R2 = 0.43, χ2(2) = 13.90, p < .001) in a clock phase modulated manner. Slow-wave sleep accumulation was observed to be larger after preceding exposure to high maximal intensity and early first light exposure (p < .05). Conclusions The quality and architecture of sleep is associated with preceding light exposure. We propose that light exposure timing and intensity do not only modulate circadian-driven aspects of sleep but also homeostatic sleep pressure. These novel ambulatory PSG findings are the first to highlight the direct relationship between light and subsequent sleep, combining knowledge of homeostatic and circadian regulation of sleep by light. Upon confirmation by interventional studies, this hypothesis could change current understanding of sleep regulation and its relationship to prior light exposure. Clinical trial details This study was not a clinical trial. The study was ethically approved and nationally registered (NL48468.042.14). PMID:29040758

Adrenal-derived stress hormones modulate ozone-induced lung injury and inflammation.

PubMed

Henriquez, Andres; House, John; Miller, Desinia B; Snow, Samantha J; Fisher, Anna; Ren, Hongzu; Schladweiler, Mette C; Ledbetter, Allen D; Wright, Fred; Kodavanti, Urmila P

2017-08-15

Ozone-induced systemic effects are modulated through activation of the neuro-hormonal stress response pathway. Adrenal demedullation (DEMED) or bilateral total adrenalectomy (ADREX) inhibits systemic and pulmonary effects of acute ozone exposure. To understand the influence of adrenal-derived stress hormones in mediating ozone-induced lung injury/inflammation, we assessed global gene expression (mRNA sequencing) and selected proteins in lung tissues from male Wistar-Kyoto rats that underwent DEMED, ADREX, or sham surgery (SHAM) prior to their exposure to air or ozone (1ppm), 4h/day for 1 or 2days. Ozone exposure significantly changed the expression of over 2300 genes in lungs of SHAM rats, and these changes were markedly reduced in DEMED and ADREX rats. SHAM surgery but not DEMED or ADREX resulted in activation of multiple ozone-responsive pathways, including glucocorticoid, acute phase response, NRF2, and PI3K-AKT. Predicted targets from sequencing data showed a similarity between transcriptional changes induced by ozone and adrenergic and steroidal modulation of effects in SHAM but not ADREX rats. Ozone-induced increases in lung Il6 in SHAM rats coincided with neutrophilic inflammation, but were diminished in DEMED and ADREX rats. Although ozone exposure in SHAM rats did not significantly alter mRNA expression of Ifnγ and Il-4, the IL-4 protein and ratio of IL-4 to IFNγ (IL-4/IFNγ) proteins increased suggesting a tendency for a Th2 response. This did not occur in ADREX and DEMED rats. We demonstrate that ozone-induced lung injury and neutrophilic inflammation require the presence of circulating epinephrine and corticosterone, which transcriptionally regulates signaling mechanisms involved in this response. Published by Elsevier Inc.

High frequency electromagnetic fields (GSM signals) affect gene expression levels in tumor suppressor p53-deficient embryonic stem cells.

PubMed

Czyz, Jaroslaw; Guan, Kaomei; Zeng, Qinghua; Nikolova, Teodora; Meister, Armin; Schönborn, Frank; Schuderer, Jürgen; Kuster, Niels; Wobus, Anna M

2004-05-01

Effects of electromagnetic fields (EMF) simulating exposure to the Global System for Mobile Communications (GSM) signals were studied using pluripotent embryonic stem (ES) cells in vitro. Wild-type ES cells and ES cells deficient for the tumor suppressor p53 were exposed to pulse modulated EMF at 1.71 GHz, lower end of the uplink band of GSM 1800, under standardized and controlled conditions, and transcripts of regulatory genes were analyzed during in vitro differentiation. Two dominant GSM modulation schemes (GSM-217 and GSM-Talk), which generate temporal changes between GSM-Basic (active during talking phases) and GSM-DTX (active during listening phases thus simulating a typical conversation), were applied to the cells at and below the basic safety limits for local exposures as defined for the general public by the International Commission on Nonionizing Radiation Protection (ICNIRP). GSM-217 EMF induced a significant upregulation of mRNA levels of the heat shock protein, hsp70 of p53-deficient ES cells differentiating in vitro, paralleled by a low and transient increase of c-jun, c-myc, and p21 levels in p53-deficient, but not in wild-type cells. No responses were observed in either cell type after EMF exposure to GSM-Talk applied at similar slot-averaged specific absorption rates (SAR), but at lower time-averaged SAR values. Cardiac differentiation and cell cycle characteristics were not affected in embryonic stem and embryonic carcinoma cells after exposure to GSM-217 EMF signals. Our data indicate that the genetic background determines cellular responses to GSM modulated EMF. Bioelectromagnetics 25:296-307, 2004. Copyright 2004 Wiley-Liss, Inc.

Deficits in the extinction of ethanol-seeking behavior following chronic intermittent ethanol exposure are attenuated with positive allosteric modulation of mGlu5.

PubMed

Gass, J T; McGonigal, J T; Chandler, L J

2017-02-01

Alcoholism is a chronic relapsing disorder characterized by periods of heavy alcohol consumption and unsuccessful attempts at abstinence. Relapse is one of the most problematic aspects in the treatment of alcoholism and is triggered by ethanol-associated cues. Extinction-based cue exposure therapies have proven ineffective in the treatment of alcoholism. However, positive allosteric modulation of mGlu5 with CDPPB enhances the extinction learning of alcohol-seeking behavior. The current study investigated the impact of chronic alcohol exposure on the extinction of ethanol-seeking behavior. Adult Wistar rats were trained to self-administer alcohol with a light/tone stimulus serving as the alcohol cue. After training, one group of rats was exposed to chronic intermittent ethanol (CIE) daily for a period of 2 weeks to induce ethanol dependence. Control rats were exposed to air for the same period of time. Both groups were then retrained to self-administer ethanol and subsequently tested for changes in extinction learning. CIE exposed rats consumed more ethanol compared to their pre-CIE levels and to control rats. During extinction training, CIE rats responded significantly more on the previously active lever and required more sessions to reach extinction criteria compared to control rats. Treatment with CDPPB facilitated extinction in control rats and attenuated the increased resistance to extinction in CIE-exposed rats. These results demonstrate that chronic ethanol exposure not only alters ethanol intake, but also the extinction of ethanol-seeking behaviors. The ability to attenuate deficits through modulation of mGlu5 provides a potential target for pharmacological manipulation that could ultimately reduce relapse in alcoholics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using Nutrition for Intervention and Prevention against Environmental Chemical Toxicity and Associated Diseases

PubMed Central

Hennig, Bernhard; Ettinger, Adrienne S.; Jandacek, Ronald J.; Koo, Sung; McClain, Craig; Seifried, Harold; Silverstone, Allen; Watkins, Bruce; Suk, William A.

2007-01-01

Background Nutrition and lifestyle are well-defined modulators of chronic diseases. Poor dietary habits (such as high intake of processed foods rich in fat and low intake of fruits and vegetables), as well as a sedentary lifestyle clearly contribute to today’s compromised quality of life in the United States. It is becoming increasingly clear that nutrition can modulate the toxicity of environmental pollutants. Objectives Our goal in this commentary is to discuss the recommendation that nutrition should be considered a necessary variable in the study of human disease associated with exposure to environmental pollutants. Discussion Certain diets can contribute to compromised health by being a source of exposure to environmental toxic pollutants. Many of these pollutants are fat soluble, and thus fatty foods often contain higher levels of persistent organics than does vegetable matter. Nutrition can dictate the lipid milieu, oxidative stress, and antioxidant status within cells. The modulation of these parameters by an individual’s nutritional status may have profound affects on biological processes, and in turn influence the effects of environmental pollutants to cause disease or dysfunction. For example, potential adverse health effects associated with exposure to polychlorinated biphenyls may increase as a result of ingestion of certain dietary fats, whereas ingestion of fruits and vegetables, rich in antioxidant and anti-inflammatory nutrients or bioactive compounds, may provide protection. Conclusions We recommend that future directions in environmental health research explore this nutritional paradigm that incorporates a consideration of the relationships between nutrition and lifestyle, exposure to environmental toxicants, and disease. Nutritional interventions may provide the most sensible means to develop primary prevention strategies of diseases associated with many environmental toxic insults. PMID:17450213

Serotonin modulates anxiety-like behaviors during withdrawal from adolescent anabolic–androgenic steroid exposure in Syrian hamsters

PubMed Central

Ricci, Lesley A.; Morrison, Thomas R.; Melloni, Richard H.

2013-01-01

From the U.S. to Europe and Australia anabolic steroid abuse remains high in the adolescent population. This is concerning given that anabolic steroid use is associated with a higher incidence of pathological anxiety that often appears during withdrawal from use. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that adolescent anabolic/androgenic steroid (AAS) exposure predisposes hamsters to heightened levels of anxiety during AAS withdrawal that is modulated by serotonin (5HT) neural signaling. In the first two sets of experiments, adolescent AAS-treated hamsters were tested for anxiety 21 days after the cessation of AAS administration (i.e., during AAS withdrawal) using the elevated plus maze (EPM), dark/light (DL), and seed finding (SF) tests and then examined for differences in 5HT afferent innervation to select areas of the brain important for anxiety. In the EPM and DL tests, adolescent AAS exposure leads to significant increases in anxiety-like response during AAS withdrawal. AAS-treated hamsters showed long-term reductions in 5HT innervation within several areas of the hamster brain implicated in anxiety, most notably the anterior hypothalamus and the central and medial amygdala. However, no differences in 5HT were found in other anxiety areas, e.g., frontal cortex and lateral septum. In the last experiment, adolescent AAS-treated hamsters were scored for anxiety on the 21st day of AAS withdrawal following the systemic administration of saline or one of three doses of fluoxetine, a selective serotonin reuptake inhibitor. Saline-treated hamsters showed high levels of AAS withdrawal-induced anxiety, while treatment with fluoxetine reduced AAS withdrawal-induced anxiety. These findings indicate that early AAS exposure has potent anxiogenic effects during AAS withdrawal that are modulated, in part, by 5HT signaling. PMID:23026540

Sensory neuropeptides modulate cigarette smoke-induced decrease in neutral endopeptidase activity in guinea pig airways.

PubMed

Kuo, H P; Lu, L C

1995-01-01

Cigarette smoke (CS) inhalation stimulates C-fibers to release sensory neuropeptides which mediate airway reflex responses to prevent irritants from entering the lower airways. When CS is inhaled via the upper airways, these airway defense responses may modulate the effect of CS on airway NEP activity and related airway hyperresponsiveness. To examine this possibility, we exposed guinea pigs to 1:10 diluted mid-tar cigarette smoke 100 puffs per day for 7 days and recorded pulmonary resistance of cumulative doses of neurokinin A (NKA, 10(-12)-10(-8) mol/kg, i.v.) or methacholine (Mch, 1-50 micrograms/kg, i.v.). NEP activity in the tracheobronchi was measured using fluorometric assay. Exposure of CS alone failed to alter the dose-response to NKA or Mch compared with air control. NEP activity in the airways after CS exposure was slightly but significantly lower than that of air control. Capsaicin pretreatment 1 week before CS exposure significantly shifted the dose-response curves of NKA, but not Mch, to the left and decreased NEP activity in the airways to a greater extent compared with CS exposure alone group. Capsaicin pretreatment alone failed to alter the responsiveness to NKA or NEP activity. CS also induced a significant increase in neutrophil counts in airways. Capsaicin pretreatment enhanced the effect of CS on neutrophil recruitment. We conclude that sensory neuropeptides may have a protective role in modulation of airways NEP activity downregulation induced by CS, probably by preventing CS from entering the lower airways or the chronic release of sensory neuropeptides induced by CS providing increased amount of substrata for NEP upregulation, and therefore modify the direct effect of CS on NEP activity and related airway hyperresponsiveness.

Host and Environmental Factors Modulate the Exposure of Free-Ranging and Farmed Red Deer (Cervus elaphus) to Coxiella burnetii

PubMed Central

Velasco Ávila, Ana Luisa; Boadella, Mariana; Beltrán-Beck, Beatriz; Barasona, José Ángel; Santos, João P. V.; Queirós, João; García-Pérez, Ana L.; Barral, Marta; Ruiz-Fons, Francisco

2015-01-01

The control of multihost pathogens, such as Coxiella burnetii, should rely on accurate information about the roles played by the main hosts. We aimed to determine the involvement of the red deer (Cervus elaphus) in the ecology of C. burnetii. We predicted that red deer populations from broad geographic areas within a European context would be exposed to C. burnetii, and therefore, we hypothesized that a series of factors would modulate the exposure of red deer to C. burnetii. To test this hypothesis, we designed a retrospective survey of 47 Iberian red deer populations from which 1,751 serum samples and 489 spleen samples were collected. Sera were analyzed by enzyme-linked immunosorbent assays (ELISA) in order to estimate exposure to C. burnetii, and spleen samples were analyzed by PCR in order to estimate the prevalence of systemic infections. Thereafter, we gathered 23 variables—within environmental, host, and management factors—potentially modulating the risk of exposure of deer to C. burnetii, and we performed multivariate statistical analyses to identify the main risk factors. Twenty-three populations were seropositive (48.9%), and C. burnetii DNA in the spleen was detected in 50% of the populations analyzed. The statistical analyses reflect the complexity of C. burnetii ecology and suggest that although red deer may maintain the circulation of C. burnetii without third species, the most frequent scenario probably includes other wild and domestic host species. These findings, taken together with previous evidence of C. burnetii shedding by naturally infected red deer, point at this wild ungulate as a true reservoir for C. burnetii and an important node in the life cycle of C. burnetii, at least in the Iberian Peninsula. PMID:26150466

Investigation of test methods, material properties and processes for solar cell encapsulants

NASA Technical Reports Server (NTRS)

Willis, P. B.

1985-01-01

The historical development of ethylene vinyl acetate (EVA) is presented, including the functional requirements, polymer selection, curing, stabilization, production and module processing. The construction and use of a new method for the accelerated aging of polymers is detailed. The method more closely resembles the conditions that may be encountered in actual module field exposure and additionally may permit service life to be predicted accurately. The use of hardboard as a low cost candidate substrate material is studied. The performance of surface antisoiling treatments useful for imparting a self cleaning property to modules is updated.

Promising therapies for treating and/or preventing androgenic alopecia.

PubMed

McElwee, K J; Shapiro, J S

2012-06-01

Androgenetic alopecia (AGA) may affect up to 70% of men and 40% of women at some point in their lifetime. While men typically present with a distinctive alopecia pattern involving hairline recession and vertex balding, women normally exhibit a diffuse hair thinning over the top of their scalps. The treatment standard in dermatology clinics continues to be minoxidil and finasteride with hair transplantation as a surgical option. Here we briefly review current therapeutic options and treatments under active investigation. Dutasteride and ketoconazole are also employed for AGA, while prostaglandin analogues latanoprost and bimatoprost are being investigated for their hair growth promoting potential. Laser treatment products available for home use and from cosmetic clinics are becoming popular. In the future, new cell mediated treatment approaches may be available for AGA. While there are a number of potential treatment options, good clinical trial data proving hair growth efficacy is limited.

Fractional non-ablative laser-assisted drug delivery leads to improvement in male and female pattern hair loss.

PubMed

Bertin, Ana Carina Junqueira; Vilarinho, Adriana; Junqueira, Ana Lúcia Ariano

2018-02-16

Androgenetic alopecia, also known as male and female pattern hair loss, is a very prevalent condition; however, approved therapeutic options are limited. Fractionated laser has been proposed to assist in penetration of topical medications to the cutaneous tissue. We present four cases of androgenetic alopecia that underwent treatment with a non-ablative erbium glass fractional laser followed by the application of topical finasteride 0,05% and growth factors including basic fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, and copper peptide 1%. During all laser treatment sessions, eight passes were performed, at 7 mJ, 3-9% of coverage and density of 120 mzt/cm 2 . A positive response was observed in all of the four patients. Photographs taken 2 weeks after the last session showed improvement in hair regrowth and density. No significant side effects were observed.

Platelet rich plasma for the management of hair loss: Better alone or in combination?

PubMed

Anitua, Eduardo; Pino, Ander; Jaén, Pedro; Navarro, Mª Rogelia

2018-06-14

Platelet-rich plasma (PRP) and autologous protein-based treatments have recently emerged as a potential therapeutic approach for hair loss-related disorders including androgenetic alopecia and alopecia areata. The safety and efficacy of repeated intradermal injections of PRP has proved to promote hair growth in a number of randomized clinical trials. Biologically active proteins and cytokines released upon platelet activation have shown to induce folliculogenesis and activate the anagen growing phase of dormant bulbs. Interestingly, further studies have revealed that combining PRP with other hair loss-related products may enhance the final performance of the treatment. These synergistic approaches include Food and Drug Administration (FDA) approved drugs such as finasteride or minoxidil, bioactive macromolecules and cell-based therapies. Here, recent research involving alone or combined therapy with platelet-rich plasma for the management of hair loss-related disorders are outlined and future prospects are discussed. © 2018 Wiley Periodicals, Inc.

Modulation of population density and size of silver nanoparticles embedded in bacterial cellulose via ammonia exposure: visual detection of volatile compounds in a piece of plasmonic nanopaper

NASA Astrophysics Data System (ADS)

Heli, B.; Morales-Narváez, E.; Golmohammadi, H.; Ajji, A.; Merkoçi, A.

2016-04-01

The localized surface plasmon resonance exhibited by noble metal nanoparticles can be sensitively tuned by varying their size and interparticle distances. We report that corrosive vapour (ammonia) exposure dramatically reduces the population density of silver nanoparticles (AgNPs) embedded within bacterial cellulose, leading to a larger distance between the remaining nanoparticles and a decrease in the UV-Vis absorbance associated with the AgNP plasmonic properties. We also found that the size distribution of AgNPs embedded in bacterial cellulose undergoes a reduction in the presence of volatile compounds released during food spoilage, modulating the studied nanoplasmonic properties. In fact, such a plasmonic nanopaper exhibits a change in colour from amber to light amber upon the explored corrosive vapour exposure and from amber to a grey or taupe colour upon fish or meat spoilage exposure. These phenomena are proposed as a simple visual detection of volatile compounds in a flexible, transparent, permeable and stable single-use nanoplasmonic membrane, which opens the way to innovative approaches and capabilities in gas sensing and smart packaging.The localized surface plasmon resonance exhibited by noble metal nanoparticles can be sensitively tuned by varying their size and interparticle distances. We report that corrosive vapour (ammonia) exposure dramatically reduces the population density of silver nanoparticles (AgNPs) embedded within bacterial cellulose, leading to a larger distance between the remaining nanoparticles and a decrease in the UV-Vis absorbance associated with the AgNP plasmonic properties. We also found that the size distribution of AgNPs embedded in bacterial cellulose undergoes a reduction in the presence of volatile compounds released during food spoilage, modulating the studied nanoplasmonic properties. In fact, such a plasmonic nanopaper exhibits a change in colour from amber to light amber upon the explored corrosive vapour exposure and from amber to a grey or taupe colour upon fish or meat spoilage exposure. These phenomena are proposed as a simple visual detection of volatile compounds in a flexible, transparent, permeable and stable single-use nanoplasmonic membrane, which opens the way to innovative approaches and capabilities in gas sensing and smart packaging. Electronic supplementary information (ESI) available: Details on the estimations of evaporation rates and limits of detection, ESI figures and author contributions. See DOI: 10.1039/c6nr00537c

Modeling photopolymers for holographic data storage applications

NASA Astrophysics Data System (ADS)

Sheridan, John T.; Kelly, John V.; Gleeson, Michael R.; Close, Ciara E.

2006-09-01

The Nonlocal Polymerization Driven Diffusion model, NPDD, is can be used to describe holographic grating formation in Acrylamide-based photopolymer. The free radical chain polymerization process results in polymer being generated nonlocal both in space and time to the point of chain initiation. Temporal nonlocality can be used to describepost exposure dark effects. Nonlinear response and the effects of dye bleaching have been examined. Both primary and bimolecular chain termination mechanisms have been included and examined. Recently 3-D, and inhibition effects have also been included. In this paper we review of our recent work. It is shown that temporal effects become most notable for short exposres and the inclusion of the nonlocal temporal response function is shown to be necessary to accurately describe the process. In particular, brief post exposure self-amplification of the refractive index modulation is noted. This is attributed to continued chain growth for a brief period after exposure. Following this a slight decay in the grating amplitude also occurs. This we believe is due to the continued diffusion of monomer after exposure. Since the sinusoidal recording pattern generates a monomer concentration gradient during the recording process monomer diffusion occurs both during and after exposure. The evolution of the refractive index modulation is determined by the respective refractive index values of the recording material components. From independent measurements it is noted that the refractive index value of the monomer is slightly less than that of the background material. Therefore as monomer diffuses back into the dark regions, a reduction in overall refractive index modulation occurs. Volume changes occurring within the material also affect the nature of grating evolution. To model these effects we employ a free volume concept. Due to the fact that the covalent single carbon bond in the polymer is up to 50% shorter than the van der Waals bond in the liquid monomer state, free volume is created when monomer is converted to polymer. For each bond conversion we assume a hole is generated which then collapses at some characteristic rate constant. The Lorentz-Lorenz relation is used to determine the overall evolution refractive index modulation and the corresponding diffraction efficiency of the resulting grating is calculated using Rigorous Coupled Wave Analysis (RCWA). The Lorentz-Lorenz relation is used to determine the overall evolution refractive index modulation and the corresponding diffraction efficiency of the resulting grating is calculated using Rigorous Coupled Wave Analysis (RCWA). Inhibition is typically observed at the start of grating growth during which the formation of polymer chains is suppressed. In this paper experiments are reported, carried out with the specific aim of understanding of these processes. The results support our description of the inhibition process in an PVA/Acrylamide based photopolymer and can be used to predict behaviour under certain conditions.

Antibody responses of mice exposed to low-power microwaves under combined, pulse-and-amplitude modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veyret, B.; Bouthet, C.; Deschaux, P.

Irradiation by pulsed microwaves (9.4 GHz, 1 microsecond pulses at 1,000/s), both with and without concurrent amplitude modulation (AM) by a sinusoid at discrete frequencies between 14 and 41 MHz, was assessed for effects on the immune system of Balb/C mice. The mice were immunized either by sheep red blood cells (SRBC) or by glutaric-anhydride conjugated bovine serum albumin (GA-BSA), then exposed to the microwaves at a low rms power density (30 microW/cm2; whole-body-averaged SAR approximately 0.015 W/kg). Sham exposure or microwave irradiation took place during each of five contiguous days, 10 h/day. The antibody response was evaluated by themore » plaque-forming cell assay (SRBC experiment) or by the titration of IgM and IgG antibodies (GA-BSA experiment). In the absence of AM, the pulsed field did not greatly alter immune responsiveness. In contrast, exposure to the field under the combined-modulation condition resulted in significant, AM-frequency-dependent augmentation or weakening of immune responses.« less

Performance Testing of Lidar Components Subjected to Space Exposure in Space via MISSE 7 Mission

NASA Technical Reports Server (NTRS)

Prasad, Narasimha S.

2012-01-01

.The objective of the Materials International Space Station Experiment (MISSE) is to study the performance of novel materials when subjected to the synergistic effects of the harsh space environment for several months. MISSE missions provide an opportunity for developing space qualifiable materials. Several laser and lidar components were sent by NASA Langley Research Center (LaRC) as a part of the MISSE 7 mission. The MISSE 7 module was transported to the international space station (ISS) via STS 129 mission that was launched on Nov 16, 2009. Later, the MISSE 7 module was brought back to the earth via the STS 134 that landed on June 1, 2011. The MISSE 7 module that was subjected to exposure in space environment for more than one and a half year included fiber laser, solid-state laser gain materials, detectors, and semiconductor laser diode. Performance testing of these components is now progressing. In this paper, the current progress on post-flight performance testing of a high-speed photodetector and a balanced receiver is discussed. Preliminary findings show that detector characteristics did not undergo any significant degradation.

Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity

PubMed Central

Donohue, Jr., Terrence M.; Thomes, Paul G.

2014-01-01

In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin–proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, we describe the history and the importance of cellular hydrolytic systems, followed by a description of each catabolic pathway and the differential modulation of each by ethanol exposure. Overall, the evidence for an involvement of these catabolic systems in the pathogenesis of alcoholic liver disease is quite strong. It underscores their importance, not only as effective means of cellular recycling and eventual energy generation, but also as essential components of cellular defense. PMID:25462063

Modulation of insulin secretion by fatty acyl analogs.

PubMed

Las, Guy; Mayorek, Nina; Dickstein, Kobie; Bar-Tana, Jacob

2006-12-01

The secretagogue, the incretin-like, and the suppressive activities of long-chain fatty acids (LCFAs) in modulating insulin secretion in vivo and in cultured islets were simulated here by beta,beta'-tetramethyl-hexadecanedioic acid (M16) and alpha,alpha'-tetrachloro-tetradecanedioic acid (Cl-DICA). M16, but not Cl-DICA, serves as a substrate for ATP-dependent CoA thioesterification but is not further metabolized. M16, but not Cl-DICA, acted as a potent insulin secretagogue in islets cultured in basal but not high glucose. Short-term exposure to M16 or Cl-DICA resulted in activation of glucose- but not arginine-stimulated insulin secretion. Long-term exposure to M16, but not to Cl-DICA, resulted in suppression of glucose-, arginine-, and K(+)-stimulated insulin secretion; inhibition of glucose-induced proinsulin biosynthesis; and depletion of islets insulin. beta-Cell mass and islet ATP content remained unaffected. Hence, nonmetabolizable LCFA analogs may highlight discrete LCFA metabolites and pathways involved in modulating insulin secretion, which could be overlooked due to the rapid turnover of natural LCFA.

Epigenetic modulation of Chlorella (Chlorella vulgaris) on exposure to polycyclic aromatic hydrocarbons.

PubMed

Yang, Mihi; Youn, Je-In; Kim, Seung Joon; Park, Jong Y

2015-11-01

DNA methylation in promoter region can be a new chemopreventive marker against polycyclic aromatic hydrocarbons (PAHs). We performed a randomized, double blind and cross-over trial (N=12 healthy females) to evaluate chlorella (Chlorella vulgaris)-induced epigenetic modulation on exposure to PAHs. The subjects consumed 4 tablets of placebo or chlorella supplement (total chlorophyll ≈ 8.3mg/tablet) three times a day before meals for 2 weeks. When the subjects consumed chlorella, status of global hypermethylation (5-methylcytosine) was reduced, compared to placebo (p=0.04). However, DNA methylation at the DNMT1 or NQO1 was not modified by chlorella. We observed the reduced levels of urinary 1-hydroxypyrene (1-OHP), a typical metabolite of PAHs, by chlorella intake (p<0.1) and a positive association between chlorella-induced changes in global hypermethylation and urinary 1-OHP (p<0.01). Therefore, our study suggests chlorella works for PAH-detoxification through the epigenetic modulation, the interference of ADME of PAHs and the interaction of mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Ethylene-Vinyl Acetate Potential Problems for Photovoltaic Packaging: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kempe, M. D.; Jorgensen, G. J.; Terwilliger, K. M.

2006-05-01

Photovoltaic (PV) devices are typically encapsulated using ethylene-vinyl acetate (EVA) to provide mechanical support, optical coupling, electrical isolation, and protection against environmental exposure. Under exposure to atmospheric water and/or ultraviolet radiation, EVA will decompose to produce acetic acid, lowering the pH and increasing the surface corrosion rates of embedded devices. Even though acetic acid is produced at a very slow rate, it may not take much to catalyze reactions that lead to rapid module deterioration. Another consideration is that the glass transition of EVA, as measured using dynamic mechanical analysis, begins at temperatures of about ?15 C. Temperatures lower thanmore » this can be reached for extended periods of time in some climates. Because of increased moduli below the glass transition temperature, a module may be more vulnerable to damage if a mechanical load is applied by snow or wind at low temperatures. Modules using EVA should not be rated for use at such low temperatures without additional low-temperature mechanical testing beyond the scope of UL 1703.« less

Ethylene-Vinyl Acetate Potential Problems for Photovoltaic Packaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kempe, M. D.; Jorgensen, G. J.; Terwilliger, K. M.

2006-01-01

Photovoltaic (PV) devices are typically encapsulated using ethylene-vinyl acetate (EVA) to provide mechanical support, optical coupling, electrical isolation, and protection against environmental exposure. Under exposure to atmospheric water and/or ultraviolet radiation, EVA will decompose to produce acetic acid, lowering the pH and increasing the surface corrosion rates of embedded devices. Even though acetic acid is produced at a very slow rate, it may not take much to catalyze reactions that lead to rapid module deterioration. Another consideration is that the glass transition of EVA, as measured using dynamic mechanical analysis, begins at temperatures of about -15 degC. Temperatures lower thanmore » this can be reached for extended periods of time in some climates. Because of increased moduli below the glass transition temperature, a module may be more vulnerable to damage if a mechanical load is applied by snow or wind at low temperatures. Modules using EVA should not be rated for use at such low temperatures without additional low-temperature mechanical testing beyond the scope of UL1703.« less

Potential Problems with Ethylene-Vinyl Acetate for Photovoltaic Packaging (Poster)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kempe, M. D.; Jorgensen, G. J.; Terwilliger, K, M.

2006-05-01

Photovoltaic (PV) devices are typically encapsulated using ethylene-vinyl acetate (EVA) to provide mechanical support electrical isolation, optical coupling, and protection against environmental exposure. Under exposure to atmospheric water and/or ultraviolet radiation, EVA will decompose to produce acetic acid, lowering the pH and increasing the surface corrosion rates of embedded devices. Even though acetic acid is produced at a very slow rate it may not take much to catalyze reactions that lead to rapid module deterioration. Another consideration is that the glass transition of EVA, as measured using dynamic mechanical analysis, begins at temperatures of about -15 C. Temperatures lower thanmore » this can be reached for extended periods of time in some climates. Due to increased moduli below the glass transition temperature, a module may be more vulnerable to damage if a mechanical load is applied by snow or wind at low temperatures. Modules using EVA should not be rated for use at such low temperatures without additional low-temperature mechanical testing beyond the scope of UL 1703.« less

Correction for Metastability in the Quantification of PID in Thin-film Module Testing: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hacke, Peter L; Johnston, Steven; Spataru, Sergiu

A fundamental change in the analysis for the accelerated stress testing of thin-film modules is proposed, whereby power changes due to metastability and other effects that may occur due to the thermal history are removed from the power measurement that we obtain as a function of the applied stress factor. The power of reference modules normalized to an initial state - undergoing the same thermal and light- exposure history but without the applied stress factor such as humidity or voltage bias - is subtracted from that of the stressed modules. For better understanding and appropriate application in standardized tests, themore » method is demonstrated and discussed for potential-induced degradation testing in view of the parallel-occurring but unrelated physical mechanisms that can lead to confounding power changes in the module.« less

Effects of repeated exposure of rats to JP-5 or JP-8 jet fuel vapor on neurobehavioral capacity and neurotransmitter levels.

PubMed

Rossi, J; Nordholm, A F; Carpenter, R L; Ritchie, G D; Malcomb, W

2001-07-20

The U.S. Naval Service is anticipating transition from the nearly exclusive use of JP-5 jet fuel to predominant use of JP-8, consistent with the primary utilization by the U.S. Army, U.S. Air Force, and the militaries of most NATO countries. To compare the relative risk of repeated exposure to JP-5 versus JP-8 vapor, groups of 32 male Sprague-Dawley rats each were exposed for 6 h/d, 5 d/wk for 6 wk (180 h) to JP-8 jet fuel vapor (1,000 +/- 10% mg/m3), IP-5 vapor (1,200 +/- 10% mg/m3), or room air control conditions. Following a 65-d rest period, rats completed 10 tests selected from the Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in performance capacity. Repeated exposure to JP-5 resulted in significant effects on only one test, forelimb grip strength (FGS), while exposure to JP-8 vapor resulted in a significant difference versus controls on appetitive reinforcer approach sensitization (ARAS). Rats were further evaluated for concentrations of major neurotransmitters and metabolites in five brain regions and in the blood serum. Levels of dopamine, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), and the serotonin metabolite homovanillic acid (HVA) were significantly modulated in various brain regions, as measured 85+ d postexposure. Similarly, serum levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were differentially modulated following JP-8 or JP-5 exposure. Results are compared to previously published research evaluating the neurotoxicity of repeated exposure to other hydrocarbon fuels and solvents.

Tobacco smoke modulates ozone-induced toxicity in rat lungs and central nervous system.

PubMed

Bhoopalan, Vanitha; Han, Sung Gu; Shah, Mrudang M; Thomas, David M; Bhalla, Deepak K

2013-01-01

Adult Sprague-Dawley (SD) male rats were exposed for a single 3 h period to air, ozone (O₃) or O₃) followed by tobacco smoke (O₃/TS). For pulmonary effects, bronchoalveolar lavage (BAL) cells and fluid were analyzed. Data revealed a significant increase in polymorphonuclear leukocytes (PMN), total protein and albumin concentrations in the O₃ group, reflecting inflammatory and toxic responses. A subsequent exposure to TS attenuated PMN infiltration into the airspaces and their recovery in the BAL. A similar reduction was observed for BAL protein and albumin in the O₃/TS group, but it was not statistically significant. We also observed a significant increase in BAL total antioxidant capacity following O₃ exposure, suggesting development of protective mechanisms for oxidative stress damage from O₃. Exposure to TS attenuated the levels of total antioxidant capacity. Lung tissue protein analysis showed a significant reduction of extracellular superoxide dismutase (EC-SOD) in the O₃ or O₃/TS group and catalase in the O₃/TS group. TS further altered O₃-induced EC-SOD and catalase protein expression, but the reductions were not significant. For effects in the central nervous system (CNS), we measured striatal dopamine levels by HPLC with electrochemical detection. O₃ exposure produced a nonsignificant decrease in the striatal dopamine content. The effect was partially reversed in the O₃/TS group. Overall, the results show that the toxicity of O₃ in the lung is modulated by TS exposure, and the attenuating trend, though nonsignificant in many cases, is contrary to the synergistic toxicity predicted for TS and O₃, suggesting limited cross-tolerance following such exposures.

Second-Language Experience Modulates Eye Movements during First- and Second-Language Sentence Reading: Evidence from a Gaze-Contingent Moving Window Paradigm

ERIC Educational Resources Information Center

Whitford, Veronica; Titone, Debra

2015-01-01

Eye movement measures demonstrate differences in first-language (L1) and second-language (L2) paragraph-level reading as a function of individual differences in current L2 exposure among bilinguals (Whitford & Titone, 2012). Specifically, as current L2 exposure increases, the ease of L2 word processing increases, but the ease of L1 word…

Epigenetics mediate environment : gene effects on occupational sensitization.

PubMed

Pacheco, Karin A

2012-04-01

Epigenetics is the study of stable modifications of fixed genomes that direct which genes are expressed and which are silenced. Epigenetic changes are modulated by environmental exposures, making epigenetics the interface between genes and environment. This has particular relevance in understanding the effect of occupational exposures on the expression of allergic disease. The goal of this review is to describe how epigenetic changes affect transcription potential, and to examine more closely the effect of specific environmental and occupational exposures on epigenetic variations that alter allergy gene transcripts and the inflammatory milieu. Gene transcription is activated when specific CpG sites are demethylated and histones are acetylated, and, conversely, silenced when sites are methylated and histones deacetylated. The development of Th1 and Th2 phenotypes, and expression of Treg cells, are now known to be modulated by epigenetic mechanisms. Workplace exposures such as tobacco smoke, particulates, diesel exhaust, polyaromatic hydrocarbons, ozone, and endotoxin, among others, suppress Treg development, and enhance expression of inflammatory cytokines and allergic phenotypes by epigenetic means. Epigenetic manipulation to open and close transcription sites provides flexibility of gene expression in response to changing environmental cues. It may also be the window whereby allergic disease in the workplace can be reduced by targeted environmental interventions.

Grapevine Plasticity in Response to an Altered Microclimate: Sauvignon Blanc Modulates Specific Metabolites in Response to Increased Berry Exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, Philip R.; Eyeghe-Bickong, Hans A.; du Plessis, Kari

In this paper, the metabolic and physiological impacts of an altered microclimate on quality-associated primary and secondary metabolites in grape (Vitis vinifera) ‘Sauvignon Blanc’ berries was determined in a high-altitude vineyard. The leaf and lateral shoot removal in the bunch zones altered the microclimate by increasing the exposure of the berries. The physical parameters (berry diameter and weight), primary metabolites (sugars and organic acids), as well as bunch temperature and leaf water potential were predominantly not affected by the treatment. The increased exposure led to higher levels of specific carotenoids and volatile terpenoids in the exposed berries, with earlier berrymore » stages reacting distinctly from the later developmental stages. Plastic/nonplastic metabolite responses could be further classified to identify metabolites that were developmentally controlled and/or responded to the treatment in a predictable fashion (assessed over two consecutive vintages). The study demonstrates that grapevine berries exhibit a degree of plasticity within their secondary metabolites and respond physiologically to the increased exposure by increasing metabolites with potential antioxidant activity. Finally, taken together, the data provide evidence that the underlying physiological responses relate to the maintenance of stress pathways by modulating antioxidant molecules in the berries.« less

Grapevine Plasticity in Response to an Altered Microclimate: Sauvignon Blanc Modulates Specific Metabolites in Response to Increased Berry Exposure

DOE PAGES

Young, Philip R.; Eyeghe-Bickong, Hans A.; du Plessis, Kari; ...

2015-12-01

In this paper, the metabolic and physiological impacts of an altered microclimate on quality-associated primary and secondary metabolites in grape (Vitis vinifera) ‘Sauvignon Blanc’ berries was determined in a high-altitude vineyard. The leaf and lateral shoot removal in the bunch zones altered the microclimate by increasing the exposure of the berries. The physical parameters (berry diameter and weight), primary metabolites (sugars and organic acids), as well as bunch temperature and leaf water potential were predominantly not affected by the treatment. The increased exposure led to higher levels of specific carotenoids and volatile terpenoids in the exposed berries, with earlier berrymore » stages reacting distinctly from the later developmental stages. Plastic/nonplastic metabolite responses could be further classified to identify metabolites that were developmentally controlled and/or responded to the treatment in a predictable fashion (assessed over two consecutive vintages). The study demonstrates that grapevine berries exhibit a degree of plasticity within their secondary metabolites and respond physiologically to the increased exposure by increasing metabolites with potential antioxidant activity. Finally, taken together, the data provide evidence that the underlying physiological responses relate to the maintenance of stress pathways by modulating antioxidant molecules in the berries.« less

Grapevine Plasticity in Response to an Altered Microclimate: Sauvignon Blanc Modulates Specific Metabolites in Response to Increased Berry Exposure.

PubMed

Young, Philip R; Eyeghe-Bickong, Hans A; du Plessis, Kari; Alexandersson, Erik; Jacobson, Dan A; Coetzee, Zelmari; Deloire, Alain; Vivier, Melané A

2016-03-01

In this study, the metabolic and physiological impacts of an altered microclimate on quality-associated primary and secondary metabolites in grape (Vitis vinifera) 'Sauvignon Blanc' berries was determined in a high-altitude vineyard. The leaf and lateral shoot removal in the bunch zones altered the microclimate by increasing the exposure of the berries. The physical parameters (berry diameter and weight), primary metabolites (sugars and organic acids), as well as bunch temperature and leaf water potential were predominantly not affected by the treatment. The increased exposure led to higher levels of specific carotenoids and volatile terpenoids in the exposed berries, with earlier berry stages reacting distinctly from the later developmental stages. Plastic/nonplastic metabolite responses could be further classified to identify metabolites that were developmentally controlled and/or responded to the treatment in a predictable fashion (assessed over two consecutive vintages). The study demonstrates that grapevine berries exhibit a degree of plasticity within their secondary metabolites and respond physiologically to the increased exposure by increasing metabolites with potential antioxidant activity. Taken together, the data provide evidence that the underlying physiological responses relate to the maintenance of stress pathways by modulating antioxidant molecules in the berries. © 2016 American Society of Plant Biologists. All Rights Reserved.

Grapevine Plasticity in Response to an Altered Microclimate: Sauvignon Blanc Modulates Specific Metabolites in Response to Increased Berry Exposure1

PubMed Central

du Plessis, Kari; Jacobson, Dan A.

2016-01-01

In this study, the metabolic and physiological impacts of an altered microclimate on quality-associated primary and secondary metabolites in grape (Vitis vinifera) ‘Sauvignon Blanc’ berries was determined in a high-altitude vineyard. The leaf and lateral shoot removal in the bunch zones altered the microclimate by increasing the exposure of the berries. The physical parameters (berry diameter and weight), primary metabolites (sugars and organic acids), as well as bunch temperature and leaf water potential were predominantly not affected by the treatment. The increased exposure led to higher levels of specific carotenoids and volatile terpenoids in the exposed berries, with earlier berry stages reacting distinctly from the later developmental stages. Plastic/nonplastic metabolite responses could be further classified to identify metabolites that were developmentally controlled and/or responded to the treatment in a predictable fashion (assessed over two consecutive vintages). The study demonstrates that grapevine berries exhibit a degree of plasticity within their secondary metabolites and respond physiologically to the increased exposure by increasing metabolites with potential antioxidant activity. Taken together, the data provide evidence that the underlying physiological responses relate to the maintenance of stress pathways by modulating antioxidant molecules in the berries. PMID:26628747

The Comparative Toxicogenomics Database: update 2017.

PubMed

Davis, Allan Peter; Grondin, Cynthia J; Johnson, Robin J; Sciaky, Daniela; King, Benjamin L; McMorran, Roy; Wiegers, Jolene; Wiegers, Thomas C; Mattingly, Carolyn J

2017-01-04

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) provides information about interactions between chemicals and gene products, and their relationships to diseases. Core CTD content (chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature) are integrated with each other as well as with select external datasets to generate expanded networks and predict novel associations. Today, core CTD includes more than 30.5 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, Gene Ontology (GO) annotations, pathways, and gene interaction modules. In this update, we report a 33% increase in our core data content since 2015, describe our new exposure module (that harmonizes exposure science information with core toxicogenomic data) and introduce a novel dataset of GO-disease inferences (that identify common molecular underpinnings for seemingly unrelated pathologies). These advancements centralize and contextualize real-world chemical exposures with molecular pathways to help scientists generate testable hypotheses in an effort to understand the etiology and mechanisms underlying environmentally influenced diseases. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Modulate chopper technique used in pyroelectric uncooled focal plane array thermal imager

NASA Astrophysics Data System (ADS)

He, Yuqing; Jin, Weiqi; Liu, Guangrong; Gao, Zhiyun; Wang, Xia; Wang, Lingxue

2002-09-01

Pyroelectric uncooled focal plane array (FPA) thermal imager has the advantages of low cost, small size, high responsibility and can work under room temperature, so it has great progress in recent years. As a matched technique, the modulate chopper has become one of the key techniques in uncooled FPA thermal imaging system. Now the Archimedes spiral cord chopper technique is mostly used. When it works, the chopper pushing scans the detector's pixel array, thus makes the pixels being exposed continuously. This paper simulates the shape of this kind of chopper, analyses the exposure time of the detector's every pixel, and also analyses the whole detector pixels' exposure sequence. From the analysis we can get the results: the parameter of Archimedes spiral cord, the detector's thermal time constant, the detector's geometrical dimension, the relative position of the detector to the chopper's spiral cord are the system's important parameters, they will affect the chopper's exposure efficiency and uniformity. We should design the chopper's relevant parameter according to the practical request to achieve the chopper's appropriate structure.

Image-receptor performance: a comparison of Trophy RVG UI sensor and Kodak Ektaspeed Plus film.

PubMed

Ludlow, J; Mol, A

2001-01-01

Objective. This study compares the physical characteristics of the RVG UI sensor (RVG) with Ektaspeed Plus film. Dose-response curves were generated for film and for each of 6 available RVG modes. An aluminum step-wedge was used to evaluate exposure latitude. Spatial resolution was assessed by using a line-pair test tool. Latitude and resolution were assessed by observers for both modalities. The RVG was further characterized by its modulation transfer function. Exposure latitude was equal for film and RVG in the periodontal mode. Other gray scale modes demonstrated much lower latitude. The average maximum resolution was 15.3 line-pairs per millimeter (lp/mm) for RVG in high-resolution mode, 10.5 lp/mm for RVG in low-resolution mode, and 20 lp/mm for film (P <.0001). Modulation transfer function measurements supported the subjective assessments. In periodontal mode, the RVG UI sensor demonstrates exposure latitude similar to that of Ektaspeed Plus film. Film images exhibit significantly higher spatial resolution than the RVG images acquired in high-resolution mode.

AFRRI (Armed Forces Radiobiology Research Institute) Annual Research Report 1 October 1982-30 September 1983.

DTIC Science & Technology

1983-09-30

glucan on granulopoiesis and macrophage genesis in mice. Cancer Research 37: 1739-1742, 1979. 2. Patchen, M. L., and Lotzova, 1. Modulation of m urine... beta - endorphin are elevated following exposure to acute stress. Therefore, the present study sought to determine if behavioml cross-tolerance could...Effects on hepatic enzymes, delayed type hypersensitivity, and postirradiation survival of mice. In: Modulation and Mediation of Cancer by Vitamins

Inclusion of an ultraviolet radiation transfer component in an urban forest effects model for predicting tree influences on potential below-canopy exposure to UVB radiation

Treesearch

Gordon M. Heisler; Richard H. Grant; David J. Nowak; Wei Gao; Daniel E. Crane; Jeffery T. Walton

2003-01-01

Evaluating the impact of ultraviolet-B radiation (UVB) on urban populations would be enhanced by improved predictions of the UVB radiation at the level of human activity. This paper reports the status of plans for incorporating a UVB prediction module into an existing Urban Forest Effects (UFORE) model. UFORE currently has modules to quantify urban forest structure,...

Prenatal exposure to drugs: effects on brain development and implications for policy and education

PubMed Central

Thompson, Barbara L.; Levitt, Pat; Stanwood, Gregg D.

2009-01-01

The effects of prenatal exposure to drugs on brain development are complex and are modulated by the timing, dose, and route of drug exposure. It is difficult to assess these effects in clinical cohorts, which are beset with multiple exposures and difficulties in documenting use patterns. This can lead to misinterpretation of research findings by the general public, the media and policy makers, who may mistakenly assume that the legal or illegal status of a drug correlates with its biological impact on fetal brain development and long-term clinical outcomes. It is important to close the gap between what science tells us about the impact of prenatal drug exposure on the fetus and the mother, and what we do programmatically with regard to at-risk populations. PMID:19277053

Modulation of mesenchymal stem cell behavior by nano- and micro-sized β-tricalcium phosphate particles in suspension and composite structures

NASA Astrophysics Data System (ADS)

Smoak, Mollie; Hogan, Katie; Kriegh, Lisa; Chen, Cong; Terrell, LeKeith B.; Qureshi, Ammar T.; Todd Monroe, W.; Gimble, Jeffrey M.; Hayes, Daniel J.

2015-04-01

Interest has grown in the use of microparticles and nanoparticles for modifying the mechanical and biological properties of synthetic bone composite structures. Micro- and nano-sized calcium phosphates are of interest for their osteoinductive behavior. Engineered composites incorporating polymers and ceramics, such as poly-l-lactic acid (PLLA) and beta-tricalcium phosphate (β-TCP), for bone tissue regeneration have been well investigated for their proliferative and osteoinductive abilities. Only limited research has been done to investigate the effects of different sizes of β-TCP particles on human mesenchymal stromal cell behavior. As such, the aim of this study was to investigate the modulations of human adipose-derived stem cell (hASCs) behavior within cell/particle and cell/composite systems as functions of particle size, concentration, and exposure time. The incorporation of nanoscale calcium phosphate resulted in improved mechanical properties and osteogenic behavior within the scaffold compared to the microscale calcium phosphate additives. Particle exposure results indicate that cytotoxicity on hASCs correlates inversely with particle size and increases with the increasing exposure time and particle concentration. Composites with increasing β-TCP content, whether microparticles or nanoparticles, were less toxic than colloidal micro- and nano-sized β-TCP particles directly supplied to hASCs. The difference in viability observed as a result of varying exposure route is likely related to the increased cell-particle interactions in the direct exposure compared to the particles becoming trapped within the scaffold/polymer matrix.

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation.

PubMed

Maldonado, Maricela; Luu, Rebeccah J; Ramos, Michael E P; Nam, Jin

2016-09-01

Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632. Copyright © 2016 Helmholtz Zentrum München. Published by Elsevier B.V. All rights reserved.

Transcriptional profiling of primary endometrial epithelial cells following acute HIV-1 exposure reveals gene signatures related to innate immunity.

PubMed

Zahoor, Muhammad Atif; Woods, Matthew William; Dizzell, Sara; Nazli, Aisha; Mueller, Kristen M; Nguyen, Philip V; Verschoor, Chris P; Kaushic, Charu

2018-04-01

Genital epithelial cells (GECs) line the mucosal surface of the female genital tract (FGT) and are the first cells that interface with both commensal microbiota and sexually transmitted pathogens. Despite the protective barrier formed by GECs, the FGT is a major site of HIV-1 infection. This highlights the importance of studying the interaction of HIV-1 and GECs. Using microarray analysis, we characterized the transcriptional profile of primary endometrial GECs grown in the presence or absence of physiological levels of E2 (10 -9  mol/L) or P4 (10 -7  mol/L) following acute exposure to HIV-1 for 6 hours. Acute exposure of primary endometrial GECs to HIV-1 resulted in the expression of genes related to inflammation, plasminogen activation, adhesion and diapedesis and interferon response. Interestingly, exposure to HIV-1 in the presence of E2 and P4 resulted in differential transcriptional profiles, suggesting that the response of primary endometrial GECs to HIV-1 exposure is modulated by female sex hormones. The gene expression signature of endometrial GECs indicates that the response of these cells may be key to determining host susceptibility to HIV-1 and that sex hormones modulate these interactions. This study allows us to explore possible mechanisms that explain the hormone-mediated fluctuation of HIV-1 susceptibility in women. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Attentional modulation of desensitization to odor.

PubMed

Fallon, Nicholas; Giesbrecht, Timo; Stancak, Andrej

2018-05-22

Subjective and behavioral responsiveness to odor diminishes during prolonged exposure. The precise mechanisms underlying olfactory desensitization are not fully understood, but previous studies indicate that the phenomenon may be modulated by central-cognitive processes. The present study investigated the effect of attention on perceived intensity during exposure to a pleasant odor. A within-subjects design was utilized with 19 participants attending 2 sessions. During each session, participants continuously rated their perceived intensity of a 10-minute exposure to a pleasant fragrance administered using an olfactometer. An auditory oddball task was implemented to manipulate the focus of attention in each session. Participants were instructed to either direct their attention toward the sounds, but still to rate odor, or to focus entirely on rating the odor. Analysis revealed three 50-second time windows with significantly lower mean intensity ratings during the distraction condition. Curve fitting of the data disclosed a linear function of desensitization in the focused attention condition compared with an exponential decay function during distraction condition, indicating an increased rate of initial desensitization when attention is distracted away from the odor. In the focused-attention condition, perceived intensity demonstrated a regular pattern of odor sensitivity occurring at approximately 1-2 minutes intervals following initial desensitization. Spectral analysis of low-frequency oscillations confirmed the presence of augmented spectral power in this frequency range during focused relative to distracted conditions. The findings demonstrate for the first time modulation of odor desensitization specifically by attentional factors, exemplifying the relevance of top-down control for ongoing perception of odor.

PESO - The Python Based Control System of the Ondrejov 2m Telescope

NASA Astrophysics Data System (ADS)

Skoda, P.; Fuchs, J.; Honsa, J.

2005-12-01

Python has been gaining a good reputation and respectability in many areas of software development. We have chosen Python after getting the new CCD detector for the coudé spectrograph of Ondřejov observatory 2m telescope. The VersArray detector from Roper Scientific came only with the closed source library PVCAM of low-level camera control functions for Linux, so we had to write the whole astronomical data acquisition system from scratch and integrate it with the current spectrograph and telescope control systems. The final result of our effort, PESO (Python Exposure System for Ondřejov) is a highly comfortable GUI-based environment allowing the observer to change the spectrograph configuration, choose the detector acquisition mode, select the exposure parameters, and monitor the exposure progress. All of the relevant information from the control computers is written into the FITS headers by the PyFITS module, and the acquired CCD frame is immediately displayed in an SAO DS9 window using XPA calls. The GTK-based front end design was drawn in the Glade visual development tool, giving the shape and position of all widgets in single XML file, which is used in Python by a simple call of the PyGlade module. We describe our experience with the design and implementation of PESO, stressing the easiness of quick changes of the GUI, together with the capability of separate testing of every module using the Python debugger, IPython.

Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages.

PubMed

Moretti, Sarah; Franchi, Silvia; Castelli, Mara; Amodeo, Giada; Somaini, Lorenzo; Panerai, Alberto; Sacerdote, Paola

2015-06-01

Cannabis use is frequent among adolescents. Its main component, delta-9-tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood. The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male mice were used. Acute THC administration induced a similar reduction of macrophage proinflammatory cytokines and an IL-10 increase in adult and adolescent mice. THC did not affect brain cytokines in adult mice, but a proinflammatory cytokine decrease was evident in the adolescent brain. A similar effect was present in the hypothalamus and hippocampus after 10 days' THC administration. In contrast, when brain cytokines were measured 47 days after the final THC administration, we observed an inverted effect in adult mice treated as adolescents, i.e., IL-1β and TNF-α increased and IL-10 decreased, indicating a shift toward neuroinflammation. These data suggest that THC exposure in adolescence has long-lasting effects on brain cytokines that parallel those present in the periphery. This modulation may affect vulnerability to immune and behavioural diseases in adulthood.

Investigation of the effects of long duration space exposure on active optical system components

NASA Technical Reports Server (NTRS)

Blue, M. D.

1994-01-01

This experiment was exposed to the space environment for 6 years on the Long Duration Exposure Facility (LDEF). It investigated quantitatively the effects of the long-duration space exposure on the relevant performance parameters of a representative set of electron-optic system components, including lasers, radiation detectors, filters, modulators, windows, and other related components. It evaluated the results and implications of the measurements indicating real or suspected degradation mechanisms. This information will be used to establish guidelines for the selection and use of components for space-based, electro-optic systems.

Evaluation of GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats.

PubMed

Hirani, Khemraj; Sharma, Ajay N; Jain, Nishant S; Ugale, Rajesh R; Chopde, Chandrabhan T

2005-07-01

Acute systemic ethanol administration is known to elevate plasma and cerebral levels of neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha, 5alpha-THP; allopregnanolone) to a concentration sufficient to potentiate GABA(A) receptors. We have earlier demonstrated that 3alpha, 5alpha-THP mediates the antidepressant-like effect of ethanol in Porsolt forced swim test. The aim of the present study is to explain the relationship between endogenous GABAergic neurosteroids and anxiolytic effect of ethanol in Sprague-Dawley rats. The mediation of 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol was assessed by pharmacological interactions of ethanol with various endogenous neurosteroidal modulators and using simulated physiological conditions of altered neurosteroid content in elevated plus maze (EPM) test. Pretreatment of 3alpha, 5alpha-THP (0.5-2.5 mug/rat, i.c.v.) or neurosteroidogenic agents such as 3alpha, 5alpha-THP precursor progesterone (5 or 10 mg/kg, i.p.), 11-beta hydroxylase inhibitor metyrapone (50 or 100 mg/kg, i.p.) or the GABA(A) receptor agonist muscimol (25 ng/rat, i.c.v.) significantly potentiated the anti-anxiety effect of ethanol (1 g/kg, i.p.). On the other hand, the GABAergic antagonistic neurosteroid dehydroepiandrosterone sulphate (DHEAS) (1 mg/kg, i.p.), the GABA(A) receptor blocker bicuculline (1 mg/kg, i.p.), the 5alpha-reductase inhibitor finasteride (50 x 2 mg/kg, s.c.) or the mitochondrial diazepam binding inhibitory receptor antagonist PK11195 (1 mg/kg, i.p.) reduced ethanol-induced preference of time spent and number of entries into open arms. Anti-anxiety effect of ethanol was abolished in adrenalectomized (ADX) rats as compared to sham-operated control. This ADX-induced blockade was restored by prior systemic injection of progesterone, signifying the contribution of peripheral steroidogenesis in ethanol anxiolysis. Socially isolated animals known to exhibit decreased brain 3alpha, 5alpha-THP and GABA(A) receptor functions displayed reduced sensitivity to the effects of ethanol and 3alpha, 5alpha-THP in EPM test. Our results demonstrated the contributory role of neuroactive steroid 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol. It is speculated that ethanol-induced modulation of endogenous GABAergic neurosteroids, especially 3alpha, 5alpha-THP, might be crucial pertinent to the etiology of 'trait' anxiety (tension reduction) and ethanol abuse.

Pupil Response and the Subliminal Mere Exposure Effect

PubMed Central

Yoshimoto, Sanae; Imai, Hisato; Kashino, Makio; Takeuchi, Tatsuto

2014-01-01

The subliminal mere exposure effect (SMEE) is the phenomenon wherein people tend to prefer patterns they have repeatedly observed without consciously identifying them. One popular explanation for the SMEE is that perceptual fluency within exposed patterns is misattributed to a feeling of preference for those patterns. Assuming that perceptual fluency is negatively correlated with the amount of mental effort needed to analyze perceptual aspects of incoming stimuli, pupil diameter should associate with SMEE strength since the former is known to reflect mental effort. To examine this hypothesis, we measured participants’ pupil diameter during exposure to subthreshold stimuli. Following exposure, a preference test was administered. Average pupil diameter throughout exposure was smaller when the SMEE was induced than when the SMEE was not induced. This supports the hypothesis that increasing perceptual fluency during mere exposure modulates autonomic nervous responses, such as pupil diameter, and eventually leads to preference. PMID:24587408

Pupil response and the subliminal mere exposure effect.

PubMed

Yoshimoto, Sanae; Imai, Hisato; Kashino, Makio; Takeuchi, Tatsuto

2014-01-01

The subliminal mere exposure effect (SMEE) is the phenomenon wherein people tend to prefer patterns they have repeatedly observed without consciously identifying them. One popular explanation for the SMEE is that perceptual fluency within exposed patterns is misattributed to a feeling of preference for those patterns. Assuming that perceptual fluency is negatively correlated with the amount of mental effort needed to analyze perceptual aspects of incoming stimuli, pupil diameter should associate with SMEE strength since the former is known to reflect mental effort. To examine this hypothesis, we measured participants' pupil diameter during exposure to subthreshold stimuli. Following exposure, a preference test was administered. Average pupil diameter throughout exposure was smaller when the SMEE was induced than when the SMEE was not induced. This supports the hypothesis that increasing perceptual fluency during mere exposure modulates autonomic nervous responses, such as pupil diameter, and eventually leads to preference.

Creation of diffraction-limited non-Airy multifocal arrays using a spatially shifted vortex beam

NASA Astrophysics Data System (ADS)

Lin, Han; Gu, Min

2013-02-01

Diffraction-limited non-Airy multifocal arrays are created by focusing a phase-modulated vortex beam through a high numerical-aperture objective. The modulated phase at the back aperture of the objective resulting from the superposition of two concentric phase-modulated vortex beams allows for the generation of a multifocal array of cylindrically polarized non-Airy patterns. Furthermore, we shift the spatial positions of the phase vortices to manipulate the intensity distribution at each focal spot, leading to the creation of a multifocal array of split-ring patterns. Our method is experimentally validated by generating the predicted phase modulation through a spatial light modulator. Consequently, the spatially shifted circularly polarized vortex beam adopted in a dynamic laser direct writing system facilitates the fabrication of a split-ring microstructure array in a polymer material by a single exposure of a femtosecond laser beam.

Candidate materials for advanced fire-resistant photovoltaic modules

NASA Technical Reports Server (NTRS)

Sugimura, R. S.; Otth, D. H.; Ross, R. G., Jr.; Arnett, J. C.; Samuelson, G.

1985-01-01

A cooperative, cost-sharing research effort to develop a technology base required to construct fire-ratable photovoltaic modules has resulted in the identification of several high-temperature, back-surface candidate materials capable of raising the fire-resistance of modules using hydrocarbon encapsulants to Class A and B levels. Advanced experimental module configurations have been developed using back surfaces consisting of Kapton, Tedlar laminates, metal-foils, and fiberglass materials with high-temperature coatings. Test results (October 1984; March 1985; May 1985; and October 1985) indicate that several of these advanced module configurations are capable of achieving Class B fire-resistance levels, while a few configurations can achieve Class A levels. The paper summarizes activities to date, discussing flammability failure mechanisms, time-temperature profiles, and results of Block V environmental exposure tests of a candidate material suitable for both Class B and Class A fire-resistance levels.

Thin film module electrical configuration versus electrical performance

NASA Technical Reports Server (NTRS)

Morel, D. L.

1985-01-01

The as made and degraded states of thin film silicon (TFS) based modules have been modelled in terms of series resistance losses. The origins of these losses lie in interface and bulk regions of the devices. When modules degrade under light exposure, increases occur in both the interface and bulk components of the loss based on series resistance. Actual module performance can thus be simulated by use of only one unknown parameter, shunt losses. Use of the simulation to optimize module design indicates that the current design of 25 cells per linear foot is near optimum. Degradation performance suggests a shift to approx. 35 cells to effect maximum output for applications not constrained to 12 volts. Earlier studies of energy based performance and tandem structures should be updated to include stability factors, not only the initial loss factor tested here, but also appropriate annealing factors.

The population dynamics of cancer: a Darwinian perspective.

PubMed

Vineis, Paolo; Berwick, Marianne

2006-10-01

Carcinogenesis, at least for some types of cancer, can be interpreted as the consequence of selection of mutated cells similar to what, in the theory of evolution, occurs at the population level. Instead of considering a population of organisms, we can refer to a population of cells belonging to multicellular organisms. Many carcinogens are mutagens, and the observed geographic distribution of cancer is, at least in part, attributable to environmental mutagens. However, the rapid change in risk for some cancers after migration suggests that carcinogenesis involves--in addition to mutations--some late event that most probably consists of the selection of cells already carrying mutations. We review a few examples of such selective pressures: finasteride in prostate cancer, vitamin supplementation in smokers, acquired resistance to chemotherapy, peripheral resistance to insulin, and sunlight and mutations in melanoma. A disease model for such a hypothesis is represented by Paroxysmal Nocturnal Hemoglobinuria (PNH). Mutations can be present at birth, as in the case of PNH, and can have a frequency much higher than the occurrence of the corresponding disease (PNH or lymphocytic leukaemia in children). However, PNH does not require a mutator phenotype, only a mutant phenotype followed by selection. A characteristic feature of cancer, instead, is likely to be the development of the mutator phenotype. We propose a 'Darwinian' model of carcinogenesis. If the model is correct, it suggests that prevention is more complex than avoiding exposure to mutagens. Mutations and genetic instability can be already present at birth. Mutations can be selected in the course of life if they increase survival advantage of the cell under certain environmental circumstances. In addition, gene-environment interactions cannot be interpreted according to a simplified linear model (based on the 'analysis of variance' concept); experimental work suggests that a more comprehensive non-linear interpretation based on the idea of 'norm of reaction' is needed.

Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.

PubMed

Bolukbasi, Yasemin; Saglam, Yucel; Selek, Ugur; Topkan, Erkan; Kataria, Anglina; Unal, Zeynep; Alpan, Vildan

2014-01-01

To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure. Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset. Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively. We found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.

Interventions for Children at Risk Due to Substance Exposure: Dealing with the Myth of Cocaine. A Series for Caregivers of Infants and Toddlers. Model for Interdisciplinary Training for Children with Handicaps: MITCH Module 13.

ERIC Educational Resources Information Center

Monroe County School District, Key West, FL.

Intended for use in Florida training programs for caregivers of infants and toddlers with disabilities, this guide presents an overview of the Model of Interdisciplinary Training for Children with Handicaps (MITCH); offers a user's guide to the series; and provides specific information for presenting Module 13, which focuses on interventions for…

Controlled Enhancemnt of Long-Term Memory by Modulating Neuronal miRNA Function

DTIC Science & Technology

2012-09-20

Faraday Ave. Carlsbad CA 92008 Prepare antisense oligonucleotides 8/1/2007 12:00:00AM 2/1/2009 12:00:00AM Sub Contractor Numbers (c): Patent Clause...with ampakines. However, ampakines that accomplish positive modulation have shown undesired clinical side effects . Another approach is to improve...of times that a mouse touches objects introduced into the cage in a fixed period of time. Objects are either “old” (prior exposure) or “new” (not