Minocycline down-regulates topical mucosal inflammation during the application of microbicide candidates.

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Liangzhu Li

Full Text Available An effective anti-human immunodeficiency virus-1 (HIV-1 microbicide should exert its action in the absence of causing aberrant activation of topical immunity that will increase the risk of HIV acquisition. In the present study, we demonstrated that the vaginal application of cellulose sulfate (CS gel induced topical mucosal inflammatory responses; the addition of minocycline to CS gel could significantly attenuate the inflammation in a mice model. The combined gel of CS plus minocycline not only reduced the production of inflammatory cytokines in cervicovaginal lavages (CVLs, also down-regulated the activation of CD4+ T cells and the recruitment of other immune cells including HIV target cells into vaginal tissues. Furthermore, an In vitro HIV-1 pseudovirus infection inhibition assay showed that the combined gel decreased the infection efficacy of different subtypes of HIV-1 pseudoviruses compared with that of CS gel alone. These results implicate that minocycline could be integrated into microbicide formulation to suppress the aberrant activation of topical mucosal immunity and enhance the safety profile during the application of microbicides.

Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

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Nel, Annalene M; Coplan, Paul; Smythe, Shanique C; McCord, Karen; Mitchnick, Mark; Kaptur, Paulina E; Romano, Joseph

2010-11-01

To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice daily on Days 2-9. Pharmacokinetics of dapivirine were assessed in plasma on Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory tests (hematology, clinical chemistry, and urinalysis), physical examinations, and assessment of adverse events. Plasma concentrations of dapivirine increased over time with gel dose and were greater on Day 10 (C(max) 31 to 471 pg/ml) than Day 1 (C(max) 23 to 80 pg/ml). T(max) was 10-12 h on Day 1, and 9 h on Day 10. Concentrations in CVF generally increased with dose but were highly variable among participants. Mean peak values ranged from 4.6-8.3 × 10(6) pg/ml on Day 1 and from 2.3-20.7 × 10(6) pg/ml on Day 10 across dose groups. Dapivirine was detectable in all tissue biopsies on Day 10 at concentrations of 1.0-356 × 10(3) pg/mg. Dapivirine was widely distributed throughout the lower genital tract with low systemic absorption when administered in a vaginal gel formulation for 10 consecutive days. The gel was safe and well tolerated.

Animal models for microbicide safety and efficacy testing.

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Veazey, Ronald S

2013-07-01

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients.

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Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim

2012-11-01

In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9 on the Upper Female Reproductive Tract: A Randomized Crossover Study.

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Karen Smith-McCune

Full Text Available Intravaginal anti-HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract might contribute to the lower-than-expected efficacy of HIV microbicides. Our objective was to study the effects of intravaginal gels on the immune microenvironment of the cervix and uterus. In this randomized crossover study, 27 healthy female volunteers used a nightly application of intravaginal nonoxynol-9 (N9 gel as a "failed" microbicide or the universal placebo gel (UPG as a "safe" gel (intervention cycles, or nothing (control cycle from the end of menses to the mid-luteal phase. At a specific time-point following ovulation, all participants underwent sample collection for measurements of T-cell phenotypes, gene expression, and cytokine/chemokine protein concentrations from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI intervention effects, for N9 and UPG relative to control. Exposure to N9 gel and UPG generated a common "harm signal" that included transcriptional up-regulation of inflammatory genes chemokine (C-C motif ligand 20 (macrophage inflammatory factor-3alpha and interleukin 8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor, and transcriptional up-regulation of inflammatory mediators glycodelin-A and osteopontin in the endometrium. These results need to be replicated with a larger sample, but underscore the need to consider the effects of microbicide agents and gel excipients on the upper female reproductive tract in studies of vaginal microbicides.

The use of supersaturation for the vaginal application of microbicides: a case study with dapivirine.

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Grammen, Carolien; Plum, Jakob; Van Den Brande, Jeroen; Darville, Nicolas; Augustyns, Koen; Augustijns, Patrick; Brouwers, Joachim

2014-11-01

In this study, we investigated the potential of supersaturation for the formulation of the poorly water-soluble microbicide dapivirine (DPV) in an aqueous vaginal gel in order to enhance its vaginal tissue uptake. Different excipients such as hydroxypropylmethylcellulose, polyethylene glycol 1000, and cyclodextrins were evaluated for their ability to inhibit precipitation of supersaturated DPV in the formulation vehicle as such as well as in biorelevant media. In vitro permeation assessment across HEC-1A cell layers demonstrated an enhanced DPV flux from supersaturated gels compared with suspension gels. The best performing supersaturated gel containing 500 μM DPV (supersaturation degree of 4) in the presence of sulfobutyl ether-beta-cyclodextrin (2.5%) appeared to be stable for at least 3 months. In addition, the gel generated a significant increase in vaginal drug uptake in rabbits as compared with suspension gels. We conclude that supersaturation is a possible strategy to enhance the vaginal concentration of hydrophobic microbicides, thereby increasing permeation into the vaginal submucosa. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.

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Whaley, Kevin J; Hanes, Justin; Shattock, Robin; Cone, Richard A; Friend, David R

2010-12-01

The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

Toll-Like Receptors and Cytokines as Surrogate Biomarkers for Evaluating Vaginal Immune Response following Microbicide Administration

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Sadhana M. Gupta

2008-01-01

Full Text Available Topical microbicides are intended for frequent use by women in reproductive age. Hence, it is essential to evaluate their impact on mucosal immune function in the vagina. In the present study, we evaluated nisin, a naturally occurring antimicrobial peptide (AMP, for its efficacy as an intravaginal microbicide. Its effect on the vaginal immune function was determined by localizing Toll-like receptors (TLRs-3, 9 and cytokines (IL-4, 6 , 10 and TNF-α in the rabbit cervicovaginal epithelium following intravaginal administration of high dose of nisin gel for 14 consecutive days. The results revealed no alteration in the expression of TLRs and cytokines at both protein and mRNA levels. However, in SDS gel-treated group, the levels were significantly upregulated with the induction of NF-κB signalling cascade. Thus, TLRs and cytokines appear as sensitive indicators for screening immunotoxic potential of candidate microbicides.

Toll-like receptors and cytokines as surrogate biomarkers for evaluating vaginal immune response following microbicide administration.

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Gupta, Sadhana M; Aranha, Clara C; Mohanty, Madhu C; Reddy, K V R

2008-01-01

Topical microbicides are intended for frequent use by women in reproductive age. Hence, it is essential to evaluate their impact on mucosal immune function in the vagina. In the present study, we evaluated nisin, a naturally occurring antimicrobial peptide (AMP), for its efficacy as an intravaginal microbicide. Its effect on the vaginal immune function was determined by localizing Toll-like receptors (TLRs-3, 9) and cytokines (IL-4, 6 , 10 and TNF-alpha) in the rabbit cervicovaginal epithelium following intravaginal administration of high dose of nisin gel for 14 consecutive days. The results revealed no alteration in the expression of TLRs and cytokines at both protein and mRNA levels. However, in SDS gel-treated group, the levels were significantly upregulated with the induction of NF-kappaB signalling cascade. Thus, TLRs and cytokines appear as sensitive indicators for screening immunotoxic potential of candidate microbicides.

Mathematical model of microbicidal flow dynamics and optimization of rheological properties for intra-vaginal drug delivery: Role of tissue mechanics and fluid rheology.

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Anwar, Md Rajib; Camarda, Kyle V; Kieweg, Sarah L

2015-06-25

Topically applied microbicide gels can provide a self-administered and effective strategy to prevent sexually transmitted infections (STIs). We have investigated the interplay between vaginal tissue elasticity and the yield-stress of non-Newtonian fluids during microbicide deployment. We have developed a mathematical model of tissue deformation driven spreading of microbicidal gels based on thin film lubrication approximation and demonstrated the effect of tissue elasticity and fluid yield-stress on the spreading dynamics. Our results show that both elasticity of tissue and yield-stress rheology of gel are strong determinants of the coating behavior. An optimization framework has been demonstrated which leverages the flow dynamics of yield-stress fluid during deployment to maximize retention while reaching target coating length for a given tissue elasticity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antiviral and immunological effects of tenofovir microbicide in vaginal herpes simplex virus 2 infection.

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Vibholm, Line; Reinert, Line S; Søgaard, Ole S; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Melchjorsen, Jesper

2012-11-01

The anti-HIV microbicide, tenofovir (TFV) gel, has been shown to decrease HIV-1 acquisition by 39% and reduce herpes simplex virus 2 (HSV-2) transmission by 51%. We evaluated the effect of a 1% TFV gel on genital HSV-2 infection in a mouse vaginal challenge model. In vitro plaque assays and luminex multiplex bead analysis were used, respectively, to measure postinfection vaginal viral shedding (day 1) and cytokine secretion (day 2). To further investigate the anti-HSV-2 properties, we evaluated the direct antiviral effect of TFV and the oral prodrug tenofovir disoproxil fumerate (TDF) in cell culture. Compared to placebo-treated mice, TFV-treated mice had significantly lower clinical scores, developed later genital lesions, and showed reduced vaginal viral shedding. Furthermore, the levels of IFN-γ, IL-2, TNF-α, and other cytokines were altered in the vaginal fluid following topical tenofovir treatment and subsequent HSV-2 challenge. Finally, we found that both TFV and TDF inhibited HSV-2 infection in vitro; TDF showed a 50-fold greater potency than TFV. In conclusion, we confirmed that the microbicide TFV had direct anti-HSV-2 effects in a murine vaginal challenge model. Therefore, this model would be suitable for evaluating present and future microbicide candidates. Furthermore, the present study warrants further investigation of TDF in microbicides.

Twice-daily application of HIV microbicides alter the vaginal microbiota.

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Ravel, Jacques; Gajer, Pawel; Fu, Li; Mauck, Christine K; Koenig, Sara S K; Sakamoto, Joyce; Motsinger-Reif, Alison A; Doncel, Gustavo F; Zeichner, Steven L

2012-12-18

Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 study of twice-daily application over 13.5 days of 1 of 3 gel products: a hydroxyethylcellulose (HEC)-based "universal" placebo (10 subjects), 6% cellulose sulfate (CS; 13 subjects), and 4% nonoxynol-9 (N-9; 12 subjects). We used mixed effects models inferred using Bayesian Markov chain Monte Carlo methods, which showed that treatment with active agents shifted the microbiota toward a community type lacking significant numbers of Lactobacillus spp. and dominated by strict anaerobes. This state of the vaginal microbiota was associated with a low or intermediate Nugent score and was not identical to bacterial vaginosis, an HIV transmission risk factor. The placebo arm contained a higher proportion of communities dominated by Lactobacillus spp., particularly L. crispatus, throughout treatment. The data suggest that molecular evaluation of microbicide effects on vaginal microbiota may be a critical endpoint that should be incorporated in early clinical assessment of microbicide candidates. Despite large prevention efforts, HIV transmission and acquisition rates remain unacceptably high. In developing countries, transmission mainly occurs through heterosexual intercourse, where women are significantly more vulnerable to infection than men. Vaginal microbicides are considered to

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes.

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Notario-Pérez, Fernando; Ruiz-Caro, Roberto; Veiga-Ochoa, María-Dolores

2017-01-01

Infection with human immunodeficiency virus (HIV) remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV.

48 CFR 752.7013 - Contractor-mission relationships.

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2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contractor-mission....7013 Contractor-mission relationships. For use in all USAID contracts involving performance overseas.... Contractor-Mission Relationships (OCT 1989) (a) The Contractor acknowledges that this contract is an...

Vaginal microbicides and teenagers.

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Rupp, Richard E; Rosenthal, Susan L

2003-10-01

Sexually active teens are at significant risk from sexually transmitted infections and girls and women bear the greatest burden of these infections. New methods, such as vaginal microbicides, would provide female controlled options. Microbicides are currently in development and thus it is timely to discuss the progress made and factors that may influence acceptability for teens. Microbicide development presents many challenges, and several different potential mechanisms of action are being explored. There is interest in these products from women and men, and specific preferences are being investigated. Adolescents, due to reproductive system immaturity, developing cognitive abilities and the psychosocial context of their relationships, present a special set of challenges in efforts to foster microbicide use. Vaginal microbicides are on the horizon. Further study into teen issues is required to develop successful strategies for marketing and encouraging adolescent use of microbicides.

Testing of viscous anti-HIV microbicides using Lactobacillus

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Moncla, B.J.; Pryke, K.; Rohan, L. C.; Yang, H.

2011-01-01

The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30 min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To...

Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes

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Notario-Pérez F

2017-06-01

Full Text Available Fernando Notario-Pérez, Roberto Ruiz-Caro, María-Dolores Veiga-Ochoa Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain Abstract: Infection with human immunodeficiency virus (HIV remains a global public health concern and is particularly serious in low- and middle-income countries. Widespread sexual violence and poverty, among other factors, increase the risk of infection in women, while currently available prevention methods are outside the control of most. This has driven the study of vaginal microbicides to prevent sexual transmission of HIV from men to women in recent decades. The first microbicides evaluated were formulated as gels for daily use and contained different substances such as surfactants, acidifiers and monoclonal antibodies, which failed to demonstrate efficacy in clinical trials. A gel containing the reverse transcriptase inhibitor tenofovir showed protective efficacy in women. However, the lack of adherence by patients led to the search for dosage forms capable of releasing the active principle for longer periods, and hence to the emergence of the vaginal ring loaded with dapivirine, which requires a monthly application and is able to reduce the sexual transmission of HIV. The future of vaginal microbicides will feature the use of alternative dosage forms, nanosystems for drug release and probiotics, which have emerged as potential microbicides but are still in the early stages of development. Protecting women with vaginal microbicide formulations would, therefore, be a valuable tool for avoiding sexual transmission of HIV. Keywords: vaginal formulations, microbicides, prevention, sexual transmission, acquired immunodeficiency syndrome (AIDS, human immunodeficiency virus (HIV

Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission

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Abusuwwa Raed

2006-06-01

Full Text Available Abstract Background Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9 and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a Directly tests for toxic effects that increase susceptibility to HSV-2, (b Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c Identifies those toxic effects that best correlate with the increased HSV susceptibility. Methods Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50 at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9, cationic (benzalkonium chloride, BZK, anionic (sodium dodecylsulfate, SDS, the pair of detergents in C31G (C14AO and C16B; one surface active agent (chlorhexidine; two non-detergents (BufferGel®, and sulfonated polystyrene, SPS; and HEC placebo gel (hydroxyethylcellulose. Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. Results A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible signs of the N9 toxic effect that increased susceptibility at 12 hours. Toxic

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women.

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Carballo-Diéguez, Alex; Balán, Ivan C; Brown, William; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Marzinke, Mark A; Hendrix, Craig W; Piper, Jeanna M; Richardson, Barbra A; Grossman, Cynthia; Johnson, Sherri; Gomez, Kailazarid; Horn, Stephanie; Kunjara Na Ayudhya, Ratiya Pamela; Patterson, Karen; Jacobson, Cindy; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H; Liu, Albert; Mayer, Kenneth H; Zorrilla, Carmen; Lama, Javier; McGowan, Ian; Cranston, Ross D

2017-01-01

Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP achieved in MTN-017 among men who have sex with men (MSM and transgender women.

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Alex Carballo-Diéguez

Full Text Available Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1 daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, 2 daily use of reduced-glycerin 1% tenofovir (RG-TFV gel applied rectally, and 3 RG-TFV gel applied before and after receptive anal intercourse (RAI-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187 were men who have sex with men and transgender women enrolled in the United States (42%, Thailand (29%, Peru (19% and South Africa (10%. Mean age was 31.4 years (range 18-64 years. Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals

Status of the SPL at CERN

CERN Document Server

Garoby, R

2007-01-01

The construction of the Large Hadron Collider at CERN is in its final phase, and commissioning with beam is scheduled to begin before the end of 2007. It is now time to prepare for increasing as much as possible the performance of this unique instrument to maximize the benefits for physics. An essential part of the proposed luminosity upgrade plan is the replacement of the CERN PS and its injectors by a 50 GeV proton synchrotron (PS2) and a 4 GeV superconducting linac (SPL). The design of the SPL has recently been updated and the optimization of its high-energy part will continue until ~2010. For the foreseen luminosity upgrade of the LHC a low-power version of the SPL (LP-SPL) is under study, which can be upgraded to a multi-megawatt machine providing beam to high-power proton users such as neutrino facilities and/or radio-active beam facilities. The construction start of the low-energy normal conducting SPL front-end, the 160 MeV "Linac4", is scheduled for January 2008, with the goal of being operational as...

Reverse transcriptase inhibitors as microbicides.

Science.gov (United States)

Lewi, Paul; Heeres, Jan; Ariën, Kevin; Venkatraj, Muthusamy; Joossens, Jurgen; Van der Veken, Pieter; Augustyns, Koen; Vanham, Guido

2012-01-01

The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a "gatekeeper" for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies.

Magnetic stripping studies for SPL

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Posocco, P; CERN. Geneva. BE Department

2010-01-01

Magnetic stripping of H- can seriously enhance the beam losses along the SPL machine. These losses depend on the beam energy, on the beam transverse distribution and on the intensity of the magnetic field. For radioprotection issues the losses must be limited to 1 W/m. In this paper we will concentrate on the stripping phenomena inside the quadrupole magnets with the aim of defining the quadrupole range for the design phase of SPL.

Microbicides 2006 conference

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McGowan Ian

2006-10-01

Full Text Available Abstract Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23–26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities.

Microbicide clinical trial adherence: insights for introduction.

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Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

2013-04-08

After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

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Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

2008-03-01

The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

International Nuclear Information System (INIS)

Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

2016-01-01

Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4. (paper)

Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

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Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

2016-10-01

Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

Microbicides in the prevention of HIV infection: current status and future directions.

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Nuttall, Jeremy

2010-07-09

More than 28 years since the first cases of HIV/AIDS, there is still no cure or vaccine. The worst affected region is sub-Saharan Africa and, increasingly, it is young women who are bearing the brunt of the epidemic. Consequently, there is an urgent need for HIV prevention options for women in developing countries. Microbicides are topical products that can be used vaginally by women to impede sexual transmission of HIV and thus represent one of the most promising prevention strategies. Efficacy trials with early nonspecific microbicide gels have so far been unsuccessful, but the field has now switched its focus to products containing highly potent and highly specific antiretroviral drugs that are easier to use, and can be formulated in a variety of dosage forms to suit individual and regional preferences. However, these products have their own challenges, with a greater likelihood of absorption, and the potential for systemic toxicities or the development of resistance in infected individuals who are unaware of their HIV status. The conduct of clinical trials is complex for all microbicides, with limited availability of trial sites, difficulties in dose selection and safety monitoring, and a lack of a truly objective measure of adherence. Once a microbicide has been shown to be safe and effective, there will need to be a clear pathway to regulatory approval, and the successful launch of a product will depend on having in place appropriate methods for distribution to the women who need it, along with a strategy for ensuring that they use it correctly. This will require substantial effort in terms of education and community engagement, and these activities need to be initiated well in advance of microbicide rollout.

In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide.

Directory of Open Access Journals (Sweden)

Lisa C Rohan

2010-02-01

Full Text Available Tenofovir gel has entered into clinical trials for use as a topical microbicide to prevent HIV-1 infection but has no published data regarding pre-clinical testing using in vitro and ex vivo models. To validate our findings with on-going clinical trial results, we evaluated topical tenofovir gel for safety and efficacy. We also modeled systemic application of tenofovir for efficacy.Formulation assessment of tenofovir gel included osmolality, viscosity, in vitro release, and permeability testing. Safety was evaluated by measuring the effect on the viability of vaginal flora, PBMCs, epithelial cells, and ectocervical and colorectal explant tissues. For efficacy testing, PBMCs were cultured with tenofovir or vehicle control gels and HIV-1 representing subtypes A, B, and C. Additionally, polarized ectocervical and colorectal explant cultures were treated apically with either gel. Tenofovir was added basolaterally to simulate systemic application. All tissues were challenged with HIV-1 applied apically. Infection was assessed by measuring p24 by ELISA on collected supernatants and immunohistochemistry for ectocervical explants. Formulation testing showed the tenofovir and vehicle control gels were >10 times isosmolar. Permeability through ectocervical tissue was variable but in all cases the receptor compartment drug concentration reached levels that inhibit HIV-1 infection in vitro. The gels were non-toxic toward vaginal flora, PBMCs, or epithelial cells. A transient reduction in epithelial monolayer integrity and epithelial fracture for ectocervical and colorectal explants was noted and likely due to the hyperosmolar nature of the formulation. Tenofovir gel prevented HIV-1 infection of PBMCs regardless of HIV-1 subtype. Topical and systemic tenofovir were effective at preventing HIV-1 infection of explant cultures.These studies provide a mechanism for pre-clinical prediction of safety and efficacy of formulated microbicides. Tenofovir was effective

Will dapivirine redeem the promises of anti-HIV microbicides? Overview of product design and clinical testing.

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das Neves, José; Martins, João Pedro; Sarmento, Bruno

2016-08-01

Microbicides are being developed in order to prevent sexual transmission of HIV. Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is one of the leading drug candidates in the field, currently being tested in various dosage forms, namely vaginal rings, gels, and films. In particular, a ring allowing sustained drug release for 1month is in an advanced stage of clinical testing. Two parallel phase III clinical trials are underway in sub-Saharan Africa and results are expected to be released in early 2016. This article overviews the development of dapivirine and its multiple products as potential microbicides, with particular emphasis being placed on clinical evaluation. Also, critical aspects regarding regulatory approval, manufacturing, distribution, and access are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Acceptability of a novel vaginal microbicide during a safety trial among low-risk women.

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Bentley, M E; Morrow, K M; Fullem, A; Chesney, M A; Horton, S D; Rosenberg, Z; Mayer, K H

2000-01-01

The increasing recognition that women who are unable or unwilling to discuss or use condoms with their sexual partners need female-controlled methods for preventing sexually transmitted diseases (STDs), including HIV, has led to considerable focus on the development of vaginal microbicides. While many such products are being tested for safety and effectiveness, clinical trials generally overlook another key factor in a product's impact on infection rates-its acceptability to users. A Phase I clinical trial of a microbicidal gel included an assessment of the product's acceptability among 27 low-risk participants. Information on acceptability was gathered from structured interviews, participants' daily diaries and unstructured exit interviews. Participants reported only minor side effects of product use, such as itching, burning and difficulty urinating; two women developed candida infections while participating in the study. None of the side effects could be conclusively linked to use of the gel. Some women noted product discharge and messiness as drawbacks of the method, but this experience varied according to how often the women applied the gel. For example, one-third of those who used it once daily said that at least some of the time, it was too "wet or drippy," compared with two-thirds of women who inserted the gel twice a day. However, participants considered these "nuisance factors" that could be outweighed by the potential protective characteristics of the product. The majority reported that they would use the product if it were available and proven efficacious, and if they perceived that they were at risk of STD infection. Additional testing of this product is urgently needed. Furthermore, as other products approach Phase I testing, acceptability assessments should be a key component of clinical trials.

Quantitative perceptual differences among over-the-counter vaginal products using a standardized methodology: implications for microbicide development.

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Mahan, Ellen D; Morrow, Kathleen M; Hayes, John E

2011-08-01

Increasing prevalence of HIV infection among women worldwide has motivated the development of female-initiated prevention methods, including gel-based microbicides. User acceptability is vital for microbicide success; however, varying cultural vaginal practices indicate multiple formulations must be developed to appeal to different populations. Perceptual attributes of microbicides have been identified as primary drivers of acceptability; however, previous studies do not allow for direct comparison of these qualities between multiple formulations. Six vaginal products were analyzed ex vivo using descriptive analysis. Perceptual attributes of samples were identified by trained participants (n=10) and rated quantitatively using scales based on a panel-developed lexicon. Data were analyzed using two-way ANOVAs for each attribute; product differences were assessed via Tukey's honestly significant difference test. Significant differences were found between products for multiple attributes. Patterns were also seen for attributes across intended product usage (i.e., contraceptive, moisturizer or lubricant). For example, Options© Gynol II® (Caldwell Consumer Health, LLC) was significantly stickier and grainier than other products. Descriptive analysis, a quantitative approach that is based on consensus lexicon usage among participants, successfully quantified perceptual differences among vaginal products. Since perceptual attributes of products can be directly compared quantitatively, this study represents a novel approach that could be used to inform rational design of microbicides. Copyright © 2011 Elsevier Inc. All rights reserved.

Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

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Dezzutti Charlene

2011-03-01

Full Text Available Abstract Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic. Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.

Microbicides in India-present and future

Directory of Open Access Journals (Sweden)

Nath A

2009-01-01

Full Text Available India continues to wage a battle against the human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS epidemic. Despite an array of preventive and control efforts directed against the disease, it continues to finds its way from the high risk groups to the general population. Women are more vulnerable to HIV/AIDS because of biological as well as socio-cultural factors. Microbicides appear to provide an attractive option as a means of protection to be used by women. At present, microbicide trials are in study phases I and II in India. The development of an ideal microbicide candidate which would be effective and confirms to user satisfaction poses a major challenge to researchers.

Nanomedicine in the development of anti-HIV microbicides.

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das Neves, José; Nunes, Rute; Rodrigues, Francisca; Sarmento, Bruno

2016-08-01

Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre-exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline. One particularly interesting approach comprises the application of nanomedicine principles to the development of novel anti-HIV microbicides, but its implications to efficacy and safety are not yet fully understood. Nanotechnology-based systems, either presenting inherent anti-HIV activity or acting as drug nanocarriers, may significantly influence features such as drug solubility, stability of active payloads, drug release, interactions between active moieties and virus/cells, intracellular drug delivery, drug targeting, safety, antiviral activity, mucoadhesive behavior, drug distribution and tissue penetration, and pharmacokinetics. The present manuscript provides a comprehensive and holistic overview of these topics as relevant to the development of vaginal and rectal microbicides. In particular, recent advances pertaining inherently active microbicide nanosystems and microbicide drug nanocarriers are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Developmental Functions of miR156-Regulated SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) Genes in Arabidopsis thaliana.

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Xu, Mingli; Hu, Tieqiang; Zhao, Jianfei; Park, Mee-Yeon; Earley, Keith W; Wu, Gang; Yang, Li; Poethig, R Scott

2016-08-01

Correct developmental timing is essential for plant fitness and reproductive success. Two important transitions in shoot development-the juvenile-to-adult vegetative transition and the vegetative-to-reproductive transition-are mediated by a group of genes targeted by miR156, SQUAMOSA PROMOTER BINDING PROTEIN (SBP) genes. To determine the developmental functions of these genes in Arabidopsis thaliana, we characterized their expression patterns, and their gain-of-function and loss-of-function phenotypes. Our results reveal that SBP-LIKE (SPL) genes in Arabidopsis can be divided into three functionally distinct groups: 1) SPL2, SPL9, SPL10, SPL11, SPL13 and SPL15 contribute to both the juvenile-to-adult vegetative transition and the vegetative-to-reproductive transition, with SPL9, SP13 and SPL15 being more important for these processes than SPL2, SPL10 and SPL11; 2) SPL3, SPL4 and SPL5 do not play a major role in vegetative phase change or floral induction, but promote the floral meristem identity transition; 3) SPL6 does not have a major function in shoot morphogenesis, but may be important for certain physiological processes. We also found that miR156-regulated SPL genes repress adventitious root development, providing an explanation for the observation that the capacity for adventitious root production declines as the shoot ages. miR156 is expressed at very high levels in young seedlings, and declines in abundance as the shoot develops. It completely blocks the expression of its SPL targets in the first two leaves of the rosette, and represses these genes to different degrees at later stages of development, primarily by promoting their translational repression. These results provide a framework for future studies of this multifunctional family of transcription factors, and offer new insights into the role of miR156 in Arabidopsis development.

Mucosal effects of tenofovir 1% gel.

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Hladik, Florian; Burgener, Adam; Ballweber, Lamar; Gottardo, Raphael; Vojtech, Lucia; Fourati, Slim; Dai, James Y; Cameron, Mark J; Strobl, Johanna; Hughes, Sean M; Hoesley, Craig; Andrew, Philip; Johnson, Sherri; Piper, Jeanna; Friend, David R; Ball, T Blake; Cranston, Ross D; Mayer, Kenneth H; McElrath, M Juliana; McGowan, Ian

2015-02-03

Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored.

Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide.

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Woolfson, A David; Malcolm, R Karl; Morrow, Ryan J; Toner, Clare F; McCullagh, Stephen D

2006-11-15

TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients

Mucosal integrity and inflammatory markers in the female lower genital tract as potential screening tools for vaginal microbicides.

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Su, H Irene; Schreiber, Courtney A; Fay, Courtney; Parry, Sam; Elovitz, Michal A; Zhang, Jian; Shaunik, Alka; Barnhart, Kurt

2011-11-01

In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety. A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI). Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1β (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel. Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study. Copyright © 2011 Elsevier Inc. All rights reserved.

Influences of geo-spatial location on pre-exposure prophylaxis use in South Africa: positioning microbicides for better product uptake.

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Govender, Eliza M; Mansoor, Leila E; Abdool Karim, Quarraisha

2017-06-01

Young women bear a disproportionately high burden of HIV infection in sub-Saharan Africa, prioritising pre-exposure prophylaxis (PrEP) can be an integral part of HIV prevention combination strategies. Women initiated HIV prevention technology options will require consistent adherence, an imperative for product effectiveness. With several PrEP clinical trials underway; exploring women's acceptability to advances in HIV prevention technologies can better facilitate demand creation for future PrEP roll out. This study utilised the opportunity of post-trial access to CAPRISA 008 women (trial) and non-trial women from three geo-spatial settings (urban, rural and peri-urban) to identify microbicide acceptability and how product associations of microbicides can influence future HIV prevention choices. Six participatory workshops using participatory action research with art-based activities and discussion groups were conducted in KwaZulu-Natal with 104 women from various geo-spatial locations and social status to understand microbicide acceptability and product associations. The data were analysed using thematic analysis. The study found that women's acceptability and product association of the tenofovir gel microbicide differed according to rural and urban areas. Most urban women identified confidence, sexiness and classiness as key associations that will encourage microbicide acceptability and use, while rural women identified respect, responsibility and confidence as the key product associations, with increased focus on the individual and collective family/community benefits of product acceptance and use. Urban-rural differences suggest a market segmentation that is contextualised to be locally responsive to promote HIV prevention technologies. Various sexual encounters further determined the types of HIV prevention technologies women would consider. In line with WHO's recommendation that PrEP should be an additional prevention choice for people at risk of HIV, this

Young women's contraceptive microbicide preferences: associations with contraceptive behavior and sexual relationship characteristics.

Science.gov (United States)

Best, Candace; Tanner, Amanda E; Hensel, Devon J; Fortenberry, J Dennis; Zimet, Gregory D

2014-03-01

In time, microbicides may provide women with dual prevention against pregnancy and STDs. Although several microbicide dimensions have been evaluated, little is known about women's preferences for contraceptive microbicides and correlates of these preferences. Acceptability of a hypothetical contraceptive microbicide cream or jelly was examined among a -clinic-based sample of 266 women in Indianapolis from 2004 (when participants were aged 14-22) to 2008. Group conjoint analyses and individual conjoint analyses were used to compare preferences with respect to four microbicide -dimensions: contraceptive ability, efficacy in relation to condoms, timing of use and texture. Pearson's product moment correlations were used to examine the relationship between preferences for a contraceptive microbicide and selected characteristics of the women. Overall, the top-rated microbicide dimensions were efficacy in relation to that of condoms and contraceptive ability (importance scores, 40.0 and 35.4 out of 100.0, respectively). When all dimension levels were compared, contraceptive ability was the most strongly preferred (part-worth utility score, 8.9), and lower efficacy than that of -condoms was the least strongly preferred (-11.9). Preference for contraceptive microbicides was positively -associated with current contraceptive use, sexual agency, partner communication, commitment to avoiding pregnancy and -perceived partner agreement about avoiding pregnancy (coefficients, 0.07-0.18). It was negatively associated with current or past nonuse of contraceptives, seeking pregnancy and perceived partner agreement about seeking -pregnancy (-0.08 to -0.14). Microbicides with dual prevention properties may be attractive to young women. Microbicide development and subsequent clinical trials should incorporate contraceptive microbicides. Copyright © 2013 by the Guttmacher Institute.

On-demand microbicide products: design matters.

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Patel, Sravan Kumar; Rohan, Lisa Cencia

2017-12-01

Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e., immediately before or after sex) can be part of an effective tool kit utilized to prevent sexual transmission of HIV. The effectiveness of prevention products is positively correlated with adherence, which is likely to depend on user acceptability of the product. The development of an efficacious and acceptable product is therefore paramount for the success of an on-demand product. Acceptability of on-demand products (e.g., gels, films, and tablets) and their attributes is influenced by a multitude of user-specific factors that span behavioral, lifestyle, socio-economic, and cultural aspects. In addition, physicochemical properties of the drug, anatomical and physiological aspects of anorectal and vaginal compartments, issues relating to large-scale production, and cost can impact product development. These factors together with user preferences determine the design space of an effective, acceptable, and feasible on-demand product. In this review, we summarize the interacting factors that together determine product choice and its target product profile.

Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

International Nuclear Information System (INIS)

Giri, Namita; Oh, Byeongtaek; Lee, Chi H.

2016-01-01

This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100"® (ES100"®), a pH-sensitive polymer. ES100"® NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100"® NPs. The morphology of the ES100"® NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100"® NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100"® NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100"® NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100"® NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100"® NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100"® NPs were taken by vaginal epithelial cells through

Performance of Superconducting Cavities as Required for the SPL

CERN Document Server

Weingarten, Wolfgang

2008-01-01

This document outlines an optimisation analysis for the RF cavities of the planned Superconducting Proton Linac (SPL) at CERN with regard to the operating frequency and temperature. The analysis is based on a phenomenological assessment of the field dependent Q-value, as taken from published test results from RF cavities of various proveniences. It turns out that the design Q-value at an accelerating gradient of 25 MV/m ($\\Beta$ = 1 cavity) of $1^{.}10^{10}$ at 704 (1408) MHz is attainable at 1.9 (1.6) K, respectively, however, with the present state-of-the-art manufacturing, at the expense of some reprocessing. The optimum of the total electrical grid power consumption (composed of RF and cryogenics) is estimated as a function of frequency and operating temperature for both the low and high power SPL. This document outlines an optimisation analysis for the RF cavities of the planned Superconducting Proton Linac (SPL) at CERN with regard to the operating frequency and temperature. The analysis is based on a p...

Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network.

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Wei, Shu; Gruber, Margaret Y; Yu, Bianyun; Gao, Ming-Jun; Khachatourians, George G; Hegedus, Dwayne D; Parkin, Isobel A P; Hannoufa, Abdelali

2012-09-18

The Arabidopsis microRNA156 (miR156) regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT) ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated) SPL15 (SPL15m) largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n) and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro interaction between DNA-binding SBP domain of SPL15

A Randomized Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures (MTN 012/IPM 010)

OpenAIRE

Cranston, Ross D.; Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W.; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M.

2014-01-01

Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 se...

File list: Pol.Spl.10.RNA_Polymerase_III.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Spl.10.RNA_Polymerase_III.AllCell mm9 RNA polymerase RNA Polymerase III Spleen ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Spl.10.RNA_Polymerase_III.AllCell.bed ...

Using design rationale to improve SPL traceability

NARCIS (Netherlands)

Galvao, I.; Aksit, Mehmet; van den Broek, P.M.; Hendriks, M.F.H.; Rashid, Awais; Royer, Jean-Claude; Rummler, Andreas

In order to improve SPL traceability by using design rationale, this chapter introduces the traceability analysis framework (TAF), which, when combined with the AMPLE Traceability Framework, provides extra traceability capabilities for variability management. The TAF is a programmable and extensible

Functional evolution in the plant SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL gene family

Directory of Open Access Journals (Sweden)

Jill Christine Preston

2013-04-01

Full Text Available The SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL family of transcription factors is functionally diverse, controlling a number of fundamental aspects of plant growth and development, including vegetative phase change, flowering time, branching, and leaf initiation rate. In natural plant populations, variation in flowering time and shoot architecture have major consequences for fitness. Likewise, in crop species, variation in branching and developmental rate impact biomass and yield. Thus, studies aimed at dissecting how the various functions are partitioned among different SPL genes in diverse plant lineages are key to providing insight into the genetic basis of local adaptation and have already garnered attention by crop breeders. Here we use phylogenetic reconstruction to reveal nine major SPL gene lineages, each of which is described in terms of function and diversification. To assess evidence for ancestral and derived functions within each SPL gene lineage, we use ancestral character state reconstructions. Our analyses suggest an emerging pattern of sub-functionalization, neo-functionalization, and possible convergent evolution following both ancient and recent gene duplication. Based on these analyses we suggest future avenues of research that may prove fruitful for elucidating the importance of SPL gene evolution in plant growth and development.

Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network

Directory of Open Access Journals (Sweden)

Wei Shu

2012-09-01

Full Text Available Abstract Background The Arabidopsis microRNA156 (miR156 regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. Results In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated SPL15 (SPL15m largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro

A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study.

Directory of Open Access Journals (Sweden)

Ian Mcgowan

Full Text Available The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK, and pharmacodynamics (PD of three tenofovir (TFV gels for rectal application. The vaginal formulation (VF gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF gel was also evaluated in the CHARM-01 study.Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial.All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively. Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection.All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection.ClinicalTrials.gov NCT01575405.

Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

Energy Technology Data Exchange (ETDEWEB)

Giri, Namita; Oh, Byeongtaek; Lee, Chi H., E-mail: leech@umkc.edu [University of Missouri at Kansas City, Division of Pharmaceutical Sciences (United States)

2016-05-15

This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100{sup ®} (ES100{sup ®}), a pH-sensitive polymer. ES100{sup ®} NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100{sup ®} NPs. The morphology of the ES100{sup ®} NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100{sup ®} NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100{sup ®} NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100{sup ®} NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100{sup ®} NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100{sup ®} NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100{sup

Vaginal microbicides for reducing the risk of sexual acquisition of HIV infection in women: systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Obiero Jael

2012-11-01

Full Text Available Abstract Background Each year more than two million people are newly infected with HIV worldwide, a majority of them through unprotected vaginal sex. More than half of new infections in adults occur in women. Male condoms and male circumcision reduce the risk of HIV acquisition; but the uptake of these methods is out of the control of women. We therefore aimed to determine the effectiveness of vaginal microbicides (a potential female-controlled method for prevention of sexual acquisition of HIV in women. Methods We conducted a comprehensive search of peer-reviewed and grey literature for publications of randomised controlled trials available by September 2012. We screened search outputs, selected studies, assessed risk of bias, and extracted data in duplicate; resolving differences by discussion and consensus. Results We identified 13 eligible trials that compared vaginal microbicides to placebo. These studies enrolled 35,905 sexually active HIV-negative women between 1996 and 2011; in Benin, Cameroon, Cote d’Ivoire, Ghana, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, Zimbabwe, India, Thailand, and the United States of America. A small trial of 889 women found that tenofovir (a nucleotide reverse transcriptase inhibitor significantly reduces the risk of HIV acquisition (risk ratio [RR] 0.63, 95% confidence intervals [CI] 0.43 to 0.93. Effectiveness data are not yet available from follow-up tenofovir trials being conducted in South Africa, Uganda, and Zimbabwe (1 trial and multiple sites in South Africa (1 trial. We found no evidence of a significant effect for nonoxynol-9 (5 trials, cellulose sulphate (2 trials, SAVVY (2 trials, Carraguard (1 trial, PRO 2000 (2 trials, and BufferGel (1 trial microbicides. The pooled RR for the effect of current experimental vaginal microbicides on HIV acquisition in women was 0.97, 95%CI 0.87 to 1.08. Although study results were homogeneous across the different drug classes (heterogeneity P�

cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal)

International Nuclear Information System (INIS)

Glasser, S.W.; Korfhagen, T.R.; Weaver, T.E.; Clark, J.C.; Pilot-Matias, T.; Meuth, J.; Fox, J.L.; Whitsett, J.A.

1988-01-01

In hyaline membrane disease of premature infants, lack of surfactant leads to pulmonary atelectasis and respiratory distress. Hydrophobic surfactant proteins of M/sub r/ = 5000-14,000 have been isolated from mammalian surfactants which enhance the rate of spreading and the surface tension lowering properties of phospholipids during dynamic compression. The authors have characterized the amino-terminal amino acid sequence of pulmonary proteolipids from ether/ethanol extracts of bovine, canine, and human surfactant. Two distinct peptides were identified and termed SPL(pVal) and SPL(Phe). An oligonucleotide probe based on the valine-rich amino-terminal amino acid sequence of SPL(pVal) was utilized to isolate cDNA and genomic DNA encoding the human protein, termed surfactant proteolipid SPL(pVal) on the basis of its unique polyvaline domain. The primary structure of a precursor protein of 20,870 daltons, containing the SPL(pVal) peptide, was deduced from the nucleotide sequence of the cDNAs. Hybrid-arrested translation and immunoprecipitation of labeled translation products of human mRNA demonstrated a precursor protein, the active hydrophobic peptide being produced by proteolytic processing. Two classes of cDNAs encoding SPL(pVal) were identified. Human SPL(pVal) mRNA was more abundant in the adult than in fetal lung. The SPL(pVal) gene locus was assigned to chromosome 8

7 CFR 70.13 - Ready-to-cook poultry and rabbits and specified poultry food products.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Ready-to-cook poultry and rabbits and specified... AGRICULTURE (CONTINUED) REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG... Poultry Products and Rabbit Products General § 70.13 Ready-to-cook poultry and rabbits and specified...

Draft Genome Sequence of Staphylococcus carnosus subsp. utilis LTH 7013, Isolated from South Tyrolean Ham

OpenAIRE

M?ller, Anne; Huptas, Christopher; Wenning, Mareike; Schmidt, Herbert; Weiss, Agnes

2015-01-01

Staphylococcus carnosus is used as a starter culture in meat fermentation, where it contributes to color formation and produces aromatic compounds. Here, we report the first draft genome sequence of an S.?carnosus subsp. utilis strain, LTH 7013, isolated from South Tyrolean ham, with potential application as a starter culture.

Perceptions of acceptability and utility of microbicides in Ghana ...

African Journals Online (AJOL)

In addition, gendered negotiation power and the implications of covert use need to be addressed in microbicide education and social marketing. Les microbicides vaginaux, une substance qui pourrait largement réduire les infections sexuellement transmises (IST) et le VIH inclus, font actuellement parti des essais cliniques.

Whither or wither microbicides?

NARCIS (Netherlands)

Grant, Robert M.; Hamer, Dean; Hope, Thomas; Johnston, Rowena; Lange, Joep; Lederman, Michael M.; Lieberman, Judy; Miller, Christopher J.; Moore, John P.; Mosier, Donald E.; Richman, Douglas D.; Schooley, Robert T.; Springer, Marty S.; Veazey, Ronald S.; Wainberg, Mark A.

2008-01-01

After disappointing results from all efficacy trials conducted to date, the field of microbicides research now faces substantial challenges. Poor coordination among interested parties and the choice of nonvalidated scientific targets for phase III studies have hampered progress and created mistrust

File list: Pol.Spl.10.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Pol.Spl.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Spl.05.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Spleen SR...X062981,SRX143838,SRX020253 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Spl.05.RNA_Polymerase_II.AllCell.bed ...

HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

Science.gov (United States)

Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

2015-01-01

Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was Maraviroc. This HIV entry inhibitor targets the host cell CCR5 coreceptor and was highly active against both untreated and semen-exposed HIV. These data help explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

Experimental and numerical models of three-dimensional gravity-driven flow of shear-thinning polymer solutions used in vaginal delivery of microbicides.

Science.gov (United States)

Kheyfets, Vitaly O; Kieweg, Sarah L

2013-06-01

HIV/AIDS is a growing global pandemic. A microbicide is a formulation of a pharmaceutical agent suspended in a delivery vehicle, and can be used by women to protect themselves against HIV infection during intercourse. We have developed a three-dimensional (3D) computational model of a shear-thinning power-law fluid spreading under the influence of gravity to represent the distribution of a microbicide gel over the vaginal epithelium. This model, accompanied by a new experimental methodology, is a step in developing a tool for optimizing a delivery vehicle's structure/function relationship for clinical application. We compare our model with experiments in order to identify critical considerations for simulating 3D free-surface flows of shear-thinning fluids. Here we found that neglecting lateral spreading, when modeling gravity-induced flow, resulted in up to 47% overestimation of the experimental axial spreading after 90 s. In contrast, the inclusion of lateral spreading in 3D computational models resulted in rms errors in axial spreading under 7%. In addition, the choice of the initial condition for shape in the numerical simulation influences the model's ability to describe early time spreading behavior. Finally, we present a parametric study and sensitivity analysis of the power-law parameters' influence on axial spreading, and to examine the impact of changing rheological properties as a result of dilution or formulation conditions. Both the shear-thinning index (n) and consistency (m) impacted the spreading length and deceleration of the moving front. The sensitivity analysis showed that gels with midrange m and n values (for the ranges in this study) would be most sensitive (over 8% changes in spreading length) to 10% changes (e.g., from dilution) in both rheological properties. This work is applicable to many industrial and geophysical thin-film flow applications of non-Newtonian fluids; in addition to biological applications in microbicide drug delivery.

Draft Genome Sequence of Staphylococcus carnosus subsp. utilis LTH 7013, Isolated from South Tyrolean Ham.

Science.gov (United States)

Müller, Anne; Huptas, Christopher; Wenning, Mareike; Schmidt, Herbert; Weiss, Agnes

2015-05-14

Staphylococcus carnosus is used as a starter culture in meat fermentation, where it contributes to color formation and produces aromatic compounds. Here, we report the first draft genome sequence of an S. carnosus subsp. utilis strain, LTH 7013, isolated from South Tyrolean ham, with potential application as a starter culture. Copyright © 2015 Müller et al.

File list: InP.Spl.10.Input_control.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: InP.Spl.20.Input_control.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

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Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned.

Science.gov (United States)

Friend, David R; Kiser, Patrick F

2013-09-01

The development of topically applied products capable of preventing vaginal and rectal transmission of HIV-1 has been on-going for nearly 20 years. Despite this, only one clinical trial has demonstrated protection against sexual transmission of HIV-1 in women. This review covers the development of microbicides, also referred to as topical pre-exposure prophylaxis (PrEP), through three stages. The first stage focused on nonspecific agents, including surfactants such as nonoxynol-9 (N-9), to prevent HIV-1 transmission. Unfortunately, N-9 enhanced susceptibility to sexual transmission of HIV-1 when evaluated for efficacy. Soon thereafter, other nonspecific agents (polyanions) were quickly moved into large efficacy trials. Due to a lack of coordination among investigators and funders, a large investment was made in a class of compounds shown ultimately to be ineffective, although poor adherence may have contributed to these findings. The second stage involved the assessment of the antiretroviral drug tenofovir, formulated as a vaginal gel, which was found to be modestly effective in a Phase IIb trial (CAPRISA-004) when dosed in a coitally-dependent manner. In another Phase IIb trial, VOICE (MTN-003), tenofovir gel was found to be ineffective when dosed once-daily in a coitally-independent manner. Based on pharmacokinetic data, it was concluded the participants were poorly adherent to this dosing regimen, leading to a lack of efficacy. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS-001), using the coitally-dependent dosing regimen employed in CAPRISA-004. We are now in the third stage of microbicide research. The antiretroviral drug dapivirine is currently in two Phase III safety and efficacy studies formulated as a vaginal ring. It is hoped that the once-monthly dosing regimen will lead to higher adherence than found in the VOICE study. It is now clear that product adherence could be the greatest challenge to demonstrating

SPL8 Acts Together with the Brassinosteroid-Signaling Component BIM1 in Controlling Arabidopsis thaliana Male Fertility

Directory of Open Access Journals (Sweden)

Shuping Xing

2013-06-01

Full Text Available The non-miR156 targeted SBP-box gene SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 8 (SPL8, plays an important role in Arabidopsis anther development, where its loss-of-function results in a semi-sterile phenotype. Fully male-sterile plants are obtained when a spl8 loss-of-function mutation is introduced into a 35S:MIR156 genetic background, thereby revealing functional redundancy between SPL8 and miR156-targeted SBP-box genes. Here, we show that BIM1, a gene encoding a bHLH protein involved in brassinosteroid signaling and embryonic patterning, functions redundantly with SPL8 in its requirement for male fertility. Although bim1 single mutants displayed a mild fertility problem due to shortened filaments in some flowers, mutation of BIM1 significantly enhanced the semi-sterile phenotype of the spl8 mutant. Expression of both SPL8 and BIM1 was detected in overlapping expression domains during early anther developmental stages. Our data suggest that in regulating anther development, SPL8 and BIM1 function cooperatively in a common complex or in synergistic pathways. Phylogenetic analysis supports the idea of an evolutionary conserved function for both genes in angiosperm anther development.

First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy.

Directory of Open Access Journals (Sweden)

Peter A Anton

Full Text Available Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.HIV-1 seronegative, sexually-abstinent men and women (N = 36 were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25% with placebo gel (1∶1∶1. Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.All 36 subjects enrolled completed the 7-14 week trial (100% retention including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm. There were 81 Grade 1 adverse events (AEs and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1(BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV

A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

Directory of Open Access Journals (Sweden)

Marla J Keller

2011-01-01

Full Text Available Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001 and fit a sigmoid E(max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development

Vaginal rings for delivery of HIV microbicides.

Science.gov (United States)

Malcolm, R Karl; Fetherston, Susan M; McCoy, Clare F; Boyd, Peter; Major, Ian

2012-01-01

Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.

The future of HIV prevention: prospects for an effective anti-HIV microbicide.

Science.gov (United States)

Nuttall, Jeremy; Romano, Joseph; Douville, Karen; Galbreath, Caroline; Nel, Annaléne; Heyward, William; Mitchnick, Mark; Walker, Saul; Rosenberg, Zeda

2007-03-01

Topical microbicides are self-administered products for prevention of HIV transmission, and they present one of the most promising strategies for combating the HIV-AIDS epidemic. The development of microbicides is a long and complicated process, with many hurdles that are unique to this class of product, including challenges in product design, in the conduct and design of clinical trials, and in obtaining licensure of a new class of products intended for use almost exclusively in developing countries. Once they have been registered, there are additional challenges to the marketing and distribution of microbicides. An overview of the types of microbicide currently in development, and a summary of the issues and the approaches being taken to address them, are provided.

Microbicide research in developing countries: have we given the ethical concerns due consideration?

Science.gov (United States)

Moodley, Keymanthri

2007-09-19

HIV prevention research has been fraught with ethical concerns since its inception. These concerns were highlighted during HIV vaccine research and have been elaborated in microbicide research. A host of unique ethical concerns pervade the microbicide research process from trial design to post-trial microbicide availability. Given the urgency of research and development in the face of the devastating HIV pandemic, these ethical concerns represent an enormous challenge for investigators, sponsors and Research Ethics Committees (RECs) both locally and internationally. Ethical concerns relating to safety in microbicide research are a major international concern. However, in the urgency to develop a medically efficacious microbicide, some of these concerns may not have been anticipated. In the risk-benefit assessment of research protocols, both medical and psycho-social risk must be considered. In this paper four main areas that have a potential for medical and/or psycho-social harm are examined. Male partner involvement is controversial in the setting of covert use of microbicides. However, given the long-term exposure of men to experimental products, this may be methodologically, ethically and legally important. Covert use of microbicides may impact negatively on relationship dynamics leading to psychosocial harm to varying extents. The unexpectedly high rates of pregnancy during clinical trials raise important methodological and ethical concerns. Enrollment of adolescents without parental consent generates ethical and legal concerns that must be carefully considered by RECs and trial sites. Finally, paradoxical outcomes in recent trials internationally have advanced the debate on the nature of informed consent and responsibility of researchers to participants who become HIV positive during or after trials. Phase 3 microbicide trials are an undisputed research and ethical priority in developing countries. However, such trials must be conducted with attention to both

Vaginal microbicides: how do you kick-start a global market?

Science.gov (United States)

1996-10-01

Efforts are underway to develop vaginal microbicides capable of protecting women against HIV and sexually transmitted disease. It was reported at the recent Vancouver international AIDS conference that 20 such products are in the preclinical stage, 13 in the early clinical stage, and two at the late clinical stage. The private sector, however, is not convinced of the commercial viability of vaginal microbicides, especially in developing countries. Johnson & Johnson has estimated there to be a US$40 million world market for vaginal microbicides, too small to garner the interest and involvement of the major research and development-based multinational pharmaceutical companies. The European Commission has therefore contracted Hillmark, a UK consultancy, to assess the market for such products in Cote d'Ivoire, Egypt, Kenya, South Africa, France, Poland, India, Thailand, Philippines, Brazil, and Venezuela. Corporate interest may be sparked by a convincing assessment of a higher market potential. Also at the Vancouver conference, the US Secretary of Health announced grant funding of US$100 million for research into microbicides.

submitter Radiation Protection Studies for CERN LINAC4/SPL Accelerator Complex

CERN Document Server

Mauro, Egidio; Silari, Marco

2009-01-01

CERN is presently designing a new chain of accelerators to replace the present Proton Synchrotron (PS) complex: a 160 MeV room-temperature H$^-$ linac (Linac4) to replace the present 50 MeV proton linac injector, a 3.5 GeV Superconducting Proton Linac (SPL) to replace the 1.4 GeV PS booster (PSB) and a 50 GeV synchrotron (named PS2) to replace the 26 GeV PS. Linac4 has been funded and the civil engineering work started in October 2008, whilst the SPL is in an advanced stage of design. Beyond injecting into the future 50 GeV PS, the ultimate goal of the SPL is to generate a 4 MW beam for the production of intense neutrino beams. The radiation protection design is driven by the latter requirement. This thesis summarizes the radiation protection studies conducted for Linac4. FLUKA Monte Carlo simulations, complemented by analytical estimates, were performed 1) to evaluate the propagation of neutrons through the waveguide, ventilation and cable ducts placed along the accelerator, 2) to estimate the radiological i...

Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

Science.gov (United States)

Nel, Annalene M; Coplan, Paul; van de Wijgert, Janneke H; Kapiga, Saidi H; von Mollendorf, Claire; Geubbels, Eveline; Vyankandondera, Joseph; Rees, Helen V; Masenga, Gileard; Kiwelu, Ireen; Moyes, Jocelyn; Smythe, Shanique C

2009-07-31

To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine. Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less. Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.

Potential Use of Antimicrobial Peptides as Vaginal Spermicides/Microbicides

Directory of Open Access Journals (Sweden)

Nongnuj Tanphaichitr

2016-03-01

Full Text Available The concurrent increases in global population and sexually transmitted infection (STI demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9, into a vaginal microbicide were unsuccessful largely due to its inefficiency to kill microbes. Furthermore, N-9 causes damage to the vaginal epithelium, thus accelerating microbes to enter the women’s body. For this reason, antimicrobial peptides (AMPs, naturally secreted by all forms of life as part of innate immunity, deserve evaluation for their potential spermicidal effects. To date, twelve spermicidal AMPs have been described including LL-37, magainin 2 and nisin A. Human cathelicidin LL-37 is the most promising spermicidal AMP to be further developed for vaginal use for the following reasons. First, it is a human AMP naturally produced in the vagina after intercourse. Second, LL-37 exerts microbicidal effects to numerous microbes including those that cause STI. Third, its cytotoxicity is selective to sperm and not to the female reproductive tract. Furthermore, the spermicidal effects of LL-37 have been demonstrated in vivo in mice. Therefore, the availability of LL-37 as a vaginal spermicide/microbicide will empower women for self-protection against unwanted pregnancies and STI.

Reverse transcriptase inhibitors as potential colorectal microbicides.

Science.gov (United States)

Herrera, Carolina; Cranage, Martin; McGowan, Ian; Anton, Peter; Shattock, Robin J

2009-05-01

We investigated whether reverse transcriptase (RT) inhibitors (RTI) can be combined to inhibit human immunodeficiency virus type 1 (HIV-1) infection of colorectal tissue ex vivo as part of a strategy to develop an effective rectal microbicide. The nucleotide RTI (NRTI) PMPA (tenofovir) and two nonnucleoside RTI (NNRTI), UC-781 and TMC120 (dapivirine), were evaluated. Each compound inhibited the replication of the HIV isolates tested in TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants. Dual combinations of the three compounds, either NRTI-NNRTI or NNRTI-NNRTI combinations, were more active than any of the individual compounds in both cellular and tissue models. Combinations were key to inhibiting infection by NRTI- and NNRTI-resistant isolates in all models tested. Moreover, we found that the replication capacities of HIV-1 isolates in colorectal explants were affected by single point mutations in RT that confer resistance to RTI. These data demonstrate that colorectal explants can be used to screen compounds for potential efficacy as part of a combination microbicide and to determine the mucosal fitness of RTI-resistant isolates. These findings may have important implications for the rational design of effective rectal microbicides.

MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3 in cynomolgus macaques.

Directory of Open Access Journals (Sweden)

Nathalie Dereuddre-Bosquet

Full Text Available In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP model of mucosal challenge with SHIV(162P3 after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control, the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50 of SHIV(162P3. All control animals were infected with a peak plasma viral load of 10(5-10(6 viral RNA (vRNA copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.

Plant made anti-HIV microbicides: a field of opportunity

CSIR Research Space (South Africa)

Lotter-Stark, HCT

2012-11-01

Full Text Available -HIV microbicides- a field of opportunity Hester C.T. Lotter-Stark1*, Edward P. Rybicki2 and Rachel K. Chikwamba1 1 Council for Scientific and Industrial Research (CSIR), Biosciences, Pretoria, South Africa. 2 Institute of Infectious Disease and Molecular... efficacious in in vitro and in vivo protection studies. For the purpose of development and access by the relevant 2 population groups, it is crucial that these microbicides be produced at low cost. For the promising protein and peptide candidate...

Neutrophil Leukocyte: Combustive Microbicidal Action and Chemiluminescence

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Robert C. Allen

2015-01-01

Full Text Available Neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple, potent, and focused. Neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen (O2 facilitating combustion. The spin conservation rules define the symmetry barrier that prevents direct reaction of diradical O2 with nonradical molecules, explaining why combustion is not spontaneous. In burning, the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical O2 to yield oxygenated radical products that further participate in reactive propagation. Neutrophil mediated combustion is by a different pathway. Changing the spin quantum state of O2 removes the symmetry restriction to reaction. Electronically excited singlet molecular oxygen (O2*1 is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe. The resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission, that is, chemiluminescence. This overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic-fermionic frontier orbital considerations. The necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism.

Microbicidal Effects of Stored Aqueous Ozone Solution Generated by Nano-bubble Technology.

Science.gov (United States)

Seki, Mineaki; Ishikawa, Tatsuya; Terada, Hiroshi; Nashimoto, Masayuki

2017-01-01

Clinically used disinfectants are often irritating and cause skin problems. Ozone water is unique among disinfectants. It does not damage skin cells and readily decomposes to oxygen without generating harmful residues. On the other hand, it rapidly loses its sanitizing activity. Recently developed nano-bubble ozone water (NBOW) can keep its sanitizing activity much longer. This study aimed to examine the microbicidal effects of NBOW after long-term storage. The concentration of ozone in NBOW was examined by measuring the NBOW redox potential. Microbicidal activity was evaluated by colony formation assays, after incubating bacteria with NBOW for set time periods. NBOW lost its microbicidal activity after 1 year of storage at 4°C. Stocked frozen, NBOW retained appreciable microbicidal activity after 1 year of storage. Mycobacterium smegmatis, one of the most disinfectant-resistant bacteria, was killed within 15 min. NBOW was resistant to freeze-thawing. NBOW that had been stored frozen possessed sufficient microbicidal activity to kill bacteria even after 1 year of storage. Moreover, it was shown that NBOW is freeze-thaw resistant. NBOW possesses desirable features rendering it an attractive alternative disinfectant. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies

Directory of Open Access Journals (Sweden)

Thurman AR

2013-10-01

Full Text Available Andrea Ries Thurman, Meredith R Clark, Jennifer Hurlburt, Gustavo F Doncel CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA Abstract: There is a renewed interest in delivering pharmaceutical products via intravaginal rings (IVRs. IVRs are flexible torus-shaped drug delivery systems that can be easily inserted and removed by the woman and that provide both sustained and controlled drug release, lasting for several weeks to several months. In terms of women's health care products, it has been established that IVRs effectively deliver contraceptive steroids and steroids for the treatment of postmenopausal vaginal atrophy. A novel application for IVRs is the delivery of antiretroviral drugs for the prevention of human immunodeficiency virus (HIV genital infection. Microbicides are antiviral drugs delivered topically for HIV prevention. Recent reviews of microbicide IVRs have focused on technologies in development and optimizing ring design. IVRs have several advantages, including the ability to deliver sustained drug doses for long periods of time while bypassing first pass metabolism in the gut. IVRs are discreet, woman-controlled, and do not require a trained provider for placement or fitting. Previous data support that women and their male sexual partners find IVRs highly acceptable. Multipurpose prevention technology (MPT products provide protection against unintended/mistimed pregnancy and reproductive tract infections, including HIV. Several MPT IVRs are currently in development. Early clinical testing of new microbicide and MPT IVRs will require a focus on safety, pharmacokinetics and pharmacodynamics. Specifically, IVRs will have to deliver tissue concentrations of drugs that are pharmacodynamically active, do not cause mucosal alterations or inflammation, and do not change the resident microbiota. The emergence of resistance to antiretrovirals will need to be investigated. IVRs should not

Shielding design for the front end of the CERN SPL.

Science.gov (United States)

Magistris, Matteo; Silari, Marco; Vincke, Helmut

2005-01-01

CERN is designing a 2.2-GeV Superconducting Proton Linac (SPL) with a beam power of 4 MW, to be used for the production of a neutrino superbeam. The SPL front end will initially accelerate 2 x 10(14) negative hydrogen ions per second up to an energy of 120 MeV. The FLUKA Monte Carlo code was employed for shielding design. The proposed shielding is a combined iron-concrete structure, which also takes into consideration the required RF wave-guide ducts and access labyrinths to the machine. Two beam-loss scenarios were investigated: (1) constant beam loss of 1 Wm(-1) over the whole accelerator length and (2) full beam loss occurring at various locations. A comparison with results based on simplified approaches is also presented.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

OpenAIRE

Gupta, Satish; Vinu,Nutan

2013-01-01

Satish Kumar Gupta, Nutan Reproductive Cell Biology Laboratory, National Institute of Immunology, New Delhi, India Abstract: Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV. Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl...

Microbicide trials for preventing HIV/AIDS in South Africa: phase II trial partricipants' experiences and psychological needs

NARCIS (Netherlands)

Pistorius, A. G.; van de Wijgert, J. H. H. M.; Sebola, M.; Friedland, B.; Nagel, E.; Bokaba, C.; Hoosen, A. A.

2004-01-01

The Microbicide Division of the Department of Medical Microbiology at MEDUNSA, South Africa, recently completed a phase II expanded safety trial of the candidate microbicide Carraguard. A microbicide is a vaginal product that women might use, if proven safe and effective, to protect themselves from

Semiscale power loss experiment S-PL-3 with primary feed and bleed plant recovery

International Nuclear Information System (INIS)

Wolf, J.R.; Streit, J.E.

1984-01-01

This paper describes an attempt to verify the accuracy of the RELAP5 model of the S-PL-3 experiment (part of the Semiscale loss-of-offsite-power test series) by comparing the RELAP5 model with actual data obtained during the experiment. Included are a description of the experiment, an analysis of preliminary results, and the comparison of posttest RELAP5 calculations with experiment data. RELAP5 modeling of the S-PL-3 transient produced qualitative agreement with experiment data

Vaginal rings for delivery of HIV microbicides

Directory of Open Access Journals (Sweden)

McCoy CF

2012-11-01

Full Text Available R Karl Malcolm, Susan M Fetherston, Clare F McCoy, Peter Boyd, Ian MajorSchool of Pharmacy, Queen's University Belfast, Belfast, UKAbstract: Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.Keywords: controlled release, sustained release, antiretroviral, dapivirine, SILCS diaphragm, silicone elastomer, thermoplastic

Novel positive regulatory role for the SPL6 transcription factor in the N TIR-NB-LRR receptor-mediated plant innate immunity.

Directory of Open Access Journals (Sweden)

Meenu S Padmanabhan

2013-03-01

Full Text Available Following the recognition of pathogen-encoded effectors, plant TIR-NB-LRR immune receptors induce defense signaling by a largely unknown mechanism. We identify a novel and conserved role for the SQUAMOSA PROMOTER BINDING PROTEIN (SBP-domain transcription factor SPL6 in enabling the activation of the defense transcriptome following its association with a nuclear-localized immune receptor. During an active immune response, the Nicotiana TIR-NB-LRR N immune receptor associates with NbSPL6 within distinct nuclear compartments. NbSPL6 is essential for the N-mediated resistance to Tobacco mosaic virus. Similarly, the presumed Arabidopsis ortholog AtSPL6 is required for the resistance mediated by the TIR-NB-LRR RPS4 against Pseudomonas syringae carrying the avrRps4 effector. Transcriptome analysis indicates that AtSPL6 positively regulates a subset of defense genes. A pathogen-activated nuclear-localized TIR-NB-LRR like N can therefore regulate defense genes through SPL6 in a mechanism analogous to the induction of MHC genes by mammalian immune receptors like CIITA and NLRC5.

[Involvement of the global regulators GrrS, RpoS, and SplIR in formation of biofilms in Serratia plymuthica].

Science.gov (United States)

Zaĭtseva, Iu V; Voloshina, P V; Liu, X; Ovadis, M I; Berg, G; Chernin, L S; Khmel', I A

2010-05-01

Most bacteria exist in the natural environment as biofilms, multicellular communities attached to hard surfaces. Biofilms have a characteristic architecture and are enclosed in the exopolymer matrix. Bacterial cells in biofilms are extremely resistant to antibacterial factors. It was shown in this work that the GrrA/GrrS system of global regulators of gene expression and the sigma S subunit of RNA polymerase (RpoS) play a significant role in positive regulation of biofilm formation in the rhizospheric bacterium Serratia plymuthica IC1270. Inactivation of grrS and rpoS genes resulted in an up to six-to-sevenfold and four-to-fivefold reduction in biofilm formation, respectively. Mutations in the grrS gene decreased the capacity of the bacterium for swarming motility. The splIR Quorum Sensing (QS) system was shown to negatively influence the biofilm formation. Transfer of the recombinant plasmid containing cloned genes splI/splR of S. plymuthica HRO-C48 into S. plymuthica IC1270 cells led to a twofold decrease of their ability to form biofilms. Inactivation of the splI gene coding for the synthase of N-acyl-homoserine lactones in S. plymuthica HRO-C48 resulted in a 2-2.5-fold increase in the level of biofilm formation, whereas the inclusion of plasmid carrying the cloned splI/splR genes into these mutant cells restored the biofilm formation to the normal level. The results obtained demonstrate that the formation of biofilms in S. plymuthica is positively regulated by the GrrA/GrrS and RpoS global regulators and is negatively regulated by the SplIR QS system.

SPL-based Proton Driver for a nu-Factory at CERN

CERN Document Server

Benedetto, E; Garoby, R; Meddahi, M

2010-01-01

The conceptual design and feasibility studies for a nu-Factory Proton Driver based on the CERN Superconducting Proton Linac (SPL) have been com- pleted. In the proposed scenario, the 4 MW proton beam (H- beam) is acceler- ated with the upgraded High Power (HP)-SPL to 5 GeV, stored in an accumu- lator ring and Þnally transported to a compressor ring, where bunch rotation takes place, in order to achieve the speciÞc time structure. We here summa- rize the choices in terms of lattice, magnet technology and RF manipulations in the two rings. The possible critical issues, such as heating of the foil for the charge-exchange injection, space-charge problems in the compressor and beam stability in the accumulator ring, have been addressed and are shown not to be show-stoppers. The analysis focuses on the baseline scenario, consider- ing 6 bunches in the accumulator, and preliminary studies are discussed for the option of 3 or a single bunch per burst.

Conceptual Design of the Low-Power and High-Power SPL A Superconducting H$^-$ Linac at CERN

CERN Document Server

Atieh, S; Aviles Santillana, I; Bartmann, W; Borburgh, J; Brunner, O; Calatroni, S; Capatina, O; Chambrillon, J; Ciapala, E; Eshraqi, M; Ferreira, L; Garoby, R; Goddard, B; Hessler, C; Hofle, W; Horvath-Mikulas, S; Junginger, T; Kozlova, E; Lebbos, E; Lettry, J; Liao, K; Lombardi, A M; Macpherson, A; Montesinos, E; Nisbet, D; Otto, T; Paoluzzi, M; Papke, K; Parma, V; Pillon, F; Posocco, P; Ramberger, S; Rossi, C; Schirm, K; Schuh, M; Scrivens, R; Torres Sanchez, R; Valuch, D; Valverde Alonso, N; Wegner, R; Weingarten, W; Weisz, S

2014-01-01

The potential for a superconducting proton linac (SPL) at CERN started to be seriously considered at the end of the 1990s. In the first conceptual design report (CDR), published in 2000 [1], most of the 352 MHz RF equipment from LEP was re-used in an 800 m long linac, and the proton beam energy was limited to 2.2 GeV. During the following years, the design was revisited and optimized to better match the needs of a high-power proton driver for neutrino physics. The result was a more compact (470 m long) accelerator capable of delivering 5 MW of beam power at 3.5 GeV, using state-of-the-art superconducting RF cavities at 704 MHz. It was described in a second CDR, published in 2006 [2]. Soon afterwards, when preparation for increasing the luminosity of the LHC by an order of magnitude beyond nominal became an important concern, a low-power SPL (LP-SPL) was studied as a key component in the renovation of the LHC injector complex. The combination of a 4 GeV LP-SPL injecting into a new 50 GeV synchrotron (PS2) was ...

Testing of viscous anti-HIV microbicides using Lactobacillus.

Science.gov (United States)

Moncla, B J; Pryke, K; Rohan, L C; Yang, H

2012-02-01

The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To demonstrate the toxicity of formulated products a new assay was developed for use with viscous and non-viscous samples that we have termed the Lactobacillus toxicity test. We found that the vortex mixing of vaginal Lactobacillus species can lead to reductions in bacterial viability. Lactobacillus can survive briefly, about 2s, but viability declines with increased vortex mixing. The addition of heat inactivated serum or bovine serum albumin, but not glycerol, prevented the decrease in bacterial viability. Bacillus atrophaeus spores also demonstrated loss of viability upon extended mixing. We observed that many of the excipients used in film formulation and the films themselves also afford protection from the killing during vortex mixing. This method is of relevance for toxicity for cidal activities of viscous products. Copyright © 2011 Elsevier B.V. All rights reserved.

Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women

NARCIS (Netherlands)

Nel, Annalene M.; Coplan, Paul; van de Wijgert, Janneke H.; Kapiga, Saidi H.; von Mollendorf, Claire; Geubbels, Eveline; Vyankandondera, Joseph; Rees, Helen V.; Masenga, Gileard; Kiwelu, Ireen; Moyes, Jocelyn; Smythe, Shanique C.

2009-01-01

To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa

Molecular Characterization of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL Gene Family in Betula luminifera

Directory of Open Access Journals (Sweden)

Xiu-Yun Li

2018-05-01

Full Text Available As a major family of plant-specific transcription factors, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL genes play vital regulatory roles in plant growth, development and stress responses. In this study, 18 SPL genes were identified and cloned from Betula luminifera. Two zinc finger-like structures and a nuclear location signal (NLS segments were existed in the SBP domains of all BlSPLs. Phylogenetic analysis showed that these genes were clustered into nine groups (group I-IX. The intron/exon structure and motif composition were highly conserved within the same group. 12 of the 18 BlSPLs were experimentally verified as the targets of miR156, and two cleavage sites were detected in these miR156-targeted BlSPL genes. Many putative cis-elements, associated with light, stresses and phytohormones response, were identified in the promoter regions of BlSPLs, suggesting that BlSPL genes are probably involved in important physiological processes and developmental events. Tissue-specific expression analysis showed that miR156-targeted BlSPLs exhibited a more differential expression pattern, while most miR156-nontargeted BlSPLs tended to be constitutively expressed, suggesting the distinct roles of miR156-targeted and nontargeted BlSPLs in development and growth of B. luminifera. Further expression analysis revealed that miR156-targeted BlSPLs were dramatically up-regulated with age, whereas mature BlmiR156 level was apparently declined with age, indicating that miR156/SPL module plays important roles in vegetative phase change of B. luminifera. Moreover, yeast two-hybrid assay indicated that several miR156-targeted and nontargeted BlSPLs could interact with two DELLA proteins (BlRGA and BlRGL, which suggests that certain BlSPLs take part in the GA regulated processes through protein interaction with DELLA proteins. All these results provide an important basis for further exploring the biological functions of BlSPLs in B. luminifera.

Adolescent girls' communication with "mothers" about topical microbicides.

Science.gov (United States)

Sunder, Punita K; Ramos, Stephanie; Short, Mary B; Rosenthal, Susan L

2006-12-01

Topical microbicides, a female-initiated method to protect against sexually transmitted infections (STI) and pregnancy, will only be effective if found acceptable. Mothers may have an influence on acceptability and use among adolescent girls. The current study examined the communication between girls and mothers to understand the potential predictors and nature of conversations regarding surrogate microbicide products. Sexually experienced girls, 14 to 21 years, were recruited for a 6-month study examining microbicide acceptability. During face-to-face interviews, qualitative data were collected regarding communication between girls and mothers. Two independent raters coded the responses, which were organized into themes. Themes were interpreted according to the conceptual understanding of mother-daughter communication. Fifty percent of the 171 girls with codable responses had a conversation with their mother. Higher levels of indirect parental monitoring were related to being more likely to have a conversation. Concrete events related to the study (i.e. receiving phone call from the researcher, having an appointment, or seeing the product) or inquiries by mothers appeared to promote conversation. Barriers to conversation included the private nature of the information and relationship issues between the mother and daughter. Conversations often addressed issues related to girls' participation in the study, although some conversations included global issues related to sexuality. Girls may talk to their mothers about new products for STI prevention, and such conversations may provide opportunities to promote use.

Progress Report on SIMULINK Modelling of RF Cavity Control for SPL Extension to LINAC4 Theory and Analysis behind Simulation Results of SPL Model Using I/Q Components in SIMULINK to Date, Including Lorentz Force Effects and Multiple Cavities Driven by Single Feedback Loop

CERN Document Server

Hernandez, M

2011-01-01

In the context of a luminosity upgrade for the LHC within the coming years, works have started on LINAC4 to provide an infrastructure for updating the LHC supplier chain. In order to achieve energy levels and particles per bunch necessary for the expected rate of events at LHC detectors and related experiments, a project proposal is underway for an appended Superconducting Proton LINAC (SPL) that will run from the normal conducting LINAC4 and LP-SPL onto the LHC supplier chain. Thus, the SPL will have two main functions: Firstly, to provide H- beam for injection into the PS2 which is compatible with LHC luminosity. For this purpose the SPL will accelerate the output beam of LINAC4 from 1GeV to 4GeV,removing, at the same time, the necessity for PSB operation in the LHC supply chain. Secondly, it will provide an infrastructure upgradeable to meet the needs of all potential high-power proton users at CERN (EURISOL) and possibly neutrino production facilities. For high-power applications of this nature the SPL wi...

Place de la splénectomie dans la prise en charge de l’hypertension portale non cirrhotique: à propos de 3 cas

Science.gov (United States)

Belhamidi, Mohamed Said; Hammi, Salah Eddine; Bouzroud, Mohamed; Benmoussa, Mustapha; ali, Abdelmounaim Ait; Bounaim, Ahmed

2017-01-01

L’hypertension portale non cirrhotique est une affection décrite pour la première fois par Guido BANTI en 1898 comme une affection associant une hypertension portale avec splénomégalie et anémie sur foie sain. Le diagnostic repose sur l’échographie abdominale, la splénoportographie et la biopsie hépatique. Le but de notre travail est d’évaluer la place de la splénectomie dans l’hypertension portale non cirrhotique à travers une étude rétrospective portant sur 3 malades dont 2 femmes et un homme pris en charge dans notre formation entre Janvier 2010 et Septembre 2016. Le diagnostic de l’hypertension portale idiopathique a été basé sur les critères suivants : une hypertension portale, la présence des varices oesophagiènnes avec une splénomégalie, l’absence de cirrhose ou d’autres affections hépatiques responsables de l’hypertension portale. La splénectomie a été réalisée chez les 3 malades. L’évolution après la splénectomie était marquée par la normalisation des signes cliniques, radiologiques et biologiques de cette affection, avec absence de récidive des varices œsophagiennes. La splénectomie associée à la ligature des varices œsophagiennes pourraient être suffisantes pour traiter ce syndrome et surtout ses conséquences sans avoir recours à une dérivation spléno-rénale. PMID:29255554

Qualitative and quantitative intravaginal targeting: key to anti-HIV-1 microbicide delivery from test tube to in vivo success.

Science.gov (United States)

Pillay, Viness; Mashingaidze, Felix; Choonara, Yahya E; Du Toit, Lisa C; Buchmann, Eckhart; Maharaj, Vinesh; Ndesendo, Valence M K; Kumar, Pradeep

2012-06-01

The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint clinically. Our review expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal microenvironmental factors including pH should be maintained at HIV-1 prohibitive acidic levels simultaneously to ward off other sexually transmitted diseases, which compromise vaginal epithelial barrier properties. Furthermore, choice of receptors to target both on HIV-1 and on target cells is vital in deterring transmission. Appropriate modeling of virus-target cell interactions as well as targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could revolutionize microbicide research, ultimately delivering a female-controlled HIV-1 prevention modality appropriately. Copyright © 2012 Wiley Periodicals, Inc.

Knowledge and perception of microbicides among healthcare ...

African Journals Online (AJOL)

2014-06-02

Jun 2, 2014 ... mankind has tried several prevention options since the onset of the ... Knowledge and perception of microbicides among healthcare providers in Calabar,. Nigeria .... primary source of reproductive health information for ... are a new group of substances that can reduce the risk .... Research process Report.

A calcite permeable reactive barrier for the remediation of Fluoride from spent potliner (SPL) contaminated groundwater

DEFF Research Database (Denmark)

Turner, B.D.; Binning, Philip John; Sloan, S.W.

2008-01-01

The use of calcite (CaCO3) as a substrate for a permeable reactive barrier (PRB) for removing fluoride from contaminated groundwater is proposed and is illustrated by application to groundwater contaminated by spent potliner leachate (SPL), a waste derived from the aluminium smelting process...... leachate indicate that the complex chemical matrix of the SPL leachate can impact fluoride removal significantly. For SPL contaminant mixtures, fluoride removal is initially less than expected from idealized, pure, solutions. However, with time, the effect of other contaminants on fluoride removal...... diminishes. Column tests also show that pH control is important for optimizing fluoride removal with the mass removed increasing with decreasing pH. Barrier pH can be regulated by CO2 addition with the point of injection being critical for optimising the remediation performance. Experimental and model...

Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy.

Science.gov (United States)

Rinehart, Matthew T; Drake, Tyler K; Robles, Francisco E; Rohan, Lisa C; Katz, David; Wax, Adam

2011-12-01

Quantitative phase microscopy is applied to image temporal changes in the refractive index (RI) distributions of solutions created by microbicidal films undergoing hydration. We present a novel method of using an engineered polydimethylsiloxane structure as a static phase reference to facilitate calibration of the absolute RI across the entire field. We present a study of dynamic structural changes in microbicidal films during hydration and subsequent dissolution. With assumptions about the smoothness of the phase changes induced by these films, we calculate absolute changes in the percentage of film in regions across the field of view.

Conceptual design of the SPL II A high-power superconducting $H^-$ linac at CERN

CERN Document Server

Baylac, M; Benedico-Mora, E; Caspers, Friedhelm; Chel, S; Deconto, J M; Duperrier, R; Froidefond, E; Garoby, R; Hanke, K; Hill, C; Hori, M; Inigo-Golfin, J; Kahle, K; Kroyer, T; Küchler, D; Lallement, J B; Lindroos, M; Lombardi, A M; López Hernández, A; Magistris, M; Meinschad, T; Millich, Antonio; Noah-Messomo, E; Pagani, C; Palladino, V; Paoluzzi, M; Pasini, M; Pierini, P; Rossi, C; Royer, J P; Sanmartí, M; Sargsyan, E; Scrivens, R; Silari, M; Steiner, T; Tückmantel, Joachim; Uriot, D; Vretenar, M

2006-01-01

An analysis of the revised physics needs and recent progress in the technology of superconducting RF cavities have led to major changes in the speci cation and in the design for a Superconducting Proton Linac (SPL) at CERN. Compared with the rst conceptual design report (CERN 2000–012) the beam energy is almost doubled (3.5 GeV instead of 2.2 GeV), while the length of the linac is reduced by 40% and the repetition rate is reduced to 50 Hz. The basic beam power is at a level of 4–5MW and the approach chosen offers enough margins for upgrades. With this high beam power, the SPL can be the proton driver for an ISOL-type radioactive ion beam facility of the next generation (`EURISOL'), and for a neutrino facility based on superbeam C beta-beam or on muon decay in a storage ring (`neutrino factory'). The SPL can also replace the Linac2 and PS Booster in the low-energy part of the CERN proton accelerator complex, improving signi cantly the beam performance in terms of brightness and intensity for the bene t of al...

Paralogous SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes differentially regulate leaf initiation and reproductive phase change in petunia.

Science.gov (United States)

Preston, Jill C; Jorgensen, Stacy A; Orozco, Rebecca; Hileman, Lena C

2016-02-01

Duplicated petunia clade-VI SPL genes differentially promote the timing of inflorescence and flower development, and leaf initiation rate. The timing of plant reproduction relative to favorable environmental conditions is a critical component of plant fitness, and is often associated with variation in plant architecture and habit. Recent studies have shown that overexpression of the microRNA miR156 in distantly related annual species results in plants with perennial characteristics, including late flowering, weak apical dominance, and abundant leaf production. These phenotypes are largely mediated through the negative regulation of a subset of genes belonging to the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family of transcription factors. In order to determine how and to what extent paralogous SPL genes have partitioned their roles in plant growth and development, we functionally characterized petunia clade-VI SPL genes under different environmental conditions. Our results demonstrate that PhSBP1and PhSBP2 differentially promote discrete stages of the reproductive transition, and that PhSBP1, and possibly PhCNR, accelerates leaf initiation rate. In contrast to the closest homologs in annual Arabidopsis thaliana and Mimulus guttatus, PhSBP1 and PhSBP2 transcription is not mediated by the gibberellic acid pathway, but is positively correlated with photoperiod and developmental age. The developmental functions of clade-VI SPL genes have, thus, evolved following both gene duplication and speciation within the core eudicots, likely through differential regulation and incomplete sub-functionalization.

The sheep as a model of preclinical safety and pharmacokinetic evaluations of candidate microbicides.

Science.gov (United States)

Holt, Jonathon D S; Cameron, David; Dias, Nicola; Holding, Jeremy; Muntendam, Alex; Oostebring, Freddy; Dreier, Peter; Rohan, Lisa; Nuttall, Jeremy

2015-07-01

When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment of the pharmacokinetics, safety, tolerability, and local toxicity of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed a 3-month general toxicology study, a preliminary pharmacokinetic study using drug-loaded vaginal gel, and a detailed assessment of the kinetics of dapivirine delivery to plasma, vaginal, and rectal fluid and rectal, vaginal, and cervical tissue over 28 days of exposure and 3 and 7 days after removal of the ring. The findings of the general toxicology study supported the existing data from both preclinical and clinical studies in that there were no signs of toxicity related to dapivirine. In addition, the presence of the physical dapivirine ring did not alter local or systemic toxicity or the pharmacokinetics of dapivirine. Pharmacokinetic studies indicated that the dapivirine ring produced significant vaginal tissue levels of dapivirine. However, no dapivirine was detected in cervical tissue samples using the methods described here. Plasma and vaginal fluid levels were lower than those in previous clinical studies, while there were detectable dapivirine levels in the rectal tissue and fluid. All tissue and fluid levels tailed off rapidly to undetectable levels following removal of the ring. The sheep represents a very useful model for the assessment of the safety and pharmacokinetics of microbicide drug delivery devices, such as the vaginal ring. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Short communication: expression of transporters and metabolizing enzymes in the female lower genital tract: implications for microbicide research.

Science.gov (United States)

Zhou, Tian; Hu, Minlu; Cost, Marilyn; Poloyac, Samuel; Rohan, Lisa

2013-11-01

Topical vaginal microbicides have been considered a promising option for preventing the male-to-female sexual transmission of HIV; however, clinical trials to date have not clearly demonstrated robust and reproducible effectiveness results. While multiple approaches may help enhance product effectiveness observed in clinical trials, increasing the drug exposure in lower genital tract tissues is a compelling option, given the difficulty in achieving sufficient drug exposure and positive correlation between tissue exposure and microbicide efficacy. Since many microbicide drug candidates are substrates of transporters and/or metabolizing enzymes, there is emerging interest in improving microbicide exposure and efficacy through local modulation of transporters and enzymes in the female lower genital tract. However, no systematic information on transporter/enzyme expression is available for ectocervical and vaginal tissues of premenopausal women, the genital sites most relevant to microbicide drug delivery. The current study utilized reverse transcriptase polymerase chain reaction (RT-PCR) to examine the mRNA expression profile of 22 transporters and 19 metabolizing enzymes in premenopausal normal human ectocervix and vagina. Efflux and uptake transporters important for antiretroviral drugs, such as P-gp, BCRP, OCT2, and ENT1, were found to be moderately or highly expressed in the lower genital tract as compared to liver. Among the metabolizing enzymes examined, most CYP isoforms were not detected while a number of UGTs such as UGT1A1 were highly expressed. Moderate to high expression of select transporters and enzymes was also observed in mouse cervix and vagina. The implications of this information on microbicide research is also discussed, including microbicide pharmacokinetics, the utilization of the mouse model in microbicide screening, as well as the in vivo functional studies of cervicovaginal transporters and enzymes.

Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference.

Science.gov (United States)

Wahren, Britta; Biswas, Priscilla; Borggren, Marie; Coleman, Adam; Da Costa, Kelly; De Haes, Winni; Dieltjens, Tessa; Dispinseri, Stefania; Grupping, Katrijn; Hallengärd, David; Hornig, Julia; Klein, Katja; Mainetti, Lara; Palma, Paolo; Reudelsterz, Marc; Seifried, Janna; Selhorst, Philippe; Sköld, Annette; Uchtenhagen, Hannes; van Gils, Marit J; Weber, Caroline; Shattock, Robin; Scarlatti, Gabriella

2010-07-26

EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training. EUROPRISE held its second annual conference in Budapest in November, 2009. The conference had 143 participants and their presentations covered aspects of vaccine and microbicide research, development and discovery. Since training is a major task of the Network, the students of the EUROPRISE PhD program summarized certain presentations and their view of the conference in this paper.

Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

Directory of Open Access Journals (Sweden)

Mainetti Lara

2010-07-01

Full Text Available Abstract EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training. EUROPRISE held its second annual conference in Budapest in November, 2009. The conference had 143 participants and their presentations covered aspects of vaccine and microbicide research, development and discovery. Since training is a major task of the Network, the students of the EUROPRISE PhD program summarized certain presentations and their view of the conference in this paper.

Comparison of the Microbicidal activity of monochloramine and iodine.

Science.gov (United States)

Arnitz, R; Nagl, M; Gottardi, W

2015-12-01

Recently, we showed that monochloramine (NH2 Cl) has a significantly stronger bactericidal and fungicidal activity than chloramine T despite its lower oxidizing power. This phenomenon was explained by increased penetration because of the higher lipophilicity and smaller bulk of NH2 Cl. As iodine (I2 ) has an even fivefold higher bulk than NH2 Cl, a comparison of both compounds regarding their microbicidal activity became the aim of this study. Aqueous solutions of I2 at a concentration of 10·7 μmol l(-1) killed 10(6) colony forming units per millilitre (CFU ml(-1) ) of Escherichia coli, Staphylococcus aureus or Pseudomonas aeruginosa to the detection limit of 10(2) CFU ml(-1) within 1 min at 20°C and pH 7·1, while a concentration of 36-355 μmol l(-1) of NH2 Cl was needed to achieve the same effect. Aspergillus fumigatus was inactivated within 5 min by 36 μmol l(-1) I2 and by 355 μmol l(-1) NH2 Cl, Candida albicans within 1 min by 10·7 μmol l(-1) I2 and by 355 μmol l(-1) NH2 Cl. The lipophilicity of I2 , determined with the octanol/water method, was three powers of 10 higher than that of NH2 Cl. The at least 10-fold stronger microbicidal activity of iodine suggests that the hindrance of penetration of the bulky molecule is outweighed by enhanced lipophilicity. The microbicidal activity of active halogen compounds increases not only with their reactivity, but also with higher lipophilicity and lower bulk, as shown recently. In this study, iodine showed a higher microbicidal activity than monochloramine and a 1000-fold higher lipophilicity. Therefore, the lipophilicity of a disinfectant may be more important than the bulk for bactericidal activity. These facts should be considered upon the design of new antiseptics and their clinical application. © 2015 The Society for Applied Microbiology.

Hypothetical Rectal Microbicide Acceptability and Factors Influencing It among Men Who Have Sex with Men in Tianjin, China.

Directory of Open Access Journals (Sweden)

Guohong Zhang

Full Text Available To measure potential acceptability of rectal microbicides and to explore factors likely to affect their acceptability among men who have sex with men (MSM.Cross-sectional and retrospective surveys were conducted in this study. A questionnaire and a scale were used to measure the acceptability score for physical and functional characteristics of hypothetical rectal microbicides. We also evaluated the involvement of other factors such as sexual behaviors, social context, etc.MSMs we interviewed showed a high acceptability to rectal microbicides, indicated by the mean acceptability score of 2.92 (SD, 0.54, scale of 1-4. The results also suggested that microbicides were preferred in a cream form that can moisten and lubricate the rectum, prevent HIV infection and go unnoticed by their partners. Multivariate analysis showed that the microbicides acceptability varied significantly by education level (β = 0.135; P = 0.028, having casual partners (β = 0.174; P = 0.007, frequency of lubricant use (β = 0.134; P = 0.031, history of HIV test (β = 0.129; P = 0.036, willingness to use lubricant (β = 0.126; P = 0.045, locus of control by partners regarding STI infection (β = 0.168; P = 0.009.A positive response to rectal microbicides among MSMs was found in our study, suggesting that rectal microbicides might have a potential market in MSMs and they might play an important role in HIV/STIs prevention as a supplement. Further studies may be considered to combine the acceptability study with clinical research together to understand the true feelings of MSMs when they use the products.

Mucosal safety of PHI-443 and stampidine as a combination microbicide to prevent genital transmission of HIV-1.

Science.gov (United States)

D'Cruz, Osmond J; Uckun, Fatih M

2007-10-01

To investigate the in vitro and in vivo mucosal safety of a nonnucleoside reverse transcriptase (RT) inhibitor (PHI-443) and a nucleoside analogue RT inhibitor (stampidine)-based anti-HIV microbicide either alone or in combination. In vitro and in vivo studies using three-dimensional vaginal epithelia integrating Langerhans cells and 16 New Zealand White rabbits, respectively. Research laboratory. Rabbits in groups of four were exposed intravaginally to a gel with and without 1% PHI-443, 1% stampidine, or 1% PHI-443 plus 1% stampidine for 14 days. Cytokine/chemokine release by three-dimensional co-cultures in the presence and absence of PHI-443 or stampidine. Histologic scoring of vaginal tissue for mucosal toxicity at 24 hours after dosing. Simultaneous evaluation of levels of 10 cytokines (granulocyte-macrophage colony-stimulating factor, interleukin-1 alpha, interleukin-13, macrophage inflammatory protein-1 beta, granulocyte colony-stimulating factor, interleukin-18, tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, and interferon-gamma) and 6 chemokines (epithelial neutrophil-activating peptide-78, interleukin-8, monocyte/macrophage chemoattractant protein-1, macrophage inflammatory protein-3 alpha, interferon-inducible protein-10, and regulated upon activation of normal T-cell expressed and secreted) in culture media by a multiplexed chemiluminescence-based immunoassay. In the rabbit model, repeated intravaginal administration of PHI-443 plus stampidine via a gel formulation at concentrations nearly 2,000 and 10,000 times higher than their respective in vitro anti-HIV IC(50) values did not result in vaginal irritation. The levels of proinflammatory cytokines/chemokines secreted by multilayered human genital epithelia integrating Langerhans cells were unaffected by prolonged exposure to PHI-443 or stampidine. The combination of PHI-443 and stampidine was noncytotoxic to vaginal epithelial cells, nonirritating to vaginal mucosa, and did not induce

Identification and functional analysis of the S-layer protein SplA of Paenibacillus larvae, the causative agent of American Foulbrood of honey bees.

Directory of Open Access Journals (Sweden)

Lena Poppinga

Full Text Available The gram-positive, spore-forming bacterium Paenibacillus larvae is the etiological agent of American Foulbrood (AFB, a globally occurring, deathly epizootic of honey bee brood. AFB outbreaks are predominantly caused by two genotypes of P. larvae, ERIC I and ERIC II, with P. larvae ERIC II being the more virulent genotype on larval level. Recently, comparative proteome analyses have revealed that P. larvae ERIC II but not ERIC I might harbour a functional S-layer protein, named SplA. We here determine the genomic sequence of splA in both genotypes and demonstrate by in vitro self-assembly studies of recombinant and purified SplA protein in combination with electron-microscopy that SplA is a true S-layer protein self-assembling into a square 2D lattice. The existence of a functional S-layer protein is novel for this bacterial species. For elucidating the biological function of P. larvae SplA, a genetic system for disruption of gene expression in this important honey bee pathogen was developed. Subsequent analyses of in vivo biological functions of SplA were based on comparing a wild-type strain of P. larvae ERIC II with the newly constructed splA-knockout mutant of this strain. Differences in cell and colony morphology suggest that SplA is a shape-determining factor. Marked differences between P. larvae ERIC II wild-type and mutant cells with regard to (i adhesion to primary pupal midgut cells and (ii larval mortality as measured in exposure bioassays corroborate the assumption that the S-layer of P. larvae ERIC II is an important virulence factor. Since SplA is the first functionally proven virulence factor for this species, our data extend the knowledge of the molecular differences between these two genotypes of P. larvae and contribute to explaining the observed differences in virulence. These results present an immense advancement in our understanding of P. larvae pathogenesis.

Compartmental transport model of microbicide delivery by an intravaginal ring

Science.gov (United States)

Geonnotti, Anthony R.; Katz, David F.

2010-01-01

Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 hours following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds. PMID:20222027

In vitro resistance profile of the candidate HIV-1 microbicide drug dapivirine.

Science.gov (United States)

Schader, Susan M; Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Moisi, Daniela; Colby-Germinario, Susan P; Wainberg, Mark A

2012-02-01

Antiretroviral-based microbicides may offer a means to reduce the sexual transmission of HIV-1. Suboptimal use of a microbicide may, however, lead to the development of drug resistance in users that are already, or become, infected with HIV-1. In such cases, the efficacy of treatments may be compromised since the same (or similar) antiretrovirals used in treatments are being developed as microbicides. To help predict which drug resistance mutations may develop in the context of suboptimal use, HIV-1 primary isolates of different subtypes and different baseline resistance profiles were used to infect primary cells in vitro in the presence of increasing suboptimal concentrations of the two candidate microbicide antiretrovirals dapivirine (DAP) and tenofovir (TFV) alone or in combination. Infections were ongoing for 25 weeks, after which reverse transcriptase genotypes were determined and scrutinized for the presence of any clinically recognized reverse transcriptase drug resistance mutations. Results indicated that suboptimal concentrations of DAP alone facilitated the emergence of common nonnucleoside reverse transcriptase inhibitor resistance mutations, while suboptimal concentrations of DAP plus TFV gave rise to fewer mutations. Suboptimal concentrations of TFV alone did not frequently result in the development of resistance mutations. Sensitivity evaluations for stavudine (d4T), nevirapine (NVP), and lamivudine (3TC) revealed that the selection of resistance as a consequence of suboptimal concentrations of DAP may compromise the potential for NVP to be used in treatment, a finding of potential relevance in developing countries.

RAF/7/013: Enhancing the Use of Isotope Hydrology in Planning, Management and Development of Water Resources (AFRA)

International Nuclear Information System (INIS)

Opiyo, A.N.

2017-01-01

The project is a follow-up of RAF/8/048. Building capacity on isotope studies in Africa. It also relates IAEA KEN 7005 project on Evaluation of Surface and Groundwater Interaction of the Kilimanjaro Aquifer applying Isotope Techniques. The main aim of the project is to carry out Hydrological, Hydrogeological and geological, hydrogeo-chemical and geochemical studies and Water resources risks and vulnerability studies. AfriWatSan Project Relates to RAF/7/013 and it contribute to the overall objective

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

Directory of Open Access Journals (Sweden)

Li Yun-Yao

2006-10-01

Full Text Available Abstract Background Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP, a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. Methods The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP, the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. Results The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate, cellulose sulfate, carrageenan, CAP (in soluble form and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold diminished in the presence of SP (33.3%. Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. Conclusion The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors.

Perceptions of vaginal microbicides as an HIV prevention method among health care providers in KwaZulu-Natal, South Africa

Directory of Open Access Journals (Sweden)

Mantell Joanne E

2007-03-01

Full Text Available Abstract Background The promise of microbicides as an HIV prevention method will not be realized if not supported by health care providers. They are the primary source of sexual health information for potential users, in both the public and private health sectors. Therefore, the aim of this study was to determine perceptions of vaginal microbicides as a potential HIV prevention method among health care providers in Durban and Hlabisa, South Africa, using a combination of quantitative and qualitative methods. Results During 2004, semi structured interviews with 149 health care providers were conducted. Fifty seven percent of hospital managers, 40% of pharmacists and 35% of nurses possessed some basic knowledge of microbicides, such as the product being used intra-vaginally before sex to prevent HIV infection. The majority of them were positive about microbicides and were willing to counsel users regarding potential use. Providers from both public and private sectors felt that an effective microbicide should be available to all people, regardless of HIV status. Providers felt that the product should be accessed over-the-counter in pharmacies and in retail stores. They also felt a need for potential microbicides to be available free of charge, and packaged with clear instructions. The media was seen by health care providers as being an effective strategy for promoting microbicides. Conclusion Overall, health care providers were very positive about the possible introduction of an effective microbicide for HIV prevention. The findings generated by this study illustrated the need for training health care providers prior to making the product accessible, as well as the importance of addressing the potential barriers to use of the product by women. These are important concerns in the health care community, and this study also served to educate them for the day when research becomes reality.

Adolescent Girls’ Communication with “Mothers” About Topical Microbicides

Science.gov (United States)

Sunder, Punita K.; Ramos, Stephanie; Short, Mary B.; Rosenthal, Susan L.

2007-01-01

Study Objective Topical microbicides, a female-initiated method to protect against sexually transmitted infections (STIs) and pregnancy, will only be effective if found acceptable. Mothers may have an influence on acceptability and use among adolescent girls. The current study examined the communication between girls and mothers to understand the potential predictors and nature of conversations regarding surrogate microbicide products. Design Sexually experienced girls, 14 to 21 years, were recruited for a 6-month study examining microbicide acceptability. During face-to-face interviews, qualitative data were collected regarding communication between girls and mothers. Two independent raters coded the responses, which were organized into themes. Themes were interpreted according to the conceptual understanding of mother-daughter communication. Results Fifty percent of the 171 girls with codable responses had a conversation with their mother. Higher levels of indirect parental monitoring were related to being more likely to have a conversation. Concrete events related to the study (i.e. receiving phone call from the researcher, having an appointment, or seeing the product) or inquiries by mothers appeared to promote conversation. Barriers to conversation included the private nature of the information and relationship issues between the mother and daughter. Conversations often addressed issues related to girls’ participation in the study, although some conversations included global issues related to sexuality. Conclusions Girls may talk to their mothers about new products for STI prevention, and such conversations may provide opportunities to promote use. PMID:17174825

How important is the myeloperoxidase microbicidal system of phagocytic cells?

Science.gov (United States)

Thong, Y H

1982-03-01

The myeloperoxidase system is presented by most immunology textbooks as a major microbicidal system of phagocytic cells. This theory, however, has not bee subjected to vigorous testing in the clinical arena. Of 14 patients with primary myeloperoxidase deficiency, only 3 had infectious complication. All 3 patients have more plausible explanation than myeloperoxidase deficiency for their infectious complications. Two of these patients were healthy until middle age when they developed systemic candidiasis after the onset of diabetes mellitus. The third patient was an infant with a maturational defect in neutrophil chemotaxis whose infectious complications ceased after the normalization of the chemotactic defect. The results of these "experiments of nature" indicate that the meyloperoxidase system is not a major microbicidal mechanism of phagocytic cells.

Acceptability of vaginal microbicides among female sex workers and their intimate male partners in two Mexico-US border cities: a mixed methods analysis.

Science.gov (United States)

Robertson, Angela M; Syvertsen, Jennifer L; Martinez, Gustavo; Rangel, M Gudelia; Palinkas, Lawrence A; Stockman, Jamila K; Ulibarri, Monica D; Strathdee, Steffanie A

2013-01-01

Female sex workers (FSWs) may benefit from pre-exposure prophylaxis (PrEP) including microbicides for HIV prevention. Since adherence is a key factor in PrEP efficacy, we explored microbicide acceptability and potential barriers to use within FSWs' intimate relationships in Tijuana and Ciudad Juárez, Mexico, where HIV prevalence is increasing. FSWs and their verified intimate (non-commercial) male partners completed quantitative and qualitative interviews from 2010 to 2012. Our complementary mixed methods design followed an iterative process to assess microbicide acceptability, explore related relationship dynamics and identify factors associated with concern about male partners' anger regarding microbicide use. Among 185 couples (n=370 individuals), interest in microbicides was high. In qualitative interviews with 28 couples, most participants were enthusiastic about microbicides for sex work contexts but some explained that microbicides could imply mistrust/infidelity within their intimate relationships. In the overall sample, nearly one in six participants (16%) worried that male partners would become angry about microbicides, which was associated with higher self-esteem among FSWs and lower self-esteem and past year conflicts causing injury within relationships among men. HIV prevention interventions should consider intimate relationship dynamics posing potential barriers to PrEP acceptability and adherence, involve male partners and promote risk communication skills.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011.

Science.gov (United States)

Ruffin, Nicolas; Borggren, Marie; Euler, Zelda; Fiorino, Fabio; Grupping, Katrijn; Hallengärd, David; Javed, Aneele; Mendonca, Kevin; Pollard, Charlotte; Reinhart, David; Saba, Elisa; Sheik-Khalil, Enas; Sköld, Annette; Ziglio, Serena; Scarlatti, Gabriella; Gotch, Frances; Wahren, Britta; Shattock, Robin J

2012-07-11

Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These - necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

Directory of Open Access Journals (Sweden)

Ruffin Nicolas

2012-07-01

Full Text Available Abstract Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines; mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.

Broad Spectrum Microbicidal Activity of Photocatalysis by TiO2

Directory of Open Access Journals (Sweden)

Yoshinobu Kubota

2013-03-01

Full Text Available Photocatalytically active titanium dioxide (TiO2 is widely used as a self-cleaning and self-disinfecting material in many applications to keep environments biologically clean. Several studies on the inactivation of bacteria and viruses by photocatalytic reactions have also been reported; however, only few studies evaluated the spectrum of the microbicidal activity with photocatalysis for various species. There is a need to confirm the expected effectiveness of disinfection by photocatalysis against multidrug-resistant bacteria and viruses. In this study, microbicidal activity of photocatalysis was evaluated by comparing the inactivation of various species of bacteria and viruses when their suspensions were dropped on the surface of TiO2-coated glass. Gram-positive bacteria, e.g., methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae, were easily inactivated by photocatalysis, whereas some gram-negative bacteria, e.g., Escherichia coli and multidrug-resistant Pseudomonas aeruginosa, were gradually inactivated by photocatalysis. Influenza virus, an enveloped virus, was significantly inactivated by photocatalysis compared with feline calicivirus, a non-enveloped virus. The effectiveness of microbicidal activity by photocatalysis may depend on the surface structure. However, they are effectively inactivated by photocatalysis on the surface of TiO2-coated glass. Our data emphasize that effective cleaning and disinfection by photocatalysis in nosocomial settings prevents pathogen transmission.

Pregnancy incidence and risk factors among women participating in vaginal microbicide trials for HIV prevention: systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Alfred Musekiwa

Full Text Available INTRODUCTION: Pregnancy is contraindicated in vaginal microbicide trials for the prevention of HIV infection in women due to the unknown maternal and fetal safety of the microbicides. Women who become pregnant are taken off the microbicide during pregnancy period but this result in reduction of the power of the trials. Strategies to reduce the pregnancy rates require an understanding of the incidence and associated risk factors of pregnancy in microbicide trials. This systematic review estimates the overall incidence rate of pregnancy in microbicide trials and describes the associated risk factors. METHODS: A comprehensive literature search was carried out to identify eligible studies from electronic databases and other sources. Two review authors independently selected studies and extracted relevant data from included studies. Meta-analysis of incidence rates of pregnancy was carried out and risk factors of pregnancy were reported narratively. RESULTS: Fifteen studies reporting data from 10 microbicide trials (N=27,384 participants were included. A total of 4,107 participants (15.0% fell pregnant and a meta-analysis of incidence rates of pregnancy from 8 microbicide trials (N=25,551 yielded an overall incidence rate of 23.37 (95%CI: 17.78 to 28.96 pregnancies per 100 woman-years. However, significant heterogeneity was detected. Hormonal injectable, intra-uterine device (IUD or implants or sterilization, older age, more years of education and condom use were associated with lower pregnancy. On the other hand, living with a man, history of pregnancy, self and partner desire for future baby, oral contraceptive use, increased number of unprotected sexual acts and inconsistent use of condoms were associated with higher pregnancy. CONCLUSIONS: The incidence rate of pregnancy in microbicide trials is high and strategies for its reduction are urgently required in order to improve the sample size and power of these trials.

Acceptability of vaginal microbicides among female sex workers and their intimate male partners in two Mexico-U.S. border cities: a mixed methods analysis

Science.gov (United States)

Robertson, Angela M.; Syvertsen, Jennifer L.; Martinez, Gustavo; Rangel, M. Gudelia; Palinkas, Lawrence A.; Stockman, Jamila K.; Ulibarri, Monica D.; Strathdee, Steffanie A.

2013-01-01

Background Female sex workers (FSWs) may benefit from pre-exposure prophylaxis (PrEP) including microbicides for HIV prevention. Since adherence is a key factor in PrEP efficacy, we explored microbicide acceptability and potential barriers to use within FSWs’ intimate relationships in Tijuana and Ciudad Juárez, Mexico, where HIV prevalence is increasing. Methods FSWs and their verified intimate (non-commercial) male partners completed quantitative and qualitative interviews from 2010–2012. Our complementary mixed methods design followed an iterative process to assess microbicide acceptability, explore related relationship dynamics, and identify factors associated with concern about male partners’ anger regarding microbicide use. Results Among 185 couples (n=370 individuals), interest in microbicides was high. In qualitative interviews with 28 couples, most participants were enthusiastic about microbicides for sex work contexts but some explained that microbicides could imply mistrust/infidelity within their intimate relationships. In the overall sample, nearly 1 in 6 participants (16%) worried that male partners would become angry about microbicides, which was associated with higher self-esteem among FSWs and lower self-esteem and past year conflict causing injury within relationships among men. Conclusions HIV prevention interventions should consider intimate relationship dynamics posing potential barriers to PrEP acceptability and adherence, involve male partners, and promote risk communication skills. PMID:23398385

The SPL-based Neutrino Super Beam

CERN Document Server

Baussan, E; Bobeth, C; Bouquerel, E; Caretta, O; Cupial, P; Davenne, T; Densham, C; Dracos, M; Fitton, M; Gaudiot, G; Kozien, M; Lacny, L; Lepers, B; Longhin, A; Loveridge, P; Osswald, F; Poussot, P; Rooney, M; Skoczen, B; Szybinski, B; Ustrzycka, A; Vassilopoulos, N; Wilcox, D; Wroblewski, A; Wurtz, J; Zeter, V; Zito, M

2012-01-01

The EUROnu Super Beam work package has studied a neutrino beam based on SPL at CERN and aimed at MEMPHYS, a large water Cherenkov detector, proposed for the Laboratoire Souterrain de Modane (Fr\\'ejus tunnel, France), with a baseline of 130 km. The aim of this proposed experiment is to study the CP violation in the neutrino sector. In the study reported here, we have developed the conceptual design of the neutrino beam, especially the target and the magnetic focusing device. Indeed, this beam present several unprecedented challenges, like the high primary proton beam power (4 MW), the high repetition rate (50 Hz) and the low energy of the protons (4.5 GeV). The design is completed by a study of all the main component of the system, starting from the transport system to guide the beam to the target up to the beam dump.

Mechanical Design and Fabrication Studies for SPL Superconducting RF Cavities

CERN Document Server

Atieh, S; Aviles Santillana, I; Capatina, O; Renaglia, T; Tardy, T; Valverde Alonso, N; Weingarten, W

2011-01-01

CERN’s R&D programme on the Superconducting Proton Linac’s (SPL) superconducting radio frequency (SRF) elliptical cavities made from niobium sheets explores new mechanical design and consequently new fabrication methods, where several opportunities for improved optimization were identified. A stainless steel helium vessel is under design rather than a titanium helium vessel using an integrated brazed transition between Nb and the SS helium vessel. Different design and fabrication aspects were proposed and the results are discussed hereafter.

Qualitative and quantitative intravaginal targeting: Key to anti-HIV-1 microbicide delivery from test tube to in vivo success

CSIR Research Space (South Africa)

Pillay, V

2012-06-01

Full Text Available employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide...

A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide

Science.gov (United States)

Shen, Hong; Iwasaki, Akiko

2006-01-01

Topical microbicides represent a promising new approach to preventing HIV and other sexually transmitted infections. TLR agonists are ideal candidates for microbicides, as they trigger a multitude of antiviral genes effective against a broad range of viruses. Although vaginal application of CpG oligodeoxynucleotides (ODNs) and poly I:C has been shown to protect mice from genital herpes infection, the mechanism by which these agents provide protection remains unclear. Here, we show that plasmacytoid DCs (pDCs) are required for CpG ODN–mediated protection against lethal vaginal challenge with herpes simplex virus type 2 (HSV-2). Moreover, we demonstrate that cells of both the hematopoietic and stromal compartments must respond to CpG ODN via TLR9 and to type I IFNs through IFN-αβ receptor (IFN-αβR) for protection. Thus, crosstalk between pDCs and vaginal stromal cells provides for optimal microbicide efficacy. Our results imply that temporally and spatially controlled targeting of CpG ODN to pDCs and epithelial cells can potentially maximize their effectiveness as microbicides while minimizing the associated inflammatory responses. PMID:16878177

Learning from the private sector: towards a keener understanding of the end-user for microbicide introduction planning.

Science.gov (United States)

Lin, Amy H; Breger, Tiffany L; Barnhart, Matthew; Kim, Ann; Vangsgaard, Charlotte; Harris, Emily

2014-01-01

In planning for the introduction of vaginal microbicides and other new antiretroviral (ARV)-based prevention products for women, an in-depth understanding of potential end-users will be critically important to inform strategies to optimize uptake and long-term adherence. User-centred private sector companies have contributed to the successful launch of many different types of products, employing methods drawn from behavioural and social sciences to shape product designs, marketing messages and communication channels. Examples of how the private sector has adapted and applied these techniques to make decisions around product messaging and targeting may be instructive for adaptation to microbicide introduction. In preparing to introduce a product, user-centred private sector companies employ diverse methods to understand the target population and their lifestyles, values and motivations. ReD Associates' observational research on user behaviours in the packaged food and diabetes fields illustrates how 'tag along' or 'shadowing' techniques can identify sources of non-adherence. Another open-ended method is self-documentation, and IDEO's mammography research utilized this to uncover user motivations that extended beyond health. Mapping the user journey is a quantitative approach for outlining critical decision-making stages, and Monitor Inclusive Markets applied this framework to identify toilet design opportunities for the rural poor. Through an iterative process, these various techniques can generate hypotheses on user drop-off points, quantify where drop-off is highest and prioritize areas of further research to uncover usage barriers. Although research constraints exist, these types of user-centred techniques have helped create effective messaging, product positioning and packaging of health products as well as family planning information. These methods can be applied to microbicide acceptability testing outside of clinical trials to design microbicide marketing

Does microbicide use in consumer products promote antimicrobial resistance? A critical review and recommendations for a cohesive approach to risk assessment.

Science.gov (United States)

Maillard, Jean-Yves; Bloomfield, Sally; Coelho, Joana Rosado; Collier, Phillip; Cookson, Barry; Fanning, Séamus; Hill, Andrew; Hartemann, Philippe; McBain, Andrew J; Oggioni, Marco; Sattar, Syed; Schweizer, Herbert P; Threlfall, John

2013-10-01

The increasing use of microbicides in consumer products is raising concerns related to enhanced microbicide resistance in bacteria and potential cross resistance to antibiotics. The recently published documents on this topic from the European Commission have spawned much interest to better understand the true extent of the putative links for the benefit of the manufacturers, regulators, and consumers alike. This white paper is based on a 2-day workshop (SEAC-Unilever, Bedford, United Kingdom; June 2012) in the fields of microbicide usage and resistance. It identifies gaps in our knowledge and also makes specific recommendations for harmonization of key terms and refinement/standardization of methods for testing microbicide resistance to better assess the impact and possible links with cross resistance to antibiotics. It also calls for a better cohesion in research in this field. Such information is crucial to developing any risk assessment framework on microbicide use notably in consumer products. The article also identifies key research questions where there are inadequate data, which, if addressed, could promote improved knowledge and understanding to assess any related risks for consumer and environmental safety.

Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides

Directory of Open Access Journals (Sweden)

Vacas-Córdoba E

2014-07-01

Full Text Available Enrique Vacas-Córdoba,1–3 Marta Galán,3,4 Francisco J de la Mata,3,4 Rafael Gómez,3,4 Marjorie Pion,1–3 M Ángeles Muñoz-Fernández1–3 1Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain; 3Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN, Madrid, Spain; 4Dendrimers for Biomedical Applications Group (BioInDen, University of Alcalá, Madrid, Spain Abstract: Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV-1 infection rates. Up until now, antiretrovirals (ARVs have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16 and naphthyl sulfonated (G2-NF16 ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as

Investigation of the Sound Pressure Level (SPL) of earphones during music listening with the use of physical ear canal models

Science.gov (United States)

Aying, K. P.; Otadoy, R. E.; Violanda, R.

2015-06-01

This study investigates on the sound pressure level (SPL) of insert-type earphones that are commonly used for music listening of the general populace. Measurements of SPL from earphones of different respondents were measured by plugging the earphone to a physical ear canal model. Durations of the earphone used for music listening were also gathered through short interviews. Results show that 21% of the respondents exceed the standard loudness/duration relation recommended by the World Health Organization (WHO).

Machine Learning for RealisticBall Detection in RoboCup SPL

OpenAIRE

Bloisi, Domenico; Del Duchetto, Francesco; Manoni, Tiziano; Suriani, Vincenzo

2017-01-01

In this technical report, we describe the use of a machine learning approach for detecting the realistic black and white ball currently in use in the RoboCup Standard Platform League. Our aim is to provide a ready-to-use software module that can be useful for the RoboCup SPL community. To this end, the approach is integrated within the official B-Human code release 2016. The complete code for the approach presented in this work can be downloaded from the SPQR Team homepage at http://spqr.diag...

Nanotech-derived topical microbicides for HIV prevention: the road to clinical development.

Science.gov (United States)

Sánchez-Rodríguez, Javier; Vacas-Córdoba, Enrique; Gómez, Rafael; De La Mata, F Javier; Muñoz-Fernández, Ma Ángeles

2015-01-01

More than three decades since its discovery, HIV infection remains one of the most aggressive epidemics worldwide, with more than 35 million people infected. In sub-Saharan Africa, heterosexual transmissions represent nearly 80% of new infections, with 50% of these occurring in women. In an effort to stop the dramatic spread of the HIV epidemic, new preventive treatments, such as microbicides, have been developed. Nanotechnology has revolutionized this field by designing and engineering novel highly effective nano-sized materials as microbicide candidates. This review illustrates the most recent advances in nanotech-derived HIV prevention strategies, as well as the main steps required to translate promising in vitro results into clinical trials. Copyright © 2014 Elsevier B.V. All rights reserved.

A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

Science.gov (United States)

Barnable, Patrick; Calenda, Giulia; Ouattara, Louise; Gettie, Agegnehu; Blanchard, James; Jean-Pierre, Ninochka; Kizima, Larisa; Rodríguez, Aixa; Abraham, Ciby; Menon, Radhika; Seidor, Samantha; Cooney, Michael L; Roberts, Kevin D; Sperling, Rhoda; Piatak, Michael; Lifson, Jeffrey D; Fernandez-Romero, Jose A; Zydowsky, Thomas M; Robbiani, Melissa; Teleshova, Natalia

2014-01-01

To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

Directory of Open Access Journals (Sweden)

Patrick Barnable

Full Text Available To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M and zinc acetate dihydrate (ZA in carrageenan (CG (MZC inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100 and MC (1∶30, the only dilution tested, but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines of vaginal (but not cervical mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74% did not significantly differ from CG (32-45%, it was within the range of protection (∼75% against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

Willingness to Use Microbicides Is Affected by the Importance of Product Characteristics, Use Parameters, and Protective Properties

Science.gov (United States)

Morrow, Kathleen M.; Fava, Joseph L.; Rosen, Rochelle K.; Vargas, Sara; Barroso, Candelaria; Christensen, Anna L.; Woodsong, Cynthia; Severy, Lawrence

2008-01-01

Background Along with efficacy, a microbicide’s acceptability will be integral to its impact on the pandemic. Understanding Product Characteristics that users find most acceptable and determining who will use which type of product are key to optimizing use effectiveness. Objectives To evaluate psychometrically the Important Microbicide Characteristics (IMC) instrument and examine its relationship to willingness to use microbicides. Results Exploratory and confirmatory factor analyses revealed 2 IMC subscales (Cronbach’s coefficient α: Product Characteristics subscale (α = 0.84) and Protective Properties subscale (α = 0.89)). Significant differences on Product Characteristics subscale scores were found for history of douching (P = 0.002) and employment status (P = 0.001). Whether a woman used a method to prevent pregnancy or sexually transmitted disease (STD) in the last 3 months (P IMC instrument serves as a template for future studies of candidate microbicides. PMID:17325607

Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

OpenAIRE

Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

2007-01-01

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivir...

Differential SPL gene expression patterns reveal candidate genes underlying flowering time and architectural differences in Mimulus and Arabidopsis.

Science.gov (United States)

Jorgensen, Stacy A; Preston, Jill C

2014-04-01

Evolutionary transitions in growth habit and flowering time responses to variable environmental signals have occurred multiple times independently across angiosperms and have major impacts on plant fitness. Proteins in the SPL family of transcription factors collectively regulate flowering time genes that have been implicated in interspecific shifts in annuality/perenniality. However, their potential importance in the evolution of angiosperm growth habit has not been extensively investigated. Here we identify orthologs representative of the major SPL gene clades in annual Arabidopsis thaliana and Mimulus guttatus IM767, and perennial A. lyrata and M. guttatus PR, and characterize their expression. Spatio-temporal expression patterns are complex across both diverse tissues of the same taxa and comparable tissues of different taxa, consistent with genic sub- or neo-functionalization. However, our data are consistent with a general role for several SPL genes in the promotion of juvenile to adult phase change and/or flowering time in Mimulus and Arabidopsis. Furthermore, several candidate genes were identified for future study whose differential expression correlates with growth habit and architectural variation in annual versus perennial taxa. Copyright © 2014 Elsevier Inc. All rights reserved.

Microbicides Development Programme: Engaging the community in the standard of care debate in a vaginal microbicide trial in Mwanza, Tanzania

Directory of Open Access Journals (Sweden)

Soteli Selephina

2009-10-01

Full Text Available Abstract Background HIV prevention research in resource-limited countries is associated with a variety of ethical dilemmas. Key amongst these is the question of what constitutes an appropriate standard of health care (SoC for participants in HIV prevention trials. This paper describes a community-focused approach to develop a locally-appropriate SoC in the context of a phase III vaginal microbicide trial in Mwanza City, northwest Tanzania. Methods A mobile community-based sexual and reproductive health service for women working as informal food vendors or in traditional and modern bars, restaurants, hotels and guesthouses has been established in 10 city wards. Wards were divided into geographical clusters and community representatives elected at cluster and ward level. A city-level Community Advisory Committee (CAC with representatives from each ward has been established. Workshops and community meetings at ward and city-level have explored project-related concerns using tools adapted from participatory learning and action techniques e.g. chapati diagrams, pair-wise ranking. Secondary stakeholders representing local public-sector and non-governmental health and social care providers have formed a trial Stakeholders' Advisory Group (SAG, which includes two CAC representatives. Results Key recommendations from participatory community workshops, CAC and SAG meetings conducted in the first year of the trial relate to the quality and range of clinic services provided at study clinics as well as broader standard of care issues. Recommendations have included streamlining clinic services to reduce waiting times, expanding services to include the children and spouses of participants and providing care for common local conditions such as malaria. Participants, community representatives and stakeholders felt there was an ethical obligation to ensure effective access to antiretroviral drugs and to provide supportive community-based care for women identified

Microbicides Development Programme: Engaging the community in the standard of care debate in a vaginal microbicide trial in Mwanza, Tanzania

Science.gov (United States)

Vallely, Andrew; Shagi, Charles; Lees, Shelley; Shapiro, Katherine; Masanja, Joseph; Nikolau, Lawi; Kazimoto, Johari; Soteli, Selephina; Moffat, Claire; Changalucha, John; McCormack, Sheena; Hayes, Richard J

2009-01-01

Background HIV prevention research in resource-limited countries is associated with a variety of ethical dilemmas. Key amongst these is the question of what constitutes an appropriate standard of health care (SoC) for participants in HIV prevention trials. This paper describes a community-focused approach to develop a locally-appropriate SoC in the context of a phase III vaginal microbicide trial in Mwanza City, northwest Tanzania. Methods A mobile community-based sexual and reproductive health service for women working as informal food vendors or in traditional and modern bars, restaurants, hotels and guesthouses has been established in 10 city wards. Wards were divided into geographical clusters and community representatives elected at cluster and ward level. A city-level Community Advisory Committee (CAC) with representatives from each ward has been established. Workshops and community meetings at ward and city-level have explored project-related concerns using tools adapted from participatory learning and action techniques e.g. chapati diagrams, pair-wise ranking. Secondary stakeholders representing local public-sector and non-governmental health and social care providers have formed a trial Stakeholders' Advisory Group (SAG), which includes two CAC representatives. Results Key recommendations from participatory community workshops, CAC and SAG meetings conducted in the first year of the trial relate to the quality and range of clinic services provided at study clinics as well as broader standard of care issues. Recommendations have included streamlining clinic services to reduce waiting times, expanding services to include the children and spouses of participants and providing care for common local conditions such as malaria. Participants, community representatives and stakeholders felt there was an ethical obligation to ensure effective access to antiretroviral drugs and to provide supportive community-based care for women identified as HIV positive during

A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.

Science.gov (United States)

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Zydowsky, Thomas M; Robbiani, Melissa

2012-11-01

Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, pinfection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.

Pregnant women's attitudes about topical microbicides for the prevention and treatment of bacterial vaginosis during pregnancy.

Science.gov (United States)

Catallozzi, Marina; Fraiz, Lauren Dapena; Hargreaves, Katharine M; Zimet, Gregory D; Stanberry, Lawrence R; Ratner, Adam J; Gelber, Shari E; Rosenthal, Susan L

2017-08-01

We sought to understand pregnant women's product preference and likelihood of use of topical microbicides for bacterial vaginosis (BV) prevention and treatment. Pregnant women (N = 196) in a obstetrics clinic completed a survey between June 2014 and January 2015 about vaginal product use for BV. This cross-sectional study explored product preferences, likelihood of product use for BV management and father of the baby (FOB) involvement. Most participants were under 30 (68%) and underrepresented minorities (47% Hispanic, 21% African-American). Most women preferred the gel (69%). Only 30% were likely to use either product for prevention of BV; 76% if high risk for BV; 83% treatment of BV. Anticipated FOB involvement in decision-making included that 46% would ask his opinion, 38% would inform him of the decision and 7% would need approval. Most (87%) would ask the FOB for reminders and 66% for insertion help. Those under 30 were more likely to agree to ask the FOB for reminders (p Product preferences may be less critical than risk perception. Involvement of the FOB in decision-making may be vital.

Direct Microbicidal Activity of Cytotoxic T-Lymphocytes

Directory of Open Access Journals (Sweden)

Paul Oykhman

2010-01-01

Full Text Available Cytotoxic T-lymphocytes (CTL are famous for their ability to kill tumor, allogeneic and virus-infected cells. However, an emerging literature has now demonstrated that CTL also possess the ability to directly recognize and kill bacteria, parasites, and fungi. Here, we review past and recent findings demonstrating the direct microbicidal activity of both CD4+ and CD8+ CTL against various microbial pathogens. Further, this review will outline what is known regarding the mechanisms of direct killing and their underlying signalling pathways.

Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

Science.gov (United States)

Rinehart, Matthew; Grab, Sheila; Rohan, Lisa; Katz, David; Wax, Adam

2014-01-01

We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010

Directory of Open Access Journals (Sweden)

Uchtenhagen Hannes

2011-04-01

Full Text Available Abstract Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda, and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.

Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010.

Science.gov (United States)

Brinckmann, Sarah; da Costa, Kelly; van Gils, Marit J; Hallengärd, David; Klein, Katja; Madeira, Luisa; Mainetti, Lara; Palma, Paolo; Raue, Katharina; Reinhart, David; Reudelsterz, Marc; Ruffin, Nicolas; Seifried, Janna; Schäfer, Katrein; Sheik-Khalil, Enas; Sköld, Annette; Uchtenhagen, Hannes; Vabret, Nicolas; Ziglio, Serena; Scarlatti, Gabriella; Shattock, Robin; Wahren, Britta; Gotch, Frances

2011-04-12

Novel, exciting intervention strategies to prevent infection with HIV have been tested in the past year, and the field is rapidly evolving. EUROPRISE is a network of excellence sponsored by the European Commission and concerned with a wide range of activities including integrated developmental research on HIV vaccines and microbicides from discovery to early clinical trials. A central and timely theme of the network is the development of the unique concept of co-usage of vaccines and microbicides. This review, prepared by the PhD students of the network captures much of the research ongoing between the partners. The network is in its 5th year and involves over 50 institutions from 13 European countries together with 3 industrial partners; GSK, Novartis and Sanofi-Pasteur. EUROPRISE is involved in 31 separate world-wide trials of Vaccines and Microbicides including 6 in African countries (Tanzania, Mozambique, South Africa, Kenya, Malawi, Rwanda), and is directly supporting clinical trials including MABGEL, a gp140-hsp70 conjugate trial and HIVIS, vaccine trials in Europe and Africa.

Threshold-dependent repression of SPL gene expression by miR156/miR157 controls vegetative phase change in Arabidopsis thaliana.

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Jia He

2018-04-01

Full Text Available Vegetative phase change is regulated by a decrease in the abundance of the miRNAs, miR156 and miR157, and the resulting increase in the expression of their targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL transcription factors. To determine how miR156/miR157 specify the quantitative and qualitative changes in leaf morphology that occur during vegetative phase change, we measured their abundance in successive leaves and characterized the phenotype of mutations in different MIR156 and MIR157 genes. miR156/miR157 decline rapidly between leaf 1&2 and leaf 3 and decrease more slowly after this point. The amount of miR156/miR157 in leaves 1&2 greatly exceeds the threshold required to specify their identity. Subsequent leaves have relatively low levels of miR156/miR157 and are sensitive to small changes in their abundance. In these later-formed leaves, the amount of miR156/miR157 is close to the threshold required to specify juvenile vs. adult identity; a relatively small decrease in the abundance of miR156/157 in these leaves produces a disproportionately large increase in SPL proteins and a significant change in leaf morphology. miR157 is more abundant than miR156 but has a smaller effect on shoot morphology and SPL gene expression than miR156. This may be attributable to the inefficiency with which miR157 is loaded onto AGO1, as well as to the presence of an extra nucleotide at the 5' end of miR157 that is mis-paired in the miR157:SPL13 duplex. miR156 represses different targets by different mechanisms: it regulates SPL9 by a combination of transcript cleavage and translational repression and regulates SPL13 primarily by translational repression. Our results offer a molecular explanation for the changes in leaf morphology that occur during shoot development in Arabidopsis and provide new insights into the mechanism by which miR156 and miR157 regulate gene expression.

Multipactor Simulations of the SPL Power Coupler

CERN Document Server

Burt, A; Dexter, A C; Calaga, R; Montesinos, E; Author, F; Author, G

2010-01-01

Mul­ti­pactor is a lim­it­ing fac­tor in many RF power cou­plers. The SPL cou­pler is pro­posed to have a con­i­cal match­ing sec­tion be­tween the win­dow and the coax­i­al sec­tion how­ev­er this sec­tion must be checked for mul­ti­pactor. Mul­ti­pactor sim­u­la­tions of the cou­pler up to a few MW's of power were per­formed using a va­ri­ety of dif­fer­ent codes and the re­sults were com­pared. Sim­u­la­tions were per­formed in the con­i­cal and straight coax­i­al sec­tions.

Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

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Martin Cranage

2008-08-01

Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

Inhibition of Human Immunodeficiency Virus Type 1 Infection by the Candidate Microbicide Dapivirine, a Nonnucleoside Reverse Transcriptase Inhibitor▿

OpenAIRE

Fletcher, P.; Harman, S.; Azijn, H.; Armanasco, N.; Manlow, P.; Perumal, D.; de Bethune, M.-P.; Nuttall, J.; Romano, J.; Shattock, R.

2008-01-01

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal micr...

High miR156 Expression Is Required for Auxin-Induced Adventitious Root Formation via MxSPL26 Independent of PINs and ARFs in Malus xiaojinensis

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Xiaozhao Xu

2017-06-01

Full Text Available Adventitious root formation is essential for the vegetative propagation of perennial woody plants. During the juvenile-to-adult phase change mediated by the microRNA156 (miR156, the adventitious rooting ability decreases dramatically in many species, including apple rootstocks. However, the mechanism underlying how miR156 affects adventitious root formation is unclear. In the present study, we showed that in the presence of the synthetic auxin indole-3-butyric acid (IBA, semi-lignified leafy cuttings from juvenile phase (Mx-J and rejuvenated (Mx-R Malus xiaojinensis trees exhibited significantly higher expression of miR156, PIN-FORMED1 (PIN1, PIN10, and rootless concerning crown and seminal roots-like (RTCS-like genes, thus resulting in higher adventitious rooting ability than those from adult phase (Mx-A trees. However, the expression of SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE26 (SPL26 and some auxin response factor (ARF gene family members were substantially higher in Mx-A than in Mx-R cuttings. The expression of NbRTCS-like but not NbPINs and NbARFs varied with miR156 expression in tobacco (Nicotiana benthamiana plants transformed with 35S:MdMIR156a6 or 35S:MIM156 constructs. Overexpressing the miR156-resistant MxrSPL genes in tobacco confirmed the involvement of MxSPL20, MxSPL21&22, and MxSPL26 in adventitious root formation. Together, high expression of miR156 was necessary for auxin-induced adventitious root formation via MxSPL26, but independent of MxPINs and MxARFs expression in M. xiaojinensis leafy cuttings.

Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry.

Directory of Open Access Journals (Sweden)

Matthew Rinehart

Full Text Available We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery.

Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor.

Science.gov (United States)

Fletcher, P; Harman, S; Azijn, H; Armanasco, N; Manlow, P; Perumal, D; de Bethune, M-P; Nuttall, J; Romano, J; Shattock, R

2009-02-01

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide. In tissue compatibility studies, dapivirine was well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants. Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades. Furthermore, dapivirine demonstrated potent activity against a wide range of NNRTI-resistant isolates. In human cervical explant cultures, dapivirine was able not only to inhibit direct infection of mucosal tissue but also to prevent the dissemination of the virus by migratory cells. Activity was retained in the presence of semen or a cervical mucus simulant. Furthermore, dapivirine demonstrated prolonged inhibitory effects: it was able to prevent both localized and disseminated infection for as long as 6 days posttreatment. The prolonged protection observed following pretreatment of genital tissue and the lack of observable toxicity suggest that dapivirine has considerable promise as a potential microbicide candidate.

Inhibition of Human Immunodeficiency Virus Type 1 Infection by the Candidate Microbicide Dapivirine, a Nonnucleoside Reverse Transcriptase Inhibitor▿

Science.gov (United States)

Fletcher, P.; Harman, S.; Azijn, H.; Armanasco, N.; Manlow, P.; Perumal, D.; de Bethune, M.-P.; Nuttall, J.; Romano, J.; Shattock, R.

2009-01-01

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide. In tissue compatibility studies, dapivirine was well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants. Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades. Furthermore, dapivirine demonstrated potent activity against a wide range of NNRTI-resistant isolates. In human cervical explant cultures, dapivirine was able not only to inhibit direct infection of mucosal tissue but also to prevent the dissemination of the virus by migratory cells. Activity was retained in the presence of semen or a cervical mucus simulant. Furthermore, dapivirine demonstrated prolonged inhibitory effects: it was able to prevent both localized and disseminated infection for as long as 6 days posttreatment. The prolonged protection observed following pretreatment of genital tissue and the lack of observable toxicity suggest that dapivirine has considerable promise as a potential microbicide candidate. PMID:19029331

Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.

Science.gov (United States)

Sepúlveda-Crespo, Daniel; Lorente, Raquel; Leal, Manuel; Gómez, Rafael; De la Mata, Francisco J; Jiménez, José Luis; Muñoz-Fernández, M Ángeles

2014-04-01

Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide. This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides. © 2014.

HIV-1 pseudovirus neutralisation by a natural compound: a potential microbicide

CSIR Research Space (South Africa)

Van den Berg, N

2011-02-01

Full Text Available . The mode of action of the compound is, however, yet to be determined. The aim is to develop a microbicide based on an indigenous plant for people infected with HIV-1. The compound will also be screened against other HIV-1 subtypes to test the neutralisation...

Vaginal microbicides save money: a model of cost-effectiveness in South Africa and the USA.

Science.gov (United States)

Verguet, S; Walsh, J A

2010-06-01

To determine the hypothetical cost-effectiveness of vaginal microbicides preventing male to female HIV transmission. A mathematical epidemiological and cost-effectiveness model using data from South Africa and the USA was used. The prospective 1-year-long intervention targeted a general population of women in a city of 1,000,000 inhabitants in two very different epidemiological settings, South Africa with a male HIV prevalence of 18.80% and the USA with a male HIV prevalence of 0.72%. The base case scenario assumes a microbicide effective at 55%, used in 30% of sexual episodes at a retail price for the public sector in South Africa of US$0.51 per use and in the USA of US$2.23 per use. In South Africa, over 1 year, the intervention would prevent 1908 infections, save US$6712 per infection averted as compared with antiretroviral treatment. In the USA, it would be more costly: over 1 year, the intervention would prevent 21 infections, amounting to a net cost per infection averted of US$405,077. However, in the setting of Washington DC, with a higher HIV prevalence, the same intervention would prevent 93 infections and save US$91,176 per infection averted. Sensitivity analyses were conducted and even a microbicide with a low effectiveness of 30% would still save healthcare costs in South Africa. A microbicide intervention is likely to be very cost-effective in a country undergoing a high-level generalised epidemic such as South Africa, but is unlikely to be cost-effective in a developed country presenting epidemiological features similar to the USA unless the male HIV prevalence exceeds 2.4%.

Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes

International Nuclear Information System (INIS)

Ketas, Thomas J.; Schader, Susan M.; Zurita, Juan; Teo, Esther; Polonis, Victoria; Lu Min; Klasse, Per Johan; Moore, John P.

2007-01-01

Inhibitors of viral entry are under consideration as topical microbicides to prevent HIV-1 sexual transmission. Small molecules targeting HIV-1 gp120 (BMS-378806) or CCR5 (CMPD167), and a peptide fusion inhibitor (C52L), each blocks vaginal infection of macaques by a SHIV. A microbicide, however, must be active against multiple HIV-1 variants. We therefore tested BMS-C (a BMS-378806 derivative), CMPD167, C52L and the CXCR4 ligand AMD3465, alone and in combination, against 25 primary R5, 12 X4 and 7 R5X4 isolates from subtypes A-G. At high concentrations (0.1-1 μM), the replication of most R5 isolates in human donor lymphocytes was inhibited by > 90%. At lower concentrations, double and triple combinations were more effective than individual inhibitors. Similar results were obtained with X4 viruses when AMD3465 was substituted for CMPD167. The R5X4 viruses were inhibited by combining AMD3465 with CMPD167, or by the coreceptor-independent compounds. Thus, combining entry inhibitors may improve microbicide effectiveness

Commercial lubricant use among HIV-negative men who have sex with men in Los Angeles: implications for the development of rectal microbicides for HIV prevention.

Science.gov (United States)

Pines, Heather A; Gorbach, Pamina M; Reback, Cathy J; Landovitz, Raphael J; Mutchler, Matt G; Mitsuyasu, Ronald

2014-01-01

To inform the development and assess potential use of rectal microbicide gels for HIV prevention among men who have sex with men (MSM), we examined the dynamics and contexts of commercial lubricant use during receptive anal intercourse (RAI) within this population. From 2007 to 2010, 168 HIV-negative MSM living in Los Angeles who practice RAI completed computer-assisted self-interviews, which collected information on their last sexual event with ≤3 recent partners, at baseline, three months, and one-year study visits. Logistic generalized linear mixed models were used to identify individual- and sexual event-level characteristics associated with commercial lubricant use during RAI at the last sexual event within 421 partnerships reported by participants over the course of follow-up. During RAI at their last sexual event, 57% of partnerships used a condom and 69% used commercial lubricant. Among partnerships that used commercial lubricant, 56% reported lubricant application by both members of the partnership, 66% first applied lubricant during sex, but before penetration, and 98% applied lubricant at multiple locations. The relationship between substance use and commercial lubricant use varied by condom use (interaction p-value = 0.01). Substance use was positively associated with commercial lubricant use within partnerships that did not use condoms during RAI at their last sexual event (AOR = 4.47, 95% [corrected] [CI]: 1.63-12.28), but no association was observed within partnerships that did use condoms (AOR = 0.66, 95% CI: 0.23-1.85). Commercial lubricant use during RAI was also positively associated with reporting more sexual partners (AOR = 1.18, 95% CI: 1.05-1.31), while older age (units = 5 years; AOR = 0.75, 95% CI: 0.61-0.94), homelessness (past year; AOR = 0.32, 95% CI: 0.13-0.76), and having sex with an older (>10 years) partner (AOR = 0.37, 95% CI: 0.14-0.95) were negatively associated with commercial lubricant use. These factors should be considered

Summary of the workshop on HOM in SPL, held at CERN June 25-26.

CERN Document Server

Lombardi, A; Weingarten, W

2009-01-01

A mini-workshop on the subject of HOMs in a superconducting proton linac was held at CERN on the 25th and 26th June 2009. The purpose of this workshop was to discuss more specifically the effects of HOMs on beam dynamics in the SPL and comparable accelerators and to provide guidelines for the specification of HOM dampers, if necessary.

A randomized male tolerance study of dapivirine gel following multiple topical penile exposures (MTN 012/IPM 010).

Science.gov (United States)

Cranston, Ross D; Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M

2014-02-01

Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be "very likely" to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug.

Effect of SPL (Spent Pot Liner) and its main components on root growth, mitotic activity and phosphorylation of Histone H3 in Lactuca sativa L.

Science.gov (United States)

Freitas, Aline Silva; Fontes Cunha, Isabela Martinez; Andrade-Vieira, Larissa Fonseca; Techio, Vânia Helena

2016-02-01

Spent Pot Liner (SPL) is a solid waste from the aluminum industry frequently disposed of in industrial landfills; it can be leached and contaminate the soil, sources of drinking water and plantations, and thus may pose a risk to human health and to ecosystems. Its composition is high variable, including cyanide, fluoride and aluminum salts, which are highly toxic and environmental pollutants. This study evaluated the effect of SPL and its main components on root growth and the mitosis of Lactuca sativa, by investigating the mechanisms of cellular and chromosomal alterations with the aid of immunolocalization. To this end, newly emerged roots of L. sativa were exposed to SPL and its main components (solutions of cyanide, fluoride and aluminum) and to calcium chloride (control) for 48h. After this, root length was measured and cell cycle was examined by means of conventional cytogenetics and immunolocalization. Root growth was inhibited in the treatments with SPL and aluminum; chromosomal and nuclear alterations were observed in all treatments. The immunolocalization evidenced normal dividing cells with regular temporal and spatial distribution of histone H3 phosphorylation at serine 10 (H3S10ph). However, SPL and its main components inhibited the phosphorylation of histone H3 at serine 10, inactivated pericentromeric regions and affected the cohesion of sister chromatids, thus affecting the arrangement of chromosomes in the metaphase plate and separation of chromatids in anaphase. In addition, these substances induced breaks in pericentromeric regions, characterized as fragile sites. Copyright © 2015 Elsevier Inc. All rights reserved.

Acceptability of microbicidal vaginal rings and oral pre-exposure prophylaxis for HIV prevention among female sex workers in a high-prevalence US city.

Science.gov (United States)

Peitzmeier, Sarah M; Tomko, Catherine; Wingo, Erin; Sawyer, Anne; Sherman, Susan G; Glass, Nancy; Beyrer, Chris; Decker, Michele R

2017-11-01

Biomedical HIV prevention tools including oral pre-exposure prophylaxis (PrEP) and vaginal microbicidal rings hold unique value for high-risk women who may have limited capacity for condom negotiation, including the key populations of sex workers and drug users. Commercial sex is a PrEP indicator in CDC guidelines, yet little is known about female sex workers' (FSWs) knowledge of and attitudes toward PrEP or the recently developed monthly vaginal microbicide rings. We describe knowledge and attitudes toward PrEP and microbicide rings in a sample of 60 mostly drug-using FSWs in Baltimore, Maryland, a high HIV-prevalence US city. Just 33% had heard of PrEP, but 65% were interested in taking daily oral PrEP and 76% were interested in a microbicide vaginal ring; 87% were interested in at least one of the two methods. Results suggest method mix will be important as biomedical tools for HIV prophylaxis are implemented and scaled up in this population, as 12% were interested in PrEP but not vaginal rings, while 19% were interested in vaginal rings but not in PrEP. Self-efficacy for daily oral adherence was high (79%) and 78% were interested in using PrEP even if condoms were still necessary. Women who had experienced recent client-perpetrated violence were significantly more interested in PrEP (86% vs 53%, p = 0.009) and microbicidal rings (91% vs 65%, p = 0.028) than women who had not recently experienced violence. No differences were observed by demographics nor HIV risk behaviors, suggesting broad potential interest in daily PrEP and monthly-use vaginal microbicides in this high-risk population.

Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

Directory of Open Access Journals (Sweden)

Ulrike Kuebler

Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

Pre-clinical development of a combination microbicide vaginal ring containing dapivirine and darunavir.

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Murphy, Diarmaid J; Desjardins, Delphine; Dereuddre-Bosquet, Nathalie; Brochard, Patricia; Perrot, Ludivine; Pruvost, Alain; Le Grand, Roger; Lagatie, Ole; Vanhooren, Leen; Feyaerts, Maxim; van Roey, Jens; Malcolm, R Karl

2014-09-01

Combination microbicide vaginal rings may be more effective than single microbicide rings at reducing/preventing sexual transmission of HIV. Here, we report the pre-clinical development and macaque pharmacokinetics of matrix-type silicone elastomer vaginal rings containing dapivirine and darunavir. Macaque rings containing 25 mg dapivirine, 100 mg dapivirine, 300 mg darunavir or 100 mg dapivirine+300 mg darunavir were manufactured and characterized by differential scanning calorimetry. In vitro release was assessed into isopropanol/water and simulated vaginal fluid. Macaque vaginal fluid and blood serum concentrations for both antiretrovirals were measured during 28 day ring use. Tissue levels were measured on day 28. Ex vivo challenge studies were performed on vaginal fluid samples and IC50 values were calculated. Darunavir caused a concentration-dependent reduction in the dapivirine melting temperature in both solid drug mixes and in the combination ring. In vitro release from rings was dependent on drug loading, the number of drugs present and the release medium. In macaques, serum concentrations of both microbicides were maintained between 10(1) and 10(2) pg/mL. Vaginal fluid levels ranged between 10(3) and 10(4) ng/g and between 10(4) and 10(5) ng/g for dapivirine and darunavir, respectively. Both dapivirine and darunavir showed very similar concentrations in each tissue type; the range of drug tissue concentrations followed the general rank order: vagina (1.8 × 10(3)-3.8 × 10(3) ng/g)  > cervix (9.4 × 10(1)-3.9 × 10(2) ng/g)  > uterus (0-108 ng/g)  > rectum (0-40 ng/g). Measured IC50 values were >2 ng/mL for both compounds. Based on these results, and in light of recent clinical progress of the 25 mg dapivirine ring, a combination vaginal ring containing dapivirine and darunavir is a viable second-generation HIV microbicide candidate. © The Author 2014. Published by Oxford University Press on behalf of the British Society for

Status of the EP Simulations and Facilities for the SPL

CERN Document Server

Calatroni, S; Macatrao, M; Skala, A; Sosin, M; de Waele, R; Withofs, Y

2011-01-01

CERN is assembling a new vertical electropolishing facility in order to process several niobium cavities of beta 1 and beta 0.65 in the context of the HP-SPL R&D programme. Electrochemical simulations are being used in order to define the optimal cathode geometry to process the cavities in a vertical position. Macroscopic properties of fluid dynamics like the Reynolds number and thermodynamics linked to the power dissipated in the process are taken into account to dimension the main system components. All the materials from the different equipments must be compatible with all chemicals within the required working temperature and pressure. To provide safe operating conditions when handling chemicals or processing cavities, specific safety and protection equipment is also foreseen.

A social ecology of rectal microbicide acceptability among young men who have sex with men and transgender women in Thailand.

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Newman, Peter A; Roungprakhon, Surachet; Tepjan, Suchon

2013-08-01

With HIV-incidence among men who have sex with men (MSM) in Bangkok among the highest in the world, a topical rectal microbicide would be a tremendous asset to prevention. Nevertheless, ubiquitous gaps between clinical trial efficacy and real-world effectiveness of existing HIV preventive interventions highlight the need to address multi-level factors that may impact on rectal microbicide implementation. We explored the social ecology of rectal microbicide acceptability among MSM and transgender women in Chiang Mai and Pattaya, Thailand. We used a qualitative approach guided by a social ecological model. Five focus groups were conducted in Thai using a semi-structured interview guide. All interviews were digitally recorded, transcribed verbatim in Thai and translated into English. We conducted thematic analysis using line-by-line and axial coding and a constant comparative method. Transcripts and codes were uploaded into a customized database programmed in Microsoft Access. We then used content analysis to calculate theme frequencies by group, and Chi-square tests and Fisher's exact test to compare themes by sexual orientation/gender expression and age. Participant's (n=37) mean age was 24.8 years (SD=4.2). The majority (70.3%) self-identified as gay, 24.3% transgender women. Product-level themes (side effects, formulation, efficacy, scent, etc.) accounted for 42%, individual (increased sexual risk, packaging/portability, timing/duration of protection) 29%, interpersonal (trust/communication, power/negotiation, stealth) 8% and social-structural (cost, access, community influence, stigma) 21% of total codes, with significant differences by sexual orientation/gender identity. The intersections of multi-level influences included product formulation and timing of use preferences contingent on interpersonal communication and partner type, in the context of constraints posed by stigma, venues for access and cost. The intersecting influence of multi-level factors on

Thrombin-induced rabbit platelet microbicidal protein is fungicidal in vitro.

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Yeaman, M R; Ibrahim, A S; Edwards, J E; Bayer, A S; Ghannoum, M A

1993-03-01

Platelet microbicidal protein (PMP) is released from platelets in response to thrombin stimulation. PMP is known to possess in vitro bactericidal activity against Staphylococcus aureus and viridans group streptococci. To determine whether PMP is active against other intravascular pathogens, we evaluated its potential fungicidal activity against strains of Candida species and Cryptococcus neoformans. Anionic resin adsorption and gel electrophoresis confirmed that the fungicidal activity of PMP resided in a small (approximately 8.5-kDa), cationic protein, identical to previous studies of PMP-induced bacterial killing (M.R. Yeaman, S.M. Puentes, D.C. Norman, and A.S. Bayer, Infect. Immun. 60:1202-1209, 1992). When assayed over a 180-min period in vitro, the susceptibilities of these fungi to PMP varied considerably. Generally, Candida albicans strains (mean survival, 33.5% +/- 6.9% [n = 6]) as well as isolates of Candida glabrata (mean survival, 50.8% +/- 2.9% [n = 2]) were the most susceptible to killing by PMP, while Candida guillermondii and Candida parapsilosis were relatively resistant to PMP-induced killing. Compared with C. albicans, C. neoformans was relatively resistant to the fungicidal activity of PMP, with a mean survival among the isolates studied of 77.4% +/- 12.4% (n = 6). Against C. albicans, PMP-induced fungicidal activity was time dependent (range, 0 to 180 min), PMP concentration dependent (range, 10 to 150 U/ml), and inversely related to the fungal inoculum (range, 5 x 10(3) to 1 x 10(5) CFU/ml). Scanning electron microscopy of PMP-exposed C. albicans and C. neoformans cells revealed extensive surface damage and collapse, suggesting that the site of PMP fungicidal action may directly or indirectly involve the fungal cell envelope.

Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

NARCIS (Netherlands)

Wahren, Britta; Biswas, Priscilla; Borggren, Marie; Coleman, Adam; Da Costa, Kelly; de Haes, Winni; Dieltjens, Tessa; Dispinseri, Stefania; Grupping, Katrijn; Hallengärd, David; Hornig, Julia; Klein, Katja; Mainetti, Lara; Palma, Paolo; Reudelsterz, Marc; Seifried, Janna; Selhorst, Philippe; Sköld, Annette; Uchtenhagen, Hannes; van Gils, Marit J.; Weber, Caroline; Shattock, Robin; Scarlatti, Gabriella

2010-01-01

EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination

Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota.

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O'Hanlon, Deirdre E; Moench, Thomas R; Cone, Richard A

2013-01-01

Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Fifty-six women with low (0-3) Nugent scores (indicating a lactobacillus-dominated vaginal microbiota) and no symptoms of reproductive tract disease or infection, provided a total of 64 cervicovaginal fluid samples using a collection method that avoided the need for sample dilution and rigorously minimized aerobic exposure. The pH of samples was measured by microelectrode immediately after collection and under a physiological vaginal concentration of CO2. Commercial enzymatic assays of total lactate and total acetate concentrations were validated for use in CVF, and compared to the more usual HPLC method. The average pH of the CVF samples was 3.5 ± 0.3 (mean ± SD), range 2.8-4.2, and the average total lactate was 1.0% ± 0.2% w/v; this is a five-fold higher average hydrogen ion concentration (lower pH) and a fivefold higher total lactate concentration than in the prior literature. The microbicidal form of lactic acid (protonated lactic acid) was therefore eleven-fold more concentrated, and a markedly more potent microbicide, than indicated by prior research. This suggests that when lactobacilli dominate the vaginal microbiota, women have significantly more lactic acid-mediated protection against infections than currently believed. Our results invite further evaluations of the prophylactic and therapeutic actions of vaginal lactic acid, whether provided in situ by endogenous lactobacilli, by probiotic lactobacilli, or by products that reinforce vaginal lactic acid.

A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

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Sandhya Boyapalle

Full Text Available Human immunodeficiency virus (HIV types 1 and 2 (HIV-1 and HIV-2 are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162 viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

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Roland R Regoes

2005-08-01

Full Text Available Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

[Effect on the microbicidal efficacy of formaldehyde, glutardialdehyde, peracetic acid, chloramine T (N-chloro-4-toluenesulfonamide), m-cresol, ethanol and benzyldimethyldodecacylammonium bromide by blood (model experiments for chemical disinfection of instruments)].

Science.gov (United States)

Spicher, G; Peters, J

1998-02-01

In a preceding paper (Zbl. Hyg. 191 [1991] 457-477) we reported on the dependence of the microbicidal efficacy of active agents of the disinfection of instruments on the amount of coagulated blood adhering to the instruments. In the present investigation, we were interested in the dependence of the microbicidal effects on the amount of blood in the solutions of the active agents. Test areas of 2 cm2 were contaminated with 50 and 100 microliters coagulating blood, respectively, containing cells of Staphylococcus aureus as test germ. The solutions of the microbicidal agents were contaminated with heparinized blood up to a concentration of 4% immediately before starting the disinfection and 24 hours before, respectively. After a period of action lasting 1 hour at 20 degrees C, the relative number of test germs capable of multiplying (N/N0) was determined. The concentration of the microbicidal substances reducing the relative number of test germs capable to multiply to 10(-4) served for estimating the dependence of the microbicidal efficacy of the agents on the blood content of the solutions. The experimental results depended on the thickness of the layer of coagulated blood. The dependence of the efficacy of the microbicidal substances on the blood content of the solutions was the higher the thinner the blood layer was. At a thickness of the layer of the coagulated blood of 0.25 mm, a blood content of the solution of 4%, and applying it immediately after adding the blood, the concentration of glutardialdehyde had to be 1.6 times that without blood to reach the same microbicidal efficacy. When applying the solution 24 hours after adding the blood, the concentration of glutardialdehyde had to be 4.2 times that without blood. The quaternary ammonium compound reacted faster with the blood than did glutardialdehyde; the respective factors were 2.6 and 4.5. The concentration factors of chloramine T were 3.3 and 3.8. Under the conditions of the test, peracetic acid exhibited

MABGEL 1: first phase 1 trial of the anti-HIV-1 monoclonal antibodies 2F5, 4E10 and 2G12 as a vaginal microbicide.

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Georgina C Morris

Full Text Available BACKGROUND: Monoclonal antibodies (mAbs which potently neutralize a broad range of HIV isolates are potential microbicide candidates. To date, topical application of mAbs in humans and their stability in vaginal secretions has not been studied. OBJECTIVES: To assess the pharmacokinetics and safety of the mAbs 2F5, 4E10 and 2G12 when applied vaginally in women. DESIGN: A randomized, double-blind, placebo-controlled phase 1 trial. METHODS: Twenty-eight healthy, sexually abstinent women administered 2.5 g of gel daily for 12 days containing either 10 or 20 mg/g of each mAb (MABGEL or placebo. Main clinical evaluations and sampling occurred at baseline, 1, 8, and 24 hours post-1st dose and 12 and 36 hours post-12th dose. RESULTS: After adjustment for dilution factors, median levels of 2F5, 4E10 and 2G12 in vaginal secretions at 1 hour post high-dose MABGEL were 7.74, 5.28 and 7.48 mg/ml respectively. Levels of 2F5 and 4E10 declined exponentially thereafter with similar estimated half-lives (4.6 and 4.3 hours. In contrast, 2G12 levels declined more rapidly in the first 8 hours, with an estimated half-life of 1.4 hours during this period. There was no evidence of systemic absorption. There were no significant differences in local or systemic adverse event rates or vaginal flora changes (by qPCR between active and placebo gel arms. Whilst at least 1 adverse event was recorded in 96% of participants, 95% were mild and none were serious. CONCLUSIONS: Vaginal application of 50 mg of each mAb daily was safe over a 12 day period. Median mAb concentrations detected at 8 hours post dose were potentially sufficient to block HIV transmission.2G12 exhibited more rapid elimination from the human vagina than 4E10 and 2F5, likely due to poor stability of 2G12 in acidic human vaginal secretions. Further research is needed to develop mAb-based vaginal microbicides and delivery systems. TRIAL REGISTRATION: ISRCTN 64808733 UK CRN Portfolio 6470.

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions.

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McNicholl, Janet M

2016-12-01

Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.

SPL^LIFT: Statically Analyzing Software Product Lines in Minutes instead of Years

DEFF Research Database (Denmark)

Bodden, Eric; Tolêdo, Társis; Ribeiro, Márcio

2013-01-01

IFDS framework for inter-procedural, finite, distributive, subset problems to an SPL-aware analysis formulated in the IDE framework, a well-known extension to IFDS. Using a full implementation based on Heros, Soot, CIDE and JavaBDD, we show that with SPLLIFT one can reuse IFDS-based analyses without...... changing a single line of code. Through experiments using three static analyses applied to four Java-based product lines, we were able to show that our approach produces correct results and outperforms the traditional approach by several orders of magnitude....

Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.

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Mukhopadhya, Indrani; Murray, Graeme I; Berry, Susan; Thomson, John; Frank, Bruce; Gwozdz, Garry; Ekeruche-Makinde, Julia; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-02-01

The objectives of this study were to comprehensively assess mRNA expression of 84 drug transporters in human colorectal biopsies and six representative cell lines, and to investigate the alteration of drug transporter gene expression after exposure to three candidate microbicidal antiretroviral (ARV) drugs (tenofovir, darunavir and dapivirine) in the colorectal epithelium. The outcome of the objectives informs development of optimal ARV-based microbicidal formulations for prevention of HIV-1 infection. Drug transporter mRNA expression was quantified from colorectal biopsies and cell lines by quantitative real-time PCR. Relative mRNA expression was quantified in Caco-2 cells and colorectal explants after induction with ARVs. Data were analysed using Pearson's product moment correlation (r), hierarchical clustering and principal component analysis (PCA). Expression of 58 of the 84 transporters was documented in colorectal biopsies, with genes for CNT2, P-glycoprotein (P-gp) and MRP3 showing the highest expression. No difference was noted between individual subjects when analysed by age, gender or anatomical site (rectum or recto-sigmoid) (r = 0.95-0.99). High expression of P-gp and CNT2 proteins was confirmed by immunohistochemical staining. Similarity between colorectal tissue and cell-line drug transporter gene expression was variable (r = 0.64-0.84). PCA showed distinct clustering of human colorectal biopsy samples, with the Caco-2 cells defined as the best surrogate system. Induction of Caco-2 cell lines with ARV drugs suggests that darunavir-based microbicides incorporating tenofovir may result in drug-drug interactions likely to affect distribution of individual drugs to sub-epithelial target cells. These findings will help optimize complex formulations of rectal microbicides to realize their full potential as an effective approach for pre-exposure prophylaxis against HIV-1 infection. © The Author 2015. Published by Oxford University Press on behalf of the

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

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Markham Richard B

2005-09-01

Full Text Available Abstract Background Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel® to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. Methods Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. Results Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye. In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected compared to saline (12 of 12 infected and a control gel (5 of 7 infected. Conclusion These

Punica granatum (Pomegranate juice provides an HIV-1 entry inhibitor and candidate topical microbicide

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Li Yun-Yao

2004-10-01

Full Text Available Abstract Background For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. Methods Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1 infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2 binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. Results HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. Conclusion These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored.

"Like Holding an Umbrella Before It Rains": Acceptability of Future Rectal Microbicides Among Men Who Have Sex With Men in India-A Modified Technology Acceptance Model.

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Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Mengle, Shruta; Nelson, Ruban; Rubincam, Clara; Kumar, Pushpesh

2017-07-01

Topical rectal microbicides (RMs) are a new prevention technology in development that aims to reduce the risk of HIV acquisition from anal sex. We examined RM acceptability among men who have sex with men (MSM) in India. We conducted a qualitative exploratory study guided by a modified Technology Acceptance Model, with 10 focus groups ( n = 61) of MSM and 10 key informant interviews. Data were explored using framework analysis. RM acceptability was influenced by technological contexts: perceived usefulness of RMs, perceived ease of use of RM and applicator, and habits around condom and lubricant use; individual and interpersonal contexts: perceived relevance and preferences for product formulation and dosing frequency; and MSM community/social contexts: perceived social approval, RM-related stigma, social support. Implementation of RMs for MSM in India may be supported by multi-level interventions that engage community-based organizations in destigmatizing and distributing RMs, ideally gel-based products that enable on-demand use before sex.

77 FR 70167 - Draft Guidance for Industry on Vaginal Microbicides: Development for the Prevention of Human...

Science.gov (United States)

2012-11-23

...] Draft Guidance for Industry on Vaginal Microbicides: Development for the Prevention of Human...: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry... Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New...

Engineering soya bean seeds as a scalable platform to produce cyanovirin-N, a non-ARV microbicide against HIV.

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O'Keefe, Barry R; Murad, André M; Vianna, Giovanni R; Ramessar, Koreen; Saucedo, Carrie J; Wilson, Jennifer; Buckheit, Karen W; da Cunha, Nicolau B; Araújo, Ana Claudia G; Lacorte, Cristiano C; Madeira, Luisa; McMahon, James B; Rech, Elibio L

2015-09-01

There is an urgent need to provide effective anti-HIV microbicides to resource-poor areas worldwide. Some of the most promising microbicide candidates are biotherapeutics targeting viral entry. To provide biotherapeutics to poorer areas, it is vital to reduce the cost. Here, we report the production of biologically active recombinant cyanovirin-N (rCV-N), an antiviral protein, in genetically engineered soya bean seeds. Pure, biologically active rCV-N was isolated with a yield of 350 μg/g of dry seed weight. The observed amino acid sequence of rCV-N matched the expected sequence of native CV-N, as did the mass of rCV-N (11 009 Da). Purified rCV-N from soya is active in anti-HIV assays with an EC50 of 0.82-2.7 nM (compared to 0.45-1.8 nM for E. coli-produced CV-N). Standard industrial processing of soya bean seeds to harvest soya bean oil does not diminish the antiviral activity of recovered rCV-N, allowing the use of industrial soya bean processing to generate both soya bean oil and a recombinant protein for anti-HIV microbicide development. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Efficacy of Tenofovir 1% Vaginal Gel in Reducing the Risk of HIV-1 and HSV-2 Infection

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Christopher McConville

2014-01-01

Full Text Available Human Immunodeficiency Virus (HIV is a retrovirus that can result in rare opportunistic infections occurring in humans. The onset of these infections is known as Acquired Immune Deficiency Syndrome (AIDS. Sexual transmission is responsible for the majority of infections 1, resulting in transmission of HIV due to infected semen or vaginal and cervical secretions containing infected lymphocytes. HIV microbicides are formulations of chemical or biological agents that can be applied to the vagina or rectum with the intention of reducing the acquisition of HIV. Tenofovir is an NRTI that is phosphorylated by adenylate kinase to tenofovir diphosphate, which in turn competes with deoxyadeosine 5′-triphosphate for incorporation into newly synthesized HIV DNA. Once incorporated, tenofovir diphosphate results in chain termination, thus inhibiting viral replication. Tenofovir has been formulated into a range of vaginal formulations, such as rings, tablets gels and films. It has been shown to safe and effective in numerous animal models, while demonstrating safety and acceptability in numerous human trials. The most encouraging results came from the CAPRISA 004 clinical trial which demonstrated that a 1% Tenofovir vaginal gel reduced HIV infection by approximately 39%.

The OsSPL16-GW7 regulatory module determines grain shape and simultaneously improves rice yield and grain quality.

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Wang, Shaokui; Li, Shan; Liu, Qian; Wu, Kun; Zhang, Jianqing; Wang, Shuansuo; Wang, Yi; Chen, Xiangbin; Zhang, Yi; Gao, Caixia; Wang, Feng; Huang, Haixiang; Fu, Xiangdong

2015-08-01

The deployment of heterosis in the form of hybrid rice varieties has boosted grain yield, but grain quality improvement still remains a challenge. Here we show that a quantitative trait locus for rice grain quality, qGW7, reflects allelic variation of GW7, a gene encoding a TONNEAU1-recruiting motif protein with similarity to C-terminal motifs of the human centrosomal protein CAP350. Upregulation of GW7 expression was correlated with the production of more slender grains, as a result of increased cell division in the longitudinal direction and decreased cell division in the transverse direction. OsSPL16 (GW8), an SBP-domain transcription factor that regulates grain width, bound directly to the GW7 promoter and repressed its expression. The presence of a semidominant GW7(TFA) allele from tropical japonica rice was associated with higher grain quality without the yield penalty imposed by the Basmati gw8 allele. Manipulation of the OsSPL16-GW7 module thus represents a new strategy to simultaneously improve rice yield and grain quality.

Microbicidal activity of neutrophils is inhibited by isolates from recurrent vaginal candidiasis (RVVC) caused by Candida albicans through fungal thioredoxin reductase.

Science.gov (United States)

Ratti, Bianca Altrão; Godoy, Janine Silva Ribeiro; de Souza Bonfim Mendonça, Patrícia; Bidóia, Danielle Lazarin; Nakamura, Tânia Ueda; Nakamura, Celso Vataru; Lopes Consolaro, Marcia Edilaine; Estivalet Svidzinski, Terezinha Inez; de Oliveira Silva, Sueli

2015-01-01

Vulvovaginal candidiasis (VVC) is characterized by an infection of the vulva and vagina, mainly caused by Candida albicans, a commensal microorganism that inhabits the vaginal, digestive, and respiratory mucosae. Vulvovaginal candidiasis affects approximately 75% of women, and 5% develop the recurrent form (RVVC). The aim of the present study was to evaluate whether neutrophils microbicidal response is triggered when activated with RVVC isolates caused by C. albicans. Our results showed that RVVC isolates induced neutrophil migration but significantly decrease the microbicidal activity of neutrophils, compared with VVC and ASS isolates. The microbicidal activity of neutrophils is highly dependent on the production of reactive oxygen species/reactive nitrogen species (ROS/RNS). However, this isolate induced detoxification of ROS/RNS produced by neutrophils, reflected by the high level of thiol groups and by the oxygen consumption. Therefore, RVVC isolates induced biochemical changes in the inflammatory response triggered by neutrophils, and these effects were mainly related to the detoxification of ROS/RNS through the thioredoxin reductase (TR), a key antioxidant enzyme in fungi. This might be one of the resistance mechanisms triggered by RVVC caused by C. albicans. Copyright © 2014 Elsevier Inc. All rights reserved.

Formulation development of retrocyclin 1 analog RC-101 as an anti-HIV vaginal microbicide product.

Science.gov (United States)

Sassi, A B; Cost, M R; Cole, A L; Cole, A M; Patton, D L; Gupta, P; Rohan, L C

2011-05-01

RC-101 is a synthetic microbicide analog of retrocyclin, which has shown in vitro activity against X4 and R5 HIV-1. In an effort to develop a safe and effective RC-101 vaginal microbicide product, we assessed safety in ex vivo macaque and human models and efficacy using in vitro and ex vivo models. A polyvinyl-alcohol vaginal film containing RC-101 (100 μg/film) was developed. Formulation assessment was conducted by evaluating disintegration, drug content, mechanical properties, and stability. Efficacy was evaluated by in vitro peripheral blood mononuclear cells (PBMC) assay and ex vivo human ectocervical tissue explant model. Ex vivo safety studies were conducted by exposing RC-101 to an excised monkey reproductive tract and excised human ectocervical tissue. RC-101 100 μg films were shown to be safe to human and monkey tissue and effective against HIV-1 in vitro and ex vivo in human ectocervical tissue. The 90% inhibitory concentration (IC90) for RC-101 films at 2,000 μg (IC90=57.5 μM) using an ex vivo model was 10-fold higher than the IC90 observed using an in vitro model (IC90=5.0 μM). RC-101 films were stable for 1 month at 25°C, with in vitro bioactivity maintained for up to 6 months. RC-101 was developed in a quick-dissolve film formulation that was shown to be safe in an ex vivo model and effective in in vitro and ex vivo models. RC-101 film formulations were shown to maintain bioactivity for a period of 6 months. Findings from the present study contribute to the development of a safe and effective topical microbicide product.

MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

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Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

2017-03-01

The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide

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Conrads Thomas P

2011-07-01

Full Text Available Abstract Background RC-101, a cationic peptide retrocyclin analog, has in vitro activity against HIV-1. Peptide drugs are commonly prone to conformational changes, oxidation and hydrolysis when exposed to excipients in a formulation or biological fluids in the body, this can affect product efficacy. We aimed to investigate RC-101 stability under several conditions including the presence of human vaginal fluids (HVF, enabling the efficient design of a safe and effective microbicide product. Stability studies (temperature, pH, and oxidation were performed by HPLC, Circular Dichroism, and Mass Spectrometry (LC-MS/MS. Additionally, the effect of HVF on formulated RC-101 was evaluated with fluids collected from healthy volunteers, or from subjects with bacterial vaginosis (BV. RC-101 was monitored by LC-MS/MS for up to 72 h. Results RC-101 was stable at pH 3, 4, and 7, at 25 and 37°C. High concentrations of hydrogen peroxide resulted in less than 10% RC-101 reduction over 24 h. RC-101 was detected 48 h after incubation with normal HVF; however, not following incubation with HVF from BV subjects. Conclusions Our results emphasize the importance of preformulation evaluations and highlight the impact of HVF on microbicide product stability and efficacy. RC-101 was stable in normal HVF for at least 48 h, indicating that it is a promising candidate for microbicide product development. However, RC-101 stability appears compromised in individuals with BV, requiring more advanced formulation strategies for stabilization in this environment.

Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides

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Li Yun-Yao

2002-11-01

Full Text Available Abstract Background Cellulose acetate phthalate (CAP in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH Methods Enzyme linked immunosorbent assays (ELISA were used to (1 study HIV-1 IIIB and BaL binding to micronized CAP; (2 detect virus disintegration; and (3 measure gp41 six-helix bundle formation. Cells containing integrated HIV-1 LTR linked to the β-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity. Results 1 HIV-1 IIIB and BaL, respectively, effectively bound to micronized CAP. 2 The interaction between HIV-1 and micronized CAP led to: (a gp41 six-helix bundle formation; (b virus disintegration and shedding of envelope glycoproteins; and (c rapid loss of infectivity. Polymers other than CAP, except Carbomer 974P, elicited gp41 six-helix bundle formation in HIV-1 IIIB but only poly(napthalene sulfonate, in addition to CAP, had this effect on HIV-1 BaL. These polymers differed with respect to their virucidal activities, the differences being more pronounced for HIV-1 BaL. Conclusions Micronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.

The Sheep as a Model of Preclinical Safety and Pharmacokinetic Evaluations of Candidate Microbicides

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Holt, Jonathon D. S.; Cameron, David; Dias, Nicola; Holding, Jeremy; Muntendam, Alex; Oostebring, Freddy; Dreier, Peter; Rohan, Lisa; Nuttall, Jeremy

2015-01-01

When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment of the pharmacokinetics, safety, tolerability, and local toxicity of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed a...

Evaluation of Three Approaches for Assessing Adherence to Vaginal Gel Application in Clinical Trials

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van der Straten, Ariane; Cheng, Helen; Mensch, Barbara; Friedland, Barbara; Katzen, Lauren; Littlefield, Sarah; Buckley, Niall; Espinoza, Lilia; Keller, Marla J.; Herold, Betsy C.; Einstein, Mark H.

2014-01-01

Background: Accurate measurement of adherence to product use is an ongoing challenge in microbicide trials. Methods: We compared adherence estimates using two applicator tests (a dye stain assay [DSA] and an ultraviolet light assay [UVA]), the Wisebag (an applicator container that electronically tracks container openings), and self-reported adherence (ability, frequency, and percent missed doses). Healthy, HIV-negative, non-pregnant US women aged 23 to 45 received a Wisebag and 32 applicators filled with placebo gel, were instructed to insert one applicator daily for 30 days, returned the Wisebag and all applicators, and completed an exit interview. Emptied applicators were tested by UVA and then DSA, and scored by two blinded readers. Positive and negative controls were randomly included in applicator batches. Results: Among 42 women enrolled, 39 completed the study. DSA and UVA yielded similar sensitivity (97% and 95%) and specificity (79% and 79%). Two participants had fully inoperable Wisebags and nine had partially inoperable Wisebags. The proportion of participants considered to have high adherence (≥80%) varied: 43% (Wisebag), 46% (UVA), 49% (DSA), and 62% to 82% (self-reports). For estimating high adherence, Wisebag had a sensitivity of 76% (95% CI, 50% to 93%) and a specificity of 85% (95% CI, 62% to 97%) compared with DSA. Although 28% of participants reported forgetting to open the Wisebag daily, 59% said it helped them remember gel use. Conclusions: DSA and UVA performed similarly. Compared with these tests, self-reports overestimated and Wisebag underestimated adherence. Although Wisebag may encourage gel use, the applicator tests currently appear more useful for measuring use in clinical trials. PMID:24220357

Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, In Vitro Evaluation, and Ex Vivo Assessment.

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Garg, Varun; Singh, Harmanpreet; Bhatia, Amit; Raza, Kaisar; Singh, Sachin Kumar; Singh, Bhupinder; Beg, Sarwar

2017-01-01

Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2-4% w/v and 0-40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 μg cm -2 drug retention in the skin, 44.312 μg cm -2  h -1 drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation.

Curcumin as a potential non-steroidal contraceptive with spermicidal and microbicidal properties.

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Naz, R K; Lough, M L

2014-05-01

Curcumin, a component of the curry powder turmeric, has immense biological properties, including anticancer effects. The objective of this study was to determine if curcumin can provide a novel non-steroidal contraceptive having both spermicidal and microbicidal properties. The effect of curcumin, with and without photosensitization, was examined on human sperm forward motility and growth of several aerobic (n=8) and anaerobic bacteria (n=4) and yeast (n=7) strains implicated in vaginosis, vaginitis, and vaginal infections in women. The effect of various concentrations of curcumin on human sperm and microbes (aerobic and anaerobic bacteria and yeast) was tested. The effect on sperm was examined by counting the sperm forward motility, and on microbes by agar and broth dilutions and colony counting. Each experiment was repeated using different semen specimens, and bacteria and yeast stocks. Curcumin caused a concentration-dependent inhibition of sperm forward motility with a total block at ≥250μM concentration. After photosensitization, the effective concentration to completely block sperm forward motility decreased 25-fold, now requiring only 10μM concentration for total inhibition. Curcumin concentrations between 100 and 500μM completely blocked the growth of all the bacteria and yeast strains tested. After photosensitization, the effective concentration to completely inhibit microbial growth decreased 10-fold for aerobic bacteria and yeast, and 5-fold for anaerobic bacteria. These findings suggest that curcumin can block sperm function and bacteria/yeast growth. It can potentially provide an ideal non-steroidal contraceptive having both spermicidal and microbicidal properties against vaginal infections. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment.

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Seay, Kieran; Khajoueinejad, Nazanin; Zheng, Jian Hua; Kiser, Patrick; Ochsenbauer, Christina; Kappes, John C; Herold, Betsy; Goldstein, Harris

2015-09-01

Epidemiological studies have demonstrated that herpes simplex virus 2 (HSV-2) infection significantly increases the risk of HIV-1 acquisition, thereby contributing to the expanding HIV-1 epidemic. To investigate whether HSV-2 infection directly facilitates mucosal HIV-1 acquisition, we used our transgenic hCD4/R5/cT1 mouse model which circumvents major entry and transcription blocks preventing murine HIV-1 infection by targeting transgenic expression of human CD4, CCR5, and cyclin T1 genes to CD4(+) T cells and myeloid-committed cells. Productive infection of mucosal leukocytes, predominantly CD4(+) T cells, was detected in all hCD4/R5/cT1 mice intravaginally challenged with an HIV-1 infectious molecular clone, HIV-Du151.2env-NLuc, which expresses an env gene (C.Du151.2) cloned from an acute heterosexually infected woman and a NanoLuc luciferase reporter gene. Lower genital tract HIV-1 infection after HIV-Du151.2env-NLuc intravaginal challenge was increased ~4-fold in hCD4/R5/cT1 mice coinfected with HSV-2. Furthermore, HIV-1 dissemination to draining lymph nodes was detected only in HSV-2-coinfected mice. HSV-2 infection stimulated local infiltration and activation of CD4(+) T cells and dendritic cells, likely contributing to the enhanced HIV-1 infection and dissemination in HSV-2-coinfected mice. We then used this model to demonstrate that a novel gel containing tenofovir disoproxil fumarate (TDF), the more potent prodrug of tenofovir (TFV), but not the TFV microbicide gel utilized in the recent CAPRISA 004, VOICE (Vaginal and Oral Interventions to Control the Epidemic), and FACTS 001 clinical trials, was effective as preexposure prophylaxis (PrEP) to completely prevent vaginal HIV-1 infection in almost half of HSV-2-coinfected mice. These results also support utilization of hCD4/R5/cT1 mice as a highly reproducible immunocompetent preclinical model to evaluate HIV-1 acquisition across the female genital tract. Multiple epidemiological studies have reported that

Update on microbicide research and development-seeking new HIV prevention tools for women

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Mertenskoetter T

2011-01-01

Full Text Available Abstract Women and girls are especially vulnerable to HIV infection in sub-Saharan Africa, and in some of those countries, prevalence among young women can be up to 3 times higher than among men of the same age. Effective HIV prevention options for women are clearly needed in this setting. Several ARV-based vaginal microbicides are currently in development for prevention of HIV transmission to women and are discussed here. The concept of pre-exposure prophylaxis for the prevention of HIV transmission to women is introduced.

In vitro inhibition of human papillomavirus following use of a carrageenan-containing vaginal gel.

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Novetsky, Akiva P; Keller, Marla J; Gradissimo, Ana; Chen, Zigui; Morgan, Stephanie L; Xue, Xiaonan; Strickler, Howard D; Fernández-Romero, José A; Burk, Robert; Einstein, Mark H

2016-11-01

To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. Sexually active US women between 19 and 35years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8-12h after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8-12h after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8-12h, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

ANALYSIS OF SOUND PRESSURE LEVEL (SPL AND LAY OUT OF ENGINES IN THE FACTORY

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Wijianto Wijianto

2017-01-01

Full Text Available Modeling layout of engines in the factory is very useful to know how many dB sound pressure level that are occur in the building in order to avoid hearing damage of employees that are caused by noise. The objective of this research is to know how many dB sound pressure level that are occur in the factory with engine composition such as boiler, diesel, turbine, motor and gear box with dimension of building are 40 m length, 35 m width and 10 m height. With MATLAB analysis can be obtain that the highest SPL is 104.7 dB and the lowest is 93.5 dB, so, this range are dangerous for human hearing. To avoid hearing damage in this area, employees must use hearing protector.

Design and Development of an Octopus Thermometric system for the 704 MHZ Single-Cell SPL Cavity at CERN

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Liao, K; Brunner, O; Ciapala, E; Glenat, D; Weingarten, W

2012-01-01

The octopus thermometric system is designed for the 704 MHz superconducting proton linac (SPL) cavity to detect hot spots and X-rays caused by normal conducting defects and the impact of emission electrons. This system features an octopus body and tentacle structure for good contact with the cavity and easy assembly, a multiplexing circuit with integrated microprocessor for efficient readout and a high density temperature sensor arrangement in order to complete a high resolution temperature and X-ray map. The first prototype is being manufactured and investigations are undergoing for further development.

Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides.

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Leyva, Francisco J; Bakshi, Rahul P; Fuchs, Edward J; Li, Liye; Caffo, Brian S; Goldsmith, Arthur J; Ventuneac, Ana; Carballo-Diéguez, Alex; Du, Yong; Leal, Jeffrey P; Lee, Linda A; Torbenson, Michael S; Hendrix, Craig W

2013-11-01

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R)-in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [(99m)Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma (99m)Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the (99m)Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of (99m)Tc-DTPA when compared to the other enemas (pgood with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

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das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2012-06-01

To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

The nonnucleoside reverse transcription inhibitor MIV-160 delivered from an intravaginal ring, but not from a carrageenan gel, protects against simian/human immunodeficiency virus-RT Infection.

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Aravantinou, Meropi; Singer, Rachel; Derby, Nina; Calenda, Giulia; Mawson, Paul; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Villegas, Guillermo; Gettie, Agegnehu; Blanchard, James; Lifson, Jeffrey D; Piatak, Michael; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia; Robbiani, Melissa

2012-11-01

We previously showed that a carrageenan (CG) gel containing 50 μM MIV-150 (MIV-150/CG) reduced vaginal simian/human immunodeficiency virus (SHIV)-RT infection of macaques (56%, p>0.05) when administered daily for 2 weeks with the last dose given 8 h before challenge. Additionally, when 100 mg of MIV-150 was loaded into an intravaginal ring (IVR) inserted 24 h before challenge and removed 2 weeks after challenge, >80% protection was observed (p<0.03). MIV-160 is a related NNRTI with a similar IC(50), greater aqueous solubility, and a shorter synthesis. To objectively compare MIV-160 with MIV-150, herein we evaluated the antiviral effects of unformulated MIV-160 in vitro as well as the in vivo protection afforded by MIV-160 delivered in CG (MIV-160/CG gel) and in an IVR under regimens used with MIV-150 in earlier studies. Like MIV-150, MIV-160 exhibited potent antiviral activity against SHIV-RT in macaque vaginal explants. However, formulated MIV-160 exhibited divergent effects in vivo. The MIV-160/CG gel offered no protection compared to CG alone, whereas the MIV-160 IVRs protected significantly. Importantly, the results of in vitro release studies of the MIV-160/CG gel and the MIV-160 IVR suggested that in vivo efficacy paralleled the amount of MIV-160 released in vitro. Hundreds of micrograms of MIV-160 were released daily from IVRs while undetectable amounts of MIV-160 were released from the CG gel. Our findings highlight the importance of testing different modalities of microbicide delivery to identify the optimal formulation for efficacy in vivo.

PRE-EXPOSURE PROPHYLAXIS FOR PREVENTION OF HIV INFECTION

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Ana Rita Diniz

2015-04-01

Full Text Available Objectives: To review existing data on Pre-Exposure Prophylaxis (PrEP for prevention of HIV infection, including the role of medical male circumcision, oral administration of antiretroviral drugs and topical microbicides. Data Sources: PubMed and www.clinicaltrials.gov. Review Methods: Comprehensive review. Results: Medical male circumcision has been shown to prevent 48-60% of new HIV-1 infections. The efficacy rate of antiretroviral drugs given per os to prevent HIV infection varies in direct association with the adherence rate (62.2% in TDF2 study with 84% adherence; 44% in iPrEx study with <50% adherence; 48% in Bangkok study with 67% adherence; 67-75% in Partners PrEP study with 82% adherence; and 6% in FEM-PrEP study with 40% adherence. As for the use of topic microbicides, the CAPRISA 004 study showed 39% reduction in HIV infection using a 1% tenofovir gel. On the other hand, PRO2000 gel showed a modest reduction of 30% which was not statistically significant. Conclusions: The studies suggest that medical male circumcision is highly cost-effective at preventing HIV infection but requires careful communication strategies to be successful. PrEP using antiretroviral drugs is also very effective but it is highly dependent on the adherence rate. As for topical microbicides, 1% tenofovir gel is currently the only promising option.

How informed is consent in vulnerable populations? Experience using a continuous consent process during the MDP301 vaginal microbicide trial in Mwanza, Tanzania

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Kavit Natujwa

2010-06-01

Full Text Available Abstract Background HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania. Methods A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs conducted immediately after their 4, 24 and 52 week follow-up visits. Results 99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews. In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy. Conclusions

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

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Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

3D MR gel dosimetry with lung equivalent gel

International Nuclear Information System (INIS)

Scherer, J.; Solleder, M.; Schiessl, I.; Bogner, L.; Herbst, M.

1998-01-01

The MR gel dosimetry is used to verify complex 3D treatment plans. Till now this method served only for dose evaluation in homogeneous phantoms. On the way to build a heterogeneous anthropomorphic gel phantom, a lung equivalent gel with the density 0.4 g/cm 3 was developed. First experiments show a 1.55 times higher dose reponse in the low density gel (LD gel). The comparison of a dose distribution in a gel/LD gel/gel slab phantom with Monte Carlo calculations shows good agreement within 5%. More over the accuray of the measuring device magnetic resonance imager was studied in respect to the now exclusive digital image processing with the software MRD (MR dosimetry). Because of the dimensions of the Fricke gel phantom an artefact correction, based on the data from the unirradiated phantom proved to be essential. (orig.) [de

Plasmid-Mediated Resistance to Thrombin-Induced Platelet Microbicidal Protein in Staphylococci: Role of the qacA Locus

OpenAIRE

Kupferwasser, Leon Iri; Skurray, Ronald A.; Brown, Melissa H.; Firth, Neville; Yeaman, Michael R.; Bayer, Arnold S.

1999-01-01

Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a small, cationic peptide released from rabbit platelets following thrombin stimulation. In vitro resistance to this peptide among strains of Staphylococcus aureus correlates with the survival advantage of such strains at sites of endothelial damage in humans as well as in experimental endovascular infections. The mechanisms involved in the phenotypic resistance of S. aureus to tPMP-1 are not fully delineated. The plasmid-encoded st...

Transdermal delivery of paeonol using cubic gel and microemulsion gel

Science.gov (United States)

Luo, Maofu; Shen, Qi; Chen, Jinjin

2011-01-01

Background The aim of this study was to develop new systems for transdermal delivery of paeonol, in particular microemulsion gel and cubic gel formulations. Methods Various microemulsion vehicles were prepared using isopropyl myristate as an oil phase, polyoxyethylated castor oil (Cremophor® EL) as a surfactant, and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel formulation, carbomer 940 was selected as the gel matrix, and consisted of 1% paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1), and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and 67% glyceryl monooleate. Results A skin permeability test using excised rat skins indicated that both the cubic gel and microemulsion gel formulations had higher permeability than did the paeonol solution. An in vivo pharmacokinetic study done in rats showed that the relative bioavailability of the cubic gel and microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively, compared with orally administered paeonol suspension. Conclusion Both the cubic gel and microemulsion gel formulations are promising delivery systems to enhance the skin permeability of paeonol, in particular the cubic gel. PMID:21904450

Effect of undecylenic acid as a topical microbicide against genital herpes infection in mice and guinea pigs.

Science.gov (United States)

Bourne, N; Ireland, J; Stanberry, L R; Bernstein, D I

1999-01-01

There is increasing interest in the use of topical microbicides to help prevent the spread of sexually transmitted diseases (STD). Undecylenic acid (UA), a monosaturated fatty acid, is the active ingredient in a number of over-the-counter (OTC) antifungal spray powders, that also exhibits in vitro antibacterial and antiviral activity, including herpes simplex virus (HSV) activity. We, therefore, evaluated UA as a topical microbicide against genital HSV infection using the murine and guinea pig models of genital herpes. Mice were administered a 20% solution of UA in polyethylene glycol (PEG) vehicle, vehicle alone or phosphate buffered saline (PBS) intravaginally immediately prior to vaginal challenge with HSV-2. Pre-treatment with UA decreased the number of mice that became infected (P < 0.001 vs. PBS or vehicle control), developed symptoms (P <0.001) or died (P <0.001). However, when treatment was extended to either 5 min prior to or after viral inoculation, protection was lost. Similar findings were found using the guinea pig model, where UA treatment completely prevented HSV-2 vaginal infection when given immediately prior to HSV-2 inoculation (P<0.001 vs. PBS or vehicle control). Thus, UA, an approved OTC medication, provided significant protection against HSV disease and infection only when applied immediately before viral inoculation, indicating that better formulations were needed to extend the duration of protection.

Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.

Directory of Open Access Journals (Sweden)

Irina A Zalenskaya

Full Text Available Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. Therefore, it is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides using a microarray gene expression profiling strategy.To this end, we compared transcriptomes of human vaginal cells (Vk2/E6E7 treated with well-characterized pro-inflammatory (PIC and non-inflammatory (NIC compounds. PICs included compounds with different mechanisms of action. Gene expression was analyzed using Affymetrix U133 Plus 2 arrays. Data processing was performed using GeneSpring 11.5 (Agilent Technologies, Santa Clara, CA.Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by PICs compared to NICs, thus distinguishing between these two groups. Functional analysis mapped 14 of these genes to immune and inflammatory responses. This was confirmed by the fact that PICs induced NFkB pathway activation in Vk2 cells. By testing microbicide candidates previously characterized in clinical trials we demonstrated that the selected PIC-associated genes properly identified compounds with mucosa-altering effects. The discriminatory power of these genes was further demonstrated after culturing vaginal cells with vaginal bacteria. Prevotella bivia, prevalent bacteria in the disturbed microbiota of bacterial vaginosis, induced strong upregulation of seven selected PIC-associated genes, while a commensal Lactobacillus gasseri associated to vaginal health did not cause any changes.In vitro evaluation of the immunoinflammatory potential of microbicides using the PIC-associated genes defined in this study could help in the initial screening of candidates prior

Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides.

Science.gov (United States)

das Neves, José; Sarmento, Bruno

2015-05-01

Polymeric nanoparticles (NPs) have the potential to provide effective and safe delivery of antiretroviral drugs in the context of prophylactic anti-HIV vaginal microbicides. Dapivirine-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) NPs were produced by an emulsion-solvent evaporation method, optimized for colloidal properties using a 3-factor, 3-level Box-Behnken experimental design, and characterized for drug loading, production yield, morphology, thermal behavior, drug release, in vitro cellular uptake, cytotoxicity and pro-inflammatory potential. Also, drug permeability/membrane retention in well-established HEC-1-A and CaSki cell monolayer models as mediated by NPs was assessed in the absence or presence of mucin. Box-Behnken design allowed optimizing monodisperse 170nm drug-loaded NPs. Drug release experiments showed an initial burst effect up to 4h, followed by sustained 24h release at pH 4.2 and 7.4. NPs were readily taken up by different genital and macrophage cell lines as assessed by fluorescence microscopy. Drug-loaded NPs presented lower or at least similar cytotoxicity as compared to the free drug, with up to around one-log increase in half-maximal cytotoxic concentration values. In all cases, no relevant changes in cell pro-inflammatory cytokine/chemokine production were observed. Dapivirine transport across cell monolayers was significantly decreased when mucin was present at the donor side with either NPs or the free drug, thus evidencing the influence of this natural glycoprotein in membrane permeability. Moreover, drug retention in cell monolayers was significantly higher for NPs in comparison with the free drug. Overall, obtained dapivirine-loaded PLGA NPs possess interesting technological and biological features that may contribute to their use as novel safe and effective vaginal microbicides. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors.

Science.gov (United States)

Dobard, Charles; Sharma, Sunita; Parikh, Urvi M; West, Rolieria; Taylor, Andrew; Martin, Amy; Pau, Chou-Pong; Hanson, Debra L; Lipscomb, Jonathan; Smith, James; Novembre, Francis; Hazuda, Daria; Garcia-Lerma, J Gerardo; Heneine, Walid

2014-03-12

Coitally delivered microbicide gels containing antiretroviral drugs are important for HIV prevention. However, to date, microbicides have contained entry or reverse transcriptase inhibitors that block early steps in virus infection and thus need to be given as a preexposure dose that interferes with sexual practices and may limit compliance. Integrase inhibitors block late steps after virus infection and therefore are more suitable for post-coital dosing. We first determined the kinetics of strand transfer in vitro and confirmed that integration begins about 6 hours after infection. We then used a repeat-challenge macaque model to assess efficacy of vaginal gels containing integrase strand transfer inhibitors when applied before or after simian/human immunodeficiency virus (SHIV) challenge. We showed that gel containing the strand transfer inhibitor L-870812 protected two of three macaques when applied 30 min before SHIV challenge. We next evaluated the efficacy of 1% raltegravir gel and demonstrated its ability to protect macaques when applied 3 hours after SHIV exposure (five of six protected; P infections showed no evidence of drug resistance in plasma or vaginal secretions despite continued gel dosing after infection. We documented rapid vaginal absorption reflecting a short pharmacological lag time and noted that vaginal, but not plasma, virus load was substantially reduced in the breakthrough infection after raltegravir gel treatment. We provide a proof of concept that topically applied integrase inhibitors protect against vaginal SHIV infection when administered shortly before or 3 hours after virus exposure.

Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination.

Science.gov (United States)

Schader, Susan M; Colby-Germinario, Susan P; Schachter, Jordana R; Xu, Hongtao; Wainberg, Mark A

2011-08-24

To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC(50)s) and combined effects were determined by calculating combination indices. Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI(50) = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI(50) = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI(50) = 0.968) and NNRTI-resistant (CI(50) = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.

Sol-Gel Glasses

Science.gov (United States)

Mukherjee, S. P.

1985-01-01

Multicomponent homogeneous, ultrapure noncrystalline gels/gel derived glasses are promising batch materials for the containerless glass melting experiments in microgravity. Hence, ultrapure, homogeneous gel precursors could be used to: (1) investigate the effect of the container induced nucleation on the glass forming ability of marginally glass forming compositions; and (2) investigate the influence of gravity on the phase separation and coarsening behavior of gel derived glasses in the liquid-liquid immiscibility zone of the nonsilicate systems having a high density phase. The structure and crystallization behavior of gels in the SiO2-GeO2 as a function of gel chemistry and thermal treatment were investigated. As are the chemical principles involved in the distribution of a second network former in silica gel matrix being investigated. The procedures for synthesizing noncrystalline gels/gel-monoliths in the SiO2-GeO2, GeO2-PbO systems were developed. Preliminary investigations on the levitation and thermal treatment of germania silicate gel-monoliths in the Pressure Facility Acoustic Levitator were done.

GelTouch

DEFF Research Database (Denmark)

Miruchna, Viktor; Walter, Robert; Lindlbauer, David

2015-01-01

We present GelTouch, a gel-based layer that can selectively transition between soft and stiff to provide tactile multi-touch feedback. It is flexible, transparent when not activated, and contains no mechanical, electromagnetic, or hydraulic components, resulting in a compact form factor (a 2mm thin...... touchscreen layer for our prototype). The activated areas can be morphed freely and continuously, without being limited to fixed, predefined shapes. GelTouch consists of a poly(N-isopropylacrylamide) gel layer which alters its viscoelasticity when activated by applying heat (>32 C). We present three different...

The gel electrophoresis markup language (GelML) from the Proteomics Standards Initiative.

Science.gov (United States)

Gibson, Frank; Hoogland, Christine; Martinez-Bartolomé, Salvador; Medina-Aunon, J Alberto; Albar, Juan Pablo; Babnigg, Gyorgy; Wipat, Anil; Hermjakob, Henning; Almeida, Jonas S; Stanislaus, Romesh; Paton, Norman W; Jones, Andrew R

2010-09-01

The Human Proteome Organisation's Proteomics Standards Initiative has developed the GelML (gel electrophoresis markup language) data exchange format for representing gel electrophoresis experiments performed in proteomics investigations. The format closely follows the reporting guidelines for gel electrophoresis, which are part of the Minimum Information About a Proteomics Experiment (MIAPE) set of modules. GelML supports the capture of metadata (such as experimental protocols) and data (such as gel images) resulting from gel electrophoresis so that laboratories can be compliant with the MIAPE Gel Electrophoresis guidelines, while allowing such data sets to be exchanged or downloaded from public repositories. The format is sufficiently flexible to capture data from a broad range of experimental processes, and complements other PSI formats for MS data and the results of protein and peptide identifications to capture entire gel-based proteome workflows. GelML has resulted from the open standardisation process of PSI consisting of both public consultation and anonymous review of the specifications.

Stacking gels: A method for maximising output for pulsed-field gel electrophoresis

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Heng See

2009-01-01

Full Text Available Pulsed field gel electrophoresis (PFGE, the gold standard of molecular typing methods, has a major disadvantage of an unusually long electrophoretic time. From the original protocol of 6 days, it was modified to 3 days and subsequently to a single day. We describe the procedure of stacking five to six gels one on top of another in order to increase and maximize the output in a shorter time without compromising the resolution and reproducibility. All the variables that affect pulsed field gels during electrophoresis were taken into consideration. We firstly optimized the parameters to be used and secondly determined whether stacking of five to six gels had any effect on the molecular separation during electrophoresis in comparison with a single gel run. DNA preparation, restriction, electrophoresis, staining and gel documentation was carried out based on previously published methods. Gels were analysed using BioNumerics and dice coefficient and unweighted pair group methods were used to generate dendrograms based on 1.5% tolerance values. Identical band profiles and band resolution-separation were seen in the PFGE patterns with single gel and multiple stacking gels. Cluster analysis further strengthened the fact that results from stacking gels were reproducible and comparable with a single gel run. This method of stacking gels saves time and maximizes the output at the same time. The run time for a single gel was about 28 hours, but with six stacked gels the run time was 54 hours compared with 28 x 6 = 168 hours if they were run separately as single gels thus saving time of 67.86%. Beside the big factor of saving time, stacking gels save resources (electricity, reagents, water, chemicals and working time by increasing the sample throughput in a shorter time without compromising on quality of data. But optimization of working parameters is vital depending on the PFGE system used.

Electrophoresis of DNA in agarose gels, polyacrylamide gels and in free solution

Science.gov (United States)

Stellwagen, Nancy C.

2009-01-01

This review describes the electrophoresis of curved and normal DNA molecules in agarose gels, polyacrylamide gels and in free solution. These studies were undertaken to clarify why curved DNA molecules migrate anomalously slowly in polyacrylamide gels but not in agarose gels. Two milestone papers are cited, in which Ferguson plots were used to estimate the effective pore size of agarose and polyacrylamide gels. Subsequent studies on the effect of the electric field on agarose and polyacrylamide gel matrices, DNA interactions with the two gel matrices, and the effect of curvature on the free solution mobility of DNA are also described. The combined results suggest that the anomalously slow mobilities observed for curved DNA molecules in polyacrylamide gels are due primarily to preferential interactions of curved DNAs with the polyacrylamide gel matrix; the restrictive pore size of the matrix is of lesser importance. In free solution, DNA mobilities increase with increasing molecular mass until leveling off at a plateau value of (3.17 ± 0.01) × 10-4 cm2/Vs in 40 mM Tris-acetate-EDTA buffer at 20°C. Curved DNA molecules migrate anomalously slowly in free solution as well as in polyacrylamide gels, explaining why the Ferguson plots of curved and normal DNAs containing the same number of base pairs extrapolate to different mobilities at zero gel concentration. PMID:19517510

Transport Phenomena in Gel

Directory of Open Access Journals (Sweden)

Masayuki Tokita

2016-05-01

Full Text Available Gel becomes an important class of soft materials since it can be seen in a wide variety of the chemical and the biological systems. The unique properties of gel arise from the structure, namely, the three-dimensional polymer network that is swollen by a huge amount of solvent. Despite the small volume fraction of the polymer network, which is usually only a few percent or less, gel shows the typical properties that belong to solids such as the elasticity. Gel is, therefore, regarded as a dilute solid because its elasticity is much smaller than that of typical solids. Because of the diluted structure, small molecules can pass along the open space of the polymer network. In addition to the viscous resistance of gel fluid, however, the substance experiences resistance due to the polymer network of gel during the transport process. It is, therefore, of importance to study the diffusion of the small molecules in gel as well as the flow of gel fluid itself through the polymer network of gel. It may be natural to assume that the effects of the resistance due to the polymer network of gel depends strongly on the network structure. Therefore, detailed study on the transport processes in and through gel may open a new insight into the relationship between the structure and the transport properties of gel. The two typical transport processes in and through gel, that is, the diffusion of small molecules due to the thermal fluctuations and the flow of gel fluid that is caused by the mechanical pressure gradient will be reviewed.

Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm

Directory of Open Access Journals (Sweden)

Jones Maureen

2010-07-01

Full Text Available Abstract Background At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1 infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. Results Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC50 was ≤ 3.5 (0.8-3.5% and the TC50 ≤ 6.3 (1.0-6.3%. All three liquid products inhibited viability of beneficial Lactobacillus species associated with vaginal health. Comparison of three different toxicity endpoints in the cervical HeLa cell line revealed that all three products affected membrane integrity, cytosolic enzyme release, and dehydrogenase enzyme activity in living cells. The juices and vinegar also exerted strong cytotoxicity in cervico-vaginal cell lines, mainly due to their acidic pH. In human cervical explant tissues, treatment with 5% lemon or lime juice

Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days.

Science.gov (United States)

Nuttall, Jeremy P; Thake, Daryl C; Lewis, Mark G; Ferkany, John W; Romano, Joseph W; Mitchnick, Mark A

2008-03-01

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine ( approximately 0.1 mg/ml [15 microCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of microg/g of tissue) and remained detectable at 24 h (mean, >or=2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application.

Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

Science.gov (United States)

Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

2008-01-01

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine (∼0.1 mg/ml [15 μCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of μg/g of tissue) and remained detectable at 24 h (mean, ≥2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application. PMID:18086845

Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development.

Directory of Open Access Journals (Sweden)

Xudong Lin

Full Text Available BACKGROUND: Approximately 80% of all new HIV-1 infections are acquired through sexual contact. Currently, there is no clinically approved microbicide, indicating a clear and urgent therapeutic need. We recently reported that palmitic acid (PA is a novel and specific inhibitor of HIV-1 fusion and entry. Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo model of human vagina, and determine its effect on Lactobacillus (L species of probiotic vaginal flora. PRINCIPAL FINDINGS: Our results show that treatment with 100-200 µM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this treatment was not toxic to the tissue or to L. crispatus and jensenii species of vaginal flora. In vitro, in a cell free system that is independent of in vivo cell associated CD4 receptor; we determined inhibition constant (Ki to be ∼2.53 µM. SIGNIFICANCE: These results demonstrate utility of PA as a model molecule for further preclinical development of a safe and potent HIV-1 entry microbicide inhibitor.

Thorium inorganic gels

International Nuclear Information System (INIS)

Genet, M.; Brandel, V.

1988-01-01

The optimum pH and concentration values of thorium salts and oxoacids or oxoacid salts which lead to transparent and stable inorganic gels have been determined. The isotherm drying process of the gel at 50 0 C leads successively to a partly dehydrated gel, then, to the formation of an unusual liquid phase and, finally to a dry amorphous solid phase which is still transparent. This kind of transparent inorganic gels and amorphous phase can be used as matrices for spectroscopic studies [fr

Colloid molecular weight estimation by gel chromatography/acrylamide gel electrophoresis

International Nuclear Information System (INIS)

Liberatore, F.A.; Dearborn, C.; Nigam, S.; Poon, C.; Camin, L.; Liteplo, M.

1984-01-01

Size or molecular weight (MW) estimation of radiolabeled collides in aqueous solutions has long been a problem. The authors have prepared several minimicroaggregated albumin colloids (mμAA) by heat denaturation of stannous-containing HSA solutions at pH 7.0, 7.5, and 8.5). The resulting colloids were labeled with Tc-99m and compared with Au-198 colloid and Tc-99m-antimony sulfide colloid (Tc-99m-Sb/sub 2/S3) by gel chromatography and gel electrophoresis. Tc-99mm-mμAA aggregated at pH 7.0 and the Au-198 colloid appeared in the external void volume of a BioRad A5.0 agarose column indicating an apparent MW of > 5 x 10/sup 6/ daltons. The pH7.5 Tc-99m-mμAA, migrated within the filtration range of the column as did a small fraction of Tc-99m-Sb/sub 2/S/sub 3/, suggesting that the MW is between 6 x 10/sup 4/ - 5 x 10/sup 6/ daltons. The Tc-99m-mμAA, aggregated at pH 8.5, had an apparent MW on gel filtration similar to that of untreated albumin, MW 6.6 x 10-/sup 4/ daltons. The mobilities of the colloids, on acrylamide disc gel electrophoresis, were consistent with the results on gel chromatography. The largest colloids, Au-198 colloid and pH 7.0 Tc-99m-mμAA, barely entered the separating gel; intermediate sized colloids, a small fraction of Tc-99m-Sb/sub 2/S/sub 3/ and pH 7.5 Tc-99m-mμAA migrated farther into the separating gel; while pH 8.5 Tc-99m-mμAA had mobility approaching that of untreated albumin. Lymphoscintigraphy studies using these colloids in animals showed the predicted, particle size-related differences in migration and clearance. The authors conclude that gel chromatography and gel electrophoresis are useful methods for estimating the apparent size of the colloidal particles

Resistance to and killing by the sporicidal microbicide peracetic acid.

Science.gov (United States)

Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; Mcdonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

2015-03-01

To elucidate the mechanisms of spore resistance to and killing by the oxidizing microbicide peracetic acid (PAA). Mutants of Bacillus subtilis lacking specific spore structures were used to identify resistance properties in spores and to understand the mechanism of action of PAA. We also assessed the effect of PAA treatment on a number of spore properties including heat tolerance, membrane integrity and germination. The spore coat is essential for spore PAA resistance as spores with defective coats were greatly sensitized to PAA treatment. Small acid-soluble spore proteins apparently provide no protection against PAA. Defects in spore germination, specifically in germination via the GerB and GerK but not the GerA germination receptors, as well as leakage of internal components suggest that PAA is active at the spore inner membrane. It is therefore likely that the inner membrane is the major site of PAA's sporicidal activity. PAA treatment targets the spore membrane, with some of its activity directed specifically against the GerB and GerK germination receptors. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Perceptions among Dutch men who have sex with men and their willingness to use rectal microbicides and oral pre-exposure prophylaxis to reduce HIV risk--a preliminary study

NARCIS (Netherlands)

Marra, Elske; Hankins, Catherine A.

2015-01-01

Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the

Internal structure analysis of particle-double network gels used in a gel organ replica

Science.gov (United States)

Abe, Mei; Arai, Masanori; Saito, Azusa; Sakai, Kazuyuki; Kawakami, Masaru; Furukawa, Hidemitsu

2016-04-01

In recent years, the fabrication of patient organ replicas using 3D printers has been attracting a great deal of attention in medical fields. However, the cost of these organ replicas is very high as it is necessary to employ very expensive 3D printers and printing materials. Here we present a new gel organ replica, of human kidney, fabricated with a conventional molding technique, using a particle-double network hydrogel (P-DN gel). The replica is transparent and has the feel of a real kidney. It is expected that gel organ replicas produced this way will be a useful tool for the education of trainee surgeons and clinical ultrasonography technologists. In addition to developing a gel organ replica, the internal structure of the P-DN gel used is also discussed. Because the P-DN gel has a complex structure comprised of two different types of network, it has not been possible to investigate them internally in detail. Gels have an inhomogeneous network structure. If it is able to get a more uniform structure, it is considered that this would lead to higher strength in the gel. In the present study we investigate the structure of P-DN gel, using the gel organ replica. We investigated the internal structure of P-DN gel using Scanning Microscopic Light Scattering (SMILS), a non-contacting and non-destructive.

Polymer gel dosimetry

Energy Technology Data Exchange (ETDEWEB)

Baldock, C [Institute of Medical Physics, School of Physics, University of Sydney (Australia); De Deene, Y [Radiotherapy and Nuclear Medicine, Ghent University Hospital (Belgium); Doran, S [CRUK Clinical Magnetic Resonance Research Group, Institute of Cancer Research, Surrey (United Kingdom); Ibbott, G [Radiation Physics, UT M D Anderson Cancer Center, Houston, TX (United States); Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria, BC (Canada); Lepage, M [Centre d' imagerie moleculaire de Sherbrooke, Departement de medecine nucleaire et de radiobiologie, Universite de Sherbrooke, Sherbrooke, QC (Canada); McAuley, K B [Department of Chemical Engineering, Queen' s University, Kingston, ON (Canada); Oldham, M [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Schreiner, L J [Cancer Centre of South Eastern Ontario, Kingston, ON (Canada)], E-mail: c.baldock@physics.usyd.edu.au, E-mail: yves.dedeene@ugent.be

2010-03-07

Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented. (topical review)

Applications of gel dosimetry

International Nuclear Information System (INIS)

Ibbott, Geoffrey S

2004-01-01

Gel dosimetry has been examined as a clinical dosimeter since the 1950s. During the last two decades, however, a rapid increase in the number of investigators has been seen, and the body of knowledge regarding gel dosimetry has expanded considerably. Gel dosimetry is still considered a research project, and the introduction of this tool into clinical use is proceeding slowly. This paper will review the characteristics of gel dosimetry that make it desirable for clinical use, the postulated and demonstrated applications of gel dosimetry, and some complications, set-backs, and failures that have contributed to the slow introduction into routine clinical use

Removing water from gels

International Nuclear Information System (INIS)

Lane, E.S.; Winter, J.A.

1982-01-01

Water is removed from a gel material by contacting the gel material with an organic liquid and contacting the organic liquid with a gas such that water is taken up by the gas. The invention, in one embodiment, may be used to dry gel materials whilst maintaining an open porous network therein. In one example, the invention is applied to gel precipitated spheres containing uranium and plutonium. (author)

Categorization of rheological scaling models for particle gels applied to casein gels

NARCIS (Netherlands)

Mellema, M.; Opheusden, van J.H.J.; Vliet, van T.

2002-01-01

Rennet-induced casein gels made from skim milk were studied rheologically. A scaling model or framework for describing the rheological behavior of gels is discussed and used for classification of the structure of casein gels. There are two main parameters in the model that describe the number of

Transporters for Antiretroviral Drugs in Colorectal CD4+ T Cells and Circulating α4β7 Integrin CD4+ T Cells: Implications for HIV Microbicides.

Science.gov (United States)

Mukhopadhya, Indrani; Murray, Graeme I; Duncan, Linda; Yuecel, Raif; Shattock, Robin; Kelly, Charles; Iannelli, Francesco; Pozzi, Gianni; El-Omar, Emad M; Hold, Georgina L; Hijazi, Karolin

2016-09-06

CD4+ T lymphocytes in the colorectal mucosa are key in HIV-1 transmission and dissemination. As such they are also the primary target for antiretroviral (ARV)-based rectal microbicides for pre-exposure prophylaxis. Drug transporters expressed in mucosal CD4+ T cells determine ARV distribution across the cell membrane and, most likely, efficacy of microbicides. We describe transporters for antiretroviral drugs in colorectal mucosal CD4+ T lymphocytes and compare gene expression with circulating α4β7+CD4+ T cells, which traffic to the intestine and have been shown to be preferentially infected by HIV-1. Purified total CD4+ T cells were obtained from colorectal tissue and blood samples by magnetic separation. CD4+ T cells expressing α4β7 integrin were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells of healthy volunteers. Expressions of 15 efflux and uptake drug transporter genes were quantified using Taqman qPCR assays. Expression of efflux transporters MRP3, MRP5, and BCRP and uptake transporter CNT2 were significantly higher in colorectal CD4+ T cells compared to circulating CD4+ T cells (p = 0.01-0.03). Conversely, circulating α4β7+CD4+ T cells demonstrated significantly higher expression of OATPD compared to colorectal CD4+ T cells (p = 0.001). To the best of our knowledge this is the first report of drug transporter gene expression in colorectal CD4+ and peripheral α4β7+CD4+ T cells. The qualitative and quantitative differences in drug transporter gene expression profiles between α4β7+CD4+ T cells and total mucosal CD4+ T cells may have significant implications for the efficacy of rectally delivered ARV-microbicides. Most notably, we have identified efflux drug transporters that could be targeted by selective inhibitors or beneficial drug-drug interactions to enhance intracellular accumulation of antiretroviral drugs.

A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation

Energy Technology Data Exchange (ETDEWEB)

Fichorova, Raina N., E-mail: rfichorova@rics.bwh.harvard.edu [Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Mendonca, Kevin; Yamamoto, Hidemi S.; Murray, Ryan [Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chandra, Neelima; Doncel, Gustavo F. [CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA (United States)

2015-06-15

Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV + 2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P < 0.05), and decreased levels of TLR2 (P < 0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P < 0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. - Highlights: • A transcriptome nuclease protection assay assessed microbicides for vaginal safety. • Biomarkers were

A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation

International Nuclear Information System (INIS)

Fichorova, Raina N.; Mendonca, Kevin; Yamamoto, Hidemi S.; Murray, Ryan; Chandra, Neelima; Doncel, Gustavo F.

2015-01-01

Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascular markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV + 2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P < 0.05), and decreased levels of TLR2 (P < 0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P < 0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. - Highlights: • A transcriptome nuclease protection assay assessed microbicides for vaginal safety. • Biomarkers were

Metal-silica sol-gel materials

Science.gov (United States)

Stiegman, Albert E. (Inventor)

2002-01-01

The present invention relates to a single phase metal-silica sol-gel glass formed by the co-condensation of a transition metal with silicon atoms where the metal atoms are uniformly distributed within the sol-gel glass as individual metal centers. Any transition metal may be used in the sol-gel glasses. The present invention also relates to sensor materials where the sensor material is formed using the single phase metal-silica sol-gel glasses. The sensor materials may be in the form of a thin film or may be attached to an optical fiber. The present invention also relates to a method of sensing chemicals using the chemical sensors by monitoring the chromatic change of the metal-silica sol-gel glass when the chemical binds to the sensor. The present invention also relates to oxidation catalysts where a metal-silica sol-gel glass catalyzes the reaction. The present invention also relates to a method of performing oxidation reactions using the metal-silica sol-gel glasses. The present invention also relates to organopolymer metal-silica sol-gel composites where the pores of the metal-silica sol-gel glasses are filled with an organic polymer polymerized by the sol-gel glass.

Study of nuclear glasses alteration gel and synthesis of some model gels; Etude du gel d`alteration des verres nucleaires et synthese de gels modeles

Energy Technology Data Exchange (ETDEWEB)

Ricol, S

1995-10-05

This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs.

Thoria sol-gel processes

International Nuclear Information System (INIS)

Matthews, R.B.

1978-10-01

Alternate fuel fabrication techniques are being developed at WNRE as part of the thorium fuel cycle program. The sol-gel techniques are attractive and this report assembles and summarizes information relating to thoria sol-gel fuels. Some background information on the behaviour and advantages of sol-gel fuel forms is presented, followed by a review of relevant colloid chemistry and an explanation of the fundamental steps of sol-gel processes. Finally, several variants to the basic process are reviewed and evaluated. (author)

Review of Fricke gel dosimeters

International Nuclear Information System (INIS)

Schreiner, L J

2004-01-01

The innovation of adding a gel matrix to the traditional Fricke dosimeter to stabilize geometric information established the field of gel dosimetry for radiation therapy. A discussion of Fricke gels provides an overview of the issues that determine the dose response of all gel dosimeters in general. In this paper we review some of the features of Fricke systems to illustrate these issues and, in addition, to motivate renewed clinical interest in Fricke gels

Gel nano-particulates against radioactivity; Des nanoparticules en gel contre la radioactivite

Energy Technology Data Exchange (ETDEWEB)

Deroin, Ph

2004-11-01

The Argonne research center (USA) has developed a 'super-gel' compound, a polymer close to those used in baby's diapers, which can reach a 90% efficiency in the radioactive decontamination of porous materials, like bricks or concrete. The contaminated materials are sprayed with a mixture of polymer gel and wetting agent with nano-particulates in suspension. Under the action of the wetting agent, radioactivity migrates from the pores to the gel and is trapped by the nano-particulates. The drying and recycling of the gel allows to reduce the volume of radioactive wastes. Short paper. (J.S.)

Polymer gel dosimeters with enhanced sensitivity for use in x-ray CT polymer gel dosimetry

International Nuclear Information System (INIS)

Jirasek, A; Hilts, M; McAuley, K B

2010-01-01

A primary limitation of current x-ray CT polymer gel dosimetry is the low contrast, and hence poor dose resolution, of dose images produced by the system. The low contrast is largely due to the low-dose sensitivity of current formulations of polymer gel for x-ray CT imaging. This study reports on the investigation of new dosimeter formulations with improved dose sensitivity for x-ray CT polymer gel dosimetry. We incorporate an isopropanol co-solvent into an N-isopropylacrylamide-based gel formulation in order to increase the total monomer/crosslinker concentration (%T) within the formulation. It is shown that gels of high %T exhibit enhanced dose sensitivity and dose resolutions over traditional formulations. The gels are shown to be temporally stable and reproducible. A single formulation (16%T) is used to demonstrate the capabilities of the x-ray CT polymer gel dosimetry system in measuring known dose distributions. A 1 L gel volume is exposed to three separate irradiations: a single-field percent depth dose, a two-field 'cross' and a three-field 'test case'. The first two irradiations are used to generate a dose calibration curve by which images are calibrated. The calibrated images are compared with treatment planning predictions and it is shown that the x-ray CT polymer gel dosimetry system is capable of capturing spatial and dose information accurately. The proposed new gel formulation is shown to be sensitive, stable and to improve the dose resolution over current formulations so as to provide a feasible gel for clinical applications of x-ray CT polymer gel dosimetry.

Design of Autonomous Gel Actuators

Directory of Open Access Journals (Sweden)

Shuji Hashimoto

2011-01-01

Full Text Available In this paper, we introduce autonomous gel actuators driven by chemical energy. The polymer gels prepared here have cyclic chemical reaction networks. With a cyclic reaction, the polymer gels generate periodical motion. The periodic motion of the gel is produced by the chemical energy of the oscillatory Belouzov-Zhabotinsky (BZ reaction. We have succeeded in making synthetic polymer gel move autonomously like a living organism. This experimental fact represents the great possibility of the chemical robot.

Optimal processing for gel electrophoresis images: Applying Monte Carlo Tree Search in GelApp.

Science.gov (United States)

Nguyen, Phi-Vu; Ghezal, Ali; Hsueh, Ya-Chih; Boudier, Thomas; Gan, Samuel Ken-En; Lee, Hwee Kuan

2016-08-01

In biomedical research, gel band size estimation in electrophoresis analysis is a routine process. To facilitate and automate this process, numerous software have been released, notably the GelApp mobile app. However, the band detection accuracy is limited due to a band detection algorithm that cannot adapt to the variations in input images. To address this, we used the Monte Carlo Tree Search with Upper Confidence Bound (MCTS-UCB) method to efficiently search for optimal image processing pipelines for the band detection task, thereby improving the segmentation algorithm. Incorporating this into GelApp, we report a significant enhancement of gel band detection accuracy by 55.9 ± 2.0% for protein polyacrylamide gels, and 35.9 ± 2.5% for DNA SYBR green agarose gels. This implementation is a proof-of-concept in demonstrating MCTS-UCB as a strategy to optimize general image segmentation. The improved version of GelApp-GelApp 2.0-is freely available on both Google Play Store (for Android platform), and Apple App Store (for iOS platform). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymer gel dosimeters with enhanced sensitivity for use in x-ray CT polymer gel dosimetry

Energy Technology Data Exchange (ETDEWEB)

Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria BC V8W 3P6 (Canada); Hilts, M [Medical Physics, BC Cancer Agency-Vancouver Island Centre, Victoria BC V6R 2B6 (Canada); McAuley, K B, E-mail: jirasek@uvic.c [Department of Chemical Engineering, Queens University, Kingston, ON K7 L 3N6 (Canada)

2010-09-21

A primary limitation of current x-ray CT polymer gel dosimetry is the low contrast, and hence poor dose resolution, of dose images produced by the system. The low contrast is largely due to the low-dose sensitivity of current formulations of polymer gel for x-ray CT imaging. This study reports on the investigation of new dosimeter formulations with improved dose sensitivity for x-ray CT polymer gel dosimetry. We incorporate an isopropanol co-solvent into an N-isopropylacrylamide-based gel formulation in order to increase the total monomer/crosslinker concentration (%T) within the formulation. It is shown that gels of high %T exhibit enhanced dose sensitivity and dose resolutions over traditional formulations. The gels are shown to be temporally stable and reproducible. A single formulation (16%T) is used to demonstrate the capabilities of the x-ray CT polymer gel dosimetry system in measuring known dose distributions. A 1 L gel volume is exposed to three separate irradiations: a single-field percent depth dose, a two-field 'cross' and a three-field 'test case'. The first two irradiations are used to generate a dose calibration curve by which images are calibrated. The calibrated images are compared with treatment planning predictions and it is shown that the x-ray CT polymer gel dosimetry system is capable of capturing spatial and dose information accurately. The proposed new gel formulation is shown to be sensitive, stable and to improve the dose resolution over current formulations so as to provide a feasible gel for clinical applications of x-ray CT polymer gel dosimetry.

Quantitation of microbicidal activity of mononuclear phagocytes: an in vitro technique.

Directory of Open Access Journals (Sweden)

Rege N

1993-01-01

Full Text Available An in vitro assay technique was set up to determine the phagocytic and microbicidal activity of a monocyte-macrophage cell line using Candida species as test organisms. The norms were determined for the activity of peritoneal macrophages of rats (24.69 +/- 2.6% phagocytosis and 35.4 +/- 5.22% ICK and human (27.89 +/- 3.63% phagocytosis and 50.91 +/- 6.3% ICK. The assay technique was used to test the degree of activation of macrophages induced by metronidazole, Tinospora cordifolia and Asparaqus racemousus and to compare their effects with a standard immunomodulator muramyl-dipeptide. All the three test agents increased the phagocytic and killing capacity of macrophages in a dose dependent manner upto a certain dose, beyond which either these activities were found to have plateaued or decreased. The optimal doses for MDP, Metronidazole, Asparagus racemosus and Tinospora cordifolia were found to be 100 micrograms, 300 mg/kg, 200 mg/kg and 100 mg/kg respectively. Patients with cirrhosis were screened for defects in monocyte function. The depressed monocyte function (20.58 +/- 5% phago and 41.24 +/- 12.19% ICK; P < 0.05 was observed indicating a compromised host defense. The utility of this candidicidal assay in experimental and clinical studies is discussed.

Polymer gels and networks

National Research Council Canada - National Science Library

Osada, Yoshihito; Khokhlov, A. R

2002-01-01

... or magnetic field, etc.). It was realized that not only can polymer gels absorb and hold a considerable volume of liquids, but they can also be forced to expel the absorbed liquid in a controlled manner. Of particular interest are hydrogels, i.e., polymer gels, which swell extensively in water. The most common hydrogels are polyelectrolyte gels: ...

HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

Directory of Open Access Journals (Sweden)

Kelly E Seaton

Full Text Available Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

Preparation of continuous alumina gel fibres by aqueous sol–gel ...

Indian Academy of Sciences (India)

Abstract. Continuous alumina gel fibres were prepared by sol–gel method. The spinning sol was prepared by mixing aluminum nitrate, lactic acid and polyvinylpyrrolidone with a mass ratio of 10:3:1·5. Thermogravimetry– differential scanning calorimetry (TG–DSC), Fourier transform infrared (FTIR) spectra, X-ray diffraction ...

The Effect of Surface Tension on the Gravity-driven Thin Film Flow of Newtonian and Power-law Fluids

Science.gov (United States)

Hu, Bin; Kieweg, Sarah L.

2012-01-01

Gravity-driven thin film flow is of importance in many fields, as well as for the design of polymeric drug delivery vehicles, such as anti-HIV topical microbicides. There have been many prior works on gravity-driven thin films. However, the incorporation of surface tension effect has not been well studied for non-Newtonian fluids. After surface tension effect was incorporated into our 2D (i.e. 1D spreading) power-law model, we found that surface tension effect not only impacted the spreading speed of the microbicide gel, but also had an influence on the shape of the 2D spreading profile. We observed a capillary ridge at the front of the fluid bolus. Previous literature shows that the emergence of a capillary ridge is strongly related to the contact line fingering instability. Fingering instabilities during epithelial coating may change the microbicide gel distribution and therefore impact how well it can protect the epithelium. In this study, we focused on the capillary ridge in 2D flow and performed a series of simulations and showed how the capillary ridge height varies with other parameters, such as surface tension coefficient, inclination angle, initial thickness, and power-law parameters. As shown in our results, we found that capillary ridge height increased with higher surface tension, steeper inclination angle, bigger initial thickness, and more Newtonian fluids. This study provides the initial insights of how to optimize the flow and prevent the appearance of a capillary ridge and fingering instability. PMID:23687391

Sealing wells with gel

Energy Technology Data Exchange (ETDEWEB)

Lopez, E C

1967-10-01

A new system is being used in Mexico to temporarily plug producing wells. The temporary seal is a gel with a catalyst. The use of this temporary plug allows gas-lift wells to be taken off production in order to carry out emergency repairs. The gel solidifies by the action of the catalyst to a high temperature (70 - 150/sup 0/C). By locating the bottom of the tubing at the top of the production interval, the gel material will go into the permeable formation, and immediately set. When the gel has solidified, it seals off the horizon that must not be stimulated, and leaves the others exposed to the acid action. When the treatment is finished, the gel, by action of the catalyst, is liquefied and removed from the formation, being produced with the oil.

Gel-eletroforese no diagnóstico da varíola Gel-electrophoresis in the smallpox diagnosis

Directory of Open Access Journals (Sweden)

Julio A. Mesquita

1972-01-01

Full Text Available O emprego de gel-eletroforese no diagnóstico da varíola, demonstrou ser ao menos trinta vezes (30X mais sensível que o teste de agar-gel, nas condições descritas (tabela I. Doze (12 espécimes, cujos testes convencionais de inoculação em ovos embrionados e de agar-gel resultaram positivos, foram testados em suas diluições originais congeladas por mais de um ano, sendo seis deles revelados por gel-eletroforese enquanto nenhum o foi por agar-gel (tabela II. Trinta e três (33 amostras isoladas no laboratório, foram testadas com material colhido de membrana cório-alantóica da primeira inoculação para o diagnóstico, conservado em glicerina 50%, resultando 15 positivas em gel-eletroforese e apenas 3 em agar-gel (tabela II. Os últimos 60 espécimes recebidos para diagnóstico, através a Campanha de Erradicação da Varíola, também resultaram negativos em gel-eletroforese, que não mostrou falsos-positivos nas condições descritas.The test of gel-electrophoresis applied to the pox virus group showed to be at least thirth times (30X more sensitive than agar-gel test on the described conditions (Table I. Twelve specimens, which were positives form Smallpox in the conventional tests of egg inoculation and agar-gel difusion test, have been screened in their original dilutions frozen for more than 1 year and six of them were still detectable by gel-eletrophoresis, while by agar-gel test any of them was positive (Table II. Thirty three Smallpox isolates have been tested with material from first egg inoculation (chorioallantoic membranes which have been stored in glycerin 50%, at - 15ºC. Fifteen of them were still positive by gel-electrophoresis and only 3 by agar-gel (Table II. The last 60 specimens received for diagnosis from Smallpox Erradication Campaign (CEV, were negatives by both tests. The gel-electrophoresis, did not show false-positives on described conditions.

Instrumental texture profile analysis of gelatin gel extracted from grouper skin and commercial (bovine and porcine) gelatin gels.

Science.gov (United States)

Rahman, Mohammad Shafiur; Al-Mahrouqi, Abdullah Issa

2009-01-01

Mechanical compression was used to study the gelling characteristics of gelatin gels. Texture profile analysis (TPA) showed that the hardness of fish and mammalian gelatin increased significantly as the concentrations of gels increased. TPA attributes of 10% fish skin gel showed significant differences from those obtained from 20% and 30% gels. In bovine and porcine cases, such generic trends were not observed. Mechanical characteristics of 10% gels of gelatin from fish skin, determined from one cycle compression, were significantly lower than other sources of gelatin gels, while bovine and porcine gels did not show any significant differences. In the case of TPA, hardness of bovine gelatin gel was highest at 41 N for 10% gel, followed by porcine (30 N) then fish skin (5 N) gelatin gels. The gels prepared from different sources did not show any generic trends when all other mechanical attributes were considered.

Compatibility between weak gel and microorganisms in weak gel-assisted microbial enhanced oil recovery.

Science.gov (United States)

Qi, Yi-Bin; Zheng, Cheng-Gang; Lv, Cheng-Yuan; Lun, Zeng-Min; Ma, Tao

2018-03-20

To investigate weak gel-assisted microbial flooding in Block Wang Long Zhuang in the Jiangsu Oilfield, the compatibility of weak gel and microbe was evaluated using laboratory experiments. Bacillus sp. W5 was isolated from the formation water in Block Wang Long Zhuang. The rate of oil degradation reached 178 mg/day, and the rate of viscosity reduction reached 75.3%. Strain W5 could produce lipopeptide with a yield of 1254 mg/L. Emulsified crude oil was dispersed in the microbial degradation system, and the average diameter of the emulsified oil particles was 18.54 μm. Bacillus sp. W5 did not affect the rheological properties of the weak gel, and the presence of the weak gel did not significantly affect bacterial reproduction (as indicated by an unchanged microbial biomass), emulsification (surface tension is 35.56 mN/m and average oil particles size is 21.38 μm), oil degradation (162 mg/day) and oil viscosity reduction (72.7%). Core-flooding experiments indicated oil recovery of 23.6% when both weak gel and Bacillus sp. W5 were injected into the system, 14.76% when only the weak gel was injected, and 9.78% with strain W5 was injected without the weak gel. The results demonstrate good compatibility between strains W5 and the weak gel and highlight the application potential of weak gel-assisted microbial flooding. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

High transparent shape memory gel

Science.gov (United States)

Gong, Jin; Arai, Masanori; Kabir, M. H.; Makino, Masato; Furukawa, Hidemitsu

2014-03-01

Gels are a new material having three-dimensional network structures of macromolecules. They possess excellent properties as swellability, high permeability and biocompatibility, and have been applied in various fields of daily life, food, medicine, architecture, and chemistry. In this study, we tried to prepare new multi-functional and high-strength gels by using Meso-Decoration (Meso-Deco), one new method of structure design at intermediate mesoscale. High-performance rigid-rod aromatic polymorphic crystals, and the functional groups of thermoreversible Diels-Alder reaction were introduced into soft gels as crosslinkable pendent chains. The functionalization and strengthening of gels can be realized by meso-decorating the gels' structure using high-performance polymorphic crystals and thermoreversible pendent chains. New gels with good mechanical properties, novel optical properties and thermal properties are expected to be developed.

Influence of pre-cooking protein paste gelation conditions and post-cooking gel storage conditions on gel texture.

Science.gov (United States)

Paker, Ilgin; Matak, Kristen E

2016-01-15

Gelation conditions affect the setting of myofibrillar fish protein gels. Therefore the impact of widely applied pre-cooking gelation time/temperature strategies and post-cooking period on the texture and color of final protein gels was determined. Four pre-cooking gelation strategies (no setting time, 30 min at 25 °C, 1 h at 40 °C or 24 h at 4 °C) were applied to protein pastes (fish protein concentrate and standard functional additives). After cooking, texture and color were analyzed either directly or after 24 h at 4 °C on gels adjusted to 25 °C. No-set gels were harder, gummier and chewier (P cooking. Gel-setting conditions had a greater (P cooking stored gels in texture and color, depending on the pre-cooking gelation strategy. Pre-cooking gelation conditions will affect final protein gel texture and color, with gel stability benefiting from a gel-setting period. However, post-cooking storage may have a greater impact on final gels, with textural attributes becoming more consistent between all samples. © 2015 Society of Chemical Industry.

Agar/gelatin bilayer gel matrix fabricated by simple thermo-responsive sol-gel transition method.

Science.gov (United States)

Wang, Yifeng; Dong, Meng; Guo, Mengmeng; Wang, Xia; Zhou, Jing; Lei, Jian; Guo, Chuanhang; Qin, Chaoran

2017-08-01

We present a simple and environmentally-friendly method to generate an agar/gelatin bilayer gel matrix for further biomedical applications. In this method, the thermally responsive sol-gel transitions of agar and gelatin combined with the different transition temperatures are exquisitely employed to fabricate the agar/gelatin bilayer gel matrix and achieve separate loading for various materials (e.g., drugs, fluorescent materials, and nanoparticles). Importantly, the resulting bilayer gel matrix provides two different biopolymer environments (a polysaccharide environment vs a protein environment) with a well-defined border, which allows the loaded materials in different layers to retain their original properties (e.g., magnetism and fluorescence) and reduce mutual interference. In addition, the loaded materials in the bilayer gel matrix exhibit an interesting release behavior under the control of thermal stimuli. Consequently, the resulting agar/gelatin bilayer gel matrix is a promising candidate for biomedical applications in drug delivery, controlled release, fluorescence labeling, and bio-imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Testing of super conducting low-beta 704 Mhz cavities at 50 Hz pulse repetition rate in view of SPL- first results

CERN Document Server

Höfle, W; Lollierou, J; Valuch, D; Chel, S; Devanz, G; Desmons, M; Piquet, O; Paparella, R; Pierini, P

2010-01-01

In the framework of the preparatory phase for the luminosity upgrade of the LHC (SLHC-PP ) it is foreseen to characterize two superconducting RF cavities and demonstrate compliance of the required SPL field stability in amplitude and phase using a prototype LLRF system. We report on the preparation for testing of two superconducting low-beta cavities at 50 Hz pulse repetition rate including the setting-up of the low level RF control system to evaluate the performance of the piezo-tuning system and cavity field stability in amplitude and phase. Results from tests with 50 Hz pulse repetition rate are presented. Simulations of the RF system will be used to predict the necessary specifications for power and bandwidth to control the cavity field and derive specifications for the RF system and its control. Exemplary results of the simulation are presented.

Chemical Gel for Surface Decontamination

International Nuclear Information System (INIS)

Jung, Chong Hun; Moon, J. K.; Won, H. J.; Lee, K. W.; Kim, C. K.

2010-01-01

Many chemical decontamination processes operate by immersing components in aggressive chemical solutions. In these applications chemical decontamination technique produce large amounts of radioactive liquid waste. Therefore it is necessary to develop processes using chemical gels instead of chemical solutions, to avoid the well-known disadvantages of chemical decontamination techniques while retaining their high efficiency. Chemical gels decontamination process consists of applying the gel by spraying it onto the surface of large area components (floors, walls, etc) to be decontaminated. The gel adheres to any vertical or complex surface due to their thixotropic properties and operates by dissolving the radioactive deposit, along with a thin layer of the gel support, so that the radioactivity trapped at the surface can be removed. Important aspects of the gels are that small quantities can be used and they show thixitropic properties : liquid during spraying, and solid when stationary, allowing for strong adherence to surfaces. This work investigates the decontamination behaviors of organic-based chemical gel for SS 304 metallic surfaces contaminated with radioactive materials

Sol-Gel Manufactured Energetic Materials

Science.gov (United States)

Simpson, Randall L.; Lee, Ronald S.; Tillotson, Thomas M.; Hrubesh, Lawrence W.; Swansiger, Rosalind W.; Fox, Glenn A.

2005-05-17

Sol-gel chemistry is used for the preparation of energetic materials (explosives, propellants and pyrotechnics) with improved homogeneity, and/or which can be cast to near-net shape, and/or made into precision molding powders. The sol-gel method is a synthetic chemical process where reactive monomers are mixed into a solution, polymerization occurs leading to a highly cross-linked three dimensional solid network resulting in a gel. The energetic materials can be incorporated during the formation of the solution or during the gel stage of the process. The composition, pore, and primary particle sizes, gel time, surface areas, and density may be tailored and controlled by the solution chemistry. The gel is then dried using supercritical extraction to produce a highly porous low density aerogel or by controlled slow evaporation to produce a xerogel. Applying stress during the extraction phase can result in high density materials. Thus, the sol-gel method can be used for precision detonator explosive manufacturing as well as producing precision explosives, propellants, and pyrotechnics, along with high power composite energetic materials.

Thixotropic gel for vadose zone remediation

Science.gov (United States)

Rhia, Brian D [Augusta, GA

2011-03-01

A thixotropic gel suitable for use in subsurface bioremediation is provided along with a process of using the gel. The thixotropic gel provides a non-migrating injectable substrate that can provide below ground barrier properties. In addition, the gel components provide for a favorable environment in which certain contaminants are preferentially sequestered in the gel and subsequently remediated by either indigenous or introduced microorganisms.

Meso-Decorated Switching-Knot Gels

Science.gov (United States)

Gong, Jin; Sawamura, Kensuke; Makino, Masato; Kabir, M. H.; Furukawa, Hidemitsu

Gels are a new material having three-dimensional network structures of macromolecules. They possess excellent properties as swellability, high permeability and biocompatibility, and have been applied in various fields of daily life, food, medicine, architecture, and chemistry .In this study, we tried to prepare new multi-functional and high-strength gels by using Meso-Decoration (Meso-Deco), one new method of structure design at intermediate mesoscale. High-performance rigid-rod aromatic polymorphic crystals. The strengthening of gels can be realized by meso-decorating the gels' structure using high-performance polymorphic crystals. New gels with good mechanical properties, novel optical properties and thermal properties are expected to be developed.

Structure of mineral gels

International Nuclear Information System (INIS)

Miranda Salvado, I.M.; Margaca, F.M.A.; Teixeira, J.

1999-01-01

Small Angle Neutron Scattering (SANS) measurements have been performed to investigate the nanoscale structure of materials of the systems xTiO 2 -(1-x)SiO 2 and xZrO 2 -(1-x)SiO 2 with x ≤ 10 mol % at different processing stages. The materials were prepared by sol-gel using the alkoxides method, in strong acidic conditions. Samples were studied as xerogels heat-treated at 120 and 850 deg. C and as wet gels at gel point and after aging. All samples showed identical microstructure at gel point, extended linear chains ∼10 nm long. The aged gel has a mass fractal structure with fractal dimension of 1.7 - 1.9. The 120 deg. C heat-treated xerogels show homogeneous oxide regions with mass fractal structure. For the 850 deg. C heat-treated xerogel the oxide regions average size has reduced and it has densified as compared to 120 deg. C heat-treated sample. (author)

77 FR 19128 - Defense Federal Acquisition Regulation Supplement: Separation of Combined Provisions and Clauses...

Science.gov (United States)

2012-03-30

.... (2) Use the provision at 252.229-7013, Tax Exemptions (Spain)-- Representation, in solicitations that... (Spain)--representation. As prescribed in 229.402-70(e)(2), use the following clause: TAX EXEMPTIONS...)--Representation. 252.229-7005, Tax Exemptions (Spain)... 252.229-7013, Tax Exemptions (Spain)--Representation...

Cyanocobalamin Nasal Gel

Science.gov (United States)

... to supply extra vitamin B12 to people who need unusually large amounts of this vitamin because they are pregnant or have certain diseases. ... Cyanocobalamin nasal gel will supply you with enough vitamin B12 only as ... it regularly. You may need to use cyanocobalamin nasal gel every week for ...

Gels and gel-derived glasses in the system Na2O-B2O3-SiO2

Science.gov (United States)

Mukherjee, S. P.

1983-01-01

The containerless melting of high-purity multicomponent homogeneous gels and gel monoliths offers a unique approach to making ultrapure multicomponent optical glasses in the reduced gravity environment of space. Procedures for preparing and characterizing gels and gel-derived glasses in the system Na2O-B2O3-SiO2 are described. Preparation is based on the polymerization reactions of alkoxysilane with trimethyl borate or boric acid and a suitable sodium compound. The chemistry of the gelling process is discussed in terms of process parameters and the gel compositions. The physicochemical nature of gels prepared by three different procedures was found to be significantly different. Infrared absorption spectra indicate finite differences in the molecular structures of the different gels. The melting of the gel powders and the transformation of porous gel monoliths to transparent 'glass' without melting are described.

Gel properties and interactions of Mesona blumes polysaccharide-soy protein isolates mixed gel: The effect of salt addition.

Science.gov (United States)

Wang, Wenjie; Shen, Mingyue; Liu, Suchen; Jiang, Lian; Song, Qianqian; Xie, Jianhua

2018-07-15

Effect of different salt ions on the gel properties and microstructure of Mesona blumes polysaccharide (MBP)-soy protein isolates (SPI) mixed gels were investigated. Sodium and calcium ions were chosen to explore their effects on the rheological behavior and gel properties of MBP-SPI mixed gels were evaluated by using rheological, X-ray diffraction, protein solubility determination, and microstructure analysis. Results showed that the addition of salt ions change the crystalline state of gels system, the crystal of gel was enhanced at low ion concentrations (0.005-0.01 M). The two peaks of gel characteristic at 8.9° and 19.9° almost disappeared at high salt ions concentrations (0.015-0.02 M), and new crystallization peaks appeared at around 30° and 45°. The elasticity, viscosity, gel strength, water holding capacity, and thermal stability of gel were increased at low ion concentration. Results showed that the main interactions which promoted gel formation and maintain the three-dimensional structure of the gel were electrostatic interactions, hydrophobic interactions, and disulfide interactions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Study of nuclear glasses alteration gel and synthesis of some model gels

International Nuclear Information System (INIS)

Ricol, S.

1995-01-01

This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs

Dapsone gel 5% in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer for the treatment of acne vulgaris: a 12-week, randomized, double-blind study.

Science.gov (United States)

Fleischer, Alan B; Shalita, Alan; Eichenfield, Lawrence F; Abramovits, William; Lucky, Anne; Garrett, Steven

2010-01-01

To evaluate the safety and efficacy of dapsone gel 5% in the treatment of acne when used in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer. This was a twelve-week, randomized, double-blind study. Patients aged 12 years and older (n=301) applied dapsone gel twice daily and were randomly assigned (1:1:1) to one of three additional treatments, applied once daily. By week 12, dapsone gel combined with any of the three additional treatments reduced the mean number of inflammatory lesions. However, the authors did not detect a significant difference in the reduction of inflammatory lesions when dapsone was used in combination with adapalene gel or with benzoyl peroxide gel compared to the dapsone plus moisturizer combination group (P=0.052 for both versus moisturizer combination). Patients treated with dapsone gel combined with adapalene showed a significantly better response in reduction in non-inflammatory and total acne lesion count than those who received the moisturizer combination. Local adverse reactions in all three treatment groups were minimal and generally mild in severity. Dapsone gel in combination with adapalene gel or benzoyl peroxide gel is safe and well tolerated for the treatment of acne vulgaris.

Silver nitrate based gel dosimeter

International Nuclear Information System (INIS)

Titus, D; Samuel, E J J; Srinivasan, K; Roopan, S M; Madhu, C S

2017-01-01

A new radiochromic gel dosimeter based on silver nitrate and a normoxic gel dosimeter was investigated using UV-Visible spectrophotometry in the clinical dose range. Gamma radiation induced the synthesis of silver nanoparticles in the gel and is confirmed from the UV-Visible spectrum which shows an absorbance peak at around 450 nm. The dose response function of the dosimeter is found to be linear upto12Gy. In addition, the gel samples were found to be stable which were kept under refrigeration. (paper)

Lignosulfonic acid exhibits broadly anti-HIV-1 activity--potential as a microbicide candidate for the prevention of HIV-1 sexual transmission.

Directory of Open Access Journals (Sweden)

Min Qiu

Full Text Available Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV, herpes simplex virus (HSV, Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA, a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide.

Surface grafted chitosan gels. Part II. Gel formation and characterization

DEFF Research Database (Denmark)

Liu, Chao; Thormann, Esben; Claesson, Per M.

2014-01-01

Responsive biomaterial hydrogels attract significant attention due to their biocompatibility and degradability. In order to make chitosan based gels, we first graft one layer of chitosan to silica, and then build a chitosan/poly(acrylic acid) multilayer using the layer-by-layer approach. After...... cross-linking the chitosan present in the polyelectrolyte multilayer, poly(acrylic acid) is partly removed by exposing the multilayer structure to a concentrated carbonate buffer solution at a high pH, leaving a surface-grafted cross-linked gel. Chemical cross-linking enhances the gel stability against...... detachment and decomposition. The chemical reaction between gluteraldehyde, the cross-linking agent, and chitosan was followed in situ using total internal reflection Raman (TIRR) spectroscopy, which provided a molecular insight into the complex reaction mechanism, as well as the means to quantify the cross...

Rheology and structure of milk protein gels

NARCIS (Netherlands)

Vliet, van T.; Lakemond, C.M.M.; Visschers, R.W.

2004-01-01

Recent studies on gel formation and rheology of milk gels are reviewed. A distinction is made between gels formed by aggregated casein, gels of `pure` whey proteins and gels in which both casein and whey proteins contribute to their properties. For casein' whey protein mixtures, it has been shown

Are women who work in bars, guesthouses and similar facilities a suitable study population for vaginal microbicide trials in Africa?

Directory of Open Access Journals (Sweden)

Andrew Vallely

2010-05-01

Full Text Available A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials.1573 women aged 16-54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573. HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020. Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance.Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings.

Antimicrobial efficacy of alcohol-based hand gels.

Science.gov (United States)

Guilhermetti, M; Marques Wiirzler, L A; Castanheira Facio, B; da Silva Furlan, M; Campo Meschial, W; Bronharo Tognim, M C; Botelho Garcia, L; Luiz Cardoso, C

2010-03-01

In recent years, several commercial alcohol-based hand gels have appeared on the market to improve the hand-cleansing compliance of healthcare workers. Although the antimicrobial efficacy of these products has been reported in different countries, few studies have investigated this subject in Brazil. In this study, we assessed the antimicrobial efficacy of 12 alcohol-based hand gels produced in Brazil, containing 70% w/w or v/v ethyl alcohol as the active ingredient, according to the European Standard EN 1500 (EN 1500). The following alcohol gels were tested: Hand Gel, Voga Gel, Solumax Solugel, Doctor Clean, Rio Gel, Clear Gel, Sevengel, Hand CHC, Gel Bac, WBL-50 Gel, Sanigel and Soft Care Gel. In addition, 70% w/w ethyl alcohol and three alcohol-based hand rubs (Sterillium, Sterillium Gel, and Spitaderm), commonly used in Europe and effective according to EN 1500, were also tested. All the products tested, except for two, were approved by the EN 1500 test protocol with a 60s application. The results confirmed the antimicrobial efficacy of the majority of the alcohol gels produced in Brazil for hand hygiene of healthcare workers. Copyright 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Agarose gel electrophoresis and polyacrylamide gel electrophoresis for visualization of simple sequence repeats.

Science.gov (United States)

Anderson, James; Wright, Drew; Meksem, Khalid

2013-01-01

In the modern age of genetic research there is a constant search for ways to improve the efficiency of plant selection. The most recent technology that can result in a highly efficient means of selection and still be done at a low cost is through plant selection directed by simple sequence repeats (SSRs or microsatellites). The molecular markers are used to select for certain desirable plant traits without relying on ambiguous phenotypic data. The best way to detect these is the use of gel electrophoresis. Gel electrophoresis is a common technique in laboratory settings which is used to separate deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) by size. Loading DNA and RNA onto gels allows for visualization of the size of fragments through the separation of DNA and RNA fragments. This is achieved through the use of the charge in the particles. As the fragments separate, they form into distinct bands at set sizes. We describe the ability to visualize SSRs on slab gels of agarose and polyacrylamide gel electrophoresis.

Preparation of zirconium molybdate gel for 99mTc gel generator

International Nuclear Information System (INIS)

Aliludin, Z.; Ohkubo, Masatake; Kushita, Kouhei

1988-09-01

Zirconium molybdate gel has excellent characteristics for use as column matrix material of 99m Tc generators. In this work, zirconium molybdate gels were prepared under different conditions; pH's of molybdate solutions from 2.5 to 7.0, Mo:Zr molar ratios from 0.7:1.0 to 1.3:1.0, drying temperatures from an ambient temperature to 200 deg C, and drying times from 1 h to 25 h. Contents of water, nitrate, molybdenum and zirconium were measured to examine the fundamental conditions in gel preparation. The Mo:Zr molar ratio was 1.0:1.0 for the most of gels obtained. A 99m Tc generator was prepared with an amorphous zirconium molybdate containing a tracer level of 99 Mo as column matrix material. Elution of 99m Tc was rapid and the average elution efficiency was 90 % for 6 ml elutions. Contents of radionuclidic impurities, Zr and Mo in the eluates, were low enough to meet the pharmacopoeia requirements for human use. (author)

Ophthalmic gels: Past, present and future.

Science.gov (United States)

Al-Kinani, Ali A; Zidan, Ghada; Elsaid, Naba; Seyfoddin, Ali; Alani, Adam W G; Alany, Raid G

2018-02-15

Aqueous gels formulated using hydrophilic polymers (hydrogels) along with those based on stimuli responsive polymers (in situ gelling or gel forming systems) continue to attract increasing interest for various eye health-related applications. They allow the incorporation of a variety of ophthalmic pharmaceuticals to achieve therapeutic levels of drugs and bioactives at target ocular sites. The integration of sophisticated drug delivery technologies such as nanotechnology-based ones with intelligent and environment responsive systems can extend current treatment duration to provide more clinically relevant time courses (weeks and months instead of hours and days) which will inevitably reduce dose frequency, increase patient compliance and improve clinical outcomes. Novel applications and design of contact lenses and intracanalicular delivery devices along with the move towards integrating gels into various drug delivery devices like intraocular pumps, injections and implants has the potential to reduce comorbidities caused by glaucoma, corneal keratopathy, cataract, diabetic retinopathies and age-related macular degeneration. This review describes ophthalmic gelling systems with emphasis on mechanism of gel formation and application in ophthalmology. It provides a critical appraisal of the techniques and methods used in the characterization of ophthalmic preformed gels and in situ gelling systems along with a thorough insight into the safety and biocompatibility of these systems. Newly developed ophthalmic gels, hydrogels, preformed gels and in situ gelling systems including the latest in the area of stimuli responsive gels, molecularly imprinted gels, nanogels, 3D printed hydrogels; 3D printed devices comprising ophthalmic gels are covered. Finally, new applications of gels in the production of artificial corneas, corneal wound healing and hydrogel contact lenses are described. Copyright © 2017 Elsevier B.V. All rights reserved.

Gel electrophoresis of inorganic cations

International Nuclear Information System (INIS)

Schoenhofer, F.; Grass, F.

1978-01-01

In order to be able to separate the largest possible amounts of substance, polyacryl amide gel (PAA) and silica gel are used as carrier for the electrophoresis. Milligramme quantities can easily be separated on PAA gel plates. Electrophoretic ion focussing considerably improves it. Separations of Sr/Y and lanthanoids were carried out. The behaviour of the readily soluble complexing agent acids on silica gel thin layers was minutely investigated and an interpretation of the focussing effect was derived. The conditions for separating radionuclides were optimized. A further improved separation can be achieved by a time sequence combination of normal electrophoresis and ion focussing. Selective isolation methods are advantageous to determine radionuclide traces in environmental samples. The selective adsorption on preformed deposits was transferred to electrophoresis. After pre-investigations on silica gel layers, strontium and barium could also be retained on PAA gel and radium on strontium sulphate in PAA, whereas the disturbing calcium can easily pass through. Cesium can also be retained by prussian blue in the electrophoresis. (orig.) [de

Initial investigation of a novel light-scattering gel phantom for evaluation of optical CT scanners for radiotherapy gel dosimetry

International Nuclear Information System (INIS)

Bosi, Stephen; Naseri, Pourandokht; Puran, Alicia; Davies, Justin; Baldock, Clive

2007-01-01

There is a need for stable gel materials for phantoms used to validate optical computerized tomography (CT) scanners used in conjunction with radiation-induced polymerizing gel dosimeters. Phantoms based on addition of light-absorbing dyes to gelatine to simulate gel dosimeters have been employed. However, to more accurately simulate polymerizing gels one requires phantoms that employ light-scattering colloidal suspensions added to the gel. In this paper, we present the initial results of using an optical CT scanner to evaluate a novel phantom in which radiation-exposed polymer gels are simulated by the addition of colloidal suspensions of varying turbidity. The phantom may be useful as a calibration transfer standard for polymer gel dosimeters. The tests reveal some phenomena peculiar to light-scattering gels that need to be taken into account when calibrating polymer gel dosimeters

Sol-gel technology for biomedical engineering

International Nuclear Information System (INIS)

Podbielska, H.; Ulatowska-Jarza, A.

2005-01-01

Sol-gel derived silica possess many promising features, including low-temperature preparation procedure, porosity, chemical and physical stability. Applications exploiting porous materials to encapsulate sensor molecules, enzymes and many other compounds, are developing rapidly. In this paper some potential applications, with emphasis on biomedical and environmental ones, are reviewed. The material preparation procedure is described and practical remarks on silica-based sol-gels are included. It is reported that sol-gels with entrapped various molecules may be used in construction of implants and coatings with bioactive properties. It is shown how to exploit the sol-gel production route for construction of sol-gel coated fiberoptic applicators for laser therapy. The applications of bioactive materials are discussed, as well. It is demonstrated that it is possible to immobilize photosensitive compounds in sol-gel matrix without loosing their photoactivity. Some examples of sol-gel based biosensors are demonstrated, as well, showing their potential for detecting various gases, toxic substances, acidity, humidity, enzymes and biologically active agents. (authors)

Water equivalence of polymer gel dosimeters

International Nuclear Information System (INIS)

Sellakumar, P.; James Jebaseelan Samuel, E.; Supe, Sanjay S.

2007-01-01

To evaluate the water equivalence and radiation transport properties of polymer gel dosimeters over the wide range of photon and electron energies 14 different types of polymer gels were considered. Their water equivalence was evaluated in terms of effective atomic number (Z eff ), electron density (ρ e ), photon mass attenuation coefficient (μ/ρ), photon mass energy absorption coefficient (μ en /ρ) and total stopping power (S/ρ) tot of electrons using the XCOM and the ESTAR database. The study showed that the effective atomic number of polymer gels were very close ( en /ρ for all polymer gels were in close agreement ( tot of electrons in polymer gel dosimeters were within 1% agreement with that of water. From the study we conclude that at lower energy (<80keV) the polymer gel dosimeters cannot be considered water equivalent and study has to be carried out before using the polymer gel for clinical application

Formation of Cell-To-Cell Connection between Bone Marrow Cells and Isolated Rat Cardiomyocytes in a Cocultivation Model

Czech Academy of Sciences Publication Activity Database

Skopalík, J.; Pásek, Michal; Rychtárik, M.; Koristek, Z.; Gabrielová, E.; Sheer, P.; Matejovič, P.; Modrianský, M.; Klabusay, M.

2014-01-01

Roč. 5, č. 5 (2014), s. 1000185 ISSN 2157-7013 Institutional support: RVO:61388998 Keywords : bone marrow * mononuclear cells * isolated cardiomyocytes * cocultivation Subject RIV: BO - Biophysics http://omicsonline.org/ open - access /formation-of-celltocell-connection-between-bone-marrow-cells- and -isolated-rat-cardiomyocytes-2157-7013.1000185.php?aid=33364

Gel nano-particulates against radioactivity

International Nuclear Information System (INIS)

Deroin, Ph.

2004-01-01

The Argonne research center (USA) has developed a 'super-gel' compound, a polymer close to those used in baby's diapers, which can reach a 90% efficiency in the radioactive decontamination of porous materials, like bricks or concrete. The contaminated materials are sprayed with a mixture of polymer gel and wetting agent with nano-particulates in suspension. Under the action of the wetting agent, radioactivity migrates from the pores to the gel and is trapped by the nano-particulates. The drying and recycling of the gel allows to reduce the volume of radioactive wastes. Short paper. (J.S.)

Antibiotic-containing hyaluronic acid gel as an antibacterial carrier: Usefulness of sponge and film-formed HA gel in deep infection.

Science.gov (United States)

Matsuno, Hiroaki; Yudoh, Kazuo; Hashimoto, Masamichi; Himeda, Yasukazu; Miyoshi, Teruzo; Yoshida, Kaoru; Kano, Syogo

2006-03-01

We have developed a novel bioabsorbable antibacterial carrier using hyaluronic acid (HA) gel for prevention and treatment of orthopedic infections. In this study, we investigated the in vivo antibacterial effects of two forms of this new material, an HA gel sponge and an HA gel film. A titanium cylinder was inserted into the intramedullary cavity of each rabbit femur, along with an HA gel sponge or HA gel film containing antibiotics. The HA gel sponge contained gentamycin, vancomycin, tobramycin, or minomycin. The HA gel film contained gentamycin or vancomycin. After 0, 7, and 14 days, the rabbit bone marrow was collected, and the antibacterial activity of the HA gel was determined by agar diffusion test. As a control, we used Septocoll, a commercially available antibacterial carrier. Both the HA gel sponge and HA gel film exhibited antibacterial activity. The present results indicate that HA gel containing antibiotics is a clinically useful bioabsorbable antibacterial carrier. Copyright 2006 Orthopaedic Research Society.

Physical Properties of Silicone Gel Breast Implants.

Science.gov (United States)

Jewell, Mark L; Bengtson, Bradley P; Smither, Kate; Nuti, Gina; Perry, TracyAnn

2018-04-28

Surgical applications using breast implants are individualized operations to fill and shape the breast. Physical properties beyond shape, size, and surface texture are important considerations during implant selection. Compare form stability, gel material properties, and shell thickness of textured shaped, textured round, and smooth round breast implants from 4 manufacturers: Allergan, Mentor, Sientra, and Establishment Labs through bench testing. Using a mandrel height gauge, form stability was measured by retention of dimensions on device movement from a horizontal to vertical supported orientation. Dynamic response of gel material (gel cohesivity, resistance to gel deformation, energy absorption) was measured using a synchronized target laser following application of graded negative pressure. Shell thickness was measured using digital thickness gauge calipers. Form stability, gel material properties, and shell thickness differed across breast implants. Of textured shaped devices, Allergan Natrelle 410 exhibited greater form stability than Mentor MemoryShape and Sientra Shaped implants. Allergan Inspira round implants containing TruForm 3 gel had greater form stability, higher gel cohesivity, greater resistance to gel deformation, and lower energy absorption than those containing TruForm 2 gel and in turn, implants containing TruForm 1 gel. Shell thickness was greater for textured versus smooth devices, and differed across styles. Gel cohesivity, resistance to gel deformation, and energy absorption are directly related to form stability, which in turn determines shape retention. These characteristics provide information to aid surgeons choosing an implant based on surgical application, patient tissue characteristics, and desired outcome.

The Effect of Gel Microstructure on Simulated Gastric Digestion of Protein Gels

NARCIS (Netherlands)

Opazo-Navarrete, Mauricio; Altenburg, Marte D.; Boom, Remko M.; Janssen, Anja E.M.

2018-01-01

The objective of this study was to analyse the impact of the gel structure obtained by different heat-induced temperatures on the in vitro gastric digestibility at pH 2. To achieve this, gels were prepared from soy protein, pea protein, albumin from chicken egg white and whey protein isolate at

Gel polymer electrolytes for batteries

Science.gov (United States)

Balsara, Nitash Pervez; Eitouni, Hany Basam; Gur, Ilan; Singh, Mohit; Hudson, William

2014-11-18

Nanostructured gel polymer electrolytes that have both high ionic conductivity and high mechanical strength are disclosed. The electrolytes have at least two domains--one domain contains an ionically-conductive gel polymer and the other domain contains a rigid polymer that provides structure for the electrolyte. The domains are formed by block copolymers. The first block provides a polymer matrix that may or may not be conductive on by itself, but that can soak up a liquid electrolyte, thereby making a gel. An exemplary nanostructured gel polymer electrolyte has an ionic conductivity of at least 1.times.10.sup.-4 S cm.sup.-1 at 25.degree. C.

Using conjoint analysis to determine the impact of product and user characteristics on acceptability of rectal microbicides for HIV prevention among Peruvian men who have sex with men.

Science.gov (United States)

Tang, Eric C; Galea, Jerome T; Kinsler, Janni J; Gonzales, Pedro; Sobieszczyk, Magdalena E; Sanchez, Jorge; Lama, Javier R

2016-05-01

Men who have sex with men (MSM) are in need of novel and acceptable HIV prevention interventions. In Peru, a Phase II clinical trial was recently completed evaluating rectally applied tenofovir gel among Peruvian MSM and transgender women. If deemed safe and acceptable, the product could move into efficacy testing, but acceptability data for similar products are needed now in order to prepare for future implementation. Peru is in need of expanded, national acceptability data among likely users. Using conjoint analysis of an online cross-sectional survey taken by 1008 Peruvian MSM and transgender women, we tested the acceptability of eight hypothetical rectal microbicide (RM) products comprising six, dual-value attributes. We also assessed the relationship of select product attributes with sample characteristics. Highest acceptability was found for a RM that was 90% effective, used before and after sex, without side effects, costing approximately $0.30, had no prescription requirement and had a single-use applicator. Product effectiveness and presence of side effects were the factors most likely to drive RM acceptance and use. Education, sexual orientation, sexual role and concern for HIV infection were also related to aspects of RM acceptability. RM acceptability was high, confirming the results of earlier, smaller studies and placing confidence in the acceptability of RMs. Analysis of the relationships with product attributes and sample characteristics underscore the need to consider the impact of factors such as sexual orientation, sexual role, level of education and concern for HIV acquisition on RM acceptability. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Comparative study on the effects of negatively-charged biopolymers on chitosan-based gels for the development of instantaneous gels

International Nuclear Information System (INIS)

Jimeno, Austin Ed B.; Chakraborty, Soma

2015-01-01

Polymeric electrolytic complexes are solutions of charged/ionized chains. These solutions of positive and negative charge can be combined to make instantaneous networks bonded by electrostatic interactions, a gel network. These electrostatic interaction allows for easy application in injectable gels as the network can be temporarily distributed with the application of force and reformed on the relief of it. Possible applications for these injectable gels include drug delivery and wound-healing. κ-Carrageenan, dextran sulfate, alginate, and chitosan are polyelectrolytic biocompatible polymers which are widely studied and used for a variety of biomedical applications. Gel networks are made by combining a negatively-charged (κ-Carrageenan, dextran sulfate, or alginate) and positively charged (chitosan) solutions. The strong electrostatic interaction between the opposite charges from the gel network and the inherent biocompatibility of the polymers allow future biomedical applications. Quat 188-modified chitosan has additional sites for electrostatic bonding, can be dissolved in neutral, basic, and acidic pH, and has shown inherent antibacterial activity. The objectives of this study are the following: to formulate chitosan-based gels mixing solutions of chitosan with solutions of either κ-Carrageenan, dextran sulfate, or alginate, study the gelation of the gels as function of time and pH (4, 7, and 9) using UV-Vis, characterize the chitosan-based gels through DSC and DMA, characterize the physiological degradation of the chitosan-based gels, and compare results with those from Quat 188-modified chitosan-based gels. Polyelectrolytic solutions of chitosan and negatively-charged biopolymer of similar viscosities were mixed. It was determined from the UV-Vis spectroscopy of the chitosan-carrageenan gels under pH7 buffer that the increase of concentration by a factor of 5 for 0.006M-0.0095M and 1.25 for 0.0095M-0.0150M Chitosan-Carrageenan gels improved gelation by the

Research on pre-staining gel electrophoresis

International Nuclear Information System (INIS)

Zhong Ruibo; Liu Yushuang; Zhang Ping; Liu Jingran; Zhao Guofen; Zhang Feng

2014-01-01

Background: Gel electrophoresis is a powerful biochemical separation technique. Most biological molecules are completely transparent in the visible region of light, so it is necessary to use staining to show the results after gel electrophoresis, and the general steps of conventional staining methods are time-consuming. Purpose: We try to develop a novel approach to simplify the gel electrophoresis: Pre-Staining Gel Electrophoresis (PSGE), which can make the gel electrophoresis results monitored in real time. Methods: Pre-stain the protein samples with Coomassie Brilliant Blue (CBB) for 30 min before loading the sample into the gel well. Results and Conclusion: PSGE can be successfully used to analyze the binding efficiency of Bovine Serum Albumin (BSA) and amphiphilic polymer via chemical coupling and physical absorption, and the double PSGE also shows a great potential in bio-analytical chemistry. (authors)

Purification of Peptide Components including Melittin from Bee Venom using gel filtration chromatography and propionic acid/urea polyacrylamide gel electrophoresis

Directory of Open Access Journals (Sweden)

Young Chon Choi

2006-06-01

Full Text Available Objectives : This study was conducted to carry out Purification of Melittin and other peptide components from Bee Venom using gel filtration chromatography and propionic acid/urea polyacrylamide gel electrophoresis Methods : Melittin and other peptide components were separated from bee venom by using gel filtration chromatography on Sephadex G-50 column in 0.05M ammonium acetate buffer. Results : Melittin and other peptide components were separated from bee venom by using gel filtration chromatography on Sephadex G-50 column in 0.05M ammonium acetate buffer. The fractions obtained from gel filtration chromatography was analyzed by using SDS-PAGE and propionic acid/urea polyacrylamide gel electrophoresis. The melittin obtained from the gel filtration contained residual amount of phospholipase A2 and a protein with molecular weight of 6,000. The contaminating proteins were removed by the second gel filtration chromatography. Conclusion : Gel filtration chromatography and propionic acid/urea polyacrylamide gel electrophoresis are useful to separate peptide components including melittin from bee venom.

Encapsulation of nanoclusters in dried gel materials via an inverse micelle/sol gel synthesis

Science.gov (United States)

Martino, Anthony; Yamanaka, Stacey A.; Kawola, Jeffrey S.; Showalter, Steven K.; Loy, Douglas A.

1998-01-01

A dried gel material sterically entrapping nanoclusters of a catalytically active material and a process to make the material via an inverse micelle/sol-gel synthesis. A surfactant is mixed with an apolar solvent to form an inverse micelle solution. A salt of a catalytically active material, such as gold chloride, is added along with a silica gel precursor to the solution to form a mixture. To the mixture are then added a reducing agent for the purpose of reducing the gold in the gold chloride to atomic gold to form the nanoclusters and a condensing agent to form the gel which sterically entraps the nanoclusters. The nanoclusters are normally in the average size range of from 5-10 nm in diameter with a monodisperse size distribution.

Polymer gel dosimeter with AQUAJOINT® as hydrogel matrix

Science.gov (United States)

Maeyama, Takuya; Ishida, Yasuhiro; Kudo, Yoshihiro; Fukasaku, Kazuaki; Ishikawa, Kenichi L.; Fukunishi, Nobuhisa

2018-05-01

We report a polymer gel dosimeter based on a new gel matrix (AQUAJOINT®) that is a thermo-irreversible hydrogel formed by mixing two types of water-based liquids at room temperature. Normoxic N-vinylpyrrolidone-based polymer gels were prepared with AQUAJOINT® instead of gelatin. This AQUAJOINT®-based gel dosimeter exhibits a 2.5-fold increase in sensitivity over a gelatin-based gel dosimeter and a linear dose-response in the dose range of 0-8 Gy. This gel has heat resistance in a jar and controlled gel properties such as viscoelastic and mechanical characters, which may be useful for deformable polymer gel dosimetry.

Nanocrystal/sol-gel nanocomposites

Science.gov (United States)

Petruska, Melissa A [Los Alamos, NM; Klimov, Victor L [Los Alamos, NM

2007-06-05

The present invention is directed to solid composites including colloidal nanocrystals within a sol-gel host or matrix and to processes of forming such solid composites. The present invention is further directed to alcohol soluble colloidal nanocrystals useful in formation of sol-gel based solid composites.

A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine.

Science.gov (United States)

Major, Ian; Boyd, Peter; Kilbourne-Brook, Maggie; Saxon, Gene; Cohen, Jessica; Malcolm, R Karl

2013-07-01

There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine. Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices. A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm. The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison effect of azithromycin gel 2% with clindamycin gel 1% in patients with acne

Directory of Open Access Journals (Sweden)

Fatemeh Mokhtari

2016-01-01

Conclusion: Azithromycin gel has medical impact at least similar to Clindamycin Gel in treatment of mild to moderate acne vulgaris, and it may be consider as suitable drug for resistant acne to conventional topical therapy.

Sol-gel synthesis of hydroxyapatite; Sintese de hidroxiapatita via sol-gel

Energy Technology Data Exchange (ETDEWEB)

Zupanski, M.D.; Lucena, M.P.P.; Bergmann, C.P., E-mail: michelledunin@yahoo.com.b [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil)

2010-07-01

Hydroxyapatite (HAp) has been established as the calcium phosphate based compound with most applications in the biological field. Among the numerous techniques for synthesis of HAp, the sol-gel processing route affords great control over purity and formed phases using low processing temperatures. In addition, the sol-gel approach offers an option for homogeneous HAp coating on metal substrates, as well as the ability to generate nanocrystalline powders. In this work, the sol-gel synthesis of HAp was investigated employing triethyl phosphate and calcium nitrate tetrahydrate as phosphorous and calcium precursors, respectively. The aging effect on phase composition and powder morphology of the final product was studied in terms of temperature and aging time. The powders were studied by using X-ray diffraction, Fourier transform infrared spectroscopy, particle size distribution by laser diffraction and scanning electron microscopy. (author)

K-Basin gel formation studies

International Nuclear Information System (INIS)

Beck, M.A.

1998-01-01

A key part of the proposed waste treatment for K Basin sludge is the elimination of reactive uranium metal by dissolution in nitric acid (Fkirnent, 1998). It has been found (Delegard, 1998a) that upon nitric acid dissolution of the sludge, a gel sometimes forms. Gels are known to sometimes impair solid/liquid separation and/or material transfer. The purpose of the work reported here is to determine the cause(s) of the gel formation and to determine operating parameters for the sludge dissolution that avoid formation of gel. This work and related work were planned in (Fkunent, 1998), (Jewett, 1998) and (Beck, 1998a). This report describes the results of the tests in (Beck, 1998a) with non-radioactive surrogates

Rubber-like poly(vinyl alcohol) gel

Energy Technology Data Exchange (ETDEWEB)

Nambu, Masao (Nippon Oil Co. Ltd., Yokohama (Japan). Central Technical Research Lab.)

1990-09-01

Anomalous poly (vinyl alcohol) gel has been found in our laboratory since 1980. The gel is prepared by repeated freezing (or freeze-dehydration) of aqueous poly (vinyl alcohol). Experiments establish the fact that anomalous gel is never produced in the course of freezing, but during sustained thawing the gelation does occur. Moreover, it was found that the softening point of the gel increases at 37degC. It is assumed that crystal nuclei are generated on freezing, then on thawing, some of them grow to very fine crystals which act as polymer network-knots (cross-linking). Additional freezing provide other seeds, which grow similarly, and these are accumulated until rubber-like gel is produced. The gel was always water-resistant at 37degC, and the potassium permanganate consumption of the extracted water layer remained far below the official restricted value for medical materials. The gel can be sterilized with gamma-rays or chlorhexidine. Moreover, it satisfies the official standards of acute toxicity, pyrogen, intracutaneous reaction, hemolyzation, and intracorporeal implantation, respectively. Applications to adhesion-preventing membrane (for joint or pericardium), tamponade (for jaw defects), electrode (for electroretinogram or artificial inner ear), artificial denture base and phantoms for magnetic resonance imaging were examined. (author) 54 refs.

Physical and chemical properties of gels. Application to protein nucleation control in the gel acupuncture technique

Science.gov (United States)

Moreno, Abel; Juárez-Martínez, Gabriela; Hernández-Pérez, Tomás; Batina, Nikola; Mundo, Manuel; McPherson, Alexander

1999-09-01

In this work, we present a new approach using analytical and optical techniques in order to determine the physical and chemical properties of silica gel, as well as the measurement of the pore size in the network of the gel by scanning electron microscopy. The gel acupuncture technique developed by García-Ruiz et al. (Mater. Res. Bull 28 (1993) 541) García-Ruiz and Moreno (Acta Crystallogr. D 50 (1994) 484) was used throughout the history of crystal growth. Several experiments were done in order to evaluate the nucleation control of model proteins (thaumatin I from Thaumatococcus daniellii, lysozyme from hen egg white and catalase from bovine liver) by the porous network of the gel. Finally, it is shown how the number and the size of the crystals obtained inside X-ray capillaries is controlled by the size of the porous structure of the gel.

Basic investigations on LCV micelle gel

International Nuclear Information System (INIS)

Ebenezer, S B; Rafic, M K; Ravindran, P B

2013-01-01

The aim of this study was to investigate the feasibility of using Leuco Crystal Violet (LCV) based micelle gel dosimeter as a quality assurance tool in radiotherapy applications. Basic properties such as absorption coefficient and diffusion of LCV gel phantom over time were evaluated. The gel formulation consisted of 25 mM Trichloroacetic acid, 1mM LCV, 4 mM Triton X-100, 4% gelatin by mass and distilled water. The advantages of using this gel are its tissue equivalence, easy and less preparation time, lower diffusion rate and it can be read with an optical scanner. We were able to reproduce some of the results of Babic et al. The peak absorption was found to be at 600 nm and hence a matrix of yellow LEDs was used as light source. The profiles obtained from projection images confirmed the diffusion of LCV gel after 6 hours of irradiation. Hence the LCV gel phantom should be read before 6 hours post irradiation to get accurate dose information as suggested previously.

Cells on Gels: Cell Behavior at the Air-Gel Interface

Science.gov (United States)

O'Bryan, Christopher; Hormel, Tristan; Bhattacharjee, Tapomoy; Sawyer, W.; Angelini, Thomas

Numerous different types of cells are often grown at air-liquid interfaces. For example, a common way to create cell spheroids is to disperse cells in a droplet of liquid media that hangs from the lid of a culture dish - the ``hanging drop'' method. Some types of epithelial cells form monolayers at the bottom of hanging drops, instead of spheroids. Corneal epithelial cells stratify and exhibit a tissue-like phenotype when attached to liquid permeable culture surfaces positioned at the air-liquid media interface (air-lifted culture). These widely used culture methods make experimentation challenging - imaging through hanging drops and air-lifted culture dishes is prohibitive. However, similar results may be achieved by culturing cells on hydrogel surfaces at the air-gel interface. In this talk we will describe a method for culturing cells at air-gel interfaces. We seed human corneal epithelial cells (hTCEpi) onto the surfaces of hydrogel networks and jammed microgels, exposed to air. Preliminary observations of cell behavior at the air-gel interface will be presented.

Synthesis and application of silica gel modified with alkoxyalcohols. Alkoxyalcohol shushoku silica gel no gosei to riyo

Energy Technology Data Exchange (ETDEWEB)

Moriguchi, T.; Ishiguro, H.; Matsubara, Y.; Yoshihara, M.; Maeshima, T.; Ito, S. (Kinki University, Osaka (Japan). Faculty of Science and Engineering)

1991-08-20

Several kinds of silica gel modified by alkoxyalcohols were synthesized by refluxing and dehyration and the organic reactions were studied when these silica gels were used as the catalyst. It could be confirmed by FT-IR spectra, DTA and elementary analysis that alkoxylalcohols adhere to the surface of silica gels without any decomposition. The acetate was produced by using alkyl halides. It was found that the modified silica gels had clearly the catalytic action for the reaction with n-hexyl bromide and dibromoethane although unmodified silica gels did not show the catalytic action. The reducing reaction of carbonyl compounds was carried out. The reaction proceeded at 25 centigrade for acetophenone, cyclohexanone, 1-indanone and 2-octanone to produce the corresponding reduction products. 11 refs., 5 figs., 4 tabs.

Integration of gel-based and gel-free proteomic data for functional analysis of proteins through Soybean Proteome Database

KAUST Repository

Komatsu, Setsuko

2017-05-10

The Soybean Proteome Database (SPD) stores data on soybean proteins obtained with gel-based and gel-free proteomic techniques. The database was constructed to provide information on proteins for functional analyses. The majority of the data is focused on soybean (Glycine max ‘Enrei’). The growth and yield of soybean are strongly affected by environmental stresses such as flooding. The database was originally constructed using data on soybean proteins separated by two-dimensional polyacrylamide gel electrophoresis, which is a gel-based proteomic technique. Since 2015, the database has been expanded to incorporate data obtained by label-free mass spectrometry-based quantitative proteomics, which is a gel-free proteomic technique. Here, the portions of the database consisting of gel-free proteomic data are described. The gel-free proteomic database contains 39,212 proteins identified in 63 sample sets, such as temporal and organ-specific samples of soybean plants grown under flooding stress or non-stressed conditions. In addition, data on organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored. Furthermore, the database integrates multiple omics data such as genomics, transcriptomics, metabolomics, and proteomics. The SPD database is accessible at http://proteome.dc.affrc.go.jp/Soybean/. Biological significanceThe Soybean Proteome Database stores data obtained from both gel-based and gel-free proteomic techniques. The gel-free proteomic database comprises 39,212 proteins identified in 63 sample sets, such as different organs of soybean plants grown under flooding stress or non-stressed conditions in a time-dependent manner. In addition, organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored in the gel-free proteomics database. A total of 44,704 proteins, including 5490 proteins identified using a gel-based proteomic technique, are stored in the SPD. It accounts for approximately 80% of all

Integration of gel-based and gel-free proteomic data for functional analysis of proteins through Soybean Proteome Database.

Science.gov (United States)

Komatsu, Setsuko; Wang, Xin; Yin, Xiaojian; Nanjo, Yohei; Ohyanagi, Hajime; Sakata, Katsumi

2017-06-23

The Soybean Proteome Database (SPD) stores data on soybean proteins obtained with gel-based and gel-free proteomic techniques. The database was constructed to provide information on proteins for functional analyses. The majority of the data is focused on soybean (Glycine max 'Enrei'). The growth and yield of soybean are strongly affected by environmental stresses such as flooding. The database was originally constructed using data on soybean proteins separated by two-dimensional polyacrylamide gel electrophoresis, which is a gel-based proteomic technique. Since 2015, the database has been expanded to incorporate data obtained by label-free mass spectrometry-based quantitative proteomics, which is a gel-free proteomic technique. Here, the portions of the database consisting of gel-free proteomic data are described. The gel-free proteomic database contains 39,212 proteins identified in 63 sample sets, such as temporal and organ-specific samples of soybean plants grown under flooding stress or non-stressed conditions. In addition, data on organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored. Furthermore, the database integrates multiple omics data such as genomics, transcriptomics, metabolomics, and proteomics. The SPD database is accessible at http://proteome.dc.affrc.go.jp/Soybean/. The Soybean Proteome Database stores data obtained from both gel-based and gel-free proteomic techniques. The gel-free proteomic database comprises 39,212 proteins identified in 63 sample sets, such as different organs of soybean plants grown under flooding stress or non-stressed conditions in a time-dependent manner. In addition, organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored in the gel-free proteomics database. A total of 44,704 proteins, including 5490 proteins identified using a gel-based proteomic technique, are stored in the SPD. It accounts for approximately 80% of all predicted proteins from

Integration of gel-based and gel-free proteomic data for functional analysis of proteins through Soybean Proteome Database

KAUST Repository

Komatsu, Setsuko; Wang, Xin; Yin, Xiaojian; Nanjo, Yohei; Ohyanagi, Hajime; Sakata, Katsumi

2017-01-01

The Soybean Proteome Database (SPD) stores data on soybean proteins obtained with gel-based and gel-free proteomic techniques. The database was constructed to provide information on proteins for functional analyses. The majority of the data is focused on soybean (Glycine max ‘Enrei’). The growth and yield of soybean are strongly affected by environmental stresses such as flooding. The database was originally constructed using data on soybean proteins separated by two-dimensional polyacrylamide gel electrophoresis, which is a gel-based proteomic technique. Since 2015, the database has been expanded to incorporate data obtained by label-free mass spectrometry-based quantitative proteomics, which is a gel-free proteomic technique. Here, the portions of the database consisting of gel-free proteomic data are described. The gel-free proteomic database contains 39,212 proteins identified in 63 sample sets, such as temporal and organ-specific samples of soybean plants grown under flooding stress or non-stressed conditions. In addition, data on organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored. Furthermore, the database integrates multiple omics data such as genomics, transcriptomics, metabolomics, and proteomics. The SPD database is accessible at http://proteome.dc.affrc.go.jp/Soybean/. Biological significanceThe Soybean Proteome Database stores data obtained from both gel-based and gel-free proteomic techniques. The gel-free proteomic database comprises 39,212 proteins identified in 63 sample sets, such as different organs of soybean plants grown under flooding stress or non-stressed conditions in a time-dependent manner. In addition, organellar proteins identified in mitochondria, nuclei, and endoplasmic reticulum are stored in the gel-free proteomics database. A total of 44,704 proteins, including 5490 proteins identified using a gel-based proteomic technique, are stored in the SPD. It accounts for approximately 80% of all

Sol-gel processing to form doped sol-gel monoliths inside hollow core optical fiber and sol-gel core fiber devices made thereby

Science.gov (United States)

Shaw, Harry C. (Inventor); Ott, Melanie N. (Inventor); Manuel, Michele V. (Inventor)

2002-01-01

A process of fabricating a fiber device includes providing a hollow core fiber, and forming a sol-gel material inside the hollow core fiber. The hollow core fiber is preferably an optical fiber, and the sol-gel material is doped with a dopant. Devices made in this manner includes a wide variety of sensors.

Sol-gel additive for systems with inorganic binders

International Nuclear Information System (INIS)

Akstinat, M.; Antenen, D.; Suter, W.

1996-01-01

A sol-gel additive for inorganic binder systems and sol-gel process for producing air-placed concrete and mortar by using such sol-gel additives are disclosed. Sol-gel additives for gel-derived inorganic binder systems (for example plaster, cement, lime, special slags, etc.) marked improve the consistency of such binder systems during processing or allow their consistency to be regulated. In addition, these sol-gel additives regulate setting times and substantially improve durability (chemical resistance, reduced permeability) and the mechanical properties of the set binder system. (author)

Sol-gel bonding of silicon wafers

International Nuclear Information System (INIS)

Barbe, C.J.; Cassidy, D.J.; Triani, G.; Latella, B.A.; Mitchell, D.R.G.; Finnie, K.S.; Short, K.; Bartlett, J.R.; Woolfrey, J.L.; Collins, G.A.

2005-01-01

Sol-gel bonds have been produced between smooth, clean silicon substrates by spin-coating solutions containing partially hydrolysed silicon alkoxides. The two coated substrates were assembled and the resulting sandwich fired at temperatures ranging from 60 to 600 deg. C. The sol-gel coatings were characterised using attenuated total reflectance Fourier transform infrared spectroscopy, ellipsometry, and atomic force microscopy, while the corresponding bonded specimens were investigated using scanning electron microscopy and cross-sectional transmission electron microscopy. Mechanical properties were characterised using both microindentation and tensile testing. Bonding of silicon wafers has been successfully achieved at temperatures as low as 60 deg. C. At 300 deg. C, the interfacial fracture energy was 1.55 J/m 2 . At 600 deg. C, sol-gel bonding provided superior interfacial fracture energy over classical hydrophilic bonding (3.4 J/m 2 vs. 1.5 J/m 2 ). The increase in the interfacial fracture energy is related to the increase in film density due to the sintering of the sol-gel interface with increasing temperature. The superior interfacial fracture energy obtained by sol-gel bonding at low temperature is due to the formation of an interfacial layer, which chemically bonds the two sol-gel coatings on each wafer. Application of a tensile stress on the resulting bond leads to fracture of the samples at the silicon/sol-gel interface

Influence of Uranium and Polivinyl Alcohol Concentration in the Feed of Sol Gel Process on the Gel Spherical Product

International Nuclear Information System (INIS)

Indra Suryawan; Endang Susiantini

2007-01-01

The gel particles have been made at various uranium and polyvinyl alcohol concentration in the sol gel process. The variables of uranium concentration were 0.3; 0.5; 0.7; 0.9; 1.1; 1.3; 1.5; 1.7; 1.9 and 2.1 M The variables of polyvinyl alcohol concentration were 0.3; 0.6; 0.9; 1.2; 1.5; 1.8; 2.1 and 2.4 M After drying the sol gel process products were heated at 300, 500 and 750°C during 4 hours. The gel particles were characterized using an optic microscope to know the shape and condition morphology of gel. From experimental result using uranium concentration of 0.3 until 2.1 M and polyvinyl alcohol of 1.8 until 2.4 M spherical and gel was formed elastic, after heating at 750°C it was unbreakable. At the concentration of polyvinyl alcohol from 0.3 to 0.5 M, the gel product was soft and broken after being dried. At the concentration of polyvinyl alcohol from 0.6 to 0.8 M, the dried gel product was not perfect. At the concentration of polyvinyl alcohol from 0.9 to 1.7 M, the gel product of gelation process was spherical and it was broken after being heated up to 300°C. (author)

Yield stress determination of a physical gel

DEFF Research Database (Denmark)

Hvidt, Søren

2013-01-01

Pluronic F127 solutions form gels in water with high elastic moduli. Pluronic gels can, however, only withstand small deformations and stresses. Different steady shear and oscillatory methods traditionally used to determine yield stress values are compared. The results show that the yield stresses...... values of these gels depend on test type and measurement time, and no absolute yield stress value can be determined for these physical gels....

Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series.

Science.gov (United States)

Becker, David; Wain, Lisa M; Chong, Yih Harng; Gosai, Sonal J; Henderson, Nina K; Milburn, Jacqui; Stott, Victoria; Wheeler, Benjamin J

2016-02-01

X-linked partial androgen insensitivity syndrome (PAIS) causes under-virilization at all stages of development. In two thirds of males, this results in micropenis. Dihydrotestosterone (DHT) is a potent androgen that is critical for male genital development, which when applied topically, has been shown to increase penile length with micropenis of varying etiologies. We present the first case series using topical DHT gel to treat micropenis in 46,XY males with PAIS, before, during, and after puberty. Three related 46,XY males with confirmed p.L712F androgen receptor mutations exhibited varying degrees of micropenis post-surgical correction. They were of pre-pubertal, peri-pubertal and adult ages, respectively. Following baseline clinical and laboratory assessments all completed a 4-month course of daily DHT gel 2.5% (androstanolone) topically to penis (0.3 mg/kg body weight), with monitoring for adverse effects. Primary outcome was change in stretched penile length (SPL) following treatment. Mixed results were obtained following topical DHT therapy. In the pre- and peri- pubertal patients, SPL changed from 2.5 cm to 3.5 cm (+40%), and 3.5 cm to 5.7 cm (+63%), respectively. In the adult patient with 1 year of prior high-dose weekly testosterone therapy, no additional change in SPL was seen. No adverse effects of topical DHT were reported or observed throughout the 4 months of treatment. Topical DHT treatment appears to be a safe and well-tolerated method of virilising micropenis both prior to and during puberty in children with PAIS. Questions remain about long-term outcomes into adulthood, and efficacy in adults with prior lengthy exposure to high-dose testosterone.

Modification of gel architecture and TBE/TAE buffer composition to minimize heating during agarose gel electrophoresis.

Science.gov (United States)

Sanderson, Brian A; Araki, Naoko; Lilley, Jennifer L; Guerrero, Gilberto; Lewis, L Kevin

2014-06-01

Agarose gel electrophoresis of DNA and RNA is routinely performed using buffers containing either Tris, acetate, and EDTA (TAE) or Tris, borate, and EDTA (TBE). Gels are run at a low, constant voltage (∼10 V/cm) to minimize current and asymmetric heating effects, which can induce band artifacts and poor resolution. In this study, alterations of gel structure and conductive media composition were analyzed to identify factors causing higher electrical currents during horizontal slab gel electrophoresis. Current was reduced when thinner gels and smaller chamber buffer volumes were used, but was not influenced by agarose concentration or the presence of ethidium bromide. Current was strongly dependent on the amount and type of EDTA used and on the concentrations of the major acid-base components of each buffer. Interestingly, resolution and the mobilities of circular versus linear plasmid DNAs were also affected by the chemical form and amount of EDTA. With appropriate modifications to gel structure and buffer constituents, electrophoresis could be performed at high voltages (20-25 V/cm), reducing run times by up to 3-fold. The most striking improvements were observed with small DNAs and RNAs (10-100 bp): high voltages and short run times produced sharper bands and higher resolution. Copyright © 2014 Elsevier Inc. All rights reserved.

Ionic liquid based multifunctional double network gel

Science.gov (United States)

Ahmed, Kumkum; Higashihara, Tomoya; Arafune, Hiroyuki; Kamijo, Toshio; Morinaga, Takashi; Sato, Takaya; Furukawa, Hidemitsu

2015-04-01

Gels are a promising class of soft and wet materials with diverse application in tissue engineering and bio-medical purpose. In order to accelerate the development of gels, it is required to synthesize multi-functional gels of high mechanical strength, ultra low surface friction and suitable elastic modulus with a variety of methods and new materials. Among many types of gel ionic gel made from ionic liquids (ILs) could be used for diverse applications in electrochemical devices and in the field of tribology. IL, a promising materials for lubrication, is a salt with a melting point lower than 100 °C. As a lubricant, ILs are characterized by an extremely low vapor pressure, high thermal stability and high ion conductivity. In this work a novel approach of making double network DN ionic gel using IL has been made utilizing photo polymerization process. A hydrophobic monomer Methyl methacrylate (MMA) has been used as a first network and a hydrophobic IL monomer, N,N-diethyl-N-(2-mthacryloylethyl)-N-methylammonium bistrifluoromethylsulfonyl)imide (DEMM-TFSI) has been used as a second network using photo initiator benzophenon and crosslinker triethylene glycol dimethacrylate (TEGDMA). The resulting DN ionic gel shows transparency, flexibility, high thermal stability, good mechanical toughness and low friction coefficient value which can be a potential candidate as a gel slider in different mechanical devices and can open a new area in the field of gel tribology.

Gels and gel-derived glasses in the Na2O-B2O3-SiO2 system. [containerless melting in space

Science.gov (United States)

Mukherjee, S. P.

1982-01-01

The containerless melting of high-purity multicomponent homogeneous gels and gel-monoliths offers a unique approach to making ultrapure multicomponent optical glasses in the reduced gravity environment of space. Procedures for preparing and characterizing gels and gel-derived glasses in the Na2O-B2O3-SiO2 system are described. Preparation is based on the polymerization reactions of alkoxysilane with trimethyl borate or boric acid and a suitable sodium compound. The chemistry of the gelling process is discussed in terms of process parameters and the gel compositions. The physicochemical nature of gels prepared by three different procedures were found to be significantly different. IR absorption spectra indicate finite differences in the molecular structures of the different gels. The melting of the gel powders and the transformation of porous gel-monoliths to transparent 'glass' without melting are described.

Improving calibration accuracy in gel dosimetry

International Nuclear Information System (INIS)

Oldham, M.; McJury, M.; Webb, S.; Baustert, I.B.; Leach, M.O.

1998-01-01

A new method of calibrating gel dosimeters (applicable to both Fricke and polyacrylamide gels) is presented which has intrinsically higher accuracy than current methods, and requires less gel. Two test-tubes of gel (inner diameter 2.5 cm, length 20 cm) are irradiated separately with a 10x10cm 2 field end-on in a water bath, such that the characteristic depth-dose curve is recorded in the gel. The calibration is then determined by fitting the depth-dose measured in water, against the measured change in relaxivity with depth in the gel. Increased accuracy is achieved in this simple depth-dose geometry by averaging the relaxivity at each depth. A large number of calibration data points, each with relatively high accuracy, are obtained. Calibration data over the full range of dose (1.6-10 Gy) is obtained by irradiating one test-tube to 10 Gy at dose maximum (D max ), and the other to 4.5 Gy at D max . The new calibration method is compared with a 'standard method' where five identical test-tubes of gel were irradiated to different known doses between 2 and 10 Gy. The percentage uncertainties in the slope and intercept of the calibration fit are found to be lower with the new method by a factor of about 4 and 10 respectively, when compared with the standard method and with published values. The gel was found to respond linearly within the error bars up to doses of 7 Gy, with a slope of 0.233±0.001 s -1 Gy -1 and an intercept of 1.106±0.005 Gy. For higher doses, nonlinear behaviour was observed. (author)

Structural studies of gels and gel-glasses in the SiO2-GeO2 system using vibrational spectroscopy

Science.gov (United States)

Mukherjee, Shyama P.; Sharma, Shiv K.

1986-01-01

GeO2 gel and gels in the SiO2-GeO2 system synthesized by the hydrolytic polycondensation of metal alkoxides have been studied by infrared and Raman spectroscopic techniques. The molecular structures, hydroxyl contents, and crystallinity of gels and gel-glasses in relation to the thermal history and GeO2 concentration were investigated. The binary compositions having up to 70 mol percent GeO2 were examined.

NMR mechanisms in gel dosimetry

International Nuclear Information System (INIS)

Schreiner, L J

2009-01-01

Nuclear magnetic resonance was critical to the development of gel dosimetry, as it established the potential for three dimensional dosimetry with chemical dosimeter systems through magnetic resonance imaging [1]. In the last two decades MRI has served as the gold standard for imaging, while NMR relaxometry has played an important role in the development and understanding of the behaviour of new gel dosimetry systems. Therefore, an appreciation of the relaxation mechanisms determining the NMR behaviour of irradiated gel dosimeters is important for a full comprehension of a considerable component of the literature on gel dosimetry. A number of excellent papers have presented this important theory, this brief review will highlight some of the salient points made previously [1-5]. The spin relaxation of gel dosimeters (which determines the dose dependence in most conventional MR imaging) is determined principally by the protons on water molecules in the system. These water protons exist in different environments, or groups (see Figure 1): on bulk water, on water hydrating the chemical species that are being modified under irradiation, and on water hydrating the gel matrix used to spatially stabilize the dosimeter (e.g., gelatin, agarose, etc). The spin relaxation depends on the inherent relaxation rate of each spin group, that is, on the relaxation rate which would be observed for the specific group if it were isolated. Also, the different water environments are not isolated from each other, and the observed relaxation rate also depends on the rate of exchange of magnetization between the groups, and on the fraction of protons in each group. In fact, the water exchanges quickly between the environments, so that relaxation is in what is usually termed the fast exchange regime. In the limit of fast exchange, the relaxation of the water protons is well characterized by a single exponential and hence by a single apparent relaxation rate. In irradiated gel dosimeters this

Conducting polymer electrodes for gel electrophoresis.

Directory of Open Access Journals (Sweden)

Katarina Bengtsson

Full Text Available In nearly all cases, electrophoresis in gels is driven via the electrolysis of water at the electrodes, where the process consumes water and produces electrochemical by-products. We have previously demonstrated that π-conjugated polymers such as poly(3,4-ethylenedioxythiophene (PEDOT can be placed between traditional metal electrodes and an electrolyte to mitigate electrolysis in liquid (capillary electroosmosis/electrophoresis systems. In this report, we extend our previous result to gel electrophoresis, and show that electrodes containing PEDOT can be used with a commercial polyacrylamide gel electrophoresis system with minimal impact to the resulting gel image or the ionic transport measured during a separation.

Conducting polymer electrodes for gel electrophoresis.

Science.gov (United States)

Bengtsson, Katarina; Nilsson, Sara; Robinson, Nathaniel D

2014-01-01

In nearly all cases, electrophoresis in gels is driven via the electrolysis of water at the electrodes, where the process consumes water and produces electrochemical by-products. We have previously demonstrated that π-conjugated polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) can be placed between traditional metal electrodes and an electrolyte to mitigate electrolysis in liquid (capillary electroosmosis/electrophoresis) systems. In this report, we extend our previous result to gel electrophoresis, and show that electrodes containing PEDOT can be used with a commercial polyacrylamide gel electrophoresis system with minimal impact to the resulting gel image or the ionic transport measured during a separation.

Sol-gel process for thermal reactor fuel fabrication

International Nuclear Information System (INIS)

Mukerjee, S.K.

2008-01-01

Full text: Sol-gel processes have revolutionized conventional ceramic technology by providing extremely fine and uniform powders for the fabrication of ceramics. The use of this technology for nuclear fuel fabrication has also been explored in many countries. Unlike the conventional sol-gel process, sol-gel process for nuclear fuels tries to eliminate the preparation of powders in view of the toxic nature of the powders particularly those of plutonium and 233 U. The elimination of powder handling thus makes this process more readily amenable for use in glove boxes or for remote handling. In this process, the first step is the preparation of microspheres of the fuel material from a solution which is then followed by vibro-compaction of these microspheres of different sizes to obtain the required smear density of fuel inside a pin. The maximum achievable packing density of 92 % makes it suitable for fast reactors only. With a view to extend the applicability of sol-gel process for thermal reactor fuel fabrication the concept of converting the gel microspheres derived from sol-gel process, to the pellets, has been under investigation for several years. The unique feature of this process is that it combines the advantages of sol-gel process for the preparation of fuel oxide gel microspheres of reproducible quality with proven irradiation behavior of the pellet fuel. One of the important pre-requisite for the success of this process is the preparation of soft oxide gel microspheres suitable for conversion to dense pellets free from berry structure. Studies on the internal gelation process, one of the many variants of sol-gel process, for obtaining soft oxide gel microspheres suitable for gel pelletisation is now under investigation at BARC. Some of the recent findings related to Sol-Gel Microsphere Pelletisation (SGMP) in urania-plutonia and thoria-urania systems will be presented

Stabilized aqueous gels and uses thereof

Energy Technology Data Exchange (ETDEWEB)

Swanson, B.L.

1978-08-29

New improved aqueous gels, and methods of using same in contacting subterranean formations, are provided. The gels are prepared by gelling an aqueous brine having incorporated therein a water-soluble cellulose ether such as a carboxymethylcellulose (CMC), and are rendered more stable to decomposition by incorporating a sulfoalkylated tannin stabilizing agent, such as a sulfomethylated quebracho (SMQ), in the gel during the preparation thereof.

Influence of colloidal silicon dioxide on gel strength, robustness, and adhesive properties of diclofenac gel formulation for topical application.

Science.gov (United States)

Lu, Zheng; Fassihi, Reza

2015-06-01

The objective of this study is to identify the extent of stiffness, adhesiveness, and thixotropic character of a three-dimensional gel network of a 1% diclofenac sodium topical gel formulation in the presence and absence of colloidal silicon dioxide (CSD) and assess its ease of application and adhesiveness using both objective and subjective analysis. The 1% diclofenac gel was mixed with different amounts of CSD (e.g., 0.5, 1, 2, 3, and 5% w/w) and allowed to equilibrate prior to testing. The texture analyzer in combination with a cone-cap assembly was used to objectively investigate the changes in spreadability and adhesiveness of the gel system before and after addition of CSD. Results indicate that an increase in pliability and adhesiveness at levels ≥2 to ≤5% w/w of CSD dispersed in the gel ensues. For subjective analysis, gels with (2% w/w) CSD and in the absence of CSD were uniformly applied to a 20-cm(2) (5 cm × 4 cm) surface area on the forearms of healthy volunteers and vehicle preferences by the volunteers regarding ease of application, durability on the skin, compliance, and feelings concerning its textural properties were assessed. It appears that changes in the gel formulation with the addition of CSD enhance gel viscosity and bonding to the skin. Results further show that changes in physical and rheological characteristics of gel containing 2% w/w CSD did not significantly change subject preferences for the gel preparations. These findings may help formulators to have additional options to develop more robust and cost-effective formulations.

SAXS study of silica sols, gels and glasses obtained by the sol gel process

International Nuclear Information System (INIS)

Santos, D.I. dos; Aegerter, M.A.

1988-01-01

Systematic SAXS studies have been performed at the LURE Synchrotron, Orsay, using an intense beam of point like cross-section to obtain information about the sol -> humid gel -> dried gel -> silica glass transformation. The intensity curves have been analysed in term of power law in log-log plots, whose exponent is related to mass and surface fractal dimensions of the structure. It was found that almost all phases present fractal structures and for the case of basic gels, is of hierarchical nature. The aerogels are formed by a dense matrix, with a smooth surface and exhibit a very narrow auto-similarity range that gives a mass fractal dimension. (author) [pt

Effects of gel composition on the radiation induced density change in PAG polymer gel dosimeters: a model and experimental investigations

International Nuclear Information System (INIS)

Hilts, M; Jirasek, A; Duzenli, C

2004-01-01

Due to a density change that occurs in irradiated polyacrylamide gel (PAG), x-ray computed tomography (CT) has emerged as a feasible method of performing polymer gel dosimetry. However, applicability of the technique is currently limited by low sensitivity of the density change to dose. This work investigates the effect of PAG composition on the radiation induced density change and provides direction for future work in improving the sensitivity of CT polymer gel dosimetry. A model is developed that describes the PAG density change (Δρ gel ) as a function of both polymer yield (%P) and an intrinsic density change, per unit polymer yield, that occurs on conversion of monomer to polymer (Δρ polymer ). %P is a function of the fraction of monomer consumed and the weight fraction of monomer in the unirradiated gel (%T). Applying the model to experimental CT and Raman spectroscopic data, two important fundamental properties of the response of PAG density to dose (Δρ gel dose response) are discovered. The first property is that Δρ polymer depends on PAG %C (cross-linking fraction of total monomer) such that low and high %C PAGs exhibit a higher Δρ polymer than do more intermediate %C PAGs. This relationship is opposite to the relationship of polymer yield to %C and is explained by the effect of %C on the type of polymer formed. The second property is that the Δρ gel dose response is linearly dependent on %T. From the model, the inference is that, at least for %T≤12%, monomer consumption and Δρ polymer depend solely on %C. In terms of optimizing CT polymer gel dosimetry for high sensitivity, these results indicate that Δρ polymer can be expected to vary with each polymer gel system and thus should be considered when choosing a polymer gel for CT gel dosimetry. However, Δρ polymer and %P cannot be maximized simultaneously and maximizing %P, by choosing gels with intermediate %C and high %T, is found to have the greatest impact on increasing the

Multi-gel casting apparatus for vertical polyacrylamide gels with in-built solution flow system and liquid level detectors.

Science.gov (United States)

Maurye, Praveen; Basu, Arpita; Bandyopadhyay, Tapas Kumar; Biswas, Jayanta Kumar; Mohanty, Bimal Prasana

2017-08-01

PAGE is the most widely used technique for the separation and biochemical analysis of biomolecules. The ever growing field of proteomics and genomics necessitates the analysis of many proteins and nucleic acid samples to understand further about the structure and function of cells. Simultaneous analysis of multiple protein samples often requires casting of many PAGE gels. Several variants of multi-gel casting/electrophoresis apparatuses are frequently used in research laboratories. Requirement of supplementary gels to match the growing demand for analyzing additional protein samples sometimes become a cause of concern. Available apparatuses are not amenable to and therefore, not recommended for any modification to accommodate additional gel casting units other than what is prescribed by the manufacturer. A novel apparatus is described here for casting multiple PAGE gels comprising four detachable components that provide enhanced practicability and performance of the apparatus. This newly modified apparatus promises to be a reliable source for making multiple gels in less time without hassle. Synchronized functioning of unique components broaden the possibilities of developing inexpensive, safe, and time-saving multi-gel casting apparatus. This apparatus can be easily fabricated and modified to accommodate desired number of gel casting units. The estimated cost (∼$300) for fabrication of the main apparatus is very competitive and effortless assembly procedure can be completed within ∼30 min. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluoride Rinses, Gels and Foams

DEFF Research Database (Denmark)

Twetman, Svante; Keller, Mette K

2016-01-01

AIM: The aim of this conference paper was to systematically review the quality of evidence and summarize the findings of clinical trials published after 2002 using fluoride mouth rinses, fluoride gels or foams for the prevention of dental caries. METHODS: Relevant papers were selected after...... (6 on fluoride mouth rinse, 10 on fluoride gel and 3 on fluoride foam); 6 had a low risk of bias while 2 had a moderate risk. All fluoride measures appeared to be beneficial in preventing crown caries and reversing root caries, but the quality of evidence was graded as low for fluoride mouth rinse......, moderate for fluoride gel and very low for acidulated fluoride foam. No conclusions could be drawn on the cost-effectiveness. CONCLUSIONS: This review, covering the recent decade, has further substantiated the evidence for a caries-preventive effect of fluoride mouth rinse, fluoride gel and foam...

Improving the large scale purification of the HIV microbicide, griffithsin.

Science.gov (United States)

Fuqua, Joshua L; Wanga, Valentine; Palmer, Kenneth E

2015-02-22

Griffithsin is a broad spectrum antiviral lectin that inhibits viral entry and maturation processes through binding clusters of oligomannose glycans on viral envelope glycoproteins. An efficient, scaleable manufacturing process for griffithsin active pharmaceutical ingredient (API) is essential for particularly cost-sensitive products such as griffithsin -based topical microbicides for HIV-1 prevention in resource poor settings. Our previously published purification method used ceramic filtration followed by two chromatography steps, resulting in a protein recovery of 30%. Our objective was to develop a scalable purification method for griffithsin expressed in Nicotiana benthamiana plants that would increase yield, reduce production costs, and simplify manufacturing techniques. Considering the future need to transfer griffithsin manufacturing technology to resource poor areas, we chose to focus modifying the purification process, paying particular attention to introducing simple, low-cost, and scalable procedures such as use of temperature, pH, ion concentration, and filtration to enhance product recovery. We achieved >99% pure griffithsin API by generating the initial green juice extract in pH 4 buffer, heating the extract to 55°C, incubating overnight with a bentonite MgCl2 mixture, and final purification with Capto™ multimodal chromatography. Griffithsin extracted with this protocol maintains activity comparable to griffithsin purified by the previously published method and we are able to recover a substantially higher yield: 88 ± 5% of griffithsin from the initial extract. The method was scaled to produce gram quantities of griffithsin with high yields, low endotoxin levels, and low purification costs maintained. The methodology developed to purify griffithsin introduces and develops multiple tools for purification of recombinant proteins from plants at an industrial scale. These tools allow for robust cost-effective production and purification of

Aging and nonlinear rheology of thermoreversible colloidal gels

Science.gov (United States)

Wagner, Norman; Gordon, Melissa; Kloxin, Christopher

Colloidal dispersions are found in a wide variety of consumer products such as paint, food and pharmaceuticals. We investigate gel formation and aging in a thermoreverible gel consisting of octadecyl-coated silica nanoparticles suspended in n-tetradecane. In this system, the octadecyl brush can undergo a phase change allowing the attractions between particles to be tuned by temperature (1,2). By probing the system with steady shear and large amplitude oscillatory shear, we have studied the effect of thermal history and shear history on gel formation and gel mechanical properties during aging. Gels were formed by approaching a common temperature from above and below to determine a reference state from which creep tests were conducted. Creep ringing was observed as expected for the viscoelastic gel. The rheological aging is interpreted in terms of the gel microstructure formed with differing thermal and shear histories to determine how processing affects structure. Recently proposed scaling laws for the rheology and structure under flow are explored within the context of gel aging (3). Through rheological and microstructural measurements, we will further the understanding of gel formation and aging in this model system which may be applied to processing conditions in an industrial setting.

On shear rheology of gel propellants

Energy Technology Data Exchange (ETDEWEB)

Rahimi, Shai; Peretz, Arie [RAFAEL, MANOR Propulsion and Explosive Systems Division, Haifa (Israel); Natan, Benveniste [Faculty of Aerospace Engineering, Technion - Israel Institute of Technology, Haifa (Israel)

2007-04-15

Selected fuel, oxidizer and simulant gels were prepared and rheologically characterized using a rotational rheometer. For fuel gelation both organic and inorganic gellants were utilized, whereas oxidizers and simulants were gelled with addition of silica and polysaccharides, respectively. The generalized Herschel-Bulkley constitutive model was found to most adequately represent the gels studied. Hydrazine-based fuels, gelled with polysaccharides, were characterized as shear-thinning pseudoplastic fluids with low shear yield stress, whereas inhibited red-fuming nitric acid (IRFNA) and hydrogen peroxide oxidizers, gelled with silica, were characterized as yield thixotropic fluids with significant shear yield stress. Creep tests were conducted on two rheological types of gels with different gellant content and the results were fitted by Burgers-Kelvin viscoelastic constitutive model. The effect of temperature on the rheological properties of gel propellant simulants was also investigated. A general rheological classification of gel propellants and simulants is proposed. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

Expression of a functional cold active β-galactosidase from Planococcus sp-L4 in Pichia pastoris.

Science.gov (United States)

Mahdian, Seyed Mohammad Amin; Karimi, Ehsan; Tanipour, Mohammad Hossein; Parizadeh, Seyed Mohammad Reza; Ghayour-Mobarhan, Majid; Bazaz, Mojtaba Mousavi; Mashkani, Baratali

2016-09-01

Lactase deficiency problem discourages many adults from consuming milk as a major source of micro- and macronutrients. Enzymatic hydrolysis of lactose is an ideal solution for this problem but such processing adds significant costs. In this study, a cold active β-galactosidase from Planococcus sp-L4 (bgal) was optimized for expression of recombinant "BGalP" in Pichia pastoris. As a result of codon optimization, the codon adaptation index was improved from 0.58 to 0.85 after replacing rare codons. After transformation of two P. pastoris strains (KM71H and GS115), the activity of BGalP enzyme was measured in the culture supernatants using ortho-Nitrophenyl-β-galactoside (ONPG). Maximal activity was recorded as 3.7U/ml on day 11 in KM71H clone #2 which was 20% higher than the best GS115 clone. Activity measurements under different conditions indicated optimal activity at pH 6.5. It was active at temperatures ranging from 0 to 55°C with deactivation occurring at or above 60°C. Protein analysis of the crude ultra-filtrate showed the enzyme was ∼75kDa and was the major constituent (85%) of the sample. This enzyme have the potential to find utility for the breakdown of lactose in chilled milk and subsequently can be deactivated by pasteurization. The use of BGalP would minimize energy consumption thus decreasing cost and also help to preserve the nutritional elements of the milk. Copyright © 2015 Elsevier Inc. All rights reserved.

Thixotropic corrosive gels for nuclear decontamination

International Nuclear Information System (INIS)

Bargues, St.

1998-01-01

The aim of this thesis was the development of corrosive gels for metallic surface decontamination. These gels formulation, based on a powerful oxidant (the cerium IV), the nitric acid, a mineral charge (silica) and a non ionic surface-active, has been developed according to the specific constraints of the nuclear industry. The objective was to prepare thixotropic gels becoming liquid after shacking to allow an easy pulverization and coming again solid to permit a perfect adhesion on the metallic surface. This rheological study of the gels has been completed by an evaluation of their corrosive properties. The last part of the work presents an industrial utilization during two years. (A.L.B.)

Structure of gels layers with cells

Science.gov (United States)

Pokusaev, B. G.; Karlov, S. P.; Vyazmin, A. V.; Nekrasov, D. A.; Zakharov, N. S.; Khramtsov, D. P.; Skladnev, D. A.; Tyupa, D. V.

2017-11-01

The structure of two-layer agarose gels containing yeast cells is investigated experimentally by spectrometry, to shed a light on the theoretical foundations for the development of bioreactors by the method of 3D bioprinting. Due to division, cells overcome the layer of the dispersion phase separating successively applied layers of the agarose gel. However a gel layer of 100 μm thick with a high concentration of silver nanoparticles completely excludes the infiltration of yeast cells through it. A special sort of agarose is suggested where the concentration of silver nanoparticles formed by cells from salt of silver can serve as an indicator of the state of the yeast cells in the volume of the gel.

Modelling of the inhomogeneous interior of polymer gels

International Nuclear Information System (INIS)

Shew, C-Y; Iwaki, Takafumi

2006-01-01

A simple model has been investigated to elucidate the mean squared displacement (MSD) of probe molecules in cross-linked polymer gels. In the model, we assume that numerous cavities distribute in the inhomogeneous interior of a gel, and probe molecules are confined within these cavities. The individual probe molecules trapped in a gel are treated as Brownian particles confined to a spherical harmonic potential. The harmonic potential is chosen to model the effective potential experienced by the probe particle in the cavity of a gel. Each field strength is corresponding to the characteristic of one type of effective cavity. Since the statistical distribution of different effective cavity sizes is unknown, several distribution functions are examined. Meanwhile, the calculated averaged MSDs are compared to the experimental data by Nisato et al (2000 Phys. Rev. E 61 2879). We find that the theoretical results of the MSD are sensitive to the shape of the distribution function. For low cross-linked gels, the best fit is obtained when the interior cavities of a gel follow a bimodal distribution. Such a result may be attributed to the presence of at least two distinct classes of cavity in gels. For high cross-linked gels, the cavities in the gel can be depicted by a single-modal uniform distribution function, suggesting that the range of cavity sizes becomes smaller. These results manifest the voids inside a gel, and the shape of distribution functions may provide the insight into the inhomogeneous interior of a gel

Actuator device utilizing a conductive polymer gel

Science.gov (United States)

Chinn, Douglas A.; Irvin, David J.

2004-02-03

A valve actuator based on a conductive polymer gel is disclosed. A nonconductive housing is provided having two separate chambers separated by a porous frit. The conductive polymer is held in one chamber and an electrolyte solution, used as a source of charged ions, is held in the second chamber. The ends of the housing a sealed with a flexible elastomer. The polymer gel is further provide with electrodes with which to apply an electrical potential across the gel in order to initiate an oxidation reaction which in turn drives anions across the porous frit and into the polymer gel, swelling the volume of the gel and simultaneously contracting the volume of the electrolyte solution. Because the two end chambers are sealed the flexible elastomer expands or contracts with the chamber volume change. By manipulating the potential across the gel the motion of the elastomer can be controlled to act as a "gate" to open or close a fluid channel and thereby control flow through that channel.

WHO guidance grounded in a comprehensive approach to sexual and reproductive health and human rights: topical pre-exposure prophylaxis

OpenAIRE

Lusti-Narasimhan, Manjula; Khosla, Rajat; Baggaley, Rachel; Temmerman, Marleen; McGrory, Elizabeth; Farley, Tim

2014-01-01

Introduction: Two new microbicide products based on topical (vaginal) application of antiretroviral drugs – 1% tenofovir gel and the dapivirine ring – are currently in late-stage clinical testing, and results on their safety and effectiveness are expected to become available in early 2015. WHO guidelines on the use of topical pre-exposure prophylaxis (topical PrEP) are important in order to ensure that these new prevention products are optimally used. Discussion: Given that these new topical ...

Modelling of erosion of bentonite gel by gel/sol flow

Energy Technology Data Exchange (ETDEWEB)

Moreno, Luis; Neretnieks, Ivars; Longcheng Liu (Chemical Engineering and Technology, School of Chemical Science and Engineering, Royal Institute of Technology, Stockholm (Sweden))

2010-11-15

Bentonite intrusion into a fracture intersecting the canister deposition hole is modelled. The model describes the expansion of the bentonite within the fracture. It accounts for the repulsive electrostatic double-layer forces, the attractive van der Waals forces and friction forces between the particles and the water. The model also takes into account the diffusion of the colloid particles in the smectite sol. Diffusion of a counterion, sodium, is accounted for as this strongly influences the double layer force and the viscosity of the gel/sol. The gel/sol is considered to be a fluid with a varying viscosity that is strongly dependent on the bentonite volume fraction in the gel and the sodium concentration in the water. Two different geometries were modelled; a rectangular and a cylindrical. The rectangular geometry was used to gain experience with the processes and mechanisms and how they interact since the cylindrical geometry was somewhat less stable numerically and more time consuming. In the rectangular geometry a fracture 1 metre long in the flow direction was modelled. In both geometries the fracture size was selected sufficiently large to ensure that the water velocity, near the distant border was nearly the same as the approaching water velocity and that the smectite concentration there was vanishingly small. It was found that the velocity of the fluid drops considerably where the bentonite volume fraction is larger than 1-2%. This is due to the strong increase in viscosity with increasing bentonite volume fraction. The loss of smectite by the slowly flowing fluid was found to be proportional to the square root of the seeping water velocity for the rectangular geometry. For the cylindrical geometry, the dependence is somewhat lower (exponent about 0.4) since the length of the gel/water interface decreases with increasing water flow rate. The penetration depth of the gel/water interface decreases with increasing water flow rate. For water velocity of the

Modelling of erosion of bentonite gel by gel/sol flow

International Nuclear Information System (INIS)

Moreno, Luis; Neretnieks, Ivars; Longcheng Liu

2010-11-01

Bentonite intrusion into a fracture intersecting the canister deposition hole is modelled. The model describes the expansion of the bentonite within the fracture. It accounts for the repulsive electrostatic double-layer forces, the attractive van der Waals forces and friction forces between the particles and the water. The model also takes into account the diffusion of the colloid particles in the smectite sol. Diffusion of a counterion, sodium, is accounted for as this strongly influences the double layer force and the viscosity of the gel/sol. The gel/sol is considered to be a fluid with a varying viscosity that is strongly dependent on the bentonite volume fraction in the gel and the sodium concentration in the water. Two different geometries were modelled; a rectangular and a cylindrical. The rectangular geometry was used to gain experience with the processes and mechanisms and how they interact since the cylindrical geometry was somewhat less stable numerically and more time consuming. In the rectangular geometry a fracture 1 metre long in the flow direction was modelled. In both geometries the fracture size was selected sufficiently large to ensure that the water velocity, near the distant border was nearly the same as the approaching water velocity and that the smectite concentration there was vanishingly small. It was found that the velocity of the fluid drops considerably where the bentonite volume fraction is larger than 1-2%. This is due to the strong increase in viscosity with increasing bentonite volume fraction. The loss of smectite by the slowly flowing fluid was found to be proportional to the square root of the seeping water velocity for the rectangular geometry. For the cylindrical geometry, the dependence is somewhat lower (exponent about 0.4) since the length of the gel/water interface decreases with increasing water flow rate. The penetration depth of the gel/water interface decreases with increasing water flow rate. For water velocity of the

Dosimetry Evolution in Teletherapy: Polimer Gel

Science.gov (United States)

Hamann, J. H.; Peixoto, J. G. P.

2018-03-01

Polymer gels evolution and chemical composition used in dosimetry. Type Composition First gels Folin’s Phenol or Gallic Acid Polymer Gel Agarose and N,N’-methylene-bis-acrylamide BANANA Bis, acrylamide, nitrous oxide and agarose BANG-1TM Bis, acrylamide, nitrogen and gelatin BANG-2TM Bis, acrylic acid, sodium hydroxide, nitrogen and gelatin BANG-3TM Bis, methacrylate acid, sodium hydroxide, nitrogen and gelatin MAGIC Methacrylate acid, ascorbic acid, gelatin and copper sulphate

Obtaining valid laboratory data in clinical trials conducted in resource diverse settings: lessons learned from a microbicide phase III clinical trial.

Directory of Open Access Journals (Sweden)

Tania Crucitti

2010-10-01

Full Text Available Over the last decade several phase III microbicides trials have been conducted in developing countries. However, laboratories in resource constrained settings do not always have the experience, infrastructure, and the capacity to deliver laboratory data meeting the high standards of clinical trials. This paper describes the design and outcomes of a laboratory quality assurance program which was implemented during a phase III clinical trial evaluating the efficacy of the candidate microbicide Cellulose Sulfate 6% (CS [1].In order to assess the effectiveness of CS for HIV and STI prevention, a phase III clinical trial was conducted in 5 sites: 3 in Africa and 2 in India. The trial sponsor identified an International Central Reference Laboratory (ICRL, responsible for the design and management of a quality assurance program, which would guarantee the reliability of laboratory data. The ICRL provided advice on the tests, assessed local laboratories, organized trainings, conducted supervision visits, performed re-tests, and prepared control panels. Local laboratories were provided with control panels for HIV rapid tests and Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG amplification technique. Aliquots from respective control panels were tested by local laboratories and were compared with results obtained at the ICRL.Overall, good results were observed. However, discordances between the ICRL and site laboratories were identified for HIV and CT/NG results. One particular site experienced difficulties with HIV rapid testing shortly after study initiation. At all sites, DNA contamination was identified as a cause of invalid CT/NG results. Both problems were timely detected and solved. Through immediate feedback, guidance and repeated training of laboratory staff, additional inaccuracies were prevented.Quality control guidelines when applied in field laboratories ensured the reliability and validity of final study data. It is essential that sponsors

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa.

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Annalene Nel

Full Text Available This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women.The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa.280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports.No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective.The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa.

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Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

2016-01-01

This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa

Science.gov (United States)

Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

2016-01-01

Background This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. Objectives The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. Methods 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. Results No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. Conclusions The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of

Sol-gel derived sorbents

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Sigman, Michael E.; Dindal, Amy B.

2003-11-11

Described is a method for producing copolymerized sol-gel derived sorbent particles for the production of copolymerized sol-gel derived sorbent material. The method for producing copolymerized sol-gel derived sorbent particles comprises adding a basic solution to an aqueous metal alkoxide mixture for a pH.ltoreq.8 to hydrolyze the metal alkoxides. Then, allowing the mixture to react at room temperature for a precalculated period of time for the mixture to undergo an increased in viscosity to obtain a desired pore size and surface area. The copolymerized mixture is then added to an immiscible, nonpolar solvent that has been heated to a sufficient temperature wherein the copolymerized mixture forms a solid upon the addition. The solid is recovered from the mixture, and is ready for use in an active sampling trap or activated for use in a passive sampling trap.

Preparation of zirconium molybdate gel generator

International Nuclear Information System (INIS)

Charoen, S.; Aungurarat, G.; Laohawilai, S.; Sukontpradit, W.; Jingjit, S.

1994-01-01

A procedure for preparation of 99mTc generator based on conversion to zirconium molybdate gel of 99Mo produced by neutron activation was reported. The gel was prepared from zirconium oxychloride solution pH 1.6, ammonium molybdate solution pH 3-5 and mole ratio of Zr:Mo 1:1 which had water content about 7-8%. Small generators containing 1-1.5 g of gel were eluted with average efficiencies of 77% and the activity peak in the first 3 ml of 10 ml of saline solution. The amount of Mo and Zr in eluates were below the acceptance limit. The gel generators of activity about 100 mCi were prepared and had the good performance in elutability and stability

Radiotherapy gel dosimetry

International Nuclear Information System (INIS)

Baldock, C.

2002-01-01

shapes and sizes while sparing normal tissue. The situation is further complicated if the normal tissues are critical organs or are particularly sensitive to radiation. Radiotherapy techniques employed to obtain a closer conformation of the dose distribution to the tumour volume are referred to as conformal radiotherapy techniques. The clinical implementation of conformal therapy has been delayed by limitations in the verification of conformal dose distributions calculated by treatment planning systems prior to the irradiation of the patient and the verification of complex treatments during its delivery to the patient. There are several aspects of conformal therapy that complicate dose verification. To achieve the dose distributions conforming to complex 3D volumes, high dose gradients arise in the treatment volume. Further, overdose or underdose regions can exist when separate radiation fields are used to deliver additional radiation. These aspects require that practical dose measurement (dosimetry) techniques be able to integrate dose over time and easily measure dose distributions in 3D with high spatial resolution. Traditional dosimeters, such as ion chambers, thermoluminescent dosimeters and radiographic film do not fulfil these requirements. Novel gel dosimetry techniques are being developed in which dose distributions can potentially be determined in vitro in 3D using anthropomorphic phantoms to simulate a clinically irradiated situation. As long ago as the 1950's, radiation-induced colour change in dyes was used to investigate radiation doses in gels. It was subsequently shown that radiation induced changes in nuclear magnetic resonance (NMR) relaxation properties of gels infused with conventional Fricke dosimetry solutions could be measured using magnetic resonance imaging (MRI). In Fricke gels, Fe 2+ ions in ferrous sulphate solutions are usually dispersed throughout a gelatin, agarose or PVA matrix. Radiation-induced changes in the dosimeters are considered to

Sol-gel preparation of uranium oxide spheres

International Nuclear Information System (INIS)

Dolezal, J.; Urbanek, V.

1978-01-01

Information is presented on problems of preparing nuclear fuel by the sol-gel method. Basic data on different process types are given. A more detailed description of the method of preparation of spherical particles of uranium oxide gel developed and used at the Nuclear Research Institute at Rez is given. Advantages and disadvantages of sol-gel materials are discussed in comparison with fuel materials prepared by classical precipitation methods. The feasibility of the sol-gel methods for preparing other materials is shortly mentioned and their application outlined. (author)

Functional coatings: the sol-gel approach

International Nuclear Information System (INIS)

Belleville, Ph.

2010-01-01

CEA's sol-gel laboratory is specialized in the development of innovative sol-gel optical coatings and has extended its application field to membrane materials and coatings for energy conversion, to electric coatings for microelectronics devices and to thin films for gas sensing. This article describes, by way of examples, the laboratory's research on sol-gel functional coatings, including nano-material synthesis, organic-inorganic hybrid-based solution preparation as well as deposition process development and prototyping. (author)

Positron annihilation lifetime studies of sol-gel transition of carrageenan gels

International Nuclear Information System (INIS)

Wakabayashi, Y.; Ito, K.; Li, H.L.; Ujihara, Y.

1996-01-01

Positron annihilation lifetime measurement was applied to study the sol-gel transition of anionic polysaccharide aqueous solutions in terms of free-volume parameters the size, intensity, and size distribution of free volumes of the gelation of K-form κ-carrageenan solutions as a function of temperature. Slight variations of free volume size and intensity against temperature were observed near 295 K. The correlation of free-volume data with other physical properties vibrational spectra (IR and Raman), conductivity, SAXS, elastic measurement, differential scanning calorimetry were investigated to understand the mechanism of sol-gel transition of carrageenan. (author)

Sol-gel growth of vanadium dioxide

International Nuclear Information System (INIS)

Speck, K.R.

1990-01-01

This thesis examines the chemical reactivity of vanadium (IV) tetrakis(t-butoxide) as a precursor for the sol-gel synthesis of vanadium dioxide. Hydrolysis and condensation of the alkoxide was studied by FTIR spectroscopy. Chemical modification of the vanadium tetraalkoxide by alcohol interchange was studied using 51 V NMR and FTIR. Vanadium dioxide thin films and powders were made from vanadium tetrakis(t-butoxide) by standard sol-gel techniques. Post-deposition heating under nitrogen was necessary to transform amorphous gels into vanadium dioxide. Crystallization of films and powders was studied by FTIR, DSC, TGA, and XRD. Gel-derived vanadium dioxide films undergo a reversible semiconductor-to-metal phase transition near 68C, exhibiting characteristic resistive and spectral changes. The electrical resistance decreased by two to three orders of magnitude and the infrared transmission sharply dropped as the material was cycled through this thermally induced phase transition. The sol-gel method was also used to make doped vanadium dioxide films. Films were doped with tungsten and molybdenum ions to effectively lower the temperature at which the transition occurs

The performance of gel technetium-99m generator

International Nuclear Information System (INIS)

Liu Yishu

2004-01-01

Technetium-99m, as one of the important radionuclides in nuclear medical science, has been widely used for diseases diagnosis in both developed and developing countries for many years. Technetium-99m can be obtained from both fission-type and gel-type Tc-99m generator. Fission-type generator was prepared by Molybdenum-99 separated from fission products of uranium-235 and gel-type was prepared by irradiating nature MoO 3 in reactor, and a series of chemical and physical processes. This paper briefly describes the manufacturing technical process of gel-type Technetium-99 generator, including the preparation of target containing nature MoO 3 , the target irradiation in reactor, gel preparation, gel filtration and drying, dried gel cracking, generator loading and activity calibration of generator. The performances of gel-type Technetium-99m generator, such as elution efficiency, elution profile, the pH, Mo breakthrough, Zirconium content, radiochemical purity, radionuclidic purity, sterility and pyrogencity of eluate, are also expatiated in detail. Comparing with fission-type Technetium-99m generator, the defects of gel-type Technetium-99m generator are enumerated and their overcoming solutions are recommended in this paper. (author)

Pouring and running a protein gel by reusing commercial cassettes.

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Hwang, Alexander C; Grey, Paris H; Cuddy, Katrina; Oppenheimer, David G

2012-02-12

The evaluation of proteins using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is a common technique used by biochemistry and molecular biology researchers. For laboratories that perform daily analyses of proteins, the cost of commercially available polyacrylamide gels (~$10/gel) can be considerable over time. To mitigate this cost, some researchers prepare their own polyacrylamide gels. Traditional methods of pouring these gels typically utilize specialized equipment and glass gel plates that can be expensive and preclude pouring many gels and storing them for future use. Furthermore, handling of glass plates during cleaning or gel pouring can result in accidental breakage creating a safety hazard, which may preclude their use in undergraduate laboratory classes. Our protocol demonstrates how to pour multiple protein gels simultaneously by recycling Invitrogen Nupage Novex minigel cassettes, and inexpensive materials purchased at a home improvement store. This economical and streamlined method includes a way to store the gels at 4°C for a few weeks. By re-using the plastic gel cassettes from commercially available gels, labs that run frequent protein gels can save significant costs and help the environment. In addition, plastic gel cassettes are extremely resistant to breakage, which makes them ideal for undergraduate laboratory classrooms.

The effects of brushing on human enamel surface roughness after NaF gel and theobromine gel exposure

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Mahardhika, A.; Noerdin, A.; Eriwati, Y. K.

2017-08-01

This study aimed to determine the effects of brushing on human enamel surface roughness after different exposure times of 200 mg/L theobromine gel (8, 16, and 32 minutes) and 2% NaF gel (16 minutes). Twenty-four human upper premolars were used and divided into four groups. Group 1 was exposed to 2% NaF gel for 16 minutes. In contrast, groups 2, 3, and 4 were exposed to 200 mg/L theobromine gel for 8 minutes, 16 minutes, and 32 minutes, and each group was then brushed for 9 minutes and 20 seconds. After the treatment, samples were tested using a surface roughness tester (Mitutoyo SJ 301, Japan). The Wilcoxon test showed significant changes (p enamel surface and then increase roughness after brushing.

Pecan drying with silica gel

Energy Technology Data Exchange (ETDEWEB)

Ghate, S.R.; Chhinnan, M.S.

1983-07-01

High moisture in-shell pecans were dried by keeping them in direct and indirect contact with silica gel to investigate their drying characteristics. In-shell pecans were also dried with ambient air from a controlled environment chamber and with air dehumidified by silica gel. Direct contact and dehumidified air drying seemed feasible approaches.

Gel chromatography of sup(99m)Tc-labelled compounds

International Nuclear Information System (INIS)

Vilcek, S.; Machan, V.; Kalincak, M.

1976-01-01

The present state of gel chromatography of sup(99m)Tc-labelled compounds is reviewed. Examples are given of gel chromatography for preparing labelled compounds and for quality control analysis and the development of new types of sup(99m)Tc-labelled compounds. The factors which influence the gel chromatography of these compounds are discussed, i.e., the nature of the elution agent, the duration of the contact of the gel and the preparation the gel type, the nature of the labelled compound. The GCS method (gel chromatography scanning) is briefly described. The advantages of gel chromatography as compared with other chromatographic techniques for sup(99m)Tc-labelled compounds are summarized. (author)

21 CFR 866.4900 - Support gel.

Science.gov (United States)

2010-04-01

... IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents § 866.4900 Support gel. (a) Identification. A support gel for clinical use is a device that consists of an agar or agarose preparation that...

Caffeine-catalyzed gels.

Science.gov (United States)

DiCiccio, Angela M; Lee, Young-Ah Lucy; Glettig, Dean L; Walton, Elizabeth S E; de la Serna, Eva L; Montgomery, Veronica A; Grant, Tyler M; Langer, Robert; Traverso, Giovanni

2018-07-01

Covalently cross-linked gels are utilized in a broad range of biomedical applications though their synthesis often compromises easy implementation. Cross-linking reactions commonly utilize catalysts or conditions that can damage biologics and sensitive compounds, producing materials that require extensive post processing to achieve acceptable biocompatibility. As an alternative, we report a batch synthesis platform to produce covalently cross-linked materials appropriate for direct biomedical application enabled by green chemistry and commonly available food grade ingredients. Using caffeine, a mild base, to catalyze anhydrous carboxylate ring-opening of diglycidyl-ether functionalized monomers with citric acid as a tri-functional crosslinking agent we introduce a novel poly(ester-ether) gel synthesis platform. We demonstrate that biocompatible Caffeine Catalyzed Gels (CCGs) exhibit dynamic physical, chemical, and mechanical properties, which can be tailored in shape, surface texture, solvent response, cargo release, shear and tensile strength, among other potential attributes. The demonstrated versatility, low cost and facile synthesis of these CCGs renders them appropriate for a broad range of customized engineering applications including drug delivery constructs, tissue engineering scaffolds, and medical devices. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gel electrolytes and electrodes

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Fleischmann, Sven; Bunte, Christine; Mikhaylik, Yuriy V.; Viner, Veronika G.

2017-09-05

Gel electrolytes, especially gel electrolytes for electrochemical cells, are generally described. In some embodiments, the gel electrolyte layers comprise components a) to c). Component a) may be at least one layer of at least one polymer comprising polymerized units of: a1) at least one monomer containing an ethylenically unsaturated unit and an amido group and a2) at least one crosslinker. Component b) may be at least one conducting salt and component c) may be at least one solvent. Electrodes may comprise the components a), d) and e), wherein component a) may be at least one layer of at least one polymer as described herein. Component d) may be at least one electroactive layer and component e) may be at least one ceramic layer. Furthermore, electrochemical cells comprising component a) which may be at least one layer of at least one polymer as described herein, are also provided.

Detection of Aspartic Proteinase Activities Using Gel Zymography.

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Perera, Handunge Kumudu Irani

2017-01-01

Gel zymography is a two-stage process where the proteins from the test sample are first separated by electrophoresis followed by the detection of the activity of hydrolytic enzymes. Many zymography procedures use sodium dodecyl sulfate (SDS) polyacrylamide gels copolymerized with an appropriate substrate. The procedure described here uses native polyacrylamide gel electrophoresis (PAGE) in the absence of both SDS and substrate. In order to visualize aspartic proteinase activity, the gel is impregnated in bovine hemoglobin at pH 3.0 for 15 min after the electrophoresis procedure. Subsequently, the gel is incubated in a humid container in the absence of hemoglobin for 1 h at 37 °C. At the end, the gel is stained with amido black and destained. Clear areas against a dark background corresponding to aspartic proteinase activities can be detected.

[Overdentures covering natural roots. The use of chlorhexidine gel].

Science.gov (United States)

Hendrikx, M J; Kramer, J E; de Baat, C

2000-03-01

To prevent caries and periodontal disease in overdenture abutment teeth, daily application of chlorhexidine gel is recommended. In order to get insight into the use of the gel, 29 overdenture wearing patients were interviewed. In addition the patients were requested to show the use of the gel. It was concluded that at any time the patients were instructed about the use of the gel. Nevertheless, a majority of the patients did not use the gel daily and in accordance with the instructions given. Application of the gel in the abutment depressions of the overdenture appeared to be a heavy task.

Development of strippable gel for surface decontamination applications

International Nuclear Information System (INIS)

Banerjee, D.; Sandhya, U.; Khot, S.A.; Srinivas, C.

2015-07-01

Strippable gels are an attractive option for decontamination of surfaces particularly when materials are to be reused after decontamination. The process in general results in good decontamination performance with minimal secondary waste generation. This paper reports on development of strippable gel formulation using polyvinyl alcohol as the gel former. Peeling behavior of the gel film improved when glycerol was used as plasticizer. Incorporation of decontaminating agents is essential for the gel to be effective, so a number of decontaminating agents were screened based on their miscibility with the gel, smooth peeling, and good decontamination performance. Based on this study, a strippable gel, ‘INDIGEL’ was formulated as a potential candidate for surface decontamination applications. Extensive trials on evaluation of decontamination performance of Indigel were done on simulated surfaces like stainless steel tray, stainless steel fume hood, PVC floor, granite and ceramic table tops. Results show that Indigel is highly effective for decontamination of surfaces contaminated with all types of radionuclides. Simplicity of its use coupled with good decontamination ability will find application in nuclear and other chemical industries. (author)

Method of making ionic liquid mediated sol-gel sorbents

Science.gov (United States)

Malik, Abdul; Shearrow, Anne M.

2017-01-31

Ionic liquid (IL)-mediated sol-gel hybrid organic-inorganic materials present enormous potential for effective use in analytical microextraction. One obstacle to materializing this prospect arises from high viscosity of ILs significantly slowing down sol-gel reactions. A method was developed which provides phosphonium-based, pyridinium-based, and imidazolium-based IL-mediated advanced sol-gel organic-inorganic hybrid materials for capillary microextraction. Scanning electron microscopy results demonstrate that ILs can serve as porogenic agents in sol-gel reactions. IL-mediated sol-gel coatings prepared with silanol-terminated polymers provided up to 28 times higher extractions compared to analogous sol-gel coatings prepared without any IL in the sol solution. This study shows that IL-generated porous morphology alone is not enough to provide effective extraction media: careful choice of the organic polymer and the precursor with close sol-gel reactivity must be made to ensure effective chemical bonding of the organic polymer to the created sol-gel material to be able to provide the desired sorbent characteristics.

Application of phase diagrams to obtain a new surfactant-based fracturing gel; Aplicacao de diagrama de fases para obtencao de um novo gel de fraturamento hidraulico

Energy Technology Data Exchange (ETDEWEB)

Dantas, Tereza N. de Castro; Santana, Vanessa C.; Dantas Neto, Afonso A.; Franca Neta, Luzia S. de; Albuquerque, Heraldo S. [Rio Grande do Norte Univ., Natal, RN (Brazil)]. E-mail: tereza@eq.ufrn.br

2003-07-01

Through pseudo ternary phases diagram was defined a gel area with the objective of obtaining a new surfactant-based fracturing gel. The surfactant used was synthesized from regional vegetable oil. Fracturing gel properties, like: viscosity, leak off coefficient and proppant-settling rate were analyzed. The obtained results with the surfactant-based gel had its properties compared with a HPG-based gel (hydroxypropyl guar). Rheological tests was accomplished at 100 s{sup -1} being varied the temperature from 26 to 86 deg C, where the surfactant-based gel showed great results. The leak off coefficient was determined by static filtration and the new gel presented smaller coefficient in relation to the HPG gel. The proppant-setting rate was also determined in the gel and, the surfactant-based gel showed good static proppant support. One can conclude that obtained gel presents compatible characteristics when compared with the HPG gel, without the inconvenience of leaving insoluble residues in the well. (author)

Energy-Efficient Bioalcohol Recovery by Gel Stripping

Science.gov (United States)

Godbole, Rutvik; Ma, Lan; Hedden, Ronald

2014-03-01

Design of energy-efficient processes for recovering butanol and ethanol from dilute fermentations is a key challenge facing the biofuels industry due to the high energy consumption of traditional multi-stage distillation processes. Gel stripping is an alternative purification process by which a dilute alcohol is stripped from the fermentation product by passing it through a packed bed containing particles of a selectively absorbent polymeric gel material. The gel must be selective for the alcohol, while swelling to a reasonable degree in dilute alcohol-water mixtures. To accelerate materials optimization, a combinatorial approach is taken to screen a matrix of copolymer gels having orthogonal gradients in crosslinker concentration and hydrophilicity. Using a combination of swelling in pure solvents, the selectivity and distribution coefficients of alcohols in the gels can be predicted based upon multi-component extensions of Flory-Rehner theory. Predictions can be validated by measuring swelling in water/alcohol mixtures and conducting h HPLC analysis of the external liquid. 95% + removal of butanol from dilute aqueous solutions has been demonstrated, and a mathematical model of the unsteady-state gel stripping process has been developed. NSF CMMI Award 1335082.

Chiromagnetic nanoparticles and gels

Science.gov (United States)

Yeom, Jihyeon; Santos, Uallisson S.; Chekini, Mahshid; Cha, Minjeong; de Moura, André F.; Kotov, Nicholas A.

2018-01-01

Chiral inorganic nanostructures have high circular dichroism, but real-time control of their optical activity has so far been achieved only by irreversible chemical changes. Field modulation is a far more desirable path to chiroptical devices. We hypothesized that magnetic field modulation can be attained for chiral nanostructures with large contributions of the magnetic transition dipole moments to polarization rotation. We found that dispersions and gels of paramagnetic Co3O4 nanoparticles with chiral distortions of the crystal lattices exhibited chiroptical activity in the visible range that was 10 times as strong as that of nonparamagnetic nanoparticles of comparable size. Transparency of the nanoparticle gels to circularly polarized light beams in the ultraviolet range was reversibly modulated by magnetic fields. These phenomena were also observed for other nanoscale metal oxides with lattice distortions from imprinted amino acids and other chiral ligands. The large family of chiral ceramic nanostructures and gels can be pivotal for new technologies and knowledge at the nexus of chirality and magnetism.

Acoustic evaluation of polymer gel dosimeters

International Nuclear Information System (INIS)

Mather, M.L.; De Deene, Y.; Baldock, C.; Whittaker, A.K.

2002-01-01

Advances in radiotherapy treatment techniques such as intensity modulated radiotherapy are placing increasing demands on radiation dosimetry for verification of dose distributions in 3D. In response, polymer gel dosimeters that are capable of recording dose distributions in 3D are currently being developed. Recently, a new technique for evaluation of absorbed dose distributions in these dosimeters using ultrasound was introduced. The current work aims to demonstrate the potential of ultrasound as an evaluation technique for polymer gel dosimeters and to investigate the ultrasound properties of two different dosimeter formulations, PAG and MAGIC gels

Polymer architecture of magnetic gels: a review

Science.gov (United States)

Weeber, Rudolf; Hermes, Melissa; Schmidt, Annette M.; Holm, Christian

2018-02-01

In this review article, we provide an introduction to ferrogels, i.e. polymeric gels with embedded magnetic particles. Due to the interplay between magnetic and elastic properties of these materials, they are promising candidates for engineering and biomedical applications such as actuation and controlled drug release. Particular emphasis will be put on the polymer architecture of magnetic gels since it controls the degrees of freedom of the magnetic particles in the gel, and it is important for the particle-polymer coupling determining the mechanisms available for the gel deformation in magnetic fields. We report on the different polymer architectures that have been realized so far, and provide an overview of synthesis strategies and experimental techniques for the characterization of these materials. We further focus on theoretical and simulational studies carried out on magnetic gels, and highlight their contributions towards understanding the influence of the gels’ polymer architecture.

Epidemic models for phase transitions: application to a physical gel

Science.gov (United States)

Bilge, A. H.; Pekcan, O.; Kara, S.; Ogrenci, A. S.

2017-09-01

Carrageenan gels are characterized by reversible sol-gel and gel-sol transitions under cooling and heating processes and these transitions are approximated by generalized logistic growth curves. We express the transitions of carrageenan-water system, as a representative of reversible physical gels, in terms of a modified Susceptible-Infected-Susceptible epidemic model, as opposed to the Susceptible-Infected-Removed model used to represent the (irreversible) chemical gel formation in the previous work. We locate the gel point Tc of sol-gel and gel-sol transitions and we find that, for the sol-gel transition (cooling), Tc > Tsg (transition temperature), i.e. Tc is earlier in time for all carrageenan contents and moves forward in time and gets closer to Tsg as the carrageenan content increases. For the gel-sol transition (heating), Tc is relatively closer to Tgs; it is greater than Tgs, i.e. later in time for low carrageenan contents and moves backward as carrageenan content increases.

Development and dosimetric evaluation of radiochromic PCDA vesicle gel dosimeters

International Nuclear Information System (INIS)

Sun, P.; Fu, Y.C.; Hu, J.; Hao, N.; Huang, W.; Jiang, B.

2016-01-01

The gel dosimeter has the unique capacity in recording radiation dose distribution in three dimensions (3D), which has the specific advantages in dosimetry measurements where steep dose gradients exist, such as in intensity-modulated radiation therapy (IMRT), brachytherapy and so on. Some 3D dosimeters, such as Fricke gel dosimeters, polymer gel dosimeters, the PRESAGE plastic dosimeters and micelle gel dosimeters have appeared recently. However, there are several disadvantages of these 3D dosimeters limit their application in radiotherapy dose verification. In this study, a novel radiochromic gel dosimeter for 3D dose verification of radiotherapy was developed by dispersing nanovesicles self-assembled by 10,12-pentacosadiynoic acid (PCDA) into the tissue equivalence gel matrix. The characteristics of radiochromic PCDA vesicle gel dosimeters were evaluated. The results indicate that these radiochromic gel dosimeters have good linear dose response to X-ray irradiation in the dose range of 2–100 Gy. In addition, the radiochromic gel dosimeters breakthrough the limitations of the existing gel dosimeters such as diffusion effect, post-radiation effect, and poor forming ability. The response of the gel dosimeter does not show any dose rate dependence, energy dependence and temperature effect, and there was no obvious difference in the gel response between single and cumulative dose of fractional irradiation. Hence, the radiochromic PCDA vesicle gel dosimeters developed in this study could be generally applied to 3D dose verification in radiotherapy. - Highlights: • A novel radiochromic gel dosimeter was developed by dispersing PCDA nanovesicles into the tissue equivalence gel matrix. • This nanovesicle overcomes the dose image blurring caused by the diffusion of monomer molecules. • This nanovesicle limits the polymer chain growth, so as to reduce the post-radiation effect. • The gel matrixes possess excellent tissue equivalence and elastic strength, which

Strippable gel for decontamination of contaminated metallic surfaces

International Nuclear Information System (INIS)

Banerjee, D.; Sandhya, U.; Khot, S.A.; Srinivas, C.; Wattal, P.K.

2013-01-01

Periodic decontamination of radioactive laboratories including fume hoods, glove boxes and all surfaces used for handling, processing and transporting radioactive materials is mandatory in all nuclear installations as this reduces spread of contamination and decreases total man rem exposure. Conventionally, chemical decontaminating agents or surfactant solutions are used for this purpose. However, this approach leads to generation of large volume of secondary radioactive waste. The use of strippable gel is an attractive alternative with low secondary waste generation particularly where removal of loose or weakly fixed contamination is necessary and also when the decontaminated material are to be reused, for e.g. decontamination of fume hoods, glove boxes, transport casks, spent fuel storage racks, control rod drive transport containers etc. Literature on gel formulations is scarce and mostly in the patent form. The sustained effort on gel formulation development has resulted in a basic gel formulation. The gel is a highly viscous water-based organic polymer, particularly suitable for application on vertical surfaces including difficult to reach metallic surfaces of complex geometry and not just limited to horizontal surfaces. The gel can be easily applied on contaminated surfaces by brushing or spraying. Curing of the gel is complete within 16-24 hours under ambient conditions and can then be removed by peeling as a dry sheet. While curing, the contaminants are trapped in gel either physically or chemically depending upon the nature of the contaminant. Salient features of cured gel include that it is water soluble and can be disposed off after immobilization in cement. Decontamination performance of the gel was initially evaluated by applying it on SS planchettes contaminated with known amount of radionuclides such as Cs(I), Co(II) and Ce(III). The measured decontamination factor was found to be in the range of 50-500, lowest for Ce(III) and highest for Co

The mechanism and properties of acid-coagulated milk gels

Directory of Open Access Journals (Sweden)

Chanokphat Phadungath

2005-03-01

Full Text Available Acid-coagulated milk products such as fresh acid-coagulated cheese varieties and yogurt areimportant dairy food products. However, little is known regarding the mechanisms involved in gel formation, physical properties of acid gels, and the effects of processing variables such as heat treatment and gelation temperature on the important physical properties of acid milk gels. This paper reviews the modern concepts of possible mechanisms involved in the formation of particle milk gel aggregation, along with recent developments including the use of techniques such as dynamic low amplitude oscillatory rheology to observe the gel formation process, and confocal laser scanning microscopy to monitor gel microstructure.

Explorative data analysis of two-dimensional electrophoresis gels

DEFF Research Database (Denmark)

Schultz, J.; Gottlieb, D.M.; Petersen, Marianne Kjerstine

2004-01-01

of gels is presented. First, an approach is demonstrated in which no prior knowledge of the separated proteins is used. Alignment of the gels followed by a simple transformation of data makes it possible to analyze the gels in an automated explorative manner by principal component analysis, to determine......Methods for classification of two-dimensional (2-DE) electrophoresis gels based on multivariate data analysis are demonstrated. Two-dimensional gels of ten wheat varieties are analyzed and it is demonstrated how to classify the wheat varieties in two qualities and a method for initial screening...... if the gels should be further analyzed. A more detailed approach is done by analyzing spot volume lists by principal components analysis and partial least square regression. The use of spot volume data offers a mean to investigate the spot pattern and link the classified protein patterns to distinct spots...

Further developments and applications of layer gel dosimetry

International Nuclear Information System (INIS)

Gambarini, G; Carrara, M; Colli, V; Gay, S; Tomatis, S

2004-01-01

The method used to perform dosimetry with Fricke-xylenol orange-infused gels in form of layers remains the most reliable method for in-phantom dose profiling and imaging in high fluxes of thermal and epithermal neutrons. Gel-dosimeters in form of layers really give the possibility not only of obtaining spatial dose distributions but also of achieving measurements of each dose contribution in neutron fields. These advantages arise from the layer-geometry thanks to which neutron transport is not sensibly altered, even if the elemental gel composition is changed adding particular isotopes (for example 10 B), as necessary to perform the separation of dose contributions. The gel matrix composition and the experimental procedures, adopted for both dosimeter preparation and analysis, have been already described in previous works. In the present work, the improvements of the method employed for gel analysis, dose imaging and gel applications are illustrated

Encapsulation of biological species in sol-gel matrices

International Nuclear Information System (INIS)

Finnie, K.S.; Bartlett, J.R.; Woolfrey, J.L.

2000-01-01

Two examples are given of the gelation of silica sols containing bio catalysts, resulting in their encapsulation in porous matrices. Urease was encapsulated in gels made from a mixture of TMOS and alkyltrimethoxysilane. Enzyme activities, monitored by measuring the rate of production of ammoniacal nitrogen as urea was decomposed, ranged up to 60% of that of the unencapsulated species. Anaerobic sulphate-reducing bacteria were encapsulated in a gel produced from colloidal silica, thus avoiding contact with alcohol. The detection of H 2 S produced in the doped gel indicated that the bacteria were able to continue normal metabolic function within the gel matrix. A gel initially doped with ∼ 5 x 10 5 cells cm -3 , exhibited an optimum sulphate reduction rate of 11 ug h -1 cm -3 ; this reduction rate was quickly re-established after storage of the gel for 14 weeks. Copyright (2000) The Australian Ceramic Society

Proceedings of the ATB Model Users Group Conference Held in Phoenix, Arizona on 8-9 February 1996.

Science.gov (United States)

1996-02-09

310 Lookout Dr. Laguna Beach, CA 92651 Phone: 714-497-8446 Fax: 714-497-7013 E-mail: Dr. Kenneth J Saczalski Environmental Research & Safety...Technologists 310 Lookout Drive Laguna Beach, CA 92651 Phone: 714-497-8446 Fax: 714-497-7013 E-mail: Mr. Michael Shanahan BTS Consulting Engineers 1725 North...Weisenfeld Honda R&D 1900 Harpers Way Torrance, CA 90501 Phone: 310-781-5844 Fax: E-mail: Dr Narayan Yoganandan Medical College of Wisconsin

Ionic liquid gel materials: applications in green and sustainable chemistry

OpenAIRE

Marr, Patricia C.; Marr, Andrew C.

2016-01-01

Ionic liquid gel materials offer a way to further utilise ionic liquids in technological applications. Combining the controlled and directed assembly of gels, with the diverse applications of ionic liquids, enables the design of a heady combination of functional tailored materials, leading to the development of task specific / functional ionic liquid gels. This review introduces gels and gel classification, focusing on ionic liquid gels and their potential roles in a more sustainable future. ...

Equipment for production of hydrogel by sol-gel method

International Nuclear Information System (INIS)

Urbanek, V.

1975-01-01

The method of uranyl gel preparation is described by the sol-gel process of the internal gelation type. A laboratory-scale equipment with an output of 1.5 kg of gel per hour was built at the Nuclear Research Institute, Rez; the diameter of the microspheres produced may vary between 0.5 and 4.0 mm. The reliability of the equipment was verified by producing several tens of kilograms of uranyl gels and of gels based on other non-nuclear materials. (author)

Electrochemical behavior of ionically crosslinked polyampholytic gel electrolytes

International Nuclear Information System (INIS)

Chen Wanyu; Tang Haitao; Ou Ziwei; Wang Hong; Yang Yajiang

2007-01-01

An ionic complex of anionic and cationic monomers was obtained by protonation of (N,N-diethylamino)ethylmethacrylate (DEA) with acrylic acid (AAc). Free radical copolymerization of the ionic complex and acrylamide (AAm), yielded the ionically crosslinked polyampholytic gel electrolytes [poly(AAc-DEA-AAm), designated as PADA] using two types of organic solvents containing a lithium salt. The PADA gel electrolyte exhibited good thermal stability shown by the DSC thermogram. The impedance analysis at temperatures ranging from -30 to 75 deg. C indicated that the ionic conductivities of the PADA gel electrolytes were rather close to those of liquid electrolytes. The temperature dependence of the ionic conductivities was found to be in accord with the Arrhenius equation. Moreover, the ionic conductivities of PADA gel electrolytes increased with an increase of the molar ratios of cationic/anionic monomers. The ionic conductivities of PADA gels prepared in solvent mixtures of propylene carbonate, ethyl methyl ether and dioxolane (3:1:1, v/v) were higher than those of PADA gels prepared in propylene carbonate only. Significantly, the ionic conductivities of two kinds of PADA gel electrolytes were in the range of 10 -3 and 10 -4 S cm -1 even at -30 deg. C. The electrochemical windows of PADA gel electrolytes measured by cyclic voltammetry were in the range from -1 V to 4.5 V

Electrophoretic Porosimetry of Sol-Gels

Science.gov (United States)

Snow, L. A.; Smith, D. D.; Sibille, L.; Hunt, A. J.; Ng, J.; Rose, M. Franklin (Technical Monitor)

2000-01-01

It has been hypothesized that gravity has an effect on the formation and resulting microstructure of sol-gels. In order to more clearly resolve the effect of gravity, pores may be non-destructively analyzed in the wet gel, circumventing the shrinkage and coarsening associated with the drying procedure. We discuss the development of an electrophoretic technique, analogous to affinity chromatography, for the determination of pore size distribution and its application to silica gels. Specifically a monodisperse charged dye is monitored by an optical densitometer as it moves through the wet gel under the influence of an electric field. The transmittance data (output) represents the convolution of the dye concentration profile at the beginning of the run (input) with the pore size distribution (transfer function), i.e. linear systems theory applies. Because of the practical difficulty in producing a delta function input dye profile we prefer instead to use a step function. Average pore size is then related to the velocity of this dye front, while the pore size distribution is related to the spreading of the front. Preliminary results of this electrophoretic porosimetry and its application to ground and space-grown samples will be discussed.

Viscoplastic fracture transition of a biopolymer gel.

Science.gov (United States)

Frieberg, Bradley R; Garatsa, Ray-Shimry; Jones, Ronald L; Bachert, John O; Crawshaw, Benjamin; Liu, X Michael; Chan, Edwin P

2018-06-13

Physical gels are swollen polymer networks consisting of transient crosslink junctions associated with hydrogen or ionic bonds. Unlike covalently crosslinked gels, these physical crosslinks are reversible thus enabling these materials to display highly tunable and dynamic mechanical properties. In this work, we study the polymer composition effects on the fracture behavior of a gelatin gel, which is a thermoreversible biopolymer gel consisting of denatured collagen chains bridging physical network junctions formed from triple helices. Below the critical volume fraction for chain entanglement, which we confirm via neutron scattering measurements, we find that the fracture behavior is consistent with a viscoplastic type process characterized by hydrodynamic friction of individual polymer chains through the polymer mesh to show that the enhancement in fracture scales inversely with the squared of the mesh size of the gelatin gel network. Above this critical volume fraction, the fracture process can be described by the Lake-Thomas theory that considers fracture as a chain scission process due to chain entanglements.

Silica scintillating materials prepared by sol-gel methods

International Nuclear Information System (INIS)

Werst, D.W.; Sauer, M.C. Jr.; Cromack, K.R.; Lin, Y.; Tartakovsky, E.A.; Trifunac, A.D.

1993-01-01

Silica was investigated as a rad-hard alternative to organic polymer hosts for organic scintillators. Silica sol-gels were prepared by hydrolysis of tetramethoxysilane in alcohol solutions. organic dyes were incorporated into the gels by dissolving in methanol at the sol stage of gel formation. The silica sol-gel matrix is very rad-hard. The radiation stability of silica scintillators prepared by this method is dye-limited. Transient radioluminescence was measured following excitation with 30 ps pulses of 20 MeV electrons

A theory for fracture of polymeric gels

Science.gov (United States)

Mao, Yunwei; Anand, Lallit

2018-06-01

A polymeric gel is a cross-linked polymer network swollen with a solvent. If the concentration of the solvent or the deformation is increased to substantial levels, especially in the presence of flaws, then the gel may rupture. Although various theoretical aspects of coupling of fluid permeation with large deformation of polymeric gels are reasonably well-understood and modeled in the literature, the understanding and modeling of the effects of fluid diffusion on the damage and fracture of polymeric gels is still in its infancy. In this paper we formulate a thermodynamically-consistent theory for fracture of polymeric gels - a theory which accounts for the coupled effects of fluid diffusion, large deformations, damage, and also the gradient effects of damage. The particular constitutive equations for fracture of a gel proposed in our paper, contain two essential new ingredients: (i) Our constitutive equation for the change in free energy of a polymer network accounts for not only changes in the entropy, but also changes in the internal energy due the stretching of the Kuhn segments of the polymer chains in the network. (ii) The damage and failure of the polymer network is taken to occur by chain-scission, a process which is driven by the changes in the internal energy of the stretched polymer chains in the network, and not directly by changes in the configurational entropy of the polymer chains. The theory developed in this paper is numerically implemented in an open-source finite element code MOOSE, by writing our own application. Using this simulation capability we report on our study of the fracture of a polymeric gel, and some interesting phenomena which show the importance of the diffusion of the fluid on fracture response of the gel are highlighted.

Gadolinium-loaded gel scintillators for neutron and antineutrino detection

Science.gov (United States)

Riddle, Catherine Lynn; Akers, Douglas William; Demmer, Ricky Lynn; Paviet, Patricia Denise; Drigert, Mark William

2016-11-29

A gadolinium (Gd) loaded scintillation gel (Gd-ScintGel) compound allows for neutron and gamma-ray detection. The unique gel scintillator encompasses some of the best features of both liquid and solid scintillators, yet without many of the disadvantages associated therewith. Preferably, the gel scintillator is a water soluble Gd-DTPA compound and water soluble fluorophores such as: CdSe/ZnS (or ZnS) quantum dot (Q-dot) nanoparticles, coumarin derivatives 7-hydroxy-4-methylcoumarin, 7-hydroxy-4-methylcoumarin-3-acetic acid, 7-hydroxycoumarin-3-carboxylic acid, and Alexa Fluor 350 as well as a carbostyril compound, carbostyril 124 in a stable water-based gel, such as methylcellulose or polyacrylamide polymers. The Gd-loaded ScintGel allows for a homogenious distribution of the Gd-DTPA and the fluorophores, and yields clean fluorescent emission peaks. A moderator, such as deuterium or a water-based clear polymer, can be incorporated in the Gd-ScintGel. The gel scintillators can be used in compact detectors, including neutron and antineutrino detectors.

Multiple-phase behavior and memory effect of polymer gel

CERN Document Server

Annaka, M; Nakahira, T; Sugiyama, M; Hara, K; Matsuura, T

2002-01-01

A poly(4-acrylamidosalicylic acid) gel (PASA gel) exhibits multiple phases as characterized by distinct degrees of swelling; the gel can take one of four different swelling values, but none of the intermediate values. The gel has remarkable memory: the phase behavior of the gel depends on whether the gel has experienced the most swollen phase or the most collapsed phase in the immediate past. The information is stored and reversibly erased in the form of a macroscopic phase transition behavior. The structure factors corresponding to these four phases were obtained by SANS, which indicated the presence of characteristic structures depending on pH and temperature, particularly in the shrunken state. (orig.)

In Vitro Cross-Resistance Profiles of Rilpivirine, Dapivirine, and MIV-150, Nonnucleoside Reverse Transcriptase Inhibitor Microbicides in Clinical Development for the Prevention of HIV-1 Infection.

Science.gov (United States)

Giacobbi, Nicholas S; Sluis-Cremer, Nicolas

2017-07-01

Rilpivirine (RPV), dapivirine (DPV), and MIV-150 are in development as microbicides. It is not known whether they will block infection of circulating nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant human immunodeficiency virus type 1 (HIV-1) variants. Here, we demonstrate that the activity of DPV and MIV-150 is compromised by many resistant viruses containing single or double substitutions. High DPV genital tract concentrations from DPV ring use may block replication of resistant viruses. However, MIV-150 genital tract concentrations may be insufficient to inhibit many resistant viruses, including those harboring K103N or Y181C. Copyright © 2017 American Society for Microbiology.

Investigating potential physicochemical errors in polymer gel dosimeters

International Nuclear Information System (INIS)

Sedaghat, Mahbod; Lepage, Martin; Bujold, Rachel

2011-01-01

Measurement errors in polymer gel dosimetry can originate either during irradiation or scanning. One concern related to the exothermic nature of polymerization reaction was that the heat released in polymer gel dosimeters during irradiation modifies their dose response. In this paper, the effect of heat released from the exothermal polymerization reaction on the dose response of a number of dosimeters was studied. In addition, we investigated whether heat-generated geometric distortion existed in newly proposed gel dosimeters that contain highly thermoresponsive polymers. Our results suggest that despite a significant internal temperature increase in some gel compositions, their dose responses are not affected when oxygen is well expelled mechanically from the gel mixture. We also report on significant pre-irradiation instability in some recently developed polymer gel dosimeters but that geometric distortions were not observed. Data obtained by a set of small calibration vials are compared to those obtained from larger phantoms, and potential physicochemical causes of deviations between them are identified.

Investigating potential physicochemical errors in polymer gel dosimeters

Energy Technology Data Exchange (ETDEWEB)

Sedaghat, Mahbod; Lepage, Martin [Centre d' imagerie moleculaire de Sherbrooke, Departement de medecine nucleaire et radiobiologie, Universite de Sherbrooke, Sherbrooke, QC (Canada); Bujold, Rachel, E-mail: martin.lepage@usherbrooke.ca [Service de radio-oncologie, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, QC (Canada)

2011-09-21

Measurement errors in polymer gel dosimetry can originate either during irradiation or scanning. One concern related to the exothermic nature of polymerization reaction was that the heat released in polymer gel dosimeters during irradiation modifies their dose response. In this paper, the effect of heat released from the exothermal polymerization reaction on the dose response of a number of dosimeters was studied. In addition, we investigated whether heat-generated geometric distortion existed in newly proposed gel dosimeters that contain highly thermoresponsive polymers. Our results suggest that despite a significant internal temperature increase in some gel compositions, their dose responses are not affected when oxygen is well expelled mechanically from the gel mixture. We also report on significant pre-irradiation instability in some recently developed polymer gel dosimeters but that geometric distortions were not observed. Data obtained by a set of small calibration vials are compared to those obtained from larger phantoms, and potential physicochemical causes of deviations between them are identified.

Natural gels in the Yucca Mountain Area, Nevada, USA

International Nuclear Information System (INIS)

Levy, S.S.

1991-01-01

Relict gels at Yucca Mountain include pore- and fracture-fillings of silica and zeolite related to diagenetic and hydrothermal alternation of vitric tuffs. Water-rich free gels in fractures at Rainier Mesa consist of smectite with or without silica-rich gel fragments. Gels are being studied for their potential role in transport of radionuclides from a nuclear-waste repository

Perceptions among Dutch men who have sex with men and their willingness to use rectal microbicides and oral pre-exposure prophylaxis to reduce HIV risk--a preliminary study.

Science.gov (United States)

Marra, Elske; Hankins, Catherine A

2015-01-01

Oral pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) tablets and topical PrEP or microbicides containing ARV drugs could help to reduce HIV incidence. These methods hold promise for men who have sex with men (MSM) who are at higher risk of acquiring HIV. This mixed-methods study in the Netherlands explored perceptions of MSM and their willingness to use oral PrEP and rectal microbicides (RM) if made available. Recruited through social media (Facebook and Twitter), 108 MSM completed online questionnaires. Seven of them consented to discuss the survey results in semi-structured interviews. Survey participants preferred a RM that could be applied before and after anal intercourse (60.8%) to daily oral PrEP (20.3%). This preference was based on anticipated user friendliness, hypothetically fewer expected adverse events, and perceptions that RM would be less likely to be confused with ARVs for treatment. Those who preferred oral PrEP had stronger beliefs in the effectiveness of pills, perceived its use as easy, and viewed not requiring sexual partner awareness as advantages. No predictive factors were found for the choice of one prevention method over the other. Although Dutch MSM perceive both oral and topical PrEP positively, many barriers exist to the introduction of these products in the Netherlands. These include lack of regulatory approval of oral PrEP, no proven efficacy as yet for RM, and strong HIV stigma within the MSM population. In-depth qualitative research is needed to further explore the perceptions of MSM to inform implementation of programmes should these HIV prevention methods become available.

Antioxidant effect of green tea on polymer gel dosimeter

International Nuclear Information System (INIS)

Samuel, E J J; Sathiyaraj, P; Deena, T; Kumar, D S

2015-01-01

Extract from Green Tea (GTE) acts as an antioxidant in acrylamide based polymer gel dosimeter. In this work, PAGAT gel was used for investigation of antioxidant effect of GTE.PAGAT was called PAGTEG (Polyacrylamide green tea extract gel dosimeter) after adding GTE. Free radicals in water cause pre polymerization of polymer gel before irradiation. Polyphenols from GTE are highly effective to absorb the free radicals in water. THPC is used as an antioxidant in polymer gel dosimeter but here we were replaced it by GTE and investigated its effect by spectrophotometer. GTE added PAGAT samples response was lower compared to THPC added sample. To increase the sensitivity of the PAGTEG, sugar was added. This study confirmed that THPC was a good antioxidant for polymer gel dosimeter. However, GTE also can be used as an antioxidant in polymer gel if use less quantity (GTE) and add sugar as sensitivity enhancer

Sillica Gel-Amine from Geothermal Sludge

Science.gov (United States)

Muljani, S.; Pujiastuti, C.; Wicaksono, P.; Lutfianingrum, R.

2018-01-01

Silica Gel-Amine (SGA) has been made from geothermal sludge by grafting amine method. Sodium silicate solution is prepared by extracted geothermal sludge powder using sodium hidroxide solution then acidification in the range of pH 5 - 9 by using tartaric acid 1N. The grafting process uses 1 ml of ammonia solution and 10 ml of toluene at a rate of 0.1 ml min-1 accompanied by a reflux process. The amine grafting is done in two methods. The first method is grafting amine in silicate solution and the second method is grafting amine in washed gel. Product SGA was confirmed by FTIR, TGA-DTG and BET characterization. The results show that the pH affects the amount of amine that is grafted onto silica gel. Differences in grafting method affect the size of the pore and surface area. SGA product prepared by grafting washed gel at pH 8 have pore diameter of 12.06 nm, surface area of 173.44 m2g-1, and mass of decomposed amine compound 0.4 mg. In the presence of amine groups on the silica gel surface, these adsorbents may be able to selectively adsorb CO2 gas from natural gas.

Some rheological properties of sodium caseinate-starch gels.

Science.gov (United States)

Bertolini, Andrea C; Creamer, Lawrence K; Eppink, Mieke; Boland, Mike

2005-03-23

The influence of sodium caseinate on the thermal and rheological properties of starch gels at different concentrations and from different botanical sources was evaluated. In sodium caseinate-starch gels, for all starches with the exception of potato starch, the sodium caseinate promoted an increase in the storage modulus and in the viscosity of the composite gel when compared with starch gels. The addition of sodium caseinate resulted in an increase in the onset temperature, the gelatinization temperature, and the end temperature, and there was a significant interaction between starch and sodium caseinate for the onset temperature, the peak temperature, and the end temperature. Microscopy results suggested that sodium caseinate promoted an increase in the homogeneity in the matrix of cereal starch gels.

A NOVEL GEL ELECTROLYTE FOR VALVE-REGULATED LEAD ACID BATTERY

Directory of Open Access Journals (Sweden)

Metin GENÇTEN

2017-03-01

Full Text Available A novel gel electrolyte system used in lead-acid batteries was investigated in this work. The gel systems were prepared by addition different amount of Al2O3, TiO2 and B2O3 into the gelled system consisting of 6 wt% fumed silica and 30 wt% sulfuric acid solution. The anodic peak currents and peak redox capacities of the gel electrolytes were characterized by cyclic voltammetric method. They decreased by the time B2O3 and Al2O3 were used as additives in fumed silica based gel electrolyte system. However, these values increased by the adding 3.0 wt% of TiO2. The solution and charge transfer resistances of the gel electrolytes were investigated by electrochemical impedance spectroscopy. While the solution resistances were lower in gel systems having different amount additives than pure fumed silica based gel, the charge transfer resistance was the lowest in gel electrolytes consisting fumed silica and fumed silica-TiO2. The battery performances were studied by obtaining discharge curves of prepared gel electrolytes. The performance of gelled systems were higher than that of non-gelled electrolyte at room temperature. The mixture of fumed silica-TiO2 was suggested an alternative gel formulation for gel VRLA batteries.

Coordination Polymer Gels by Electron Beam

Energy Technology Data Exchange (ETDEWEB)

Lee, Ji Ha; Cho, Young Je; Jung, Jong Hwa [Gyeongsang National Univ., Jinju (Korea, Republic of)

2011-07-01

Hydrogenation of a pyridine derivative possessing tetrazole moieties as end groups, without long alkyl chain groups, results in the formation of a Mg(NO{sub 3}){sub 2} coordination polymer gel. The polymer exhibits a strong fluorescence enhancement upon gel formation. 1 can also be gloated with a variety of magnesium anions such as SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, Cl{sup -}, Br{sup -} and I{sup -}, indicating that the coordination polymer gel formation of 1 does not strongly depends on anions. The Seam and ABM images of Mg{sup 2+} coordination polymer gel 1 display a flabbier network with several micrometers long, widths in the range 60-70 nm and thicknesses of about 3 nm. In addition, photophysical studies show that the hydrogel exhibits a typical {pi}-{pi} transition and gives rise to high fluorescence behavior. The coordination polymer hydrogel exhibits viscoelastic behavior as evidenced from the rheological studies.

PCR amplification on microarrays of gel immobilized oligonucleotides

Science.gov (United States)

Strizhkov, Boris; Tillib, Sergei; Mikhailovich, Vladimir; Mirzabekov, Andrei

2003-11-04

The invention relates two general methods for performing PCR amplification, combined with the detection and analysis of the PCR products on a microchip. In the first method, the amplification occurs both outside and within a plurality of gel pads on a microchip, with at least one oligonucleotide primer immobilized in a gel pad. In the second method, PCR amplification also takes place within gel pads on a microchip, but the pads are surrounded by a hydrophobic liquid such as that which separates the individual gel pads into environments which resemble micro-miniaturized test tubes.

Protein electrophoretic migration data from custom and commercial gradient gels

Directory of Open Access Journals (Sweden)

Andrew J. Miller

2016-12-01

Full Text Available This paper presents data related to the article “A method for easily customizable gradient gel electrophoresis” (A.J. Miller, B. Roman, E.M. Norstrom, 2016 [1]. Data is presented on the rate of electrophoretic migration of proteins in both hand-poured and commercially acquired acrylamide gradient gels. For each gel, migration of 9 polypeptides of various masses was measured upon completion of gel electrophoresis. Data are presented on the migration of proteins within separate lanes of the same gel as well as migration rates from multiple gels.

Fabrication and Optimization of a PAGATA Gel Dosimeter: Increasing the Melting Point of the PAGAT Gel Dosimeter with Agarose Additive

Directory of Open Access Journals (Sweden)

Bakhtiar Azadbakht

2010-12-01

Full Text Available Introduction: The PAGAT polymer gel dosimeter melts at 30 ˚C and even at room temperature during the summer, so it needs to be kept in a cool place such as a refrigerator. To increase the stability of the PAGAT gel, different amounts of agarose were added to the PAGAT gel composition and the PAGATA gel was manufactured. Material and Methods: The PAGATA gel vials were irradiated using a Co-60 machine. Then, the samples were evaluated using a 1.5 T Siemens MRI scanner. The ingredients of the PAGATA normoxic gel dosimeter were 4.5% N-N' methylen-bis-acrylamide, 4.5% acrylamide, 4.5% gelatine, 5 mM tetrakis (THPC, 0.01 mM hydroquinone (HQ, 0.5% agarose and 86% de-ionized water (HPLC. Results: Melting point and sensitivity of the PAGAT gel dosimeter with addition of 0.0, 0.3, 0.5, 1.0, 1.5 and 2.0% of agarose were measured, in which the melting points were increased to 30, 82, 86, 88, 89 and 90°C and their sensitivities found to be 0.113, 0.1059, 0.125, 0.122, 0.115 and 0.2  respectively. Discussion and Conclusions: Adding agarose increased the sensitivity and background R2 of the evaluated samples. The optimum amount of agarose was found to be 0.5% regarding these parameters and also the melting point of the gel dosimeter. A value of 0.5% agarose was found to be an optimum value considering the increase of sensitivity to 0.125 and melting point to 86°C but at the expense of increasing the background R2 to 4.530.

Implementation of MRI gel dosimetry in radiation therapy

International Nuclear Information System (INIS)

Baeck, S.Aa.J.

1998-12-01

Gel dosimetry was used together with magnetic resonance imaging (MRI) to measure three-dimensional absorbed dose distributions in radiation therapy. Two different dosimeters were studied: ferrous- and monomer gel, based on the principles of radiation-induced oxidation and polymerisation, respectively. Single clinical electron and photon beams were evaluated and gel dose distributions were mainly within 2% of conventional detector results. The ferrous-gel was also used for clinical proton beams. A decrease in signal per absorbed dose was found close to the end of the range of the protons (15-20%). This effect was explained as a linear energy transfer dependence, further supported with Monte Carlo simulations. A method for analysing and comparing data from treatment planning system (TPS) and gel measurements was developed. The method enables a new pixel by pixel evaluation, isodose comparison and dose volume histogram verification. Two standard clinical radiation therapy procedures were examined using the developed TPS verification method. The treatment regimes included several beams of different radiation qualities. The TPS calculated data were in very good agreement with the dose distribution measured by the ferrous-gel. However, in a beam abutment region, larger dose difference was found. Beam adjustment errors and a minor TPS underestimation of the lateral scatter contribution outside the primary electron beam may explain the discrepancy. The overall uncertainty in the ferrous-gel dose determination was considerably reduced using an optimised MRI acquisition protocol and a new MRI scanner. The relative dose uncertainty was found to be better than 3.3% for all dose levels (95% confidence level). Using the method developed for comparing measured gel data with calculated treatment plans, the gel dosimetry method was proven to be a useful tool for radiation treatment planning verification

Implementation of MRI gel dosimetry in radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Baeck, S.Aa.J

1998-12-01

Gel dosimetry was used together with magnetic resonance imaging (MRI) to measure three-dimensional absorbed dose distributions in radiation therapy. Two different dosimeters were studied: ferrous- and monomer gel, based on the principles of radiation-induced oxidation and polymerisation, respectively. Single clinical electron and photon beams were evaluated and gel dose distributions were mainly within 2% of conventional detector results. The ferrous-gel was also used for clinical proton beams. A decrease in signal per absorbed dose was found close to the end of the range of the protons (15-20%). This effect was explained as a linear energy transfer dependence, further supported with Monte Carlo simulations. A method for analysing and comparing data from treatment planning system (TPS) and gel measurements was developed. The method enables a new pixel by pixel evaluation, isodose comparison and dose volume histogram verification. Two standard clinical radiation therapy procedures were examined using the developed TPS verification method. The treatment regimes included several beams of different radiation qualities. The TPS calculated data were in very good agreement with the dose distribution measured by the ferrous-gel. However, in a beam abutment region, larger dose difference was found. Beam adjustment errors and a minor TPS underestimation of the lateral scatter contribution outside the primary electron beam may explain the discrepancy. The overall uncertainty in the ferrous-gel dose determination was considerably reduced using an optimised MRI acquisition protocol and a new MRI scanner. The relative dose uncertainty was found to be better than 3.3% for all dose levels (95% confidence level). Using the method developed for comparing measured gel data with calculated treatment plans, the gel dosimetry method was proven to be a useful tool for radiation treatment planning verification 103 refs, 20 figs, 6 tabs

Agarose gel electrophoresis for the separation of DNA fragments.

Science.gov (United States)

Lee, Pei Yun; Costumbrado, John; Hsu, Chih-Yuan; Kim, Yong Hoon

2012-04-20

Agarose gel electrophoresis is the most effective way of separating DNA fragments of varying sizes ranging from 100 bp to 25 kb(1). Agarose is isolated from the seaweed genera Gelidium and Gracilaria, and consists of repeated agarobiose (L- and D-galactose) subunits(2). During gelation, agarose polymers associate non-covalently and form a network of bundles whose pore sizes determine a gel's molecular sieving properties. The use of agarose gel electrophoresis revolutionized the separation of DNA. Prior to the adoption of agarose gels, DNA was primarily separated using sucrose density gradient centrifugation, which only provided an approximation of size. To separate DNA using agarose gel electrophoresis, the DNA is loaded into pre-cast wells in the gel and a current applied. The phosphate backbone of the DNA (and RNA) molecule is negatively charged, therefore when placed in an electric field, DNA fragments will migrate to the positively charged anode. Because DNA has a uniform mass/charge ratio, DNA molecules are separated by size within an agarose gel in a pattern such that the distance traveled is inversely proportional to the log of its molecular weight(3). The leading model for DNA movement through an agarose gel is "biased reptation", whereby the leading edge moves forward and pulls the rest of the molecule along(4). The rate of migration of a DNA molecule through a gel is determined by the following: 1) size of DNA molecule; 2) agarose concentration; 3) DNA conformation(5); 4) voltage applied, 5) presence of ethidium bromide, 6) type of agarose and 7) electrophoresis buffer. After separation, the DNA molecules can be visualized under uv light after staining with an appropriate dye. By following this protocol, students should be able to: Understand the mechanism by which DNA fragments are separated within a gel matrix Understand how conformation of the DNA molecule will determine its mobility through a gel matrix Identify an agarose solution of appropriate

Pulsed-field gel electrophoresis of bacterial chromosomes.

Science.gov (United States)

Mawer, Julia S P; Leach, David R F

2013-01-01

The separation of fragments of DNA by agarose gel electrophoresis is integral to laboratory life. Nevertheless, standard agarose gel electrophoresis cannot resolve fragments bigger than 50 kb. Pulsed-field gel electrophoresis is a technique that has been developed to overcome the limitations of standard agarose gel electrophoresis. Entire linear eukaryotic chromosomes, or large fragments of a chromosome that have been generated by the action of rare-cutting restriction endonucleases, can be separated using this technique. As a result, pulsed-field gel electrophoresis has many applications, from karyotype analysis of microbial genomes, to the analysis of chromosomal strand breaks and their repair intermediates, to the study of DNA replication and the identification of origins of replication. This chapter presents a detailed protocol for the preparation of Escherichia coli chromosomal DNA that has been embedded in agarose plugs, digested with the rare-cutting endonuclease NotI, and separated by contour-clamped homogeneous field electrophoresis. The principles in this protocol can be applied to the separation of all fragments of DNA whose size range is between 40 kb and 1 Mb.

The Synthesis of a Novel Cellulose Physical Gel

Directory of Open Access Journals (Sweden)

Jiufang Duan

2014-01-01

Full Text Available Cellulose possessing β-cyclodextrin (β-CD was used as a host molecule and cellulose possessing ferrocene (Fc as a guest polymer. Infrared spectra, differential scanning calorimetry (DSC, ultraviolet spectroscopy (UV, and contact angle analysis were used to characterise the material structure and the inclusion behaviour. The results showed that the β-CD-cellulose and the Fc-cellulose can form inclusion complexes. Moreover, ferrocene oxidation, and reduction of state can be adjusted by sodium hypochlorite (NaClO as an oxidant and glutathione (GSH as a reductant. In this study, a physical gel based on β-CD-cellulose/Fc-cellulose was formed under mild conditions in which autonomous healing between cut surfaces occurred after 24 hours. The physical gel can be controlled in the sol-gel transition. The compressive strength of the Fc-cellulose/β-CD-cellulose gel increased with increased cellulose concentration. The host-guest interaction between the side chains of cellulose could strengthen the gel. The cellulose physical gel may eventually be used as a stimulus-responsive, healing material in biomedical applications.

Applications of sol gel ceramic coatings

International Nuclear Information System (INIS)

Barrow, D.

1996-01-01

The sol gel method is a chemical technique in which polycrystalline ceramic films are fabricated from a solution of organometallic precursors. The technique is attractive for many industrial applications because it is a simple (films are processed in air), flexible (can be used to coat complex geometries) and cost effective (does not require expensive equipment) process. In addition, dense, high quality coatings can be achieved at much lower temperatures than is generally required for sintering bulk ceramics. In this paper the conventional sol gel method and the new datec process are reviewed and potential applications of sol gel coatings in automotive, aerospace, petrochemical, nuclear and electronic industries are discussed. (orig.)

The Gel Generator option

International Nuclear Information System (INIS)

Boyd, R.E.

1999-01-01

The development of a national policy for guaranteeing an ample supply of 99m Tc to nuclear medicine, involves issues which go beyond the means by which radioactivation is achieved. Indeed, in such an exercise the pragmatic dictates of business and the sensitivities of politics must also be taken into account. Furthermore where a preference towards the nuclear reactor or the potential of cyclotrons is being questioned, the debate is incomplete if the only options that are considered are the fission-based 99 Mo generator versus the direct cyclotron production of 99m Tc. There is a third option (also neutron γ-based), an alternative to the fission 99 Mo generator, which ought not be overlooked. The application of low specific activity (n,γ) 99 Mo to a new type of generator, the Gel Generator, has been the focus of much research, particularly in Australia and more recently in China. After the initial concept had been established in the laboratory, the Australian researchers then undertook a comprehensive program of tests on the Gel Generator to assess its potential, either in the clinical laboratory or the centralised radiopharmacy, for supplying 99m Tc suitable for nuclear medicine. The outcome of this program was a clear indication that the Gel Generator innovation had the capability to provide both technical and economic advantages to the nuclear medicine industry. These advantages are described. Since that time the Gel Generator has been selected for routine use in China where it now satisfies more than 30% of the 99m Tc demand. (author)

Meso-decorated self-healing gels: network structure and properties

Science.gov (United States)

Gong, Jin; Sawamura, Kensuke; Igarashi, Susumu; Furukawa, Hidemitsu

2013-04-01

Gels are a new material having three-dimensional network structures of macromolecules. They possess excellent properties as swellability, high permeability and biocompatibility, and have been applied in various fields of daily life, food, medicine, architecture, and chemistry. In this study, we tried to prepare new multi-functional and high-strength gels by using Meso-Decoration (Meso-Deco), one new method of structure design at intermediate mesoscale. High-performance rigid-rod aromatic polymorphic crystals, and the functional groups of thermoreversible Diels-Alder reaction were introduced into soft gels as crosslinkable pendent chains. The functionalization and strengthening of gels can be realized by meso-decorating the gels' structure using high-performance polymorphic crystals and thermoreversible pendent chains. New gels with good mechanical properties, novel optical properties and thermal properties are expected to be developed.

Contaminant containment using polymer gel barriers

NARCIS (Netherlands)

Darwish, M.I.M.; Rowe, R.K.; Maarel, van der J.R.C.; Pel, L.; Huinink, H.P.; Zitha, P.L.J.

2004-01-01

Polymer gels are well known in the oil industry, but their potential for use as barriers to contaminant transport has not previously received significant study. As a first step, this paper examines the potential for a polyelectrolyte gel to serve as a barrier to the migration of sodium chloride. Two

Sol-gel synthesis of hydroxyapatite

International Nuclear Information System (INIS)

Zupanski, M.D.; Lucena, M.P.P.; Bergmann, C.P.

2010-01-01

Hydroxyapatite (HAp) has been established as the calcium phosphate based compound with most applications in the biological field. Among the numerous techniques for synthesis of HAp, the sol-gel processing route affords great control over purity and formed phases using low processing temperatures. In addition, the sol-gel approach offers an option for homogeneous HAp coating on metal substrates, as well as the ability to generate nanocrystalline powders. In this work, the sol-gel synthesis of HAp was investigated employing triethyl phosphate and calcium nitrate tetrahydrate as phosphorous and calcium precursors, respectively. The aging effect on phase composition and powder morphology of the final product was studied in terms of temperature and aging time. The powders were studied by using X-ray diffraction, Fourier transform infrared spectroscopy, particle size distribution by laser diffraction and scanning electron microscopy. (author)

Fundamentals of Polymer Gel Dosimeters

Science.gov (United States)

McAuley, Kim B.

2006-12-01

The recent literature on polymer gel dosimetry contains application papers and basic experimental studies involving polymethacrylic-acid-based and polyacrylamide-based gel dosimeters. The basic studies assess the relative merits of these two most commonly used dosimeters, and explore the effects of tetrakis hydroxymethyl phosphonium chloride (THPC) antioxidant on dosimeter performance. Polymer gel dosimeters that contain THPC or other oxygen scavengers are called normoxic dosimeters, because they can be prepared under normal atmospheric conditions, rather than in a glove box that excludes oxygen. In this review, an effort is made to explain some of the underlying chemical phenomena that affect dosimeter performance using THPC, and that lead to differences in behaviour between dosimeters made using the two types of monomer systems. Progress on the development of new more effective and less toxic dosimeters is also reported.

Injectable biocompatible and biodegradable pH-responsive hollow particle gels containing poly(acrylic acid): the effect of copolymer composition on gel properties.

Science.gov (United States)

Halacheva, Silvia S; Adlam, Daman J; Hendow, Eseelle K; Freemont, Tony J; Hoyland, Judith; Saunders, Brian R

2014-05-12

The potential of various pH-responsive alkyl (meth)acrylate ester- and (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA), to form pH-sensitive biocompatible and biodegradable hollow particle gel scaffolds for use in non-load-bearing soft tissue regeneration have been explored. The optimal copolymer design criteria for preparation of these materials have been established. Physical gels which are both pH- and redox-sensitive were formed only from PMMA-AA copolymers. MMA is the optimal hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g., MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels were prepared at physiological pH range from concentrated dispersions of swollen, hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels with lower AA contents feature lower swelling ratios, mechanical strengths, and ductilities. Increasing the swelling ratio (e.g., through increasing AA content) decreased the intraparticle elasticity; however, intershell contact and gel elasticity were found to increase. The mechanical properties and performance of the gels were tuneable upon varying the copolymers' compositions and the structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were more elastic and ductile. The biodegradability and cytotoxicity of the new hollow particle gels were tested for the first time and related to their composition, mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels have shown good biocompatibility, biodegradability, strength, and interconnected porosity and therefore have good potential as a tissue repair agent.

White-light-emitting supramolecular gels.

Science.gov (United States)

Praveen, Vakayil K; Ranjith, Choorikkat; Armaroli, Nicola

2014-01-07

Let there be light, let it be white: Recent developments in the use of chromophore-based gels as scaffolds for the assembly of white-light-emitting soft materials have been significant. The main advantage of this approach lies in the facile accommodation of selected luminescent components within the gel. Excitation-energy-transfer processes between these components ultimately generate the desired light output. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sol-gel-state of hydrated zirconium dioxide

International Nuclear Information System (INIS)

Karakchiev, L.G.; Lyakhov, N.Z.

1995-01-01

The change in viscosity and density of a system in the course of sol-gel-xerogel has been traced. The size and molecular mass of particles in sol have been determined. Initial sol is practically a monodisperse system. Gel is a spatial net of similar particles. Reversible character of sol-gel transition with a change in water content in the system suggests instability of the bond between the particles in the structure of the solid state body formed. 11 refs.; 4 figs

Molecular Gels Materials with Self-Assembled Fibrillar Networks

CERN Document Server

Weiss, Richard G

2006-01-01

Molecular gels and fibrillar networks – a comprehensive guide to experiment and theory Molecular Gels: Materials with Self-Assembled Fibrillar Networks provides a comprehensive treatise on gelators, especially low molecular-mass gelators (LMOGs), and the properties of their gels. The structures and modes of formation of the self-assembled fibrillar networks (SAFINs) that immobilize the liquid components of the gels are discussed experimentally and theoretically. The spectroscopic, rheological, and structural features of the different classes of LMOGs are also presented. Many examples of the application of the principal analytical techniques for investigation of molecular gels (including SANS, SAXS, WAXS, UV-vis absorption, fluorescence and CD spectroscopies, scanning electron, transmission electron and optical microscopies, and molecular modeling) are presented didactically and in-depth, as are several of the theories of the stages of aggregation of individual LMOG molecules leading to SAFINs. Several actua...

DNA gel electrophoresis: the reptation model(s).

Science.gov (United States)

Slater, Gary W

2009-06-01

DNA gel electrophoresis has been the most important experimental tool to separate DNA fragments for several decades. The introduction of PFGE in the 1980s and capillary gel electrophoresis in the 1990s made it possible to study, map and sequence entire genomes. Explaining how very large DNA molecules move in a gel and why PFGE is needed to separate them has been an active field of research ever since the launch of the journal Electrophoresis. This article presents a personal and historical overview of the development of the theory of gel electrophoresis, focusing on the reptation model, the band broadening mechanisms, and finally the factors that limit the read length and the resolution of electrophoresis-based sequencing systems. I conclude with a short discussion of some of the questions that remain unanswered.

Performance of Magnetic Filter for Separation of Magnetic Gel Particles

OpenAIRE

栗延, 俊太郎; 尾崎, 博明; 渡辺, 恒雄; クリノブ, シュンタロウ; オザキ, ヒロアキ; ワタナベ, ツネオ; Shuntaro, KURINOBU; Hiroaki, OZAKI; Tuneo, WATANABE

2003-01-01

We have developed a new wastewater treatment process using magnetic gel particles containing immobilized microorganisms and magnetic particles. The performance of magnetic gel particles using a magnetic filter is very important to control the process. In this study, the performance of a magnetic filter was studied for magnetic gel, particles. Agar particles containing magnetite particles were used as gel particles. The recovery and the relative retention area of magnetic gel particles on the ...

Development of an injectable chitosan/marine collagen composite gel

International Nuclear Information System (INIS)

Wang Wei; Itoh, Soichiro; Aizawa, Tomoyasu; Demura, Makoto; Okawa, Atsushi; Sakai, Katsuyoshi; Ohkuma, Tsuneo

2010-01-01

A chitosan/marine-originated collagen composite has been developed. This composite gel was characterized and its biocompatibility, as well as an inflammatory reaction, was observed. The chitosan gel including N-3-carboxypropanoil-6-O-(carboxymethyl) chitosan of 3 mol%, 6-O-(carboxymethyl) chitosan of 62 mol% and 6-O-(carboxymethyl) chitin of 35 mol% was prepared and compounded with the salmon atelocollagen (SA) gel at different mixture ratios. The composite gels were injected subcutaneously in to the back of rats. The specimens were harvested for a histological survey as well as a tumor necrosis factor-alpha (TNF-α) assay by ELISA. The inflammatory cell infiltration and release of TNF-α were successively controlled low with the ratio of SA to chitosan at 10:90 or 20:80. The SA gel first, within 2 weeks, and then chitosan in the composite gel were slowly absorbed after implantation, followed by soft tissue formation. It is expected that this composite gel will be available as a carrier for tissue filler and drug delivery systems.

A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen

Energy Technology Data Exchange (ETDEWEB)

Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J, E-mail: wang@ym.edu.tw [Institute of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Li-Nung St., Shih-Pai, Taipei, Taiwan 112 (China)

2011-04-15

Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen

International Nuclear Information System (INIS)

Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J

2011-01-01

Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

Role of gel dosimeters in boron neutron capture therapy

International Nuclear Information System (INIS)

Khajeali, Azim; Farajollahi, Ali Reza; Khodadadi, Roghayeh; Kasesaz, Yaser; Khalili, Assef

2015-01-01

Gel dosimeters have acquired a unique status in radiotherapy, especially with the advent of the new techniques in which there is a need for three-dimensional dose measurement with high spatial resolution. One of the techniques in which the use of gel dosimeters has drawn the attention of the researchers is the boron neutron capture therapy. Exploring the history of gel dosimeters, this paper sets out to study their role in the boron neutron capture therapy dosimetric process. - Highlights: • Gel dosimeters have been investigated. • Conventional dosimetric proses of BNCT has been investigated. • Role of gel dosimeters in BNCT has been investigated

Fast Processing of Sol-Gel TCO

NARCIS (Netherlands)

Deelen, J. van; Rem, M.; Arfsten, N.; Buskens, P.P.

2016-01-01

TCOs are usually deposited using sputtering or chemical vapor deposition, which have a yield of typically 50-75%. The sol gel method does not need low pressure and can be done with a high precursor yield in the range of 90 – 100%. Sol gel enables also the TCO function as a planarization or

Freeze-dried, mucoadhesive system for vaginal delivery of the HIV microbicide, dapivirine: optimisation by an artificial neural network.

Science.gov (United States)

Woolfson, A David; Umrethia, Manish L; Kett, Victoria L; Malcolm, R Karl

2010-03-30

Dapivirine mucoadhesive gels and freeze-dried tablets were prepared using a 3x3x2 factorial design. An artificial neural network (ANN) with multi-layer perception was used to investigate the effect of hydroxypropyl-methylcellulose (HPMC): polyvinylpyrrolidone (PVP) ratio (X1), mucoadhesive concentration (X2) and delivery system (gel or freeze-dried mucoadhesive tablet, X3) on response variables; cumulative release of dapivirine at 24h (Q(24)), mucoadhesive force (F(max)) and zero-rate viscosity. Optimisation was performed by minimising the error between the experimental and predicted values of responses by ANN. The method was validated using check point analysis by preparing six formulations of gels and their corresponding freeze-dried tablets randomly selected from within the design space of contour plots. Experimental and predicted values of response variables were not significantly different (p>0.05, two-sided paired t-test). For gels, Q(24) values were higher than their corresponding freeze-dried tablets. F(max) values for freeze-dried tablets were significantly different (2-4 times greater, p>0.05, two-sided paired t-test) compared to equivalent gels. Freeze-dried tablets having lower values for X1 and higher values for X2 components offered the best compromise between effective dapivirine release, mucoadhesion and viscosity such that increased vaginal residence time was likely to be achieved. Copyright (c) 2009 Elsevier B.V. All rights reserved.

ANALISA DAYA SERAP SILIKA GEL BERBAHAN DASAR ABU SEKAM PADI

Directory of Open Access Journals (Sweden)

Hendriwan Fahmi

2016-08-01

Full Text Available Rice husk ash Silica Gel is aproduct which call be used in preventing the humidity by absorbing the water ion on the water andonthe air. This absorbing isbased onthe size, the composition and the total amount ofpolluter which contained on the Silica Gel. The purpose of making this silica gel is to seehow much thiskind of Silica Gel can absorb and compare it to the synthetic one,and also processing rise husk ashto be something useful, Ion water can be absorbed much more by using this natural silica gel if it is compared to the synthetic silica gel. This is because of its capable inabsorbing more –OHand O from water and air. Afterdoing a research with column method, silica gel was beingput in 50 ml water. Fromthis research, natural silica can absorb much more water (0.0010 gr/ml, 0.285 % water level ofweigh in comparing with synthetic one (0.008gr/ml with 0.248 %water level ofweight andsintering (0,007 gr/ml 0.253%water level and non-sintering silica gel contains 39.22 % weight of silica, 30.93 %weight of sintering silica gel, and 33.40 % of the synthetic. More silica and water level, means more total amount of absorbing. This silica gel application is considered with capability ofabsorbing andthe level of the water.

Characterization of a humic gel synthesized from an activated epoxy silica gel

International Nuclear Information System (INIS)

Barbot, C.; Pieri, J.; Durand, J.P.; Goudard, F.; Czerwinski, K.; Vial, M.; Buckau, G.; Kim, J.I.; Moulin, V.

2002-01-01

Purified humic acid has been covalently bound on activated epoxy silica gel particles. Determination of physical properties and chemical properties was conducted in order to characterize the material at different stages of the preparation. FTIR spectra and the PEC of the surface bound humic acid is very similar to that of humic acid starting material. This shows that the humic acid was not deteriorated during the surface binding process. This humic gel can be used as an analogue for sediment associated humic acid, with the advantage that covalently bound humic acid does not desorb, and thus allows for simple species separation between non-complexed and humic bound metal ions in batch and column experiments

A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action.

Science.gov (United States)

Fetherston, Susan M; Boyd, Peter; McCoy, Clare F; McBride, Marcella C; Edwards, Karen-Leigh; Ampofo, Stephen; Malcolm, R Karl

2013-02-14

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25mg dapivirine and various quantities of maraviroc (50-400mg) were manufactured and in vitro release assessed. The 25mg dapivirine and 100mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing. Copyright © 2012 Elsevier B.V. All rights reserved.

Volume phase transitions of cholesteric liquid crystalline gels.

Science.gov (United States)

Matsuyama, Akihiko

2015-05-07

We present a mean field theory to describe anisotropic deformations of a cholesteric elastomer without solvent molecules and a cholesteric liquid crystalline gel immersed in isotropic solvents at a thermal equilibrium state. Based on the neoclassical rubber theory of nematic elastomers, we derive an elastic energy and a twist distortion energy, which are important to determine the shape of a cholesteric elastomer (or gel). We demonstrate that when the elastic energy dominates in the free energy, the cholesteric elastomer causes a spontaneous compression in the pitch axis and elongates along the director on the plane perpendicular to the pitch axis. Our theory can qualitatively describe the experimental results of a cholesteric elastomer. We also predict the first-order volume phase transitions and anisotropic deformations of a gel at the cholesteric-isotropic phase transition temperature. Depending on a chirality of a gel, we find a prolate or oblate shape of cholesteric gels.

Volume phase transitions of cholesteric liquid crystalline gels

Energy Technology Data Exchange (ETDEWEB)

Matsuyama, Akihiko, E-mail: matuyama@bio.kyutech.ac.jp [Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Kawazu 680-4, Iizuka, Fukuoka 820-8502 (Japan)

2015-05-07

We present a mean field theory to describe anisotropic deformations of a cholesteric elastomer without solvent molecules and a cholesteric liquid crystalline gel immersed in isotropic solvents at a thermal equilibrium state. Based on the neoclassical rubber theory of nematic elastomers, we derive an elastic energy and a twist distortion energy, which are important to determine the shape of a cholesteric elastomer (or gel). We demonstrate that when the elastic energy dominates in the free energy, the cholesteric elastomer causes a spontaneous compression in the pitch axis and elongates along the director on the plane perpendicular to the pitch axis. Our theory can qualitatively describe the experimental results of a cholesteric elastomer. We also predict the first-order volume phase transitions and anisotropic deformations of a gel at the cholesteric-isotropic phase transition temperature. Depending on a chirality of a gel, we find a prolate or oblate shape of cholesteric gels.

Laser CT evaluation on normoxic PAGAT gel dosimeter

International Nuclear Information System (INIS)

Kumar, D S; Samuel, E J J; Watanabe, Y

2013-01-01

Optical computed tomography has been shown to be a potentially useful imaging tool for the radiation therapy physicists. In radiation therapy, researchers have used optical CT for the readout of 3D dosimeters. The purpose of this paper is to describe the initial evaluation of a newly fabricated laser CT scanner for 3D gel dosimetry which works using the first generation principle. A normoxic PAGAT (Polyacrylamide Gelatin and Tetrakis) gel is used as a dosimeter for this analysis. When a laser passes through the gel phantom, absorption and scattering of photon take place. The optical attenuation coefficient of the laser can be obtained by measuring its intensity after passing through the gel by a sensor. The scanner motion is controlled by a computer program written in Microsoft Visual C++. Reconstruction and data analysis on the irradiated gel phantom is performed by suitable algorithm using Matlab software.

Optical CT evaluation on normoxic polymer gel dosimeter

International Nuclear Information System (INIS)

Samuel, E. James Jebaseelan

2013-01-01

Optical computed tomography has been shown to be a potentially useful imaging tool for the radiation therapy physicists. In radiation therapy, researchers have used optical CT for the readout of 3D dosimeters. The purpose of this paper is to explicate the initial evaluation of a newly fabricated laser CT scanner for '3D gel dosimetry' which works in the first generation principle. The normoxic PAGAT (Polyacrylamide Gelatin and Tetrakis) gel is used as a dosimeter for this analysis. When laser passes through this gel phantom, absorption and scattering of photon take place. The optical attenuation coefficient of the laser can be obtained by measuring its intensity after passing through the gel by a sensor.The scanner motion is controlled by the program written in Microsoft Visual C++. Reconstruction and data analysis on the irradiated gel phantom is performed by suitable algorithm using Matlab software. (author)

Sol-gel materials for optofluidics - process and applications

DEFF Research Database (Denmark)

Mikkelsen, Morten Bo Lindholm

2011-01-01

This Ph.D. thesis is concerned with the use of sol-gel materials in optofluidic applications and the physics of DNA molecules in nanoconfinement. The bottom-up formation of solid material, which is provided by the sol-gel process, enables control of the chemical composition and porosity...... of the material. At early stages of gelation, thin gel coatings can be structured by nanoimprint lithography, and purely inorganic silica materials can be obtained by subsequent thermal annealing. The sol-gel process thus constitutes a unique method for nanofabrication of silica materials of special properties....... In this work, sol-gel silica is introduced as a new material class for the fabrication of lab-on-a-chip devices for DNA analysis. An imprint process with a rigid, non-permeable stamp was developed, which enabled fabrication of micro- and nanofluidic silica channels in a single process step without use of any...

Non-stationary heat transfer in gels applied to biotehnology

Directory of Open Access Journals (Sweden)

Pokusaev Boris

2017-01-01

Full Text Available Unsteady heat transfer in agarose gels of various concentrations was studied in order to make a breakthrough in the technology of 3-D additive bioprinting. Data on the kinetics of the phase transformation was obtained using spectroscopy as a function of temperature during the formation of agarose hydrogel. The dynamics of aging was investigated for gels of different densities. The time dependence of the structural changes was obtained. Particular attention was paid to the changes in the structure of the gel due to the processes of evaporation of the liquid during the gel formation and during long-term storage. Experiments were performed to determine the dynamics of the temperature fields simultaneously with heat flux measurements during the formation of agarose gels from different initial concentrations. A technique based on experimental data for the computations of the thermophysical coefficients of agarose gels was developed.

A method for easily customizable gradient gel electrophoresis.

Science.gov (United States)

Miller, Andrew J; Roman, Brandon; Norstrom, Eric

2016-09-15

Gradient polyacrylamide gel electrophoresis is a powerful tool for the resolution of polypeptides by relative mobility. Here, we present a simplified method for generating polyacrylamide gradient gels for routine analysis without the need for specialized mixing equipment. The method allows for easily customizable gradients which can be optimized for specific polypeptide resolution requirements. Moreover, the method eliminates the possibility of buffer cross contamination in mixing equipment, and the time and resources saved with this method in place of traditional gradient mixing, or the purchase of pre-cast gels, are noteworthy given the frequency with which many labs use gradient gel SDS-PAGE. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison effect of azithromycin gel 2% with clindamycin gel 1% in patients with acne.

Science.gov (United States)

Mokhtari, Fatemeh; Faghihi, Gita; Basiri, Akram; Farhadi, Sadaf; Nilforoushzadeh, Mohammadali; Behfar, Shadi

2016-01-01

Acne vulgaris is the most common skin disease. Local and systemic antimicrobial drugs are used for its treatment. But increasing resistance of Propionibacterium acnes to antibiotics has been reported. In a double-blind clinical trial, 40 patients with mild to moderate acne vulgaris were recruited. one side of the face was treated with Clindamycin Gel 1% and the other side with Azithromycin Topical Gel 2% BID for 8 weeks and then they were assessed. Average age was 21. 8 ± 7 years. 82.5% of them were female. Average number of papules, pustules and comedones was similarly reduced in both groups and, no significant difference was observed between the two groups (P > 0.05, repeated measurs ANOVA). The mean indexes of ASI and TLC also significantly decreased during treatment in both groups, no significant difference was observed between the two groups. (P > 0.05, repeated measurs ANOVA). Also, impact of both drugs on papules and pustules was 2-3 times greater than the effect on comedones. Average satisfaction score was not significant between the two groups (P = 0.6, repeated measurs ANOVA). finally, frequency distribution of complications was not significant between the two groups (P > 0.05, Fisher Exact test). Azithromycin gel has medical impact at least similar to Clindamycin Gel in treatment of mild to moderate acne vulgaris, and it may be consider as suitable drug for resistant acne to conventional topical therapy.

Magneto-dependent stress relaxation of magnetorheological gels

KAUST Repository

Xu, Yangguang; Liu, Taixiang; Liao, G J; Lubineau, Gilles

2017-01-01

The stress relaxation behaviors of magnetorheological (MR) gels under stepwise shear loading are systematically investigated. The particle-enhanced effect, the magneto-induced effect, and the temperature-enhanced effect on the stress relaxation of MR gels are discussed. For further analysis of the magneto-induced stress relaxation mechanism in MR gels, a phenomenological model is established to describe the stress relaxation behavior of the matrix and the magnetic particle chains. All characteristic parameters introduced in the model, i.e. relaxation time, instantaneous modulus, and stable modulus, have well-defined physical meanings and are fitted based on the experimental results. The influence of each parameter on the macroscopic response is discussed and it is found that the relaxation stress induced by the magneto-mechanical coupling effect plays an important role in the stress relaxation process of MR gels.

Magneto-dependent stress relaxation of magnetorheological gels

KAUST Repository

Xu, Yangguang

2017-09-01

The stress relaxation behaviors of magnetorheological (MR) gels under stepwise shear loading are systematically investigated. The particle-enhanced effect, the magneto-induced effect, and the temperature-enhanced effect on the stress relaxation of MR gels are discussed. For further analysis of the magneto-induced stress relaxation mechanism in MR gels, a phenomenological model is established to describe the stress relaxation behavior of the matrix and the magnetic particle chains. All characteristic parameters introduced in the model, i.e. relaxation time, instantaneous modulus, and stable modulus, have well-defined physical meanings and are fitted based on the experimental results. The influence of each parameter on the macroscopic response is discussed and it is found that the relaxation stress induced by the magneto-mechanical coupling effect plays an important role in the stress relaxation process of MR gels.

Maize Arabinoxylan Gels as Protein Delivery Matrices

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Ana Luisa Martínez-López

2009-04-01

Full Text Available The laccase induced gelation of maize bran arabinoxylans at 2.5% (w/v in the presence of insulin or β-lactoglobulin at 0.1% (w/v was investigated. Insulin and β-lacto-globulin did not modify either the gel elasticity (9 Pa or the cross-links content (0.03 and 0.015 mg di- and triferulic acids/mg arabinoxylan, respectively. The protein release capability of the gel was also investigated. The rate of protein release from gels was dependent on the protein molecular weight. The apparent diffusion coefficient was 0.99 × 10-7 and 0.79 × 10-7 cm2/s for insulin (5 kDa and β-lactoglobulin (18 kDa, respectively. The results suggest that maize bran arabinoxylan gels can be potential candidates for the controlled release of proteins.

Pulsed field gel electrophoresis a practical guide

CERN Document Server

Birren, Bruce

1993-01-01

Pulsed Field Gel Electrophoresis: A Practical Guide is the first laboratory manual to describe the theory and practice of this technique. Based on the authors' experience developing pulsed field gel instruments and teaching procedures, this book provides everything a researcher or student needs to know in order to understand and carry out pulsed field gel experiments. Clear, well-tested protocols assume only that users have a basic familiarity with molecular biology. Thorough coverage of useful data, theory, and applications ensures that this book is also a lasting resource for more adv

SPI Conformance Gel Applications in Geothermal Zonal Isolation

Energy Technology Data Exchange (ETDEWEB)

Burns, Lyle [Clean Tech Innovations, Bartlesville, OK (United States)

2017-08-08

Zonal isolation in geothermal injection and producing wells is important while drilling the wells when highly fractured geothermal zones are encountered and there is a need to keep the fluids from interfering with the drilling operation. Department of Energy’s (DOE) Energy Efficiency and Renewable Energy (EERE) objectives are to advance technologies to make it more cost effective to develop, produce, and monitor geothermal reservoirs and produce geothermal energy. Thus, zonal isolation is critical to well cost, reservoir evaluation and operations. Traditional cementing off of the lost circulation or thief zones during drilling is often done to stem the drilling mud losses. This is an expensive and generally unsuccessful technique losing the potential of the remaining fracture system. Selective placement of strong SPI gels into only the offending fractures can maintain and even improve operational efficiency and resource life. The SPI gel system is a unique silicate based gel system that offers a promising solution to thief zones and conformance problems with water and CO2 floods and potentially geothermal operations. This gel system remains a low viscosity fluid until an initiator (either internal such as an additive or external such as CO2) triggers gelation. This is a clear improvement over current mechanical methods of using packers, plugs, liners and cementing technologies that often severely damage the highly fractured area that is isolated. In the SPI gels, the initiator sets up the fluid into a water-like (not a precipitate) gel and when the isolated zone needs to be reopened, the SPI gel may be removed with an alkaline solution without formation damage occurring. In addition, the SPI gel in commercial quantities is expected to be less expensive than competing mechanical systems and has unique deep placement possibilities. This project seeks to improve upon the SPI gel integrity by modifying the various components to impart temperature stability for use in

Charge-regularized swelling kinetics of polyelectrolyte gels: Elasticity and diffusion

Science.gov (United States)

Sen, Swati; Kundagrami, Arindam

2017-11-01

We apply a recently developed method [S. Sen and A. Kundagrami, J. Chem. Phys. 143, 224904 (2015)], using a phenomenological expression of osmotic stress, as a function of polymer and charge densities, hydrophobicity, and network elasticity for the swelling of spherical polyelectrolyte (PE) gels with fixed and variable charges in a salt-free solvent. This expression of stress is used in the equation of motion of swelling kinetics of spherical PE gels to numerically calculate the spatial profiles for the polymer and free ion densities at different time steps and the time evolution of the size of the gel. We compare the profiles of the same variables obtained from the classical linear theory of elasticity and quantitatively estimate the bulk modulus of the PE gel. Further, we obtain an analytical expression of the elastic modulus from the linearized expression of stress (in the small deformation limit). We find that the estimated bulk modulus of the PE gel decreases with the increase of its effective charge for a fixed degree of deformation during swelling. Finally, we match the gel-front locations with the experimental data, taken from the measurements of charged reversible addition-fragmentation chain transfer gels to show an increase in gel-size with charge and also match the same for PNIPAM (uncharged) and imidazolium-based (charged) minigels, which specifically confirms the decrease of the gel modulus value with the increase of the charge. The agreement between experimental and theoretical results confirms general diffusive behaviour for swelling of PE gels with a decreasing bulk modulus with increasing degree of ionization (charge). The new formalism captures large deformations as well with a significant variation of charge content of the gel. It is found that PE gels with large deformation but same initial size swell faster with a higher charge.

Cost Analysis of Treating Neonatal Hypoglycemia with Dextrose Gel.

Science.gov (United States)

Glasgow, Matthew J; Harding, Jane E; Edlin, Richard

2018-04-03

To evaluate the costs of using dextrose gel as a primary treatment for neonatal hypoglycemia in the first 48 hours after birth compared with standard care. We used a decision tree to model overall costs, including those specific to hypoglycemia monitoring and treatment and those related to the infant's length of stay in the postnatal ward or neonatal intensive care unit, comparing the use of dextrose gel for treatment of neonatal hypoglycemia with placebo, using data from the Sugar Babies randomized trial. Sensitivity analyses assessed the impact of dextrose gel cost, neonatal intensive care cost, cesarean delivery rate, and costs of glucose monitoring. In the primary analysis, treating neonatal hypoglycemia using dextrose gel had an overall cost of NZ$6863.81 and standard care (placebo) cost NZ$8178.25; a saving of NZ$1314.44 per infant treated. Sensitivity analyses showed that dextrose gel remained cost saving with wide variations in dextrose gel costs, neonatal intensive care unit costs, cesarean delivery rates, and costs of monitoring. Use of buccal dextrose gel reduces hospital costs for management of neonatal hypoglycemia. Because it is also noninvasive, well tolerated, safe, and associated with improved breastfeeding, buccal dextrose gel should be routinely used for initial treatment of neonatal hypoglycemia. Australian New Zealand Clinical Trials Registry: ACTRN12608000623392. Copyright © 2018 Elsevier Inc. All rights reserved.

Electroblotting from Polyacrylamide Gels.

Science.gov (United States)

Goldman, Aaron; Ursitti, Jeanine A; Mozdzanowski, Jacek; Speicher, David W

2015-11-02

Transferring proteins from polyacrylamide gels onto retentive membranes is now primarily used for immunoblotting. A second application that was quite common up to about a decade ago was electroblotting of proteins for N-terminal and internal sequencing using Edman chemistry. This unit contains procedures for electroblotting proteins from polyacrylamide gels onto a variety of membranes, including polyvinylidene difluoride (PVDF) and nitrocellulose. In addition to the commonly used tank or wet transfer system, protocols are provided for electroblotting using semidry and dry systems. This unit also describes procedures for eluting proteins from membranes using detergents or acidic extraction with organic solvents for specialized applications. Copyright © 2015 John Wiley & Sons, Inc.