Nitrogen, phosphorus, calcium, and magnesium applied individually or as a slow release or controlled release fertilizer increase growth

USDA-ARS?s Scientific Manuscript database

The U.S. Environmental Protection Agency (USEPA) has restricted concentrated animal feeding operation(CAFO) release of waste products into U.S. waters. These waste products must be disposed of using best management practices. Most of the waste is spread on cropland, but some operations have found ot...

Multi-unit dosage formulations of theophylline for controlled release applications.

PubMed

Uhumwangho, Michael U; Okor, Roland S

2007-01-01

The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The corresponding values of m infinity and t infinity for the tablets were (240 mg, 9 h), (180 mg, 11 h) and (128 mg, 12 h) against the set target (200 mg, 12 h). The indication is that tableting rather than encapsulation can more effectively control drug release from the systems.

Controlled release of curcumin from poly(HEMA-MAPA) membrane.

PubMed

Caka, Müşerref; Türkcan, Ceren; Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

2017-05-01

In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

INTERACTION OF CLIMATE AND LAND USE IN FUTURE TERRESTRIAL CARBON STORAGE AND RELEASE

EPA Science Inventory

The processes controlling total carbon (C) storage and release from the terrestrial biosphere are still poorly quantified. e conclude from analysis of paleodata and climate biome model output that terrestrial C exchanges since the last glacial maximum (LGM) were dominated by slow...

Preparation and properties of a coated slow-release and water-retention biuret phosphoramide fertilizer with superabsorbent.

PubMed

Jin, Shuping; Yue, Guoren; Feng, Lei; Han, Yuqi; Yu, Xinghai; Zhang, Zenghu

2011-01-12

In this investigation, a novel water-insoluble slow-release fertilizer, biuret polyphosphoramide (BPAM), was formulated and synthesized from urea, phosphoric acid (H(3)PO(4)), and ferric oxide (Fe(2)O(3)). The structure of BPAM was characterized by Fourier transform infrared (FTIR) spectroscopy. Subsequently, a coated slow-release BPAM fertilizer with superabsorbent was prepared by ionic cross-linked carboxymethylchitosan (the core), acrylic acid, acrylamide, and active carbon (the coating). The variable influences on the water absorbency were investigated and optimized. Component analysis results showed that the coated slow-release BPAM contained 5.66% nitrogen and 11.7% phosphorus. The property of water retention, the behavior of slow release of phosphorus, and the capacity of adsorption of cations were evaluated, and the results revealed that the product not only had good slow-release property and excellent water retention capacity but also higher adsorption capacities of cations in saline soil.

Slow-release fluoride devices for the control of dental decay.

PubMed

Chong, Lee Yee; Clarkson, Jan E; Dobbyn-Ross, Lorna; Bhakta, Smriti

2014-11-28

Slow-release fluoride devices have been investigated as a potentially cost-effective method of reducing dental caries in people with high risk of disease. To evaluate the effectiveness and safety of different types of slow-release fluoride devices on preventing, arresting, or reversing the progression of carious lesions on all surface types of primary (deciduous) and permanent teeth. We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 13 August 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 7), MEDLINE via Ovid (1946 to 13 August 2014), and EMBASE via Ovid (1980 to 13 August 2014). We searched the US National Institutes of Health Trials Register and the World Health Organization (WHO) International Clinical Trials Registry Platform. We placed no restrictions on the language or date of publication when searching the electronic databases.We first published the review in 2006. The update in 2013 found 302 abstracts, but none of these met the inclusion criteria of the review. Parallel randomised controlled trials (RCTs) comparing slow-release fluoride devices with an alternative fluoride treatment, placebo, or no intervention in all age groups. The main outcomes measures sought were changes in numbers of decayed, missing, and filled teeth or surfaces (DMFT/DMFS in permanent teeth or dmft/dmfs in primary teeth), and progression of carious lesions through enamel and into dentine. We conducted data collection and analysis using standard Cochrane review methods. At least two review authors independently performed all the key steps in the review such as screening of abstracts, application of inclusion criteria, data extraction, and risk of bias assessment. We resolved discrepancies through discussions or arbitration by a third or fourth review author. We found no evidence comparing slow-release fluoride devices against other types of fluoride therapy.We found only one double-blind RCT involving 174 children comparing a slow-release fluoride device (glass beads with fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth) against control (glass beads without fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth). This study was assessed to be at high risk of bias. The study recruited children from seven schools in an area of deprivation that had low levels of fluoride in the water. The mean age at the beginning of the study was 8.8 years and at the termination was 10.9 years. DMFT in permanent teeth or dmft in primary teeth was greater than one at the start of the study and greater than one million colony-forming units of Streptococcus mutans per millilitre of saliva.Although 132 children were still included in the trial at the two-year completion point, examination and statistical analysis was performed on only the 63 children (31 in intervention group, 32 in control group) who had retained the beads (retention rate was 47.7% at two years). Among these 63 children, caries increment was reported to be statistically significantly lower in the intervention group than in the control group (DMFT: mean difference -0.72, 95% confidence interval (CI) -1.23 to -0.21; DMFS: mean difference -1.52, 95% CI -2.68 to -0.36 (very low quality evidence)). Although this difference was clinically significant, it only holds true for those children who maintain the fluoride beads; over 50% of children did not retain the beads.Harms were not reported within the trial report. Evidence for other outcomes sought in this review (progression to of caries lesion, dental pain, healthcare utilisation data) were also not reported. There is insufficeint evidence to determine the caries-inhibiting effect of slow-release fluoride glass beads. The body of evidence available is of very low quality and there is a potential overestimation of benefit to the average child. The applicability of the findings to the wider population is unclear; the study had included children from a deprived area that had low levels of fluoride in drinking water, and were considered at high risk of carries. In addition, the evidence was only obtained from children who still had the bead attached at two years (48% of all available children); children who had lost their slow-release fluoride devices earlier might not have benefited as much from the devices.

Slow-release fluoride devices for the control of dental decay.

PubMed

Chong, Lee-Yee; Clarkson, Jan E; Dobbyn-Ross, Lorna; Bhakta, Smriti

2018-03-01

Slow-release fluoride devices have been investigated as a potentially cost-effective method of reducing dental caries in people with high risk of disease. This is the second update of the Cochrane Review first published in 2006 and previously updated in 2014. To evaluate the effectiveness and safety of different types of slow-release fluoride devices on preventing, arresting, or reversing the progression of carious lesions on all surface types of primary (deciduous) and permanent teeth. Cochrane Oral Health's Information Specialist searched the following electronic databases: Cochrane Oral Health's Trials Register (to 23 January 2018); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 12) in the Cochrane Library (searched 23 January 2018); MEDLINE Ovid (1946 to 23 January 2018); and Embase Ovid (1980 to 23 January 2018). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials (23 January 2018). We placed no restrictions on the language or date of publication when searching the electronic databases. Parallel randomised controlled trials (RCTs) comparing slow-release fluoride devices with an alternative fluoride treatment, placebo, or no intervention in all age groups. The main outcome measures sought were changes in numbers of decayed, missing, and filled teeth or surfaces (DMFT/DMFS in permanent teeth or dmft/dmfs in primary teeth), and progression of carious lesions through enamel and into dentine. We conducted data collection and analysis using standard Cochrane review methods. At least two review authors independently performed all the key steps in the review such as screening of abstracts, application of inclusion criteria, data extraction, and risk of bias assessment. We resolved discrepancies through discussions or arbitration by a third or fourth review author. We found no evidence comparing slow-release fluoride devices against other types of fluoride therapy.We found only one double-blind RCT involving 174 children comparing a slow-release fluoride device (glass beads with fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth) against control (glass beads without fluoride were attached to buccal surfaces of right maxillary first permanent molar teeth). This study was assessed to be at high risk of bias. The study recruited children from seven schools in an area of deprivation that had low levels of fluoride in the water. The mean age at the beginning of the study was 8.8 years and at the termination was 10.9 years. DMFT in permanent teeth or dmft in primary teeth was greater than one at the start of the study and greater than one million colony-forming units of Streptococcus mutans per millilitre of saliva.Although 132 children were still included in the trial at the two-year completion point, examination and statistical analysis was performed on only the 63 children (31 in intervention group, 32 in control group) who had retained the beads (retention rate was 47.7% at 2 years). Among these 63 children, caries increment was reported to be statistically significantly lower in the intervention group than in the control group (DMFT: mean difference -0.72, 95% confidence interval (CI) -1.23 to -0.21; DMFS: mean difference -1.52, 95% CI -2.68 to -0.36 (very low-quality evidence)). Although this difference was clinically significant, it only holds true for those children who maintain the fluoride beads; over 50% of children did not retain the beads.Harms were not reported within the trial report. Evidence for other outcomes sought in this review (progression to of caries lesion, dental pain, healthcare utilisation data) were also not reported. There is insufficient evidence to determine the caries-inhibiting effect of slow-release fluoride glass beads. The body of evidence available is of very low quality and there is a potential overestimation of benefit to the average child. The applicability of the findings to the wider population is unclear; the study had included children from a deprived area that had low levels of fluoride in drinking water, and were considered at high risk of caries. In addition, the evidence was only obtained from children who still had the bead attached at 2 years (48% of all available children); children who had lost their slow-release fluoride devices earlier might not have benefited as much from the devices.

[Use of new tools for controlling triatomines in different entomologic situations in the American continent].

PubMed

Oliveira Filho, A M

1997-01-01

The field results of new tools for triatomine control developed under the sponsorship of WHO/TDR are reported: a) A slow-release "paint" containing malathion; b) fumigant cans containing cypermethrin and DDVP, and c) sensor boxes for the detection of triatomine infestations. Field assays were performed in Chile, Honduras and Paraguay against Triatoma infestans, T. dimidiata and Rhodnius prolixus, accordingly to a standard protocol designed by a WHO experts committee. Preliminary 6 months post-treatment results for the three countries show an efficient control when insecticide paints were used indoors and in the peridomicilium, keeping reinfestation near zero. The final results presented for Chile two years post-treatment confirmed the superiority of the slow-release "paints". Sensor boxes were less effective than man/hour captures in the detection of infested houses.

Activated-Lignite-Based Super Large Granular Slow-Release Fertilizers Improve Apple Tree Growth: Synthesis, Characterizations, and Laboratory and Field Evaluations.

PubMed

Tang, Yafu; Wang, Xinying; Yang, Yuechao; Gao, Bin; Wan, Yongshan; Li, Yuncong C; Cheng, Dongdong

2017-07-26

In this work, lignite, a low-grade coal, was modified using the solid-phase activation method with the aid of a Pd/CeO 2 nanoparticle catalyst to improve its pore structure and nutrient absorption. Results indicate that the adsorption ability of the activated lignite to NO 3 - , NH 4 + , H 2 PO 4 - , and K + was significantly higher than that of raw lignite. The activated lignite was successfully combined with the polymeric slow-release fertilizer, which exhibits typical slow-release behavior, to prepare the super large granular activated lignite slow-release fertilizer (SAF). In addition to the slow-release ability, the SAF showed excellent water-retention capabilities. Soil column leaching experiments further confirmed the slow-release characteristics of the SAF with fertilizer nutrient loss greatly reduced in comparison to traditional and slow-release fertilizers. Furthermore, field tests of the SAF in an orchard showed that the novel SAF was better than other tested fertilizers in improve the growth of young apple trees. Findings from this study suggest that the newly developed SAF has great potential to be used in apple cultivation and production systems in the future.

The mouse cornea micropocket angiogenesis assay.

PubMed

Rogers, Michael S; Birsner, Amy E; D'Amato, Robert J

2007-01-01

The mouse corneal micropocket angiogenesis assay uses the avascular cornea as a canvas to study angiogenesis in vivo. Through the use of standardized slow-release pellets, a predictable angiogenic response is generated over the course of 5 d and then quantified. Uniform slow-release pellets are prepared by mixing purified angiogenic growth factors such as basic fibroblast growth factor or vascular endothelial growth factor with sucralfate (a stabilizer) and Hydron (poly-HEMA (poly(2-hydroxyethyl methacrylate)) to allow slow release). This mixture is applied to a mesh that controls unit size and then allowed to harden. A micropocket is surgically created in the mouse cornea and a pellet implanted. Five days later, the area of the cornea overgrown by the angiogenic response is measured using a slit lamp. A skilled investigator can implant and grade 40 eyes in about 2.5 h. The results of the assay are used to assess the ability of potential therapeutic molecules or genetic differences to modulate angiogenesis in vivo.

Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation.

PubMed

Han, Dehui; Tong, Xia; Zhao, Yue

2012-02-07

We report the design and demonstration of a dual-stimuli-responsive block copolymer (BCP) micelle with increased complexity and control. We have synthesized and studied a new amphiphilic ABA-type triblock copolymer whose hydrophobic middle block contains two types of stimuli-sensitive functionalities regularly and repeatedly positioned in the main chain. Using a two-step click chemistry approach, disulfide and o-nitrobenzyle methyl ester groups are inserted into the main chain, which react to reducing agents and light, respectively. With the end blocks being poly(ethylene oxide), micelles formed by this BCP possess a core that can be disintegrated either rapidly via photocleavage of o-nitrobenzyl methyl esters or slowly through cleavage of disulfide groups by a reducing agent in the micellar solution. This feature makes possible either burst release of an encapsulated hydrophobic species from disintegrated micelles by UV light, or slow release by the action of a reducing agent, or release with combined fast-slow rate profiles using the two stimuli.

Gold and Iron Oxide Nanoparticle-Based Ethylcellulose Nanocapsules for Cisplatin Drug Delivery

PubMed Central

Sathish Kumar, Kannaiyan; Jaikumar, Vasudevan

2011-01-01

The present study is aimed at the overall improvement in the efficacy, reduced toxicity and enhancement of therapeutic index of cisplatin. Nanocapsules of cisplatin containing ethylcellulose have been prepared using solvent evaporation technique under ambient conditions. The prepared nanocapsules were used for controlled drug release of anticancer agents with gold and iron oxide nanoparticles. The drug-entrapped nanocapsules were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fourier transform infrared (FTIR) studies indicated the absence of chemical interactions between the drug, polymer and metal nanoparticles. The drug loaded nanoparticles are spherical in shape and had average diameter in the range of 100-300 nm. Drug release study showed that the acidic media provided a faster release than the phosphate buffer media. These findings were also compared statistically through calculating mean, standard deviation and coefficient of variation for various polymer nanocapsules. However, the drug release for gold nanoparticles/anticancer drug (Au-cis) incorporated ethylcellulose nanocapsules was controlled and slow compared to iron oxide nanoparticles-cisplatin incorporated ethylcellulose nanocapsules. Hence, gold nanoparticles act as good trapping agents which slow down the rate of drug release from nanocapsules. PMID:24250373

Nitrate capture and slow release in biochar amended compost and soil.

PubMed

Hagemann, Nikolas; Kammann, Claudia I; Schmidt, Hans-Peter; Kappler, Andreas; Behrens, Sebastian

2017-01-01

Slow release of nitrate by charred organic matter used as a soil amendment (i.e. biochar) was recently suggested as potential mechanism of nutrient delivery to plants which may explain some agronomic benefits of biochar. So far, isolated soil-aged and composted biochar particles were shown to release considerable amounts of nitrate only in extended (>1 h) extractions ("slow release"). In this study, we quantified nitrate and ammonium release by biochar-amended soil and compost during up to 167 h of repeated extractions in up to six consecutive steps to determine the effect of biochar on the overall mineral nitrogen retention. We used composts produced from mixed manures amended with three contrasting biochars prior to aerobic composting and a loamy soil that was amended with biochar three years prior to analysis and compared both to non-biochar amended controls. Composts were extracted with 2 M KCl at 22°C and 65°C, after sterilization, after treatment with H2O2, after removing biochar particles or without any modification. Soils were extracted with 2 M KCl at 22°C. Ammonium was continuously released during the extractions, independent of biochar amendment and is probably the result of abiotic ammonification. For the pure compost, nitrate extraction was complete after 1 h, while from biochar-amended composts, up to 30% of total nitrate extracted was only released during subsequent extraction steps. The loamy soil released 70% of its total nitrate amount in subsequent extractions, the biochar-amended soil 58%. However, biochar amendment doubled the amount of total extractable nitrate. Thus, biochar nitrate capture can be a relevant contribution to the overall nitrate retention in agroecosystems. Our results also indicate that the total nitrate amount in biochar amended soils and composts may frequently be underestimated. Furthermore, biochars could prevent nitrate loss from agroecosystems and may be developed into slow-release fertilizers to reduce global N fertilizer demands.

An oxygen slow-releasing material and its application in water remediation as oxygen supplier.

PubMed

Zhou, Yanbo; Fang, Xingbin; Zhang, Zhiqing; Hu, Yonghua; Lu, Jun

2017-11-01

In this study, an oxygen slow-releasing material (OSRM) consisting of calcium peroxide (CaO 2 ), stearic acid (SA) and quartz sand was used to improve oxygen supply during bioremediation. The oxygen-releasing rates of CaO 2 powder and OSRM with different SA contents were investigated. The efficacy of OSRM as an oxygen supplier was assessed by water remediation experiments using activated sludge. Results showed that CaO 2 powder was effectively embedded by SA under anhydrous conditions. The oxygen-releasing rate decreased with increasing SA contents. Moreover, the OSRM exhibited higher oxygen-releasing capacity, and more effective pH control ability than CaO 2 powder. The water remediation experiments showed better removal of COD and [Formula: see text] with OSRM as the oxygen supplier. These results provided detailed information when CaO 2 was applied as the oxygen supplier in water remediation, which can serve as references for field application of bioremediation.

Slow-release fertilizers 101

Treesearch

Robin Rose

2002-01-01

Slow release fertilizers have been in common use within the horticultural industry for decades. Probably the mostly commonly heard of product is Scott's Osmocote which has been around for a quite a long time. However, some time ago slow release fertilizers moved out of the potted greenhouse environment and onto golf courses, suburban lawns and bushes, and orchards...

Kinetic Analysis of Drug Release from Compounded Slow-release Capsules of Liothyronine Sodium (T3).

PubMed

Bakhteyar, Hamid; Cassone, Clayton; Kohan, Hamed Gilzad; Sani, Shabnam N

2017-01-01

The purpose of this study was to formulate extemporaneously compounded Liothyronine Sodium (T3) slow-release capsules and to evaluate their in vitro drug release performance. Twenty-one formulations containing T3 (7.5 µg) with various compositions of two different grades of Methocel E4M and K100M premium (30% to 90%), and/or SimpleCap/Lactose (10% to 70%) were examined. Quality assessment of the capsules was conducted by standard quality control criteria of the United States Pharmacopeia (i.e., weight variation, content uniformity) to ensure their compliance. The dissolution release profile of the formulations was evaluated using United States Pharmacopeia Apparatus type II (paddle method) at a speed of 50 rpm and temperature of 37°C in phosphate buffered saline media ( pH = 7.2 to 7.4). Aliquots from the media were taken periodically up to 24 hours and analyzed using a validated enzyme-linked immunosorbent assay method. The cumulative percentage of drug release for each formulation was fitted to eleven major release kinetic equations to determine the best-fit model of drug release, as well as the mechanism of release. Assay sensitivity was as low as 1 ng/mL and the optimal calibration range was found to be between 0 ng/mL and 7.5 ng/mL, which corresponded well with the average physiological plasma concentrations of T3. Liothyronine sodium with either SimpleCap (100%) or Methocel E4M (100%) exhibited slowrelease kinetic patterns of Peppas and Zero Order, respectively. The formulation with SimpleCap (100%) had a higher percentage of drug release (as compared to 100% Methocel E4M) within the first four hours; this formulation released 80% of the drug within 12 hours when the release was plateaued thereafter. The formulation with 30% Methocel E4M and 70% SimpleCap released 100% of the drug within the initial 12 hours and exhibited a Zero Order slow-release kinetic pattern. In general, the release kinetic rate of the formulations containing Methocel K100M appeared to be slower than Methocel E4M. This alteration may be due to a higher molecular weight and apparent viscosity of Methocel K100M. While most of the formulations were fitted to a slow-release kinetic pattern, several others including Methocel E4M 100%, 30% Methocel E4M+ 70% Simple Cap, 40% Methocel K100M+ 60% SimpleCap, 50% Methocel K100M+ 50% SimpleCap, 30% Methocel E4M+ 70% Lactose, 90% Methocel E4M+ 10% Lactose, 40% Methocel K100M+ 60% Lactose, and 50% Methocel K100M+ 50% Lactose followed an ideal slow-release kinetic pattern of Zero Order or Higuchi. The results of this study successfully demonstrated the optiomal composition of slow-release compounded capsules of T3. Future studies are warranted to evaluate the in vivo performance of the optimal formulations and to establish an in vitro-in vivo correlation. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Brain Basics: Understanding Sleep

MedlinePlus

... slow, and muscles relax even further. Your body temperature drops and eye movements stop. Brain wave activity ... functions from daily fluctuations in wakefulness to body temperature, metabolism, and the release of hormones. They control ...

Nitrate capture and slow release in biochar amended compost and soil

PubMed Central

Kammann, Claudia I.; Schmidt, Hans-Peter; Kappler, Andreas; Behrens, Sebastian

2017-01-01

Slow release of nitrate by charred organic matter used as a soil amendment (i.e. biochar) was recently suggested as potential mechanism of nutrient delivery to plants which may explain some agronomic benefits of biochar. So far, isolated soil-aged and composted biochar particles were shown to release considerable amounts of nitrate only in extended (>1 h) extractions (“slow release”). In this study, we quantified nitrate and ammonium release by biochar-amended soil and compost during up to 167 h of repeated extractions in up to six consecutive steps to determine the effect of biochar on the overall mineral nitrogen retention. We used composts produced from mixed manures amended with three contrasting biochars prior to aerobic composting and a loamy soil that was amended with biochar three years prior to analysis and compared both to non-biochar amended controls. Composts were extracted with 2 M KCl at 22°C and 65°C, after sterilization, after treatment with H2O2, after removing biochar particles or without any modification. Soils were extracted with 2 M KCl at 22°C. Ammonium was continuously released during the extractions, independent of biochar amendment and is probably the result of abiotic ammonification. For the pure compost, nitrate extraction was complete after 1 h, while from biochar-amended composts, up to 30% of total nitrate extracted was only released during subsequent extraction steps. The loamy soil released 70% of its total nitrate amount in subsequent extractions, the biochar-amended soil 58%. However, biochar amendment doubled the amount of total extractable nitrate. Thus, biochar nitrate capture can be a relevant contribution to the overall nitrate retention in agroecosystems. Our results also indicate that the total nitrate amount in biochar amended soils and composts may frequently be underestimated. Furthermore, biochars could prevent nitrate loss from agroecosystems and may be developed into slow-release fertilizers to reduce global N fertilizer demands. PMID:28199354

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

Physicochemical Characteristics and Slow Release Performances of Chlorpyrifos Encapsulated by Poly(butyl acrylate-co-styrene) with the Cross-Linker Ethylene Glycol Dimethacrylate.

PubMed

Wang, Yu; Gao, Zideng; Shen, Feng; Li, Yang; Zhang, Sainan; Ren, Xueqin; Hu, Shuwen

2015-06-03

Chlorpyrifos' application and delivery to the target substrate needs to be controlled to improve its use. Herein, poly(butyl acrylate-co-styrene) (poly(BA/St)) and poly(BA/St/ethylene glycol dimethacrylate (EGDMA)) microcapsules loaded with chlorpyrifos as a slow release formulation were prepared by emulsion polymerization. The effects of structural characteristics on the chlorpyrifos microcapsule particle size, entrapment rate (ER), pesticide loading (PL), and release behaviors in ethyl alcohol were investigated. Fourier transform infrared and thermogravimetric analysis confirmed the successful entrapment of chlorpyrifos. The ER and PL varied with the BA/St monomer ratio, chlorpyrifos/monomer core-to-shell ratio, and EGDMA cross-linker content with consequence that suitable PL was estimated to be smaller than 3.09% and the highest ER was observed as 96.74%. The microcapsule particle size (88.36-101.8 nm) remained mostly constant. The extent of sustainable release decreased with increasing content of BA, St, or chlorpyrifos in the oil phase. Specifically, an adequate degree of cross-linking with EGMDA (0.5-2.5%) increased the extent of sustainable release considerably. However, higher levels of cross-linking with EGDMA (5-10%) reduced the extent of sustainable release. Chlorpyrifos release from specific microcapsules (monomer ratio 1:2 with 0.5% EGDMA or 5 g chlopyrifos) tended to be a diffusion-controlled process, while for others, the kinetics probably indicated the initial rupture release.

[Effects of Organic and Inorganic Slow-Release Compound Fertilizer on Different Soils Microbial Community Structure].

PubMed

Wang, Fei; Yuan, Ting; Gu, Shou-kuan; Wang, Zheng-yin

2015-04-01

As a new style fertilizer, slow-control release fertilizer had been an important subject in recent years, but few researches were about soil microbial community structure diversity. Phospholipid fatty acid method was used to determined the microbial community structure diversity of acid soil and slight alkaline soil applied with slow-release compound fertilizer (SRF), chemical fertilizer (CF) and common compound fertilizer (CCF) at the 10th, 30th, 60th and 90th day under the constant temperature incubation condition. Results indicated that various bacteria (i. e 13:0, i14:0,14:0, i15:0, a15:0, i16:0, 16:12OH, 16:1w5c,16:0, i17:0, a17:0, cy17:0, 17:02OH, i18:0, 18:0 and cy19:0w8c), two actinomycetes (10Me17:0 and 10Me18:0) and only one fungus (18:1 w9c) were detected in two soils after applying slow-release compound fertilizer and other fertilizers during the whole incubation period. SRF could significantly increase the fungi PLFA content by 8.3% and 6.8% at the early stage (the 10th day and 30th day) compared with CF, as well as significantly increase by 22.7% and 17.1% at the late stage (the 60th day and 90th day) compared with CCF in acid soil. SRF significantly increased bacteria, fungi and gram positive bacteria compared with CF and CCF in incubation period (except at the 30th day) in slight alkaline soil. SRF could significantly improve the ratio of normal saturated fatty acid and monounsaturated fatty acid at the 30th day and 90th days in acid soil compared with no fertilizer (CK), CF and CCF, while as to slight alkaline soil, SRF was significantly greater than that of CK, CF and CCF only at the 60th day. SRF could significantly decrease the ratio of iso PLFA and anteiso PLFA in acid soil (in 30-90 days) and slight alkaline soil (in 10-60 days). For two soils PLFA varieties, contents and ratios of microbial community, slow-release compound fertilizer increased soil microbial PLFA varieties and contents, and decreased the influence to microbial survival environment, especially for the acid soil. Through the research of slow-release compound fertilizer on soil microbial community structure diversity, it could provide a scientific basis for widely application of slow-release compound fertilizer in agricultural production.

Alginate Beads as Synthetic Inoculant Carriers for Slow Release of Bacteria That Affect Plant Growth †‡

PubMed Central

Bashan, Yoav

1986-01-01

Uniform synthetic beads were developed as carriers for the bacterial inoculation of plants. The beads are made of sodium alginate and skim milk and contain a large reservoir of bacterial culture which releases the bacteria at a slow and constant rate. The beads are biodegradable and produce no environmental pollution. The strength of the beads, the rate of bacterial release, and the time of their survival in the soil can be controlled by several hardening treatments. The final product, lyophilized beads, is simple to use and is applied to the seeds concomitantly with sowing. The released bacteria are available for root colonization immediately at seed germination. Dry beads containing bacteria can be stored at ambient temperature over a long period without loss of bacterial content; storage requires a limited space, and the quality control of a number of bacteria in the bead is simple. The level of plant inoculation with beads was similar to that with previously used peat inoculants, but the former method yielded more consistent results, as the frequency of inoculated plants was much higher. The former method provides a different approach for inoculation of plants with beneficial rhizosphere bacteria. Images PMID:16347055

Development of formulations to improve the controlled-release of linalool to be applied as an insecticide.

PubMed

Lopez, M D; Maudhuit, A; Pascual-Villalobos, M J; Poncelet, D

2012-02-08

In recent studies, insecticide activity of a monoterpene, linalool, has been demonstrated, finding, however, limitations in application because of its rapid volatilization. Potential effectiveness of microcapsules and effects of various types of matrices on its stability as controlled-release systems for the slow volatilization of linalool to be applied as insecticide were evaluated. To study controlled-release, linalool was entrapped into microcapsules, inclusion complexes, and beads, obtained by different methods, inverse gelation (IG1, IG2, IG3, IG4, and IG5), oil-emulsion-entrapment (OEE), interfacial coacervation (INCO), and chemical precipitation (Cyc5 and Cyc10). The encapsulation yield turned out to be different for each formulation, reaching the maximum retention for IG1 and OEE. In controlled-release, OEE followed by INCO presented a long time necessary for releasing as a result of the presence of glycerol or chitosan. These results pointed out remarkable differences in the release behavior of linalool depending on matrix composition and the method of encapsulation.

Controlled and extended drug release behavior of chitosan-based nanoparticle carrier.

PubMed

Yuan, Q; Shah, J; Hein, S; Misra, R D K

2010-03-01

Controlled drug release is presently gaining significant attention. In this regard, we describe here the synthesis (based on the understanding of chemical structure), structural morphology, swelling behavior and drug release response of chitosan intercalated in an expandable layered aluminosilicate. In contrast to pure chitosan, for which there is a continuous increase in drug release with time, the chitosan-aluminosilicate nanocomposite carrier was characterized by controlled and extended release. Drug release from the nanocomposite particle carrier occurred by degradation of the carrier to its individual components or nanostructures with a different composition. In both the layered aluminosilicate-based mineral and chitosan-aluminosilicate nanocomposite carriers the positively charged chemotherapeutic drug strongly bound to the negatively charged aluminosilicate and release of the drug was slow. Furthermore, the pattern of drug release from the chitosan-aluminosilicate nanocomposite carrier was affected by pH and the chitosan/aluminosilicate ratio. The study points to the potential application of this hybrid nanocomposite carrier in biomedical applications, including tissue engineering and controlled drug delivery. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Double loaded self-decomposable SiO2 nanoparticles for sustained drug release

NASA Astrophysics Data System (ADS)

Zhao, Saisai; Zhang, Silu; Ma, Jiang; Fan, Li; Yin, Chun; Lin, Ge; Li, Quan

2015-10-01

Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases.Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03029c

Fast and slow active control of combustion instabilities in liquid-fueled combustors

NASA Astrophysics Data System (ADS)

Lee, Jae-Yeon

This thesis describes an experimental investigation of two different novel active control approaches that are employed to suppress combustion instabilities in liquid-fueled combustors. A "fast" active controller requires continuous modulation of the fuel injection rate at the frequency of the instability with proper phase and gain. Use of developed optical tools reveals that the "fast" active control system suppresses the instability by changing the nearly flat distribution of the phase between pressure and heat release oscillations to a gradually varying phase distribution, thus dividing the combustion zone into regions that alternately damp and drive combustor oscillations. The effects of these driving/damping regions tend to counter one another, which result in significant damping of the unstable oscillations. In contrast, a "slow" active controller operates at a rate commensurate with that at which operating conditions change during combustor operation. Consequently, "slow" controllers need infrequent activation in response to changes in engine operating conditions to assure stable operation at all times. Using two types of fuel injectors that can produce large controllable variation of fuel spray properties, it is shown that by changing the spray characteristics it is possible to significantly damp combustion instabilities. Similar to the aforementioned result of the "fast" active control study, "slow" change of the fuel spray properties also modifies the nearly flat phase distribution during unstable operation to a gradually varying phase distribution, resulting in combustor "stabilization". Furthermore, deconvolutions of CH*-chemiluminescence images reveal the presence of vortex-flame interaction during unstable operation. Strong driving of instabilities occurs where the mean axial velocity of the flow is approximately zero, a short distance downstream of the flame holder where a significant fraction of the fuel burns in phase with the pressure oscillations. It is shown that the "fast" and "slow" active control approaches suppress combustion instabilities in a different manner. Nevertheless, the both control approaches successfully suppress combustion instabilities by modifying the temporal and spatial behavior of the combustion process heat release that is responsible for driving the instability.

Nanostructured Diclofenac Sodium Releasing Material

NASA Astrophysics Data System (ADS)

Nikkola, L.; Vapalahti, K.; Harlin, A.; Seppälä, J.; Ashammakhi, N.

2008-02-01

Various techniques have been developed to produce second generation biomaterials for tissue repair. These include extrusion, molding, salt leaching, spinning etc, but success in regenerating tissues has been limited. It is important to develop porous material, yet with a fibrous structure for it to be biomimetic. To mimic biological tissues, the extra-cellular matrix usually contains fibers in nano scale. To produce nanostructures, self-assembly or electrospinning can be used. Adding a drug release function to such a material may advance applications further for use in controlled tissue repair. This turns the resulting device into a multifunctional porous, fibrous structure to support cells and drug releasing properties in order to control tissue reactions. A bioabsorbable poly(ɛ-caprolactone-co-D,L lactide) 95/5 (PCL) was made into diluted solution using a solvent, to which was added 2w-% of diclofenac sodium (DS). Nano-fibers were made by electrospinning onto substrate. Microstructure of the resulting nanomat was studied using SEM and drug release profiles with UV/VIS spectroscopy. Thickness of the electrospun nanomat was about 2 mm. SEM analysis showed that polymeric nano-fibers containing drug particles form a highly interconnected porous nano structure. Average diameter of the nano-fibers was 130 nm. There was a high burst peak in drug release, which decreased to low levels after one day. The used polymer has slow a degradation rate and though the nanomat was highly porous with a large surface area, drug release rate is slow. It is feasible to develop a nano-fibrous porous structure of bioabsorbable polymer, which is loaded with test drug. Drug release is targeted at improving the properties of biomaterial for use in controlled tissue repair and regeneration.

Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

PubMed

Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

2016-01-01

In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design. Copyright © 2015 Elsevier B.V. All rights reserved.

Slow-release fertilizer

NASA Technical Reports Server (NTRS)

Golden, Dadigamuwage C. (Inventor); Ming, Douglas W. (Inventor)

1995-01-01

A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

Slow-release fertilizer

NASA Technical Reports Server (NTRS)

Ming, Douglas W. (Inventor); Golden, D. C. (Inventor)

1992-01-01

A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

Slow-release fertilizer

NASA Astrophysics Data System (ADS)

Ming, Douglas W.; Golden, D. C.

1992-10-01

A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

A novel controlled release formulation of the Pin1 inhibitor ATRA to improve liver cancer therapy by simultaneously blocking multiple cancer pathways.

PubMed

Yang, Dayun; Luo, Wensong; Wang, Jichuang; Zheng, Min; Liao, Xin-Hua; Zhang, Nan; Lu, Wenxian; Wang, Long; Chen, Ai-Zheng; Wu, Wen-Guo; Liu, Hekun; Wang, Shi-Bin; Zhou, Xiao Zhen; Lu, Kun Ping

2018-01-10

Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide largely due to lack of effective targeted drugs to simultaneously block multiple cancer-driving pathways. The identification of all-trans retinoic acid (ATRA) as a potent Pin1 inhibitor provides a promising candidate for HCC targeted therapy because Pin1 is overexpressed in most HCC and activates numerous cancer-driving pathways. However, the efficacy of ATRA against solid tumors is limited due to its short half-life of 45min in humans. A slow-releasing ATRA formulation inhibits solid tumors such as HCC, but can be used only in animals. Here, we developed a one-step, cost-effective route to produce a novel biocompatible, biodegradable, and non-toxic controlled release formulation of ATRA for effective HCC therapy. We used supercritical carbon dioxide process to encapsulate ATRA in largely uniform poly L-lactic acid (PLLA) microparticles, with the efficiency of 91.4% and yield of 68.3%, and ~4-fold higher C max and AUC over the slow-releasing ATRA formulation. ATRA-PLLA microparticles had good biocompatibility, and significantly enhanced the inhibitory potency of ATRA on HCC cell growth, improving IC 50 by over 3-fold. ATRA-PLLA microparticles exerted its efficacy likely through degrading Pin1 and inhibiting multiple Pin1-regulated cancer pathways and cell cycle progression. Indeed, Pin1 knock-down abolished ATRA inhibitory effects on HCC cells and ATRA-PLLA did not inhibit normal liver cells, as expected because ATRA selectively inhibits active Pin1 in cancer cells. Moreover ATRA-PLLA microparticles significantly enhanced the efficacy of ATRA against HCC tumor growth in mice through reducing Pin1, with a better potency than the slow-releasing ATRA formulation, consistent with its improved pharmacokinetic profiles. This study illustrates an effective platform to produce controlled release formulation of anti-cancer drugs, and ATRA-PLLA microparticles might be a promising targeted drug for HCC therapy as PLLA is biocompatible, biodegradable and nontoxic to humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Epidemiological evaluations of the efficacy of slow-released praziquantel-medicated bars for dogs in the prevention and control of cystic echinococcosis in man and animals.

PubMed

Wei, Jiao; Cheng, Fu; Qun, Qu; Nurbek; Xu, Shi-Dong; Sun, Li-Feng; Han, Xin-Kui; Muhan; Han, Ling-Ling; Irixiati; Jie, Peng; Zhang, Ke-Jiu; Islayin; Chai, Jun-jie

2005-12-01

To assess the epidemiological efficacy of type SRP III slow-released praziquantel-medicated bars for dogs in the prevention and control of cystic echinococcosis in man and livestock, praziquantel-medicated bars were implanted subcutaneously in over 90% of dogs in villages in north Xinjiang, China, where cystic echinococcosis is highly endemic. After implantation, infection rate of Echinococcus granulosus in dogs, specific antibodies in children and prevalence of echinococcosis in one-year-old lambs were observed for 3 years. Coproantigen of E. granulosus was positive in 41.2% of the dogs at the start of experiment. In the second and third year after medicated-bar implantation, coproantigen was undetectable in any dogs examined, while 3.0% of dogs were positive at the end of the fourth year. The antibody positive rate in 7-year-old pupils, that was 41.2% before the experiment, declined gradually and it was 5.4% in the fourth year, while children in the non-intervention control area showed 30.6% seropositivity. The prevalence of hydatid disease in children aged 7-16 years also declined significantly. The prevalence of hydatidosis in lambs one year of age was 44.8% in the first year, dropping to 10.7% in the fourth year, while in the non-intervention control area the level of infection was 46.4%. These results demonstrated not only that the slow released praziquantel-medicated bars efficiently blocked reinfection in dogs at least for 2 years, but also the measure was effective in preventing transmission of cystic echinococcosis to both man and livestock.

Immunological release of histamine and slow-reacting substance in domestic fowl.

PubMed Central

Chand, N; Eyre, P

1978-01-01

Immunological release of histamine from the whole blood of the sensitized chickens was demonstrated. Compound 48/80 (a potent histamine releaser) released histamine from isolated chicken lung. The sensitizing antigens (bovine albumin or horse plasma) did not release histamine from the lung. Bovine albumin and horse plasma released slow-reacting substance of anaphylaxis only from the lungs of adult domestic fowl and not from ileum or lungs of immature chickens. PMID:84701

Ammonoxidised lignins as slow nitrogen-releasing soil amendments and CO₂-binding matrix.

PubMed

Liebner, Falk; Pour, Georg; de la Rosa Arranz, José Maria; Hilscher, André; Rosenau, Thomas; Knicker, Heike

2011-09-05

Nitrogen (N) is a major nutrient element controlling the cycling of organic matter in the biosphere. Its availability in soils is closely related to biological productivity. In order to reduce the negative environmental impact, associated with the application of mineral N-fertilizers, the use of ammonoxidised technical lignins is suggested. They can act as potential slow N-release fertilisers which concomitantly may increase C sequestration of soils by its potential to bind CO₂. The idea of our study was to combine an improved chemical characterisation of ammonoxidised ligneous matter as well as their CO₂-binding potential, with laboratory pot experiments, performed to enable an evaluation of their behaviour and stability during the biochemical reworking occurring in active soils.

Na2S, a fast-releasing H2S donor, given as suppository lowers blood pressure in rats.

PubMed

Tomasova, Lenka; Drapala, Adrian; Jurkowska, Halina; Wróbel, Maria; Ufnal, Marcin

2017-10-01

Hydrogen sulfide (H 2 S) is involved in blood pressure control. The available slow-releasing H 2 S-donors are poorly soluble in water and their ability to release H 2 S in biologically relevant amounts under physiological conditions is questionable. Therefore, new slow-releasing donors or new experimental approaches to fast-releasing H 2 S donors are needed. Hemodynamics and ECG were recorded in male, anesthetized Wistar Kyoto rats (WKY) and in Spontaneously hypertensive rats (SHR) at baseline and after: 1) intravenous (iv) infusion of vehicle or Na 2 S; 2) administration of vehicle suppositories or Na 2 S suppositories. Intravenously administered vehicle and vehicle suppositories did not affect mean arterial blood pressure (MABP) and heart rate (HR). Na 2 S administered iv caused a significant, but transient (2-5min) decrease in MABP. Na 2 S suppositories produced a dose-dependent hypotensive response that lasted ∼45min in WKY and ∼75-80min in SHR. It was accompanied by a decrease in HR in WKY, and an increase in HR in SHR. Na 2 S suppositories did not produce a significant change in corrected QT, an indicator of cardiotoxicity. Na 2 S suppositories increased blood level of thiosulfates, products of H 2 S oxidation. Na 2 S administered in suppositories exerts a prolonged hypotensive effect in rats, with no apparent cardiotoxic effect. SHR and WKY differ in hemodynamic response to the H 2 S donor. Suppository formulation of fast-releasing H 2 S donors may be useful in research, if a reference slow-releasing H 2 S donor is not available. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Development of a CO2 releasing co-formulation 1 based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae

USDA-ARS?s Scientific Manuscript database

CO2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO2 emitting formulations need to be developed. This work aimed at the development of a slow release bead system in order to bridge the gap between application and hatching of...

Controlled release from thermo-sensitive PNVCL-co-MAA electrospun nanofibers: The effects of hydrophilicity/hydrophobicity of a drug.

PubMed

Liu, Lin; Bai, Shaoqing; Yang, Huiqin; Li, Shubai; Quan, Jing; Zhu, Limin; Nie, Huali

2016-10-01

The thermo-sensitive copolymer poly(N-vinylcaprolactam-co-methacrylic acid) (PNVCL-co-MAA) was synthesized by free radical polymerization and the resulting nanofibers were fabricated using an electrospinning process. The molecular weight of the copolymer was adjusted by varying the content of methacrylic acid (MAA) while keeping that of N-vinylcaprolactam (NVCL) constant. Hydrophilic captopril and hydrophobic ketoprofen were used as model drugs, and PNVCL-co-MAA nanofibers were used as the drug carrier to investigate the effects of drug on its release properties from nanofibers at different temperatures. The results showed that slow release over several hours was observed at 40°C (above the lower critical solution temperature (LCST) of PNVCL-co-MAA), while the drugs exhibited a burst release of several seconds at 20°C (below the LCST). Drug release slowed with increasing content of the hydrophobic monomer NVCL. The hydrophilic captopril was released at a higher rate than the hydrophobic ketoprofen. The drug release characteristics were dependent on the temperature, the portion of hydrophilic groups and hydrophobic groups in the copolymer and hydrophilicity/hydrophobicity of drug. Study on the mechanism of release showed that Korsmeyer-Peppas model as a major drug release mechanism. Given these results, the PNVCL-co-MAA copolymers are proposed to have useful applications in intellectual drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydro-Mechanical Modelling of Slow Slip Phenomena at the Subduction Interface.

NASA Astrophysics Data System (ADS)

Petrini, C.; Gerya, T.; Madonna, C.; van Dinther, Y.

2016-12-01

Subduction zones experience a spectrum of slip phenomena, ranging from large devastating megathrust earthquakes to aseismic slow slip events. Slow slip events, lasting hours to years and being perceptible only by instruments, are believed to have the capability to induce large earthquakes. It is also repeatedly proposed that such slow events are controlled by fluid-rock interactions along the subduction interface, thus calling for development of fully coupled seismo-hydro-mechanical modeling approaches to identify their physics and controlling parameters. We present a newly developed finite difference visco-elasto-plastic numerical code with marker-in-cell technique, which fully couples mechanical deformation and fluid flow. We use this to investigate how the presence of fluids in the pore space of a (de)compacting rock matrix affects elastic stress accumulation and release along a fluid-bearing subduction interface. The model simulates the spontaneous occurrence of quasi-periodic slow slip phenomena along self-consistently forming highly localized shearbands, which accommodate shear displacement between two plates. The produced elastic rebound events show a slip velocity on the order of cm/yr, which is in good agreement with measured data. The governing gradual strength decrease along the slowly propagating shear bands is related to a drop in total pressure caused by shear localization at nearly constant (slightly decreasing) fluid pressure. Gradual reduction of the difference between the total and fluid pressure decreases brittle/plastic strength of fluid-bearing rocks along the shear bands, thus providing a dynamic feedback mechanism for the accumulated elastic stress release at the subduction interface.

The controlled release of tilmicosin from silica nanoparticles.

PubMed

Song, Meirong; Li, Yanyan; Fai, Cailing; Cui, Shumin; Cui, Baoan

2011-06-01

The aim of this study was to use silica nanoparticles as the carrier for controlled release of tilmicosin. Tilmicosin was selected as a drug model molecule because it has a lengthy elimination half-life and a high concentration in milk after subcutaneous administration. Three samples of tilmicosin-loaded silica nanoparticles were prepared with different drug-loading weight. The drug-loading weight in three samples, as measured by thermal gravimetric analysis, was 29%, 42%, and 64%, respectively. With increased drug-loading weight, the average diameter of the drug-loaded silica nanoparticles was increased from 13.4 to 25.7 nm, and the zeta potential changed from-30.62 to-6.78 mV, indicating that the stability of the drug-loaded particles in the aqueous solution decreases as drug-loading weight increases. In vitro release studies in phosphate-buffered saline showed the sample with 29% drug loading had a slow and sustained drug release, reaching 44% after 72 h. The release rate rose with increased drug-loading weight; therefore, the release of tilmicosin from silica nanoparticles was well-controlled by adjusting the drug loading. Finally, kinetics analysis suggested that drug released from silica nanoparticles was mainly a diffusion-controlled process.

Giving greater consideration to cross-drainage discharge from forest roads

Treesearch

Pamela J. Edwards; Gregory L. Evans

2004-01-01

Erosion below the outlets of cross drains (e.g., culverts'and broad-based dips) on forest roads in the central Appalachians is common but controllable. Erosion control below cross drains must take the form of reduced water discharged through each cross-drainage structure, slowed release of water, and/or adequate roughness for energy dissipation and water...

Controlled release of TGF-beta 1 from RADA self-assembling peptide hydrogel scaffolds

PubMed Central

Zhou, Ao; Chen, Shuo; He, Bin; Zhao, Weikang; Chen, Xiaojun; Jiang, Dianming

2016-01-01

Bioactive mediators, cytokines, and chemokines have an important role in regulating and optimizing the synergistic action of materials, cells, and cellular microenvironments for tissue engineering. RADA self-assembling peptide hydrogels have been proved to have an excellent ability to promote cell proliferation, wound healing, tissue repair, and drug delivery. Here, we report that D-RADA16 and L-RADA16-RGD self-assembling peptides can form stable second structure and hydrogel scaffolds, affording the slow release of growth factor (transforming growth factor cytokine-beta 1 [TGF-beta 1]). In vitro tests demonstrated that the plateau release amount can be obtained till 72 hours. Moreover, L-RADA16, D-RADA16, and L-RADA16-RGD self-assembling peptide hydrogels containing TGF-beta 1 were used for 3D cell culture of bone mesenchymal stem cells of rats for 2 weeks. The results revealed that these three RADA16 peptide hydrogels had a significantly favorable influence on proliferation of bone mesenchymal stem cells and hold some promise in slow and sustained release of growth factor. PMID:27703332

Polyoxometalate coordination induced controllable release of quinolone in hybrid film

NASA Astrophysics Data System (ADS)

Yang, Fan; Li, Yang; Lv, Yu-Guang; Zhou, Shu-Jing; Li, Si; Gao, Guang-Gang; Liu, Hong

2018-05-01

Due to some side effects of quinolones in vivo, it is an urgent issue to extend their new applications in vitro. In this paper, structure-determined vanadium-quinolone functionalized polymolybdates of (NH4)2 [(γ-Mo8O26){VO(CF)2}2] (1) and (NH4)2 [(γ-Mo8O26){VO(NF)2}2] (2) (CF = ciprofloxacin; NF = norfloxacin) have been designed and synthesized. Complex 1 or 2 features a γ-type [Mo8O26]4- polyanion functionalized by two monocapped vanadium-quinolone complexes. Different H-bonds and π···π interactions allow 1 or 2 to form a 2D layered structure at solid state. When complex 1 or 2 is transferred into polyvinyl alcohol (PVA) film, its release rate in solution is lower than that of CF- or NF-PVA film and thus forming a novel quinolone delivery system. This is the first time that slow release effect of quinolone is achieved by polyoxometalate coordination effect. The slow release of 1 or 2 in PVA film is mainly ascribed to the coordination of quinolone with polyoxometalate anions.

Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

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

Szegedi, A., E-mail: szegedi@chemres.h; Popova, M.; Goshev, I.

2011-05-15

MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choicemore » of mesoporous material with the appropriate structural characteristics and surface functionality. -- Graphical Abstract: Ibuprofen delivery from the parent and amino-modified spherical MCM-41 materials with 100 nm (small) and 500 nm (large) particle sizes. Display Omitted Highlights: {yields} Spherical type MCM-41 and SBA-15 with different particle sizes were modified by APTES. {yields} Adsorption and release rate of ibuprofen were compared. {yields} High degree of ibuprofen loading, slow release rate for MCM-41, the opposite for SBA-15. {yields} MCM-41 with 100 nm particles was more stable and showed slower release rate« less

Effects of formulation variables and post-compression curing on drug release from a new sustained-release matrix material: polyvinylacetate-povidone.

PubMed

Shao, Z J; Farooqi, M I; Diaz, S; Krishna, A K; Muhammad, N A

2001-01-01

A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

Preparation and properties of a double-coated slow-release and water-retention urea fertilizer.

PubMed

Liang, Rui; Liu, Mingzhu

2006-02-22

A double-coated, slow-release, and water-retention urea fertilizer (DSWU) was prepared by cross-linked poly(acrylic acid)-containing urea (PAAU) (the outer coating), polystyrene (PS) (the inner coating), and urea granule (the core). Elemental analysis results showed that the nitrogen content of the product was 33.6 wt %. The outer coating (PAAU) regulated the nitrogen release rate and protected the inner coating from damage. The slow-release property of the product was investigated in water and in soil. The possible mechanism of nitrogen release was proposed. The influences of PS coating percentage, temperature, water absorbency, and pH on the release of nitrogen were also investigated. It was found that PS coating percentage, temperature, and water absorbency had a significant influence on the release of nitrogen. However, the pH had no effect. The water-retention property of the product was also investigated. The results showed that the product not only had a good slow-release property but also excellent water-retention capacity, which could effectively improve the utilization of fertilizer and water resources. The results of the present work indicated that the DSWU would find good application in agriculture and horticulture, especially in drought-prone areas where the availability of water is insufficient.

Slow-release L-Cysteine (Acetium®) Lozenge Is an Effective New Method in Smoking Cessation. A Randomized, Double-blind, Placebo-controlled Intervention.

PubMed

Syrjänen, Kari; Eronen, Katja; Hendolin, Panu; Paloheimo, Lea; Eklund, Carita; Bäckström, Anna; Suovaniemi, Osmo

2017-07-01

Because of the major health problems and annual economic burden caused by cigarette smoking, effective new tools for smoking intervention are urgently needed. Our previous randomized controlled trial (RCT) provided promising results on the efficacy of slow-release L-cysteine lozenge in smoking intervention, but the study was not adequately powered. To confirm in an adequately-powered study the results of the previous RCT implicating that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium® lozenge, Biohit Oyj, Helsinki), would assist in smoking cessation by reducing acetaldehyde-enhanced nicotine addiction. On this matter, we undertook a double-blind, randomized, placebo-controlled trial comparing Acetium® lozenge and placebo in smoking intervention. A cohort of 1,998 cigarette smokers were randomly allocated to intervention (n=996) and placebo arms (n=1,002). At baseline, smoking history was recorded by a questionnaire, with nicotine dependence testing according to the Fagerström scale (FTND). The subjects used smoking diary recording the daily numbers of cigarettes, lozenges and subjective sensations of smoking. The data were analysed separately for point prevalence of abstinence (PPA) and prolonged abstinence (PA) endpoints. Altogether, 753 study subjects completed the trial per protocol (PP), 944 with violations (mITT), and the rest (n=301) were lost to follow-up (LTF). During the 6-month intervention, 331 subjects stopped smoking; 181 (18.2%) in the intervention arm and 150 (15.0%) in the placebo arm (OR=1.43; 95%CI=1.09-1.88); p=0.010). In the PP group, 170 (45.3%) quitted smoking in the intervention arm compared to 134 (35.4%) in the placebo arm (OR=1.51, 95%CI=1.12-2.02; p=0.006). In multivariate (Poisson regression) model, decreased level of smoking pleasure (p=0.010) and "smoking sensations changed" were powerful independent predictors of quit events (IRR=12.01; 95%CI=1.5-95.6). Acetium® lozenge, herein confirmed in an adequately powered study to be an effective means to aid smoking quit, represents a major breakthrough in the development of smoking intervention methods, because slow-release L-cysteine is non-toxic, with no side-effects or limitations of use. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion.

PubMed

Li, Yongcheng; Lu, Ming; Wu, Chuanbin

2017-11-10

The purpose of this study was to explore poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) as a novel release-modifier to tailor the drug release from ethylcellulose (EC)-based mini-matrices prepared via hot melt extrusion (HME). Quetiapine fumarate (QF) was selected as model drug. QF/EC/PVP VA64 mini-matrices were extruded with 30% drug loading. The physical state of QF in extruded mini-matrices was characterized using differential scanning calorimetry, X-ray powder diffraction, and confocal Raman microscopy. The release-controlled ability of PVP VA64 was investigated and compared with that of xanthan gum, crospovidone, and low-substituted hydroxypropylcellulose. The influences of PVP VA64 content and processing temperature on QF release behavior and mechanism were also studied. The results indicated QF dispersed as the crystalline state in all mini-matrices. The release of QF from EC was very slow as only 4% QF was released in 24 h. PVP VA64 exhibited the best ability to enhance the drug release as compared with other three release-modifiers. The drug release increased to 50-100% in 24 h with the addition of 20-40% PVP VA64. Increasing processing temperature slightly slowed down the drug release by decreasing free volume and pore size. The release kinetics showed good fit with the Ritger-Peppas model. The values of release exponent (n) increased as PVP VA64 is added (0.14 for pure EC, 0.41 for 20% PVP VA64, and 0.61 for 40% PVP VA64), revealing that the addition of PVP VA64 enhanced the erosion mechanism. This work presented a new polymer blend system of EC with PVP VA64 for sustained-release prepared via HME.

Preparation and Properties of a Novel Semi-IPN Slow-Release Fertilizer with the Function of Water Retention.

PubMed

Xiang, Yang; Ru, Xudong; Shi, Jinguo; Song, Jiang; Zhao, Haidong; Liu, Yaqing; Guo, Dongdong; Lu, Xin

2017-12-20

A new semi-interpenetrating polymer network (semi-IPN) slow-release fertilizer (SISRF) with water absorbency, based on the kaolin-g-poly(acrylic acid-co-acrylic amide) (kaolin-g-P(AA-co-AM)) network and linear urea-formaldehyde oligomers (UF), was prepared by solution polymerization. Nutrients phosphorus and potassium were supplied by adding dipotassium hydrogen phosphate during the preparation process. The structure and properties of SISRF were characterized by various characterization methods. SISRF showed excellent water absorbency of 68 g g -1 in tap water. The slow-release behavior of nutrients and water-retention capacity of SISRF were also measured. Meanwhile, the swelling kinetics was well described by a pseudo-second-order kinetics model. Results suggested the formation of SISRF with simultaneously good slow-release and water-retention capacity, which was expected to apply in modern agriculture and horticulture.

Boar semen controlled delivery system: storage and in vitro spermatozoa release.

PubMed

Torre, M L; Faustini, M; Norberti, R; Stacchezzini, S; Maggi, L; Maffeo, G; Conte, U; Vigo, D

2002-12-13

Swine spermatozoa were encapsulated in barium alginate and protamine-barium alginate membranes to lengthen their preservation time and to provide a means of controlling their release. Precocious acrosome reactions and secondary anomalies were measured as indices of semen quality. These characteristics were observed for two forms of encapsulated spermatozoa when stored at 18 and 38 degrees C for 24 h and for semen diluted in a classical extender at both temperatures. The results indicate that encapsulation enhances semen preservation, providing protection against membrane damage upon dilution. The effect is even more evident at the higher temperature (38 degrees C), where cell metabolism is higher. An in vitro release test of spermatozoa showed a massive cell delivery from barium alginate capsules within 6 h, and a slow release from protamine-barium alginate capsules. The properties of spermatozoa 24 h after release did not differ from the semen stored at the same temperature in capsules, indicating that the release process does not impair semen quality.

Buffers and Oscillations in Intracellular Ca2+ Dynamics

PubMed Central

Falcke, Martin

2003-01-01

I model the behavior of intracellular Ca2+ release with high buffer concentrations. The model uses a spatially discrete array of channel clusters. The channel subunit dynamics is a stochastic representation of the DeYoung-Keizer model. The calculations show that the concentration profile of fast buffer around an open channel is more localized than that of slow buffers. Slow buffers allow for release of larger amounts of Ca2+ from the endoplasmic reticulum and hence bind more Ca2+ than fast buffers with the same dissociation constant and concentration. I find oscillation-like behavior for high slow buffer concentration and low Ca2+ content of the endoplasmic reticulum. High concentration of slow buffer leads to oscillation-like behavior by repetitive wave nucleation for high Ca2+ content of the endoplasmic reticulum. Localization of Ca2+ release by slow buffer, as used in experiments, can be reproduced by the modeling approach. PMID:12524263

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

NASA Astrophysics Data System (ADS)

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

2016-06-01

Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix-a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30-47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3-35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.

A prominent anchoring effect on the kinetic control of drug release from mesoporous silica nanoparticles (MSNs).

PubMed

Tran, Vy Anh; Lee, Sang-Wha

2018-01-15

This work demonstrated kinetically controlled release of model drugs (ibuprofen, FITC) from well-tailored mesoporous silica nanoparticles (MSNs) depending on the surface charges and molecular sizes of the drugs. The molecular interactions between entrapped drugs and the pore walls of MSNs controlled the release of the drugs through the pore channels of MSNs. Also, polydopamine (PDA) layer-coated MSNs (MSNs@PDA) was quite effective to retard the release of large FITC, in contrast to a slight retardation effect on relatively small Ibuprofen. Of all things, FITC (Fluorescein isothiocyanate)-labeled APTMS (3-aminopropyltrimethoxysilane) (APTMS-FITC conjugates) grafted onto the MSNs generate a pinch-effect on the pore channel (so-called a prominent anchoring effect), which was highly effective in trapping (or blocking) drug molecules at the pore mouth of the MSNs. The anchored APTMS-FITC conjugates provided not only tortuous pathways to the diffusing molecules, but also sustained release of the ibuprofen over a long period of time (∼7days). The fast release kinetics was predicted by an exponential equation based on Fick's law, while the slow release kinetics was predicted by Higuchi model. Copyright © 2017 Elsevier Inc. All rights reserved.

MO-AB-BRA-02: Modeling Nanoparticle-Eluting Spacer Degradation During Brachytherapy Application with in Situ Dose-Painting

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

Boateng, F; Ngwa, W; Harvard Medical School, Boston, MA

Purpose: Brachytherapy application with in situ dose-painting using gold nanoparticles (GNP) released from GNP-loaded brachytherapy spacers has been proposed as an innovative approach to increase therapeutic efficacy during brachytherapy. This work investigates the dosimetric impact of slow versus burst release of GNP from next generation biodegradable spacers. Methods: Mathematical models were developed based on experimental data to study the release of GNP from a spacer designed with FDA approved poly(lactic-co-glycolic acid) (PLGA) polymer. The diffusion controlled released process and PLGA polymer degradation kinetics was incorporated in the calculations for the first time. An in vivo determined diffusion coefficient was usedmore » for determining the concentration profiles and corresponding dose enhancement based on initial GNP-loading concentrations of 7 mg/g. Results: The results showed that there is significant delay before the concentration profile of GNP diffusion in the tumor is similar to that when burst release is assumed as in previous studies. For example, in the case of burst release after spacer administration, it took up to 25 days for all the GNP to be released from the spacer using diffusion controlled release process only. However, it took up to 45 days when a combined model for both diffusion and polymer degradation processes was used. Based on the tumor concentration profiles, a significant dose enhancement factor (DEF >20%), could be attained at a tumor distances of 5 mm from a spacer loaded with 10 nm GNP sizes. Conclusion: The results highlight the need to take the slow release of GNP from spacers and factors such as biodegradation of polymers into account in research development of GNP-eluting spacers for brachytherapy applications with in-situ dose-painting using gold nanoparticles. The findings suggest that I-125 may be the more appropriate for such applications given the relatively longer half-live compared to other radioisotopes like Pd-103 and Cs-131.« less

Synthesis and characterization of zinc adeninate metal-organic frameworks (bioMOF1) as potential anti-inflammatory drug delivery material

NASA Astrophysics Data System (ADS)

Usman, Ken Aldren S.; Buenviaje, Salvador C.; Razal, Joselito M.; Conato, Marlon T.; Payawan, Leon M.

2018-05-01

Zn8(ad)4(BPDC)6O•2Me2NH2 (bioMOF1), a porous metal-organic framework with zinc-adeninate secondary building units (SBUs), interconnected via biphenyldicarboxylate linkers, shows great potential for drug delivery applications due to its non-toxic and biocompatible components (zinc and adenine). In this study, bioMOF1 crystals synthesized solvothermally at 130°C for 24 hours, were characterized thoroughly and loaded with a known anti-inflammatory drug, nimesulide (NIM). The crystalline nature of the material was confirmed using powder x-ray diffraction crystallography (PXRD) along with morphology assessment using focused-ion beam/field emission scanning electron microscopy (FIB/FESEM). NIM was introduced to the crystals via solvent exchange accompanied with vigorous stirring and quantified using thermogravimetric analysis (TGA) with loading saturation of ˜30% attained during the 2nd to 3rd day of drug immersion. Drug release in phosphate buffer saline and in deionized water was done to monitor the kinetic of drug release in vitro. The drug release showed a controlled discharge profile which slowed down at the 24th and 48th hour of release. Drug release in buffer showed a faster release of drug from the material, which means that the presence of cations in the solution could further trigger the release of drug. Slow drug release was observed for all of the set-ups with maximum % drug release of 24.47%, and 16.14% for the bioMOF1 in buffer and bioMOF1 in water respectively for the span of 48 hours.

A review of slow-release fluoride devices.

PubMed

Toumba, K J; Al-Ibrahim, N S; Curzon, M E J

2009-09-01

Fluoride has been used to combat dental caries using a number of different clinical approaches. An exciting relatively new development is fluoride slow-releasing devices that consistently elevate intra-oral fluoride levels of plaque and saliva for prolonged periods of up to two years. The literature on the use of slow-releasing fluoride devices in dentistry were reviewed. A Medline search on key words was carried out. All papers in English were individually reviewed. Slow-releasing fluoride devices have been shown to be effective in elevating salivary fluoride levels in both animals and human studies and to enhance the remineralisation of dental enamel. They have been demonstrated to be safe to use and without the risk of fluoride toxicity. A double blind randomised clinical trial demonstrated 76% fewer new carious surface increment in high caries-risk children after two years. These devices have a number of potential uses in dentistry and in particular have great potential for caries prevention of non-compliant high caries-risk groups.

Controlled release of chlorhexidine digluconate using β-cyclodextrin and microfibrillated cellulose.

PubMed

Lavoine, Nathalie; Tabary, Nicolas; Desloges, Isabelle; Martel, Bernard; Bras, Julien

2014-09-01

This study aims to develop a high-performance delivery system using microfibrillated cellulose (MFC)-coated papers as a controlled release system combined with the well-known drug delivery agent, β-cyclodextrin (βCD). Chlorhexidine digluconate (CHX), an antibacterial molecule, was mixed with a suspension of MFC or a βCD solution or mixed with both the substances, before coating onto a cellulosic substrate. The intermittent diffusion of CHX (i.e., diffusion interrupted by the renewal of the release medium periodically) was conducted in an aqueous medium, and the release mechanism of CHX was elucidated by field emission gun-scanning electron microscopy, SEM, NMR, and Fourier transform infrared analyses. According to the literature, both βCD and MFC are efficient controlled delivery systems. This study indicated that βCD releases CHX more gradually and over a longer period of time compared to MFC, which is mainly due to the ability of βCD to form an inclusion complex with CHX. Furthermore from the release study, a complementary action when the two compounds were combined was deduced. MFC mainly affected the burst effect, while βCD primarily controlled the amount of CHX released over time. In this paper, two different types of controlled release systems are proposed and compared. Depending on the final application, the use of βCD alone would release low amounts of active molecules over time (slow delivery), whereas the combination of β-cyclodextrin and MFC would be more suitable for the release of higher amounts of active molecules over time (rapid delivery). Copyright © 2014 Elsevier B.V. All rights reserved.

Adaptation of Slow Myofibers: The Effect of Sustained BDNF Treatment of Extraocular Muscles in Infant Nonhuman Primates

PubMed Central

Willoughby, Christy L.; Fleuriet, Jérome; Walton, Mark M.; Mustari, Michael J.; McLoon, Linda K.

2015-01-01

Purpose. We evaluated promising new treatment options for strabismus. Neurotrophic factors have emerged as a potential treatment for oculomotor disorders because of diverse roles in signaling to muscles and motor neurons. Unilateral treatment with sustained release brain-derived neurotrophic factor (BDNF) to a single lateral rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop in correlation with extraocular muscle (EOM) changes during the critical period for development of binocularity. Methods. The lateral rectus muscles of one eye in two infant macaques were treated with sustained delivery of BDNF for 3 months. Eye alignment was assessed using standard photographic methods. Muscle specimens were analyzed to examine the effects of BDNF on the density, morphology, and size of neuromuscular junctions, as well as myofiber size. Counts were compared to age-matched controls. Results. No change in eye alignment occurred with BDNF treatment. Compared to control muscle, neuromuscular junctions on myofibers expressing slow myosins had a larger area. Myofibers expressing slow myosin had larger diameters, and the percentage of myofibers expressing slow myosins increased in the proximal end of the muscle. Expression of BDNF was examined in control EOM, and observed to have strongest immunoreactivity outside the endplate zone. Conclusions. We hypothesize that the oculomotor system adapted to sustained BDNF treatment to preserve normal alignment. Our results suggest that BDNF treatment preferentially altered myofibers expressing slow myosins. This implicates BDNF signaling as influencing the slow twitch properties of EOM. PMID:26030102

Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates.

PubMed

Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M; Mustari, Michael J; McLoon, Linda K

2015-06-01

We evaluated promising new treatment options for strabismus. Neurotrophic factors have emerged as a potential treatment for oculomotor disorders because of diverse roles in signaling to muscles and motor neurons. Unilateral treatment with sustained release brain-derived neurotrophic factor (BDNF) to a single lateral rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop in correlation with extraocular muscle (EOM) changes during the critical period for development of binocularity. The lateral rectus muscles of one eye in two infant macaques were treated with sustained delivery of BDNF for 3 months. Eye alignment was assessed using standard photographic methods. Muscle specimens were analyzed to examine the effects of BDNF on the density, morphology, and size of neuromuscular junctions, as well as myofiber size. Counts were compared to age-matched controls. No change in eye alignment occurred with BDNF treatment. Compared to control muscle, neuromuscular junctions on myofibers expressing slow myosins had a larger area. Myofibers expressing slow myosin had larger diameters, and the percentage of myofibers expressing slow myosins increased in the proximal end of the muscle. Expression of BDNF was examined in control EOM, and observed to have strongest immunoreactivity outside the endplate zone. We hypothesize that the oculomotor system adapted to sustained BDNF treatment to preserve normal alignment. Our results suggest that BDNF treatment preferentially altered myofibers expressing slow myosins. This implicates BDNF signaling as influencing the slow twitch properties of EOM.

The properties of antimicrobial films derived from poly(lactic acid)/starch/chitosan blended matrix.

PubMed

Bie, Pingping; Liu, Peng; Yu, Long; Li, Xiaoxi; Chen, Ling; Xie, Fengwei

2013-10-15

An antimicrobial material with a slow release property was developed based on poly(lactic acid)/starch/chitosan blends, in which chitosan acted as an antimicrobial agent while PLA and starch together were used as a slow-releasing device. An increase in the starch content drastically improved the hydrophilicity of the blends, which was favorable for the diffusion of the embedded chitosan. Moreover, the release of chitosan was observed to occur in two stages, with a very fast release stage initially and a slow but durable release stage as the latter. These two stages exhibited the effectiveness and long residual action of antimicrobial property of the blends respectively, demonstrating the suitability to be used for foods with high water activity, such as fresh meat. The tensile and thermal properties further verified the promising use of the blend material in packaging. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Control of extracellular dopamine at dendrite and axon terminals

PubMed Central

Ford, Christopher P.; Gantz, Stephanie C.; Phillips, Paul E. M.; Williams, John T.

2010-01-01

Midbrain dopamine neurons release dopamine from both axons and dendrites. The mechanism underlying release at these different sites has been proposed to differ. This study used electrochemical and electrophysiological methods to compare the time course and calcium-dependence of somatodendritc dopamine release in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) to that of axonal dopamine release in the dorsal striatum. The amount of dopamine released in the striatum was ~20 fold greater than in cell body regions of the VTA or SNc. However the calcium dependence and time to peak of the dopamine transients were similar. These results illustrate an unexpected overall similarity in the mechanisms of dopamine release in the striatum and cell body regions. To examine how diffusion regulates the time course of dopamine following release, dextran was added to the extracellular solution to slow diffusion. In the VTA, dextran slowed the rate of rise and fall of the extracellular dopamine transient as measured by fast-scan cyclic voltammetry (FSCV) yet did not alter the kinetics of the dopamine dependent inhibitory post-synaptic current (IPSC). Dextran failed to significantly alter the time course of the rise and fall of the dopamine transient in the striatum suggesting a more influential role for reuptake in the striatum. The conclusion is that the time course of dopamine within the extracellular space of the VTA is dependent on both diffusion and reuptake, whereas the activation of D2-receptors on dopamine neurons is primarily limited by reuptake. PMID:20484639

Non-Faradaic Electrochemical Detection of Exocytosis from Mast and Chromaffin Cells Using Floating-Gate MOS Transistors.

PubMed

Jayant, Krishna; Singhai, Amit; Cao, Yingqiu; Phelps, Joshua B; Lindau, Manfred; Holowka, David A; Baird, Barbara A; Kan, Edwin C

2015-12-21

We present non-faradaic electrochemical recordings of exocytosis from populations of mast and chromaffin cells using chemoreceptive neuron MOS (CνMOS) transistors. In comparison to previous cell-FET-biosensors, the CνMOS features control (CG), sensing (SG) and floating gates (FG), allows the quiescent point to be independently controlled, is CMOS compatible and physically isolates the transistor channel from the electrolyte for stable long-term recordings. We measured exocytosis from RBL-2H3 mast cells sensitized by IgE (bound to high-affinity surface receptors FcεRI) and stimulated using the antigen DNP-BSA. Quasi-static I-V measurements reflected a slow shift in surface potential () which was dependent on extracellular calcium ([Ca]o) and buffer strength, which suggests sensitivity to protons released during exocytosis. Fluorescent imaging of dextran-labeled vesicle release showed evidence of a similar time course, while un-sensitized cells showed no response to stimulation. Transient recordings revealed fluctuations with a rapid rise and slow decay. Chromaffin cells stimulated with high KCl showed both slow shifts and extracellular action potentials exhibiting biphasic and inverted capacitive waveforms, indicative of varying ion-channel distributions across the cell-transistor junction. Our approach presents a facile method to simultaneously monitor exocytosis and ion channel activity with high temporal sensitivity without the need for redox chemistry.

Non-Faradaic Electrochemical Detection of Exocytosis from Mast and Chromaffin Cells Using Floating-Gate MOS Transistors

PubMed Central

Jayant, Krishna; Singhai, Amit; Cao, Yingqiu; Phelps, Joshua B.; Lindau, Manfred; Holowka, David A.; Baird, Barbara A.; Kan, Edwin C.

2015-01-01

We present non-faradaic electrochemical recordings of exocytosis from populations of mast and chromaffin cells using chemoreceptive neuron MOS (CνMOS) transistors. In comparison to previous cell-FET-biosensors, the CνMOS features control (CG), sensing (SG) and floating gates (FG), allows the quiescent point to be independently controlled, is CMOS compatible and physically isolates the transistor channel from the electrolyte for stable long-term recordings. We measured exocytosis from RBL-2H3 mast cells sensitized by IgE (bound to high-affinity surface receptors FcεRI) and stimulated using the antigen DNP-BSA. Quasi-static I-V measurements reflected a slow shift in surface potential () which was dependent on extracellular calcium ([Ca]o) and buffer strength, which suggests sensitivity to protons released during exocytosis. Fluorescent imaging of dextran-labeled vesicle release showed evidence of a similar time course, while un-sensitized cells showed no response to stimulation. Transient recordings revealed fluctuations with a rapid rise and slow decay. Chromaffin cells stimulated with high KCl showed both slow shifts and extracellular action potentials exhibiting biphasic and inverted capacitive waveforms, indicative of varying ion-channel distributions across the cell-transistor junction. Our approach presents a facile method to simultaneously monitor exocytosis and ion channel activity with high temporal sensitivity without the need for redox chemistry. PMID:26686301

A new ovitrap made of slow release natural materials containing pyriproxyfen for Aedes aegypti (Diptera:Culicidae) control.

PubMed

Juan, Laura; Seccacini, Emilia; Zerba, Eduardo; Licastro, Susana

2013-07-01

ABSTRACT This initial study is aimed to measure the performance of incorporating pyriproxyfen in natural materials with low environmental impact to obtain slow release formulations that can be used as larvicidal or autocidal ovitraps avoiding hatched Aedes aegypti (L.) eggs to emerge as adults. Hollow candles made of beeswax or paraffin:stearin 1:1 mixture containing pyriproxyfen 0.01 and 0.05% were prepared and used as holding water containers for larval bioassay. Pyriproxyfen was released quickly into the larvae-breeding water. Ae. aegypti larvae were introduced immediately after the addition of tap water to the hollow candles (t = 1 min) or after 1, 4, and 8 h. More than 40% of the larvae did not emerge as adults for t = 1 min, reaching 80-100% when the larvae were added after 1 or 4 h, respectively. The hollow candles were kept at room temperature, and water was replaced every 15 d. Bioassays performed every 30 d showed that the residual activity obtained for both matrices and both concentrations of pyriproxyfen was higher than 360 d, with 100% inhibition of adult emergence.

Dynamics of neuroendocrine stress response: bistability, timing, and control of hypocortisolism

NASA Astrophysics Data System (ADS)

D'Orsogna, Maria; Chou, Tom; Kim, Lae

The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in its activity are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. We characterize ``normal'' and ``diseased'' states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), by circulating glucocorticoids such as cortisol (CORT). Our model includes ultradian oscillations, CRH self-upregulation of CRH release, and distinguishes two components of negative feedback by cortisol on circulating CRH levels: a slow direct suppression of CRH synthesis and a fast indirect effect on CRH release. The slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. We find that the timing of traumatic events may be an important factor in determining if and how the hallmarks of depressive disorders will manifest. Our model also suggests a mechanism whereby exposure therapy of stress disorders may act to normalize downstream dysregulation of the HPA axis.

Multifunctional slow-release organic-inorganic compound fertilizer.

PubMed

Ni, Boli; Liu, Mingzhu; Lü, Shaoyu; Xie, Lihua; Wang, Yanfang

2010-12-08

Multifunctional slow-release organic-inorganic compound fertilizer (MSOF) has been investigated to improve fertilizer use efficiency and reduce environmental pollution derived from fertilizer overdosage. The special fertilizer is based on natural attapulgite (APT) clay used as a matrix, sodium alginate used as an inner coating and sodium alginate-g-poly(acrylic acid-co-acrylamide)/humic acid (SA-g-P(AA-co-AM)/HA) superabsorbent polymer used as an outer coating. The coated multielement compound fertilizer granules were produced in a pan granulator, and the diameter of the prills was in the range of 2.5-3.5 mm. The structural and chemical characteristics of the product, as well as its efficiency in slowing the nutrients release, were examined. In addition, a mathematical model for nutrient release from the fertilizer was applied to calculate the diffusion coefficient D of nutrients in MSOF. The degradation of the SA-g-P(AA-co-AM)/HA coating was assessed by examining the weight loss with incubation time in soil. It is demonstrated that the product prepared by a simple route with good slow-release property may be expected to have wide potential applications in modern agriculture and horticulture.

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

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

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

In spite of the massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Here we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases, and we usemore » molecular simulations to demonstrate it. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Finally, our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.« less

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

PubMed Central

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

2016-01-01

Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release. PMID:27306967

Nanostructural control of methane release in kerogen and its implications to wellbore production decline

DOE PAGES

Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

2016-06-16

In spite of the massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Here we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases, and we usemore » molecular simulations to demonstrate it. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Finally, our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.« less

Leaching behavior of U, Mn, Sr, and Pb from different particle-size fractions of uranium mill tailings.

PubMed

Liu, Bo; Peng, Tongjiang; Sun, Hongjuan

2017-06-01

Pollution by the release of heavy metals from tailings constitutes a potential threat to the environment. To characterize the processes governing the release of Mn, Sr, Pb, and U from the uranium mill tailings, a dynamic leaching test was applied for different size of uranium mill tailings samples. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) were performed to determine the content of Mn, Sr, Pb, and U in the leachates. The release of mobile Mn, Sr, Pb, and U fraction was slow, being faster in the initial stage and then attained a near steady-state condition. The experimental results demonstrate that the release of Mn, Sr, Pb, and U from uranium mill tailings with different size fractions is controlled by a variety of mechanisms. Surface wash-off is the release mechanism for Mn. The main release mechanism of Sr and Pb is the dissolution in the initial leaching stage. For U, a mixed process of wash-off and diffusion is the controlling mechanism.

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

PubMed Central

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

2011-01-01

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

Brown dog tick, Rhipicephalus sanguineus sensu lato, infestation of susceptible dog hosts is reduced by slow release of semiochemicals from a less susceptible host.

PubMed

de Oliveira Filho, Jaires Gomes; Ferreira, Lorena Lopes; Sarria, André Lucio Franceschini; Pickett, John A; Birkett, Michael A; Mascarin, Gabriel Moura; de León, Adalberto A Pérez; Borges, Lígia Miranda Ferreira

2017-01-01

Domestic dog breeds are hosts for the brown dog tick, Rhipicephalus sanguineus sensu lato, but infestation levels vary among breeds. Beagles are less susceptible to tick infestations than English cocker spaniels due to enhanced production of 2-hexanone and benzaldehyde that act as volatile tick repellents. We report the use of prototype slow-release formulations of these compounds to reduce the burden of R. sanguineus s. l. on English cocker spaniel dogs. Twelve dogs were randomly assigned to two groups with six dogs each. The treated group received collars with slow-release formulations of the compounds attached, while the control group received collars with clean formulations attached. Five environmental infestations were performed, with the number of ticks (at all stages) on the dogs being counted twice a day for 45days. The counts on the number of tick stages found per dog were individually fitted to linear mixed effects models with repeated measures and normal distribution for errors. The mean tick infestation in the treated group was significantly lower than in the control group. For larvae and nymphs, a decrease in tick infestation was observed at the fifth count, and for adults, lower average counts were observed in all counts. The compounds did not interfere with the distribution of the ticks on the body of the dogs, as a similar percentage of ticks was found on the anterior half of the dogs (54.5% for the control group and 56.2% for the treated group). The biological and reproductive parameters of the ticks were not affected by the repellents. This study highlights for the first time the potential use of a novel allomone (repellent)-based formulation for reduction of tick infestation on susceptible dogs. Copyright © 2016 Elsevier GmbH. All rights reserved.

[Effect of slow-release aminophylline on pulmonary function in obstructive respiratory disease(author's transl)].

PubMed

Wiessmann, K J

1975-09-05

The effects on pulmonary function of a slow-release preparation of an oral broncholytic drug (containing 350 mg aminophylline, released over eight hours) was tested on 26 patients in a double-blind trial. There was a marked reduction of airway resistance and stimulation of breathing with decreased dynamic work of breathing. Distinctly improved alveolar function was demonstrated especially in a fall of arterial CO2 tension, but in some cases there was probably an increase in distribution abnormality. Central haemodynamic changes with a decreased in pulmonary artery pressure and changes in the other values lasted for more than ten hours on the first day of treatment, and were demonstrable on the fourth day even before the drug was taken that day. The criteria of an effective broncholytic slow-release drug with sustained effect were thus fulfilled.

Poly(ethylene glycol)/chitosan/sodium glycerophosphate gel replaced the joint capsule with slow-release lubricant after joint surgery.

PubMed

Lu, Hailin; Ren, Shanshan; Li, Xing; Guo, Junde; Dong, Guangneng; Li, Jianhui; Gao, Li

2018-08-01

Body fluid is normally the only lubricant after joint replacement surgery, but wear problems have occurred because body fluid has poor lubrication ability. However, traditional lubricant would be diluted by body fluids and then absorbed by the human body. Therefore, an injectable gel with the ability to slow-release lubricant was designed to replace the joint capsule. The proposed gel, poly(ethylene glycol)/chitosan/sodium glycerophosphate (PEG/CS/GP) composite gel was then tested. The tribology results showed that the PEG/CS/GP gel had excellent slow-release properties, especially under pressure, and the PEG played an important role in improving the gel's rheological and mechanical properties. Moreover, this study revealed that the release solution had a good lubrication effect because the PEG and GP could crosslink via the hydrogen bond effect.

Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.

PubMed

Rigamonti, A E; Bini, S; Grugni, G; Agosti, F; De Col, A; Mallone, M; Cella, S G; Sartorio, A

2014-10-01

The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far. Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions. © 2013 John Wiley & Sons Ltd.

Moss antheridia are desiccation tolerant: Rehydration dynamics influence sperm release in Bryum argenteum.

PubMed

Stark, Lloyd R; McLetchie, D Nicholas; Greenwood, Joshua L; Eppley, Sarah M

2016-05-01

Free-living sperm of mosses are known to be partially desiccation tolerant. We hypothesized that mature moss antheridia should also tolerate desiccation and that rehydration to partial turgor (prehydration) or rehydration to full turgor (rehydration) before immersion in water is required for full recovery from any damaging effects of prior desiccation. Bryum argenteum (silvery-thread moss) was grown in continuous culture for several months, produced mature perigonia (clusters of antheridia), and these were subjected to a slow rate of drying (∼36 h from full turgor to desiccation) and equilibration with 50% relative humidity. Perigonia were prehydrated (exposed to a saturated atmosphere) or rehydrated (planted upright in saturated media) for 0, 45, 90, 135, 180, and 1440 min, then immersed in sterile water. Time to first sperm mass release, number of antheridia releasing sperm masses, and the integrity of the first sperm mass released were assessed. Rehydration of dried antheridia for at least 3 h before immersion in water resulted in antheridia functioning similar to control undried antheridia. Compared with rehydration, prehydration was not effective in the recovery of antheridia from desiccation. For the first time, moss antheridia are shown to be fully desiccation tolerant at a functional level, capable of releasing fully functional sperm following a slow drying event provided the antheridia are allowed to rehydrate at least 3 h before immersion in water. © 2016 Botanical Society of America.

COMPARISON OF TRICHLOROETHYLENE REDUCTIVE DEHALOGENATION BY MICROBIAL COMMUNITIES STIMULATED ON SILICON-BASED ORGANIC COMPOUNDS AS SLOW-RELEASE ANAEROBIC SUBSTRATES. (R828772C001)

EPA Science Inventory

Microcosm studies were conducted to demonstrate the effectiveness of tetrabutoxysilane (TBOS) as a slow-release anaerobic substrate to promote reductive dehalogenation of trichloroethylene (TCE). The abiotic hydrolysis of TBOS and tetrakis(2-ethylbutoxy)silane (TKEBS), and the...

An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release Control by Multiple Channels at a CNS Synapse

PubMed Central

Keller, Daniel; Babai, Norbert; Kochubey, Olexiy; Han, Yunyun; Markram, Henry; Schürmann, Felix; Schneggenburger, Ralf

2015-01-01

The spatial arrangement of Ca2+ channels and vesicles remains unknown for most CNS synapses, despite of the crucial importance of this geometrical parameter for the Ca2+ control of transmitter release. At a large model synapse, the calyx of Held, transmitter release is controlled by several Ca2+ channels in a "domain overlap" mode, at least in young animals. To study the geometrical constraints of Ca2+ channel placement in domain overlap control of release, we used stochastic MCell modelling, at active zones for which the position of docked vesicles was derived from electron microscopy (EM). We found that random placement of Ca2+ channels was unable to produce high slope values between release and presynaptic Ca2+ entry, a hallmark of domain overlap, and yielded excessively large release probabilities. The simple assumption that Ca2+ channels can be located anywhere at active zones, except below a critical distance of ~ 30 nm away from docked vesicles ("exclusion zone"), rescued high slope values and low release probabilities. Alternatively, high slope values can also be obtained by placing all Ca2+ channels into a single supercluster, which however results in significantly higher heterogeneity of release probabilities. We also show experimentally that high slope values, and the sensitivity to the slow Ca2+ chelator EGTA-AM, are maintained with developmental maturation of the calyx synapse. Taken together, domain overlap control of release represents a highly organized active zone architecture in which Ca2+ channels must obey a certain distance to docked vesicles. Furthermore, domain overlap can be employed by near-mature, fast-releasing synapses. PMID:25951120

Preparation and properties of a double-coated slow-release NPK compound fertilizer with superabsorbent and water-retention.

PubMed

Wu, Lan; Liu, Mingzhu; Rui Liang

2008-02-01

A double-coated slow-release NPK compound fertilizer with superabsorbent and water-retention was prepared by crosslinked poly(acrylic acid)/diatomite - containing urea (the outer coating), chitosan (the inner coating), and water-soluble granular fertilizer NPK (the core). The effects of the amount of crosslinker, initiator, degree of neutralization of acrylic acid, initial monomer and diatomite concentration on water absorbency were investigated and optimized. The water absorbency of the product was 75 times its own weight if it was allowed to swell in tap water at room temperature for 2 h. Atomic absorption spectrophotometer and element analysis results showed that the product contained 8.47% potassium (shown by K(2)O), 8.51% phosphorus (shown by P(2)O(5)), and 15.77% nitrogen. We also investigated the water-retention property of the product and the slow release behavior of N, P and K in the product. This product with excellent slow release and water-retention capacity, being nontoxic in soil and environment-friendly, could be especially useful in agricultural and horticultural applications.

Prolonged and continuous antibacterial and anti-biofilm activities of thin films embedded with gentamicin-loaded mesoporous silica nanoparticles

NASA Astrophysics Data System (ADS)

Tamanna, Tasnuva; Landersdorfer, Cornelia B.; Ng, Hooi Jun; Bulitta, Jürgen B.; Wood, Peter; Yu, Aimin

2018-05-01

The application of mesoporous silica nanoparticles (MSNs) in drug delivery systems has become highly attractive since the early 2000s. In this study, thin-film coatings embedded with gentamicin-loaded mesoporous silica nanoparticles (MSN-G) were prepared to provide antibacterial and anti-biofilm activity over a prolonged period of time. The prolonged and continuous activity of MSN-G films against Staphylococcus aureus throughout the release period was studied via two methods, namely, (1) disc diffusion of released gentamicin and (2) by shifting the MSN-G thin film to a new agar plate at certain time intervals. The expansion of the inhibition zone from 4.6 ± 0.5 to 9.7 ± 0.5 mm as caused by the released fraction of gentamicin from the first week to the eighth week indicated the controlled and slow release behaviour of loaded antibiotic and prolonged antibacterial efficacy of these films. In addition, the appearance of an inhibition zone after each shifting of the film to a new agar plate was persistent up to 103 days which confirmed that thin films successively prevented bacterial growth over a long period of time. In addition, the anti-biofilm activity of MSN-G films was evaluated by imaging bacterial cells attachment via confocal laser scanning microscopy and scanning electron microscopy. Remarkably, the anti-biofilm performance remained active for more than 2 months. To the best of our knowledge, such a slow and controlled release of antibiotic from nanoparticle embedded thin films with uninterrupted, continuous, and prolonged antibacterial effect for more than 2 months has not been reported yet.

Enhanced bone formation in the vicinity of porous β-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

PubMed

Kamikura, Keita; Minatoya, Tsutomu; Terada-Nakaishi, Michiko; Yamamoto, Shoko; Sakai, Yasuo; Furusawa, Toshitake; Matsushima, Yuta; Unuma, Hidero

2017-09-01

It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous β-tricalcium phosphate (β-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The β-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified β-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous β-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine β-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A β-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.

PubMed

Dinh, Van Vuong; Suh, Yun-Suhk; Yang, Han-Kwang; Lim, Yong Taik

2016-12-01

We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 μm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

PubMed Central

Nahire, Rahul; Haldar, Manas K.; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H.; Katti, Kalpana S.; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

2013-01-01

Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging. PMID:23394107

Comparing slow and fast rupture in laboratory experiments

NASA Astrophysics Data System (ADS)

Aben, F. M.; Brantut, N.; David, E.; Mitchell, T. M.

2017-12-01

During the brittle failure of rock, elastically stored energy is converted into a localized fracture plane and surrounding fracture damage, seismic radiation, and thermal energy. However, the partitioning of energy might vary with the rate of elastic energy release during failure. Here, we present the results of controlled (slow) and dynamic (fast) rupture experiments on dry Lanhélin granite and Westerly granite samples, performed under triaxial stress conditions at confining pressures of 50 and 100 MPa. During the tests, we measured sample shortening, axial load and local strains (with 2 pairs of strain gauges glued directly onto the sample). In addition, acoustic emissions (AEs) and changes in seismic velocities were monitored. The AE rate was used as an indicator to manually control the axial load on the sample to stabilize rupture in the quasi-static failure experiments. For the dynamic rupture experiments a constant strain rate of 10-5 s-1 was applied until sample failure. A third experiment, labeled semi-controlled rupture, involved controlled rupture up to a point where the rupture became unstable and the remaining elastic energy was released dynamically. All experiments were concluded after a macroscopic fracture had developed across the whole sample and frictional sliding commenced. Post-mortem samples were epoxied, cut and polished to reveal the macroscopic fracture and the surrounding damage zone. The samples failed with average rupture velocities varying from 5x10-6 m/s up to >> 0.1 m/s. The analyses of AE locations on the slow ruptures reveal that within Westerly granite samples - with a smaller grain size - fracture planes are disbanded in favor of other planes when a geometrical irregularity is encountered. For the coarser grained Lanhélin granite a single fracture plane is always formed, although irregularities are recognized as well. The semi-controlled experiments show that for both rock types the rupture can become unstable in response to these irregularities. In Westerly granite, slow rupture experiments tend to produce complex fracture patterns while during the dynamic rupture experiments secondary rupture planes are not formed. These findings show that grain or flaw size, flaw distribution, and rupture speed strongly influence fracture localization and propagation.

Controlled release of agrochemicals intercalated into montmorillonite interlayer space.

PubMed

Wanyika, Harrison

2014-01-01

Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil.

Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

PubMed Central

2014-01-01

Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil. PMID:24696655

Layered double hydroxides as adsorbents and carriers of the herbicide (4-chloro-2-methylphenoxy)acetic acid (MCPA): systems Mg-Al, Mg-Fe and Mg-Al-Fe.

PubMed

Bruna, F; Celis, R; Pavlovic, I; Barriga, C; Cornejo, J; Ulibarri, M A

2009-09-15

Hydrotalcite-like compounds [Mg(3)Al(OH)(8)]Cl x 4H(2)O; [Mg(3)Fe(OH)(8)]Cl x 4H(2)O; [Mg(3)Al(0.5)Fe(0.5)(OH)(8)]Cl x 4H(2)O (LDHs) and calcined product of [Mg(3)Al(OH)(8)]Cl x 4H(2)O, Mg(3)AlO(4.5) (HT500), were studied as potential adsorbents of the herbicide MCPA [(4-chloro-2-methylphenoxy)acetic acid] as a function of pH, contact time and pesticide concentration, and also as support for the slow release of this pesticide, with the aim to reduce the hazardous effects that it can pose to the environment. The information obtained in the adsorption study was used for the preparation of LDH-MCPA complexes. The results showed high and rapid adsorption of MCPA on the adsorbents as well as that MCPA formulations based on LDHs and HT500 as pesticide supports displayed controlled release properties and reduced herbicide leaching in soil columns compared to a standard commercial MCPA formulation. Thereby, we conclude that the LDHs employed in this study can be used not only as adsorbents to remove MCPA from aqueous solutions, but also as supports for the slow release of this highly mobile herbicide, thus controlling its immediate availability and leaching.

Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

NASA Astrophysics Data System (ADS)

Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

Biochemical stability of organic matter in soils amended with organic slow N-release fertilizer derived from charred plant residues and ammonoxidized lignin

NASA Astrophysics Data System (ADS)

Knicker, Heike; de la Rosa, José Maria; López Martín, María; Clemente Barragan, Reyes; Liebner, Falk

2013-04-01

As an important plant nutrient, N that has been removed from the soil by plant growth is replaced mainly by the use of synthetic fertilizers. Although this practice has dramatically increased food production, the unintended costs to the environment and human health due to surplus and inefficient application have also been substantial. Major losses of N to the environment can be minimized if "sustainable" agricultural practices are combined with reasonable fertilization. The latter can be achieved by applying slow N-release fertilizers. Here, the N is incorporated into an organic matrix, which after its amendment to soils, slowly decompose, allowing the liberation of the nutrient. Deriving from organic waste, such an amendment helps to efficiently recycle resources and increases the C sequestration potential of soils. However, in order to turn this approach into a successful strategy, the material has to be bioavailable but still sufficiently recalcitrant to ensure slow and controlled N-release. In the present study, we tested potential slow N-release fertilizers recycled from organic waste for their biochemical stability in soils. They comprised N-rich charred grass residues and N-lignin derived from waste of the pulp and paper industry and enriched in N by ammonoxidation. The substrates were mixed with soil of an Histic Humaquept and subsequently subjected to microbial degradation at 28°C in a Respicond IV Apparatus for 10 weeks. Additionally, soil material without organic amendment and soils mixed with lignin or charcoal both with and without KNO3 were included into the experiment. During the degradation experiment the CO2 production was determined on an hourly base. The degradation rate constants and the mean residence times were calculated using a double exponential decay model (pools with fast and slow turnover). Alterations of the chemical composition of the organic matter during degradation were studied by solid-state 13C NMR spectroscopy. First results indicated that without N addition, lignin only slightly altered the degradation rate of the slow turning soil organic matter pool (mean residence time of the slow pool: 10 years). Additional fertilization with KNO3, increased the respective mean residence time, possibly because the presence of easily available N decreased the activity of the lignolytic enzymes. A comparable behavior was observed for the experiment with the barbeque charcoal. However, application of N-lignin resulted in faster degradation, possibly because the restricted N-availability augmented the decomposition of the lignin backbone. The N-rich charred grass residues/soil mixture, on the other hand, showed mean residence times being in the range observed for the soil without amendment and fertilization, indicating comparable degradation rates of soil organic matter and grass char. The present results confirm the close relationship between N availability and C degradation of soil organic matter. Producing slow N-release fertilizers, one has to bear in mind that not only the C/N ratio but also the quality of the organic carbon and nitrogen determines the degradation rate of the substrate and thus the availability of the applied N.

QUICK RELEASABLE DRIVE

DOEpatents

Dickson, J.J.

1958-07-01

A quick releasable mechanical drive system suitable for use in a nuclear reactor is described. A small reversible motor positions a control rod by means of a worm and gear speed reducer, a magnetic torque clutch, and a bell crank. As the control rod is raised to the operating position, a heavy coil spring is compressed. In the event of an emergency indicated by either a''scram'' signal or a power failure, the current to the magnetic clutch is cut off, thereby freeing the coil spring and the bell crank positioner from the motor and speed reduction gearing. The coil spring will immediately act upon the bell crank to cause the insertion of the control rod. This arrangement will allow the slow, accurate positioning of the control rod during reactor operation, while providing an independent force to rapidly insert the rod in the event of an emergency.

Hydrogen peroxide increases depolarization-induced contraction of mechanically skinned slow twitch fibres from rat skeletal muscles.

PubMed

Plant, David R; Lynch, Gordon S; Williams, David A

2002-03-15

The effect of exogenous hydrogen peroxide (H(2)O(2)) on excitation-contraction (E-C) coupling and sarcoplasmic reticulum (SR) function was compared in mechanically skinned slow twitch fibres (prepared from the soleus muscles) and fast twitch fibres (prepared from the extensor digitorum longus; EDL muscles) of adult rats. Equilibration (5 min) with 1 mM H(2)O(2) diminished the ability of the Ca(2+)-depleted SR to reload Ca(2+) in both slow (P < 0.01) and fast twitch fibres (P < 0.05) compared to control. Under conditions when all Ca(2+) uptake was prevented, 1 mM H(2)O(2) increased SR Ca(2+) "leak" in fast twitch fibres by 24 +/- 5 % (P < 0.05), but leak was not altered in slow twitch fibres. Treatment with 1 mM H(2)O(2) also increased the peak force of low [caffeine] contracture by approximately 45% in both fibre types compared to control (P < 0.01), which could be partly reversed following treatment with 10 mM dithiothreitol (DTT). The changes in SR function caused by 1 mM H(2)O(2) were associated with an approximately 65% increase in the peak height of depolarization-induced contractile response (DICR) in slow twitch fibres, compared to control (no H(2)O(2); P < 0.05). In contrast, peak contractile force of fast twitch fibres was not altered by 1 mM H(2)O(2) treatment. Equilibration with 5 mM H(2)O(2) induced a spontaneous force response in both slow and fast twitch fibres, which could be partly reversed by 2 min treatment with 10 mM DTT. Peak DICR was also increased approximately 40% by 5 mM H(2)O(2) in slow twitch fibres compared to control (no H(2)O(2); P < 0.05). Our results indicate that exogenous H(2)O(2) increases depolarization-induced contraction of mechanically skinned slow but not fast twitch fibres. The increase in depolarization-induced contraction in slow twitch fibres might be mediated by an increased SR Ca(2+) release during contraction and/or an increase in Ca(2+) sensitivity.

Hydrogen peroxide increases depolarization-induced contraction of mechanically skinned slow twitch fibres from rat skeletal muscles

PubMed Central

Plant, David R; Lynch, Gordon S; Williams, David A

2002-01-01

The effect of exogenous hydrogen peroxide (H2O2) on excitation-contraction (E-C) coupling and sarcoplasmic reticulum (SR) function was compared in mechanically skinned slow twitch fibres (prepared from the soleus muscles) and fast twitch fibres (prepared from the extensor digitorum longus; EDL muscles) of adult rats. Equilibration (5 min) with 1 mm H2O2 diminished the ability of the Ca2+-depleted SR to reload Ca2+ in both slow (P < 0.01) and fast twitch fibres (P < 0.05) compared to control. Under conditions when all Ca2+ uptake was prevented, 1 mm H2O2 increased SR Ca2+ ‘leak’ in fast twitch fibres by 24 ± 5 % (P < 0.05), but leak was not altered in slow twitch fibres. Treatment with 1 mm H2O2 also increased the peak force of low [caffeine] contracture by ∼45 % in both fibre types compared to control (P < 0.01), which could be partly reversed following treatment with 10 mm dithiothreitol (DTT). The changes in SR function caused by 1 mm H2O2 were associated with an ∼65 % increase in the peak height of depolarization-induced contractile response (DICR) in slow twitch fibres, compared to control (no H2O2; P < 0.05). In contrast, peak contractile force of fast twitch fibres was not altered by 1 mm H2O2 treatment. Equilibration with 5 mm H2O2 induced a spontaneous force response in both slow and fast twitch fibres, which could be partly reversed by 2 min treatment with 10 mm DTT. Peak DICR was also increased ∼40 % by 5 mm H2O2 in slow twitch fibres compared to control (no H2O2; P < 0.05). Our results indicate that exogenous H2O2 increases depolarization-induced contraction of mechanically skinned slow but not fast twitch fibres. The increase in depolarization-induced contraction in slow twitch fibres might be mediated by an increased SR Ca2+ release during contraction and/or an increase in Ca2+ sensitivity. PMID:11897857

Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

PubMed

Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

2016-07-01

Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intracellular calcium movements during excitation–contraction coupling in mammalian slow-twitch and fast-twitch muscle fibers

PubMed Central

Hollingworth, Stephen

2012-01-01

In skeletal muscle fibers, action potentials elicit contractions by releasing calcium ions (Ca2+) from the sarcoplasmic reticulum. Experiments on individual mouse muscle fibers micro-injected with a rapidly responding fluorescent Ca2+ indicator dye reveal that the amount of Ca2+ released is three- to fourfold larger in fast-twitch fibers than in slow-twitch fibers, and the proportion of the released Ca2+ that binds to troponin to activate contraction is substantially smaller. PMID:22450485

Methoxy-modified kaolinite as a novel carrier for high-capacity loading and controlled-release of the herbicide amitrole

PubMed Central

Tan, Daoyong; Yuan, Peng; Annabi-Bergaya, Faïza; Liu, Dong; He, Hongping

2015-01-01

Methoxy-modified kaolinite was used as a novel carrier for loading and release of the herbicide 3-amino-1,2,4-triazole, known as amitrole (abbreviated here as AMT). The methoxy modification made the interlayer space of the kaolinite available for AMT intercalation. The AMT loading content in methoxy-modified kaolinite reached up to 20.8 mass% (twice the loading content by unmodified kaolinite). About 48% of this amount is located in the interlayer space. The release profiles of the AMT fit with the modified Korsmeyer-Peppas model. Due to the diffusional restriction of the intercalated AMT by the lamellar structure of the kaolinite and the strong electrostatic attraction between the intercalated AMT and the kaolinite, a slow release of AMT from the methoxy-modified kaolinite was achieved. These results show that the methoxy-modification is a facile method to make the interlayer space of kaolinite available for hosting other guest molecules. The methoxy-modified kaolinite is a promising candidate for high-capacity loading and controlled-release of other molecules such as drugs, agrochemicals, and biochemicals. PMID:25747124

Methoxy-modified kaolinite as a novel carrier for high-capacity loading and controlled-release of the herbicide amitrole

NASA Astrophysics Data System (ADS)

Tan, Daoyong; Yuan, Peng; Annabi-Bergaya, Faïza; Liu, Dong; He, Hongping

2015-03-01

Methoxy-modified kaolinite was used as a novel carrier for loading and release of the herbicide 3-amino-1,2,4-triazole, known as amitrole (abbreviated here as AMT). The methoxy modification made the interlayer space of the kaolinite available for AMT intercalation. The AMT loading content in methoxy-modified kaolinite reached up to 20.8 mass% (twice the loading content by unmodified kaolinite). About 48% of this amount is located in the interlayer space. The release profiles of the AMT fit with the modified Korsmeyer-Peppas model. Due to the diffusional restriction of the intercalated AMT by the lamellar structure of the kaolinite and the strong electrostatic attraction between the intercalated AMT and the kaolinite, a slow release of AMT from the methoxy-modified kaolinite was achieved. These results show that the methoxy-modification is a facile method to make the interlayer space of kaolinite available for hosting other guest molecules. The methoxy-modified kaolinite is a promising candidate for high-capacity loading and controlled-release of other molecules such as drugs, agrochemicals, and biochemicals.

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

PubMed

Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

2014-01-01

Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

Modulation of Starch Digestion for Slow Glucose Release through “Toggling” of Activities of Mucosal α-Glucosidases*

PubMed Central

Lee, Byung-Hoo; Eskandari, Razieh; Jones, Kyra; Reddy, Kongara Ravinder; Quezada-Calvillo, Roberto; Nichols, Buford L.; Rose, David R.; Hamaker, Bruce R.; Pinto, B. Mario

2012-01-01

Starch digestion involves the breakdown by α-amylase to small linear and branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the mucosal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). MGAM and SI are anchored to the small intestinal brush-border epithelial cells, and each contains a catalytic N- and C-terminal subunit. All four subunits have α-1,4-exohydrolytic glucosidase activity, and the SI N-terminal subunit has an additional exo-debranching activity on the α-1,6-linkage. Inhibition of α-amylase and/or α-glucosidases is a strategy for treatment of type 2 diabetes. We illustrate here the concept of “toggling”: differential inhibition of subunits to examine more refined control of glucogenesis of the α-amylolyzed starch malto-oligosaccharides with the aim of slow glucose delivery. Recombinant MGAM and SI subunits were individually assayed with α-amylolyzed waxy corn starch, consisting mainly of maltose, maltotriose, and branched α-limit dextrins, as substrate in the presence of four different inhibitors: acarbose and three sulfonium ion compounds. The IC50 values show that the four α-glucosidase subunits could be differentially inhibited. The results support the prospect of controlling starch digestion rates to induce slow glucose release through the toggling of activities of the mucosal α-glucosidases by selective enzyme inhibition. This approach could also be used to probe associated metabolic diseases. PMID:22851177

Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.

PubMed

Wang, Lexi; Wang, Aiping; Zhao, Xiaolei; Liu, Ximing; Wang, Dan; Sun, Fengying; Li, Youxin

2012-05-10

Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application. Copyright © 2012 Elsevier B.V. All rights reserved.

Intravascular Drug Release Kinetics Dictate Arterial Drug Deposition, Retention, and Distribution

PubMed Central

Balakrishnan, Brinda; Dooley, John F.; Kopia, Gregory; Edelman, Elazer R.

2007-01-01

Millions of patients worldwide have received drug-eluting stents to reduce their risk for in-stent restenosis. The efficacy and toxicity of these local therapeutics depend upon arterial drug deposition, distribution, and retention. To examine how administered dose and drug release kinetics control arterial drug uptake, a model was created using principles of computational fluid dynamics and transient drug diffusion-convection. The modeling predictions for drug elution were validated using empiric data from stented porcine coronary arteries. Inefficient, minimal arterial drug deposition was predicted when a bolus of drug was released and depleted within seconds. Month-long stent-based drug release efficiently delivered nearly continuous drug levels, but the slow rate of drug presentation limited arterial drug uptake. Uptake was only maximized when the rates of drug release and absorption matched, which occurred for hour-long drug release. Of the two possibly means for increasing the amount of drug on the stent, modulation of drug concentration potently impacts the magnitude of arterial drug deposition, while changes in coating drug mass affect duration of release. We demonstrate the importance of drug release kinetics and administered drug dose in governing arterial drug uptake and suggest novel drug delivery strategies for controlling spatio-temporal arterial drug distribution. PMID:17868948

Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties.

PubMed

Shi, Meng; Yang, Yi-Yan; Chaw, Cheng-Shu; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

2003-04-29

The poly(orthoester) (POE)-poly(D,L-lactide-co-glycolide) (50:50) (PLGA) double-walled microspheres with 50% POE in weight were loaded with hydrophilic bovine serum albumin (BSA) and hydrophobic cyclosporin A (CyA). Most of the BSA and CyA was entrapped within the shell and core, respectively, because of the difference in their hydrophilicity. The morphologies and release mechanisms of proteins-loaded double-walled POE/PLGA microspheres were investigated. Scanning electron microscope studies revealed that the CyA-BSA-loaded double-walled POE/PLGA microspheres yielded a more porous surface and PLGA shell than those without BSA. The neat POE and PLGA yielded slow and incomplete CyA and BSA release. In contrast, nearly complete BSA and more than 95% CyA were released in a sustained manner from the double-walled POE/PLGA microspheres. Both the BSA- and CyA-BSA-loaded POE/PLGA microspheres yielded a sustained BSA release over 5 days. The CyA release pattern of the CyA-loaded double-walled POE/PLGA microspheres was biphasic, characterized by a slow release over 15 days followed by a sustained release over 27 days. However, the CyA-BSA-loaded double-walled POE/PLGA microspheres provided a more constant and faster CyA release due to their more porous shell. In the CyA-BSA-loaded double-walled POE/PLGA microspheres system, the PLGA layer acted as a carrier for BSA and mild reservoir for CyA. During the first 5 days, most BSA was released from the shell but only 14% CyA was left from the microspheres. Subsequently, more than 80% CyA were released in the next 25 days. The distinct structure of double-walled POE/PLGA microspheres would make an interesting device for controlled delivery of therapeutic agents.

Revealing the cascade of slow transients behind a large slow slip event

NASA Astrophysics Data System (ADS)

Frank, W.; Rousset, B.; Lasserre, C.; Campillo, M.

2017-12-01

Capable of reaching similar magnitudes to large megathrust earthquakes (Mw > 7), slow slip events play a major role in accommodating tectonic motion on plate boundaries. These slip transients are the slow release of built-up tectonic stress that are geodetically imaged as a predominantly aseismic rupture, which is smooth in both time and space. We demonstrate here that large slow slip events are in fact a complex cascade of short-duration slow transients. Using a dense catalog of low-frequency earthquakes as a guide, we investigate the Mw 7.5 slow slip event that occurred in 2006 along the subduction interface 40 km beneath Guerrero, Mexico. We show that while the long-period surface displacement as recorded by GPS suggests a six month duration, motion in the direction of tectonic release only sporadically occurs over 55 days and its surface signature is attenuated by rapid relocking of the plate interface. These results demonstrate that our current conceptual model of slow and continuous rupture is an artifact of low-resolution geodetic observations of a superposition of small, clustered slip events. Our proposed description of slow slip as a cascade of slow transients implies that we systematically overestimate the duration T and underestimate the moment magnitude M of large slow slip events.

Neural and neuroendocrine adaptations to microgravity and ground-based models of microgravity.

PubMed

Edgerton, V R; Roy, R R; Recktenwald, M R; Hodgson, J A; Grindeland, R E; Kozlovskaya, I

2000-12-01

The functional properties of the motor system of humans and non-human primates are readily responsive to microgravity. There is a growing body of evidence that significant adaptations occur in the spinal cord and muscle in response to prolonged exposure to microgravity. Further, there is evidence that the processing of sensory information from the periphery, particularly that input associated with the function of muscle tendons and joints, is significantly altered as a result of prolonged microgravity. We present evidence that the fundamental neural mechanisms that control the relative activity of the motor pools of a slow and fast extensor muscle is changed such that a slow, postural muscle is less readily activated during locomotion following spaceflight. Another type of change observed in mammals exposed to spaceflight relates to the release of a growth factor, called bioassayable growth hormone, which is thought to be released from the pituitary. When an individual generates a series of isometric plantarflexor contractions, the plasma levels of bioassayable growth hormone increases significantly. This response is suppressed after several days of continuous bedrest or spaceflight. These results suggest a unique neuroendocrine control system and demonstrate its sensitivity to chronic patterns of proprioceptive input associated with load-bearing locomotion.

Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women.

PubMed

Setchell, Kenneth D R; Brzezinski, Amnon; Brown, Nadine M; Desai, Pankaj B; Melhem, Murad; Meredith, Trevor; Zimmer-Nechimias, Linda; Wolfe, Brian; Cohen, Yoram; Blatt, Yoav

2005-03-23

Pharmacokinetic studies of soybean isoflavones have shown that following oral ingestion, the two major isoflavones, daidzin and genistin, are hydrolyzed in the intestine, rapidly absorbed into the peripheral circulation, and eliminated from the body with a terminal half-life of 7-8 h. These characteristics make maintenance of steady-state plasma isoflavone concentrations difficult to attain unless there is repeated daily ingestion of foods or supplements containing isoflavones. In an attempt to sustain more constant plasma isoflavone concentrations, a new slow-release formulation of a soybean isoflavone extract was prepared by microencapsulation with a mixture of hydroxypropylcellulose and ethylcellulose to alter its dissolution characteristics. In vitro experiments confirmed slow aqueous dissolution of isoflavones from this formulation when compared with the conventional isoflavone extract. The pharmacokinetics of this slow-release isoflavone extract was studied in 10 healthy postmenopausal women after oral administration of a single capsule containing the equivalent of 22.3 mg of genistein and 7.47 mg of daidzein expressed as aglycons. A comparison of the key pharmacokinetic parameters obtained in this study with those established in extensive studies performed previously in this laboratory indicated that the mean residence time of genistein and daidzein increased 2-fold with microencapsulation. These findings are indicative of a decreased rate of absorption, consistent with the observed slow in vitro dissolution rate. These findings show that it is feasible to employ polymer matrices that slow the aqueous dissolution for preparing sustained-release formulations of soy isoflavones. Further studies to optimize such formulations are warranted.

Delivery of DNA vaccines by agarose hydrogel implants facilitates genetic immunization in cattle.

PubMed

Toussaint, J F; Dubois, A; Dispas, M; Paquet, D; Letellier, C; Kerkhofs, P

2007-01-26

The present study demonstrates the interest of two slow-release systems as vaccination tools in cattle. Two experiments show that a first intradermal administration of one DNA vaccine dose combined with the slow-release of a second dose conduct to a priming of the bovine herpesvirus 1-specific immune response similar to the one generated by two discrete administrations 4 weeks apart. The first experiment demonstrates the efficacy of the slow-release system with well-characterized Alzet osmotic pumps, whereas the second experiment extends the same concept with innovative agarose hydrogel implants. These latter implants are cheaper and more convenient than the osmotic pumps or repeated intradermal administrations since they contribute to an efficient priming of the immune response in a single manipulation of the animals.

Sarcoplasmic reticulum calcium release compared in slow-twitch and fast-twitch fibres of mouse muscle.

PubMed

Baylor, S M; Hollingworth, S

2003-08-15

Experiments were carried out to compare the amplitude and time course of Ca2+ release from the sarcoplasmic reticulum (SR) in intact slow-twitch and fast-twitch mouse fibres. Individual fibres within small bundles were injected with furaptra, a low-affinity, rapidly responding Ca2+ indicator. In response to a single action potential at 16 degrees C, the peak amplitude and half-duration of the change in myoplasmic free [Ca2+] (Delta[Ca2+]) differed significantly between fibre types (slow-twitch: peak amplitude, 9.4 +/- 1.0 microM (mean +/- S.E.M.); half-duration, 7.7 +/- 0.6 ms; fast-twitch: peak amplitude 18.5 +/- 0.5 microM; half-duration, 4.9 +/- 0.3 ms). SR Ca2+ release was estimated from Delta[Ca2+] with a computational model that calculated Ca2+ binding to the major myoplasmic Ca2+ buffers (troponin, ATP and parvalbumin); buffer concentrations and reaction rate constants were adjusted to reflect fibre-type differences. In response to an action potential, the total concentration of released Ca2+ (Delta[CaT]) and the peak rate of Ca2+ release ((d/dt)Delta[CaT]) differed about 3-fold between the fibre types (slow-twitch: Delta[CaT], 127 +/- 7 microM; (d/dt)Delta[CaT], 70 +/- 6 microM ms-1; fast-twitch: Delta[CaT], 346 +/- 6 microM; (d/dt)Delta[CaT], 212 +/- 4 microM ms-1). In contrast, the half-duration of (d/dt)Delta[CaT] was very similar in the two fibre types (slow-twitch, 1.8 +/- 0.1 ms; fast-twitch, 1.6 +/- 0.0 ms). When fibres were stimulated with a 5-shock train at 67 Hz, the peaks of (d/dt)Delta[CaT] in response to the second and subsequent shocks were much smaller than that due to the first shock; the later peaks, expressed as a fraction of the amplitude of the first peak, were similar in the two fibre types (slow-twitch, 0.2-0.3; fast-twitch, 0.1-0.3). The results support the conclusion that individual SR Ca2+ release units function similarly in slow-twitch and fast-twitch mammalian fibres.

Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres

PubMed Central

Yuen, Michaela; Cooper, Sandra T.; Marston, Steve B.; Nowak, Kristen J.; McNamara, Elyshia; Mokbel, Nancy; Ilkovski, Biljana; Ravenscroft, Gianina; Rendu, John; de Winter, Josine M.; Klinge, Lars; Beggs, Alan H.; North, Kathryn N.; Ottenheijm, Coen A.C.; Clarke, Nigel F.

2015-01-01

Dominant mutations in TPM3, encoding α-tropomyosinslow, cause a congenital myopathy characterized by generalized muscle weakness. Here, we used a multidisciplinary approach to investigate the mechanism of muscle dysfunction in 12 TPM3-myopathy patients. We confirm that slow myofibre hypotrophy is a diagnostic hallmark of TPM3-myopathy, and is commonly accompanied by skewing of fibre-type ratios (either slow or fast fibre predominance). Patient muscle contained normal ratios of the three tropomyosin isoforms and normal fibre-type expression of myosins and troponins. Using 2D-PAGE, we demonstrate that mutant α-tropomyosinslow was expressed, suggesting muscle dysfunction is due to a dominant-negative effect of mutant protein on muscle contraction. Molecular modelling suggested mutant α-tropomyosinslow likely impacts actin–tropomyosin interactions and, indeed, co-sedimentation assays showed reduced binding of mutant α-tropomyosinslow (R168C) to filamentous actin. Single fibre contractility studies of patient myofibres revealed marked slow myofibre specific abnormalities. At saturating [Ca2+] (pCa 4.5), patient slow fibres produced only 63% of the contractile force produced in control slow fibres and had reduced acto-myosin cross-bridge cycling kinetics. Importantly, due to reduced Ca2+-sensitivity, at sub-saturating [Ca2+] (pCa 6, levels typically released during in vivo contraction) patient slow fibres produced only 26% of the force generated by control slow fibres. Thus, weakness in TPM3-myopathy patients can be directly attributed to reduced slow fibre force at physiological [Ca2+], and impaired acto-myosin cross-bridge cycling kinetics. Fast myofibres are spared; however, they appear to be unable to compensate for slow fibre dysfunction. Abnormal Ca2+-sensitivity in TPM3-myopathy patients suggests Ca2+-sensitizing drugs may represent a useful treatment for this condition. PMID:26307083

Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres.

PubMed

Yuen, Michaela; Cooper, Sandra T; Marston, Steve B; Nowak, Kristen J; McNamara, Elyshia; Mokbel, Nancy; Ilkovski, Biljana; Ravenscroft, Gianina; Rendu, John; de Winter, Josine M; Klinge, Lars; Beggs, Alan H; North, Kathryn N; Ottenheijm, Coen A C; Clarke, Nigel F

2015-11-15

Dominant mutations in TPM3, encoding α-tropomyosinslow, cause a congenital myopathy characterized by generalized muscle weakness. Here, we used a multidisciplinary approach to investigate the mechanism of muscle dysfunction in 12 TPM3-myopathy patients. We confirm that slow myofibre hypotrophy is a diagnostic hallmark of TPM3-myopathy, and is commonly accompanied by skewing of fibre-type ratios (either slow or fast fibre predominance). Patient muscle contained normal ratios of the three tropomyosin isoforms and normal fibre-type expression of myosins and troponins. Using 2D-PAGE, we demonstrate that mutant α-tropomyosinslow was expressed, suggesting muscle dysfunction is due to a dominant-negative effect of mutant protein on muscle contraction. Molecular modelling suggested mutant α-tropomyosinslow likely impacts actin-tropomyosin interactions and, indeed, co-sedimentation assays showed reduced binding of mutant α-tropomyosinslow (R168C) to filamentous actin. Single fibre contractility studies of patient myofibres revealed marked slow myofibre specific abnormalities. At saturating [Ca(2+)] (pCa 4.5), patient slow fibres produced only 63% of the contractile force produced in control slow fibres and had reduced acto-myosin cross-bridge cycling kinetics. Importantly, due to reduced Ca(2+)-sensitivity, at sub-saturating [Ca(2+)] (pCa 6, levels typically released during in vivo contraction) patient slow fibres produced only 26% of the force generated by control slow fibres. Thus, weakness in TPM3-myopathy patients can be directly attributed to reduced slow fibre force at physiological [Ca(2+)], and impaired acto-myosin cross-bridge cycling kinetics. Fast myofibres are spared; however, they appear to be unable to compensate for slow fibre dysfunction. Abnormal Ca(2+)-sensitivity in TPM3-myopathy patients suggests Ca(2+)-sensitizing drugs may represent a useful treatment for this condition. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Slow-release NPK fertilizer encapsulated by carboxymethyl cellulose-based nanocomposite with the function of water retention in soil.

PubMed

Olad, Ali; Zebhi, Hamid; Salari, Dariush; Mirmohseni, Abdolreza; Reyhani Tabar, Adel

2018-09-01

In this study, new slow release fertilizer encapsulated by superabsorbent nanocomposite was prepared by in-situ graft polymerization of sulfonated-carboxymethyl cellulose (SCMC) with acrylic acid (AA) in the presence of polyvinylpyrrolidone (PVP), silica nanoparticles and nitrogen (N), phosphorous (P), and potassium (K) (NPK) fertilizer compound. The prepared materials were characterized by FT-IR, XRD and scanning electron microscopy (SEM) techniques. The incorporation of NPK fertilizer into hydrogel nanocomposite network was verified by results of these analyses. Also, the swelling behavior in various pH and saline solutions as well as water retention capability of the prepared hydrogel nanocomposite was evaluated. The fertilizer release behavior of the NPK loaded hydrogel nanocomposite was in good agreement with the standard of Committee of European Normalization (CEN), indicating its excellent slow release property. These good characteristics revealed that the hydrogel nanocomposite fertilizer formulation can be practically used in agricultural and horticultural applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Nanomedicines for Inflammatory Arthritis: Head-To-Head Comparison of Glucocorticoid-Containing Polymers, Micelles and Liposomes

PubMed Central

Crielaard, Bart J.; Dusad, Anand; Lele, Subodh M.; Rijcken, Cristianne J. F.; Metselaar, Josbert M; Kostková, Hana; Etrych, Tomáš; Ulbrich, Karel; Kiessling, Fabian; Mikuls, Ted R.; Hennink, Wim E.; Storm, Gert; Lammers, Twan; Wang, Dong

2014-01-01

As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-crosslinked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow) and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single i.v. injection, the formulations with the slower drug release kinetics (i.e. M-Dex and P-Dex-slow) maintained longer duration of therapeutic activity than those with relatively faster drug release kinetics, resulting in better joint protection. This finding will be instructional in the future development and optimization of nanomedicines for the clinical management of rheumatoid arthritis. The outcome of this study also illustrates the value of such head-to-head comparison studies in translational nanomedicine research. PMID:24341611

Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.

PubMed

Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

2012-01-01

We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.

Hollow microspheres of diclofenac sodium - a gastroretentive controlled delivery system.

PubMed

Bv, Basavaraj; R, Deveswaran; S, Bharath; Abraham, Sindhu; Furtado, Sharon; V, Madhavan

2008-10-01

Most of the floating systems have an inherent drawback of high variability in the GI transit time, invariably affecting the bioavailability of drug. To overcome it, a multiple unit floating system with extended GI transit time, capable of distributing widely throughout the GIT for effective enteric release of the drug has been sought. Microballoons loaded with drug in their outer polymer shells were prepared by novel emulsion solvent diffusion method. The ethanol: dicloromethane solution of drug and Eudragit-S were poured into an aqueous solution of PVA that was thermally controlled at 40 degrees C. The gas phase generated in the dispersed polymer droplet by the evaporation of solvent formed an internal cavity in the microsphere of the polymer with the drug. The flowability of the resulting microballoons improved when compared to pure drug. The microballoons on floatation along with the surfactant, floated continuously for more than 12 hours in the acidic medium in-vitro conditions. The in-vitro drug release profile of the formulation in the simulated gastric buffer showed no drug release, which emphasizes the enteric release property and in simulated intestinal buffer, a slow and controlled drug release of 60 to 84% was obtained over a period of 8 hours. Drug release was significantly affected by increased drug to polymer concentration at pH 6.8. The formulation was found to be physically and chemically stable as per the ICH guidelines.

Nanoparticle-based brachytherapy spacers for delivery of localized combined chemoradiation therapy.

PubMed

Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G; Sridhar, Srinivas

2015-02-01

In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthesis of a novel slow-release potassium fertilizer from modified Pidgeon magnesium slag by potassium carbonate.

PubMed

Li, Yongling; Cheng, Fangqin

2016-08-01

A novel slow-release potassium fertilizer (SPF) was synthesized using Pidgeon magnesium slag (PMS) and potassium carbonate, which could minimize fertilizer nutrient loss and PMS disposal problems. Orthogonal experiments were conducted to determine the optimum conditions for synthesis. The potassium (K)-bearing compounds of SPF existed mainly in the form of crystalline phases Ca1.197K0.166SiO4, K2MgSiO4, and K4CaSi3O9, and in the noncrystalline phase. The active silicon content of SPF was 2.09 times as much as that of magnesium slag, and the slow-release character of SPF met the requirement for partly slow-release fertilizer in the national standard (GB/T23348-2009). The best models for describing the K release kinetics in water and 2% citric acid were the Elovich model and the first-order model, respectively. The heavy metal contents of SPF conformed to the national standard for organic-inorganic compound fertilizers, and the leaching mass concentrations of heavy metals and Fluorine were far lower than the limit values of the identification standard for hazardous waste identification for extraction toxicity (GB5085.3-2007), and also met the class II quality standard for ground water. The environmental risk of SPF is therefore very low, but because SPF is alkaline, its effect on soil pH should be taken into account. PMS is the solid waste resulting from the production of magnesium metal by Pidgeon's reduction process. Utilization of PMS in the high-technology and high-value areas may promote the high-efficiency development of worldwide collection metallic magnesium industry and contribute to the reduction of emissions of fine dust to air. This paper presents one of the new techniques in the use of PMS as a slow-release fertilizer by adding K2CO3. The product can serve as a very cost-effective and reliable artificial fertilizer.

Subjective effects of slow-release bupropion versus caffeine as determined in a quasi-naturalistic setting.

PubMed

Zernig, Gerald; De Wit, Harriet; Telser, Stefan; Nienhusmeier, Matthias; Wakonigg, Gudrun; Sturm, Katja; Berger, Iris; Kemmler, Georg; Saria, Alois

2004-04-01

Bupropion (BUP), which in its slow-release formulation (Zyban) is used as a smoking-cessation drug, increases dopamine overflow in the nucleus accumbens and serves as a reinforcer in animal experiments, both suggesting that BUP may possess some abuse liability. The present study examined if BUP produced subjective effects indicative of abuse liability in a quasi-naturalistic setting, with caffeine (CAF) serving as a positive control. In a randomized double-blind crossover design, male smokers (n = 50) ingested two doses (interdosing interval, 6 h) of placebo (PLC), 178 mg CAF, or 150 mg slow-release BUP in their normal mid-week work environment. They completed questionnaires administered by telephone at regular intervals. CAF significantly increased ratings of 'pleasant effects' (p = 0.008) and 'high' (p = 0.03), whereas BUP produced a 'high' of only very moderate size (p = 0.02). In 3 subjects each, BUP or CAF produced ratings of 'pleasant effects' that were >9-fold higher than those for PLC. Finally, BUP increased the number of cigarettes smoked by 29% (i.e., from 24 to 31 per day; p = 0.004) only in those subjects who were unable to report any effect of either BUP or CAF. CAF had no effect on cigarette consumption. These findings suggest that BUP, like CAF, might be of some abuse liability in a small subgroup of smokers (i.e., 6% each of the present sample), and it may transiently increase, rather than decrease, smoking during early phases of treatment in continuing smokers. Copyright 2004 S. Karger AG, Basel

Controlled release of tocopherols from polymer blend films

NASA Astrophysics Data System (ADS)

Obinata, Noe

Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies obtained using conventional and smart blending greatly affected tocopherol release. Strong correlation was observed between morphology and release rate: multilayer, slow release; co-continuous and fiber, moderate; disperse: fast release. Results indicate that morphology can be manipulated by polymer composition and processing method, and release rates of tocopherols are varied with polymer morphology. Manipulating polymer compositions and film morphologies may provide a means to control the release of tocopherols from food contact films.

Observational Evidence for the Associated Formation of Blobs and Raining Inflows in the Solar Corona

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

Sanchez-Diaz, E.; Rouillard, A. P.; Lavraud, B.

The origin of the slow solar wind is still a topic of much debate. The continual emergence of small transient structures from helmet streamers is thought to constitute one of the main sources of the slow wind. Determining the height at which these transients are released is an important factor in determining the conditions under which the slow solar wind forms. To this end, we have carried out a multipoint analysis of small transient structures released from a north–south tilted helmet streamer into the slow solar wind over a broad range of position angles during Carrington Rotation 2137. Combining themore » remote-sensing observations taken by the Solar-TErrestrial RElations Observatory ( STEREO ) mission with coronagraphic observations from the SOlar and Heliospheric Observatory ( SOHO ) spacecraft, we show that the release of such small transient structures (often called blobs), which subsequently move away from the Sun, is associated with the concomitant formation of transient structures collapsing back toward the Sun; the latter have been referred to by previous authors as “raining inflows.” This is the first direct association between outflowing blobs and raining inflows, which locates the formation of blobs above the helmet streamers and gives strong support that the blobs are released by magnetic reconnection.« less

Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue.

PubMed

Lai, Yen-Ho; Chiang, Chih-Sheng; Kao, Tzu-Hsun; Chen, San-Yuan

2018-01-01

Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy. In this study, we developed a size-changeable "Trojan Horse" nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; ~20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added. With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to 60% accumulated drug at 6 h, but a slow release kinetic (~20%) was detected in the PTX from the GSs, indicating that THNCs enable controllable release of LST and PTX drugs for penetration into the tumor tissue. The in vitro cell viability in a 3D tumor spheroid model indicated that the PTX-loaded GSs liberated from THNCs showed deeper penetration as well as higher cytotoxicity, reducing a tumor spheroid to half its original size and collapsing the structure of the tumor microenvironment. The results demonstrate that the THNCs with controlled drug release and deep penetration of magnetic GSs show great potential for cancer therapy.

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Acetylcholine Neuromodulation in Normal and Abnormal Learning and Memory: Vigilance Control in Waking, Sleep, Autism, Amnesia and Alzheimer’s Disease

PubMed Central

Grossberg, Stephen

2017-01-01

Adaptive Resonance Theory, or ART, is a neural model that explains how normal and abnormal brains may learn to categorize and recognize objects and events in a changing world, and how these learned categories may be remembered for a long time. This article uses ART to propose and unify the explanation of diverse data about normal and abnormal modulation of learning and memory by acetylcholine (ACh). In ART, vigilance control determines whether learned categories will be general and abstract, or specific and concrete. ART models how vigilance may be regulated by ACh release in layer 5 neocortical cells by influencing after-hyperpolarization (AHP) currents. This phasic ACh release is mediated by cells in the nucleus basalis (NB) of Meynert that are activated by unexpected events. The article additionally discusses data about ACh-mediated tonic control of vigilance. ART proposes that there are often dynamic breakdowns of tonic control in mental disorders such as autism, where vigilance remains high, and medial temporal amnesia, where vigilance remains low. Tonic control also occurs during sleep-wake cycles. Properties of Up and Down states during slow wave sleep arise in ACh-modulated laminar cortical ART circuits that carry out processes in awake individuals of contrast normalization, attentional modulation, decision-making, activity-dependent habituation, and mismatch-mediated reset. These slow wave sleep circuits interact with circuits that control circadian rhythms and memory consolidation. Tonic control properties also clarify how Alzheimer’s disease symptoms follow from a massive structural degeneration that includes undermining vigilance control by ACh in cortical layers 3 and 5. Sleep disruptions before and during Alzheimer’s disease, and how they contribute to a vicious cycle of plaque formation in layers 3 and 5, are also clarified from this perspective. PMID:29163063

Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.

PubMed

Peng, Yifeng; Tellier, Liane E; Temenoff, Johnna S

2016-08-16

Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases.

Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices.

PubMed

Gavini, E; Alamanni, M C; Cossu, M; Giunchedi, P

2005-08-01

Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.

Neuropeptide transmission in brain circuits

PubMed Central

van den Pol, Anthony N.

2014-01-01

Neuropeptides are found in many mammalian CNS neurons where they play key roles in modulating neuronal activity. In contrast to amino acid transmitter release at the synapse, neuropeptide release is not restricted to the synaptic specialization, and after release, a neuropeptide may diffuse some distance to exert its action through a G-protein coupled receptor. Some neuropeptides such as hypocretin/orexin are synthesized only in single regions of the brain, and the neurons releasing these peptides probably have similar functional roles. Other peptides such as neuropeptide Y (NPY) are synthesized throughout the brain, and neurons that synthesize the peptide in one region have no anatomical or functional connection with NPY neurons in other brain regions. Here, I review converging data revealing a complex interaction between slow-acting neuromodulator peptides and fast-acting amino acid transmitters in the control of energy homeostasis, drug addiction, mood and motivation, sleep-wake states, and neuroendocrine regulation. PMID:23040809

Magnetic mesoporous silica nanoparticles for potential delivery of chemotherapeutic drugs and hyperthermia.

PubMed

Tao, Cuilian; Zhu, Yufang

2014-11-07

Magnetic mesoporous silica (MMS) nanoparticles with controllable magnetization have been synthesized by encapsulating Fe3O4 nanoparticles in a mesoporous silica matrix. The structure, magnetic heating capacity and drug delivery ability of MMS nanoparticles were evaluated. The results showed that MMS nanoparticles had an average particle size of 150 nm and showed low cytotoxicity and efficient cell uptake ability. MMS nanoparticles exhibited a sustained drug release in the medium of pH 5.0, but a very slow release in the medium of pH 7.4. On the other hand, MMS nanoparticles could controllably generate heat to reach the hyperthermia temperature within a short time upon exposure to an alternating magnetic field due to the superparamagnetic behavior and controllable magnetization. Therefore, MMS nanoparticles could provide a promising multifunctional platform for the combination of chemotherapy and hyperthermia for cancer therapy.

Study of BSA protein adsorption/release on hydroxyapatite nanoparticles

NASA Astrophysics Data System (ADS)

Swain, Sanjaya Kumar; Sarkar, Debasish

2013-12-01

Three different spherical, rod and fibrous morphologies of hydroxyapatite (HA) nanoparticles have been prepared through control over the processing parameters like temperature, pH and Ca:P ratio. Protein adsorption/release with respect to HA nanoparticle morphologies are investigated using model protein bovine serum albumin (BSA). BSA adsorption on HA nanoparticles follows Langmuir adsorption isotherm. Thermal analysis and FT-IR spectrum confirms the BSA adhesion and retention of their secondary structure. High surface area with high Ca:P ratio nanorod adsorbs relatively more amount (28 mg BSA/gm of nanorod HA) of BSA within 48 h in comparison with counterpart fibroid and spherical morphologies. Slow and steady BSA release (75 wt% of adsorbed BSA in 96 h) from nanorod HA is found as futuristic drug delivery media.

Efficacy of methoprene for mosquito control in storm water catch basins

USGS Publications Warehouse

Butler, M.; LeBrun, R.A.; Ginsberg, H.S.; Gettman, A.D.

2006-01-01

This study evaluated the efficacy of methoprene, a widely used juvenile hormone mimic, formulated as 30-day slow release Altosid? pellets, at controlling mosquitoes in underground storm water drainage catch basins. Data from applications to ?-sized cement catch basins in the laboratory, field observations from treated and untreated basins, and an experiment that confined mosquito larvae in floating emergence jars in catch basins showed that methoprene effectively controlled mosquitoes for a month under field conditions and substantially longer under laboratory conditions when applied at a dose of 3.5 g pellets per average-sized catch basin.

Can entomophagous nematodes slow the spread of invasive pest populations? The case study of Beddingia siricidicola released for the management of Sirex noctilio

Treesearch

Juan C. Corley; José M. Villacide; Andrew M. Liebhold

2014-01-01

Though rarely used in this way, biological control could potentially be exploited for managing spread of invasive species. Because spread of invasive species emerges from the combined action of population growth and dispersal, natural enemies that affect either of these processes should also affect spread. Dispersal of parasitoid species plays a key role in determining...

ATP Released by Electrical Stimuli Elicits Calcium Transients and Gene Expression in Skeletal Muscle*

PubMed Central

Buvinic, Sonja; Almarza, Gonzalo; Bustamante, Mario; Casas, Mariana; López, Javiera; Riquelme, Manuel; Sáez, Juan Carlos; Huidobro-Toro, Juan Pablo; Jaimovich, Enrique

2009-01-01

ATP released from cells is known to activate plasma membrane P2X (ionotropic) or P2Y (metabotropic) receptors. In skeletal muscle cells, depolarizing stimuli induce both a fast calcium signal associated with contraction and a slow signal that regulates gene expression. Here we show that nucleotides released to the extracellular medium by electrical stimulation are partly involved in the fast component and are largely responsible for the slow signals. In rat skeletal myotubes, a tetanic stimulus (45 Hz, 400 1-ms pulses) rapidly increased extracellular levels of ATP, ADP, and AMP after 15 s to 3 min. Exogenous ATP induced an increase in intracellular free Ca2+ concentration, with an EC50 value of 7.8 ± 3.1 μm. Exogenous ADP, UTP, and UDP also promoted calcium transients. Both fast and slow calcium signals evoked by tetanic stimulation were inhibited by either 100 μm suramin or 2 units/ml apyrase. Apyrase also reduced fast and slow calcium signals evoked by tetanus (45 Hz, 400 0.3-ms pulses) in isolated mouse adult skeletal fibers. A likely candidate for the ATP release pathway is the pannexin-1 hemichannel; its blockers inhibited both calcium transients and ATP release. The dihydropyridine receptor co-precipitated with both the P2Y2 receptor and pannexin-1. As reported previously for electrical stimulation, 500 μm ATP significantly increased mRNA expression for both c-fos and interleukin 6. Our results suggest that nucleotides released during skeletal muscle activity through pannexin-1 hemichannels act through P2X and P2Y receptors to modulate both Ca2+ homeostasis and muscle physiology. PMID:19822518

Muscovite is protective against non-steroidal anti-inflammatory drug-induced small bowel injury

PubMed Central

Huang, Chen; Lu, Bin; Fan, Yi-Hong; Zhang, Lu; Jiang, Ning; Zhang, Shuo; Meng, Li-Na

2014-01-01

AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We recruited and screened thirty-two healthy volunteers who were randomly allocated equally into two groups: an NSAID control group, who received 75 mg slow-release diclofenac, twice daily for 14 d; and an NSAID-muscovite group, who received 3 g of muscovite in addition to the 75 mg of slow-release diclofenac, twice daily for 14 d. For gastroprotection, both groups were administered 20 mg/d of the proton pump inhibitor omeprazole. All eligible subjects underwent video capsule endoscopy (CE) prior to and 14 d after treatment. RESULTS: Thirty subjects (NSAID-muscovite group, n =16; NSAID control group, n =14) finally completed the whole trail. At the baseline CE examination, no statistically significant differences between the two groups have been observed. However, after 14 d of drug treatment, a significant difference was observed in the percentage of subjects with mucosal breaks when comparing the NSAID-muscovite group with the NSAID control group. While 71.4% (10/14) of subjects in the NSAID control group had at least one mucosal break, co-administration of muscovite in the NSAID-muscovite group reduced the rate to 31.3% (5/16) (P = 0.028). Moreover, higher number of mucosal breaks was found in the NSAID control group vs that in the NSAID-muscovite group (P < 0.05). CONCLUSION: Muscovite co-therapy reduced the incidence of small intestinal injury after 14 d of diclofenac administration. PMID:25152605

A slow earthquake sequence on the San Andreas fault

USGS Publications Warehouse

Linde, A.T.; Gladwin, M.T.; Johnston, M.J.S.; Gwyther, R.L.; Bilham, R.G.

1996-01-01

EARTHQUAKES typically release stored strain energy on timescales of the order of seconds, limited by the velocity of sound in rock. Over the past 20 years, observations and laboratory experiments have indicated that capture can also occur more slowly, with durations up to hours. Such events may be important in earthquake nucleation and in accounting for the excess of plate convergence over seismic slip in subduction zones. The detection of events with larger timescales requires near-field deformation measurements. In December 1992, two borehole strainmeters close to the San Andreas fault in California recorded a slow strain event of about a week in duration, and we show here that the strain changes were produced by a slow earthquake sequence (equivalent magnitude 4.8) with complexity similar to that of regular earthquakes. The largest earthquakes associated with these slow events were small (local magnitude 3.7) and contributed negligible strain release. The importance of slow earthquakes in the seismogenic process remains an open question, but these observations extend the observed timescale for slow events by two orders of magnitude.

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro.

PubMed

Wu, Gui; Wu, Weigang; Zheng, Qixin; Li, Jingfeng; Zhou, Jianbo; Hu, Zhilei

2014-07-19

Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants' surfaces were observed with electron microscope. The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a "nest-shaped" way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day's release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was an ideal drug delivery system for the antibiotics. Biocompatibility tests demonstrated that the INH-PLLA implant did not have cytotoxicity. The multilayer donut-shaped tablet provided a new constant slow release method after an initial burst for the topical application of the antibiotic.

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

PubMed Central

2014-01-01

Background Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Methods Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants’ surfaces were observed with electron microscope. Results The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a “nest-shaped” way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day’s release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Conclusions Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was an ideal drug delivery system for the antibiotics. Biocompatibility tests demonstrated that the INH-PLLA implant did not have cytotoxicity. The multilayer donut-shaped tablet provided a new constant slow release method after an initial burst for the topical application of the antibiotic. PMID:25038793

Antibiotic release from biodegradable PHBV microparticles.

PubMed

Sendil, D; Gürsel, I; Wise, D L; Hasirci, V

1999-05-20

For the treatment of periodontal diseases, design of a controlled release system seemed very appropriate for an effective, long term result. In this study a novel, biodegradable microbial polyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV of various valerate contents containing a well established antibiotic, tetracycline, known to be effective against many of the periodontal disease related microorganisms, was used in the construction of a controlled release system. Tetracycline was loaded in the PHBV microspheres and microcapsules both in its acidic (TC) and in neutral form (TCN). Microcapsules of PHBV were prepared under different conditions using w/o/w double emulsion and their properties such as encapsulation efficiency, loading, release characteristics, and morphological properties were investigated. It was found that concentration of emulsifiers polyvinyl alcohol (PVA) and gelatin (varied between 0-4%) influenced the encapsulation efficiency appreciably. In order to increase encapsulation efficiency (from the obtained range of 18.1-30.1%) and slow down the release of the highly soluble tetracycline.HCl, it was neutralized with NaOH. Encapsulation efficiency of neutralized tetracycline was much higher (51.9-65.3%) due to the insoluble form of the drug used during encapsulation. The release behaviour of neither of the drugs was found to be of zero order. Rather the trends fitted reasonably well to Higuchi's approach for release from spherical micropheres. Biodegradability was not an appreciable parameter in the release from microcapsules because release was complete before any signs of degradation were observed.

Integrating sol-gel with cold plasmas modified porous polycaprolactone membranes for the drug-release of silver-sulfadiazine and ketoprofen

NASA Astrophysics Data System (ADS)

Mangindaan, Dave; Chen, Chao-Ting; Wang, Meng-Jiy

2012-12-01

A controlled release system composed of surface modified porous polycaprolactone (PCL) membranes combined with a layer of tetraorthosilicate (TEOS)-chitosan sol-gel was reported in this study. PCL is a hydrophobic, semi-crystalline, and biodegradable polymer with a relatively slow degradation rate. The drugs chosen for release experiments were silver-sulfadiazine (AgSD) and ketoprofen which were impregnated in the TEOS-chitosan sol-gel. The surface modification was achieved by O2 plasma and the surfaces were characterized by water contact angle (WCA) measurements, atomic force microscope (AFM), scanning electron microscope and electron spectroscopy for chemical analysis (ESCA). The results showed that the release of AgSD on O2 plasma treated porous PCL membranes was prolonged when compared with the pristine sample. On the contrary, the release rate of ketoprofen revealed no significant difference on pristine and plasma treated PCL membranes. The prepared PCL membranes showed good biocompatibility for the wound dressing biomaterial applications.

Two release rates from monolithic carboxymethyl starch tablets: formulation, characterization, and in vitro/in vivo evaluation.

PubMed

Le, Tien Canh; Mateescu, Mircea Alexandru

2017-08-01

Most of non-steroidal anti-inflammatory drugs (NSAIDs) including ibuprofen at more than 1200 mg/day may generate gastrointestinal and cardiovascular side effects. Bilayer or multiparticulate devices have been developed for controlled release in order to prevent undesired side effects. A new "two release rate (2RR) monolithic tablets" approach is now proposed for controlled release of poorly soluble drugs, particularly NSAIDs. Ibuprofen was used as model drug. This concept is based on a calcium carboxymethyl-starch (CaCMS) complex as a novel, low-cost excipient for monolithic dosage forms easy to manufacture by direct compaction. The in vitro dissolution from CaCMS formulations (tablets containing 400 or 600 mg active principle) showed two distinct release rates: (i) an initial fast release (for 30 min in simulated gastric fluid) of about 200 mg ibuprofen, an amount similar to the dosage of conventional immediate-release form (Motrin® 200 mg), and (ii) a slow release of remaining about 200 or 400 mg for a period of 12 h. A preliminary in vivo study (beagle dogs) showed pharmacokinetic parameters of one single controlled-release dosage of ibuprofen (400 mg) formulated with CaCMS, near equivalence with multiple doses (three tablets of 200 mg ibuprofen) of conventional Motrin®. A marked reduction (with 33%) of administered dose (400 instead 600 mg) was achieved by the new formulation with equivalent therapeutic effects. This dose reduction may be beneficial and is expected to minimize side damage risks. Although the present study was limited to NSAIDs, the 2RR concept can be applied for other drugs, particularly for subjects unable to follow frequent administrations.

Chitosan nanoparticle based delivery systems for sustainable agriculture.

PubMed

Kashyap, Prem Lal; Xiang, Xu; Heiden, Patricia

2015-01-01

Development of technologies that improve food productivity without any adverse impact on the ecosystem is the need of hour. In this context, development of controlled delivery systems for slow and sustained release of agrochemicals or genetic materials is crucial. Chitosan has emerged as a valuable carrier for controlled delivery of agrochemicals and genetic materials because of its proven biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The major advantages of encapsulating agrochemicals and genetic material in a chitosan matrix include its ability to function as a protective reservoir for the active ingredients, protecting the ingredients from the surrounding environment while they are in the chitosan domain, and then controlling their release, allowing them to serve as efficient gene delivery systems for plant transformation or controlled release of pesticides. Despite the great progress in the use of chitosan in the area of medical and pharmaceutical sciences, there is still a wide knowledge gap regarding the potential application of chitosan for encapsulation of active ingredients in agriculture. Hence, the present article describes the current status of chitosan nanoparticle-based delivery systems in agriculture, and to highlight challenges that need to be overcome. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-oped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

PubMed Central

Handa, Hitesh; Brisbois, Elizabeth J.; Major, Terry C.; Refahiyat, Lahdan; Amoako, Kagya A.; Annich, Gail M.; Bartlett, Robert H.; Meyerhoff, Mark E.

2013-01-01

Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion and activation that can be released from a NO donor species, such as diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) within a polymer coating. In this study, various Food and Drug Administration approved poly(lactic-co-glycolic acid) (PLGA) species were evaluated as additives to promote a prolonged NO release from DBHD/N2O2 within a plasticized poly(vinyl chloride) (PVC) matrix. When using an ester-capped PLGA additive with a slow hydrolysis time, the resulting coatings continuously release between 7–18×10-10 mol cm-2 min-1 NO for 14 d at 37°C in PBS buffer. The corresponding pH changes within the polymer films were visualized using pH sensitive indicators and are shown to correlate with the extended NO release pattern. The optimal combined diazeniumdiolate/PLGA-doped NO release (NOrel) PVC coating was evaluated in vitro and its effect on the hemodynamics was also studied within a 4 h in vivo extracorporeal circulation (ECC) rabbit model of thrombogenicity. Four out of 7 control circuits clotted within 3 h, whereas all the NOrel coated circuits were patent after 4 h. Platelet counts on the NOrel ECC were preserved (79 ± 11% compared to 54 ± 6% controls). The NOrel coatings showed a significant decrease in the thrombus area as compared to the controls. Results suggest that by using ester-capped PLGAs as additives to a conventional plasticized PVC material containing a lipophilic diazeniumdiolates, the NO release can be prolonged for up to 2 weeks by controlling the pH within the organic phase of the coating. PMID:23914297

Absorption of p,p'-dichlorodiphenyldichloroethylene and dieldrin in largemouth bass from a 60-D slow-release pellet and detection using a novel enzyme-linked immunosorbent assay method for blood plasma

USGS Publications Warehouse

Muller, Jennifer K.; Sepulveda, Maria S.; Borgert, Christopher J.; Gross, Timothy S.

2005-01-01

This work describes the uptake of two organochlorine pesticides from slow-release pellets by largemouth bass and the utility of a blood plasma enzyme-linked immunosorbent assay (ELISA) method for exposure verification. We measured blood and tissue levels by gas chromatography/mass spectrometry and by a novel ELISA method, and present a critical comparison of the results.

Efficacy of tebuconazole embedded in biodegradable poly-3-hydroxybutyrate to inhibit the development of Fusarium moniliforme in soil microecosystems.

PubMed

Volova, Tatiana G; Prudnikova, Svetlana V; Zhila, Natalia O; Vinogradova, Olga N; Shumilova, Anna A; Nikolaeva, Elena D; Kiselev, Evgeniy G; Shishatskaya, Ekaterina I

2017-05-01

An important line of research is the development of a new generation of formulations with targeted and controlled release of the pesticide, using matrices made from biodegradable materials. In this study, slow-release formulations of the fungicide tebuconazole (TEB) have been prepared by embedding it into the matrix of poly-3-hydroxybutyrate (P3HB) in the form of films, microgranules and pellets. The average rates of P3HB degradation were determined by the geometry of the formulation, reaching, for 63 days, 0.095-0.116, 0.081-0.083 and 0.030-0.055 mg day -1 for films, microgranules and pellets respectively. The fungicidal activity of P3HB/TEB against the plant pathogen Fusarium moniliforme was compared with that of the commercial formulation Raxil Ultra. A pronounced fungicidal effect of the experimental P3HB/TEB formulations was observed in 2-4 weeks after application, and it was retained for 8 weeks, without affecting significantly the development of soil aboriginal microflora. TEB release can be regulated by the process employed to fabricate the formulation and the fungicide loading, and the TEB accumulates in the soil gradually, as the polymer is degraded. The experimental forms of TEB embedded in the slowly degraded P3HB can be used as a basis for developing slow-release fungicide formulations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Synthesizing slow-release fertilizers via mechanochemical processing for potentially recycling the waste ferrous sulfate from titanium dioxide production.

PubMed

Li, Xuewei; Lei, Zhiwu; Qu, Jun; Li, Zhao; Zhou, Xiaowen; Zhang, Qiwu

2017-01-15

The goal of this study is aimed to develop a novel process to recycle the ferrous sulfate, the by-product of titanium dioxide industry. Zinc sulfate was added in the process of milling ferrous sulfate with calcium carbonate (CaCO 3 ). The sulfates were transformed into carbonates to serve as slow-release fertilizers by co-grinding the starting materials of FeSO 4 ·7H 2 O, ZnSO 4 ·7H 2 O, and CaCO 3 with small amounts of water in a planetary ball mill. The prepared samples were characterized by X-ray diffraction (XRD) analysis and quantitative measurements of the soluble ratios in water and 2% citric acid solution. It was found that Fe and Zn ions as sulfates were successfully combined with CaCO 3 to form the corresponding Fe and Zn carbonates respectively. After milling, the release ratios of Fe and Zn nutrients in distilled water could be controlled at 0.1% and 0.7% respectively. Meanwhile, the release ratios of them in 2% citric acid solution were almost 98% and 100%. Milling speed was the critical parameter to facilitate the transformation reaction. The proposed process, as an easy and economical route, exhibits evident advantages, namely allowing the use of widely available and low-cost CaCO 3 as well as industrial wastes of heavy metal sulfates as starting samples to prepare applicable products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Natural mycorrhizal colonization of pines on reclaimed surface mines in Virginia. [Pinus strobus; Pinus taeda; Pinus virginiana

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

Schoenholtz, S.H.; Burger, J.A.; Torbert, J.L.

The effects of spoil type, slow-release fertilization, and weed control using glyphosate on the degree of ectomycorrhizal colonization of container-grown white (Pinus strobus L.), loblolly (P. taeda L.), and Virginia (P. virginiana Mill.) pines were studied on two strip mined sites (sandstone vs. siltstone overburden material) in southwestern Virginia. Although some seedlings were successfully colonized at both sites, the number of seedlings colonized and the proportion of short-root colonization per seedling were consistently higher on the sandstone spoil. On both sites, loblolly and Virginia pines had more ectomycorrhizal formation than white pine. Foliar P levels of all three species onmore » the sandstone spoil and of loblolly pine on the siltstone spoil were significantly correlated with ectomycorrhizal development. The degree of ectomycorrhizal formation for any of the species on either spoil was not decreased by slow-release fertilization or glyphosate applications. These results indicate that natural mycorrhizal colonization is compatible with these cultural treatments, and that colonization from indigenous fungal species may be adequate, eliminating the need for artificial inoculation.« less

Is nifedipine a suitable first-line treatment for essential hypertension in general practice?

PubMed

Sullivan, F M; Murray, T S; Gaw, N; Langan, J J; Adams-Strump, B J

1987-11-01

Nifedipine has been used in hypertension, mainly as a third-line drug for rapid blood pressure reduction, for over 10 years. More recently it has been shown to be effective and safe in reducing mild to moderate blood pressure when used alone in a slow release formulation. A placebo-controlled study investigating the efficacy and safety of nifedipine in comparison with cyclopenthiazide-potassium has now been carried out by 4 general practitioners in the Glasgow area. Ninety-four patients were entered into the study. After a 4-week placebo run-in phase, patients were randomly allocated to receive either slow-release nifedipine 20 mg b.d., or cyclopenthiazide 0.25 mg with 8.1 mmol potassium daily. The dose was doubled at week 8 for non-responders, and at week 12 the alternative drug was added if there was still no response. The patients were studied for up to 28 weeks. Nifedipine was found to have similar blood pressure lowering efficacy to cyclopenthiazide-potassium, but withdrawals from nifedipine due to side-effects at an early stage were more common.

Core-shell nanofibers of curcumin/cyclodextrin inclusion complex and polylactic acid: Enhanced water solubility and slow release of curcumin.

PubMed

Aytac, Zeynep; Uyar, Tamer

2017-02-25

Core-shell nanofibers were designed via electrospinning using inclusion complex (IC) of model hydrophobic drug (curcumin, CUR) with cyclodextrin (CD) in the core and polymer (polylactic acid, PLA) in the shell (cCUR/HPβCD-IC-sPLA-NF). CD-IC of CUR and HPβCD was formed at 1:2 molar ratio. The successful formation of core-shell nanofibers was revealed by TEM and CLSM images. cCUR/HPβCD-IC-sPLA-NF released CUR slowly but much more in total than PLA-CUR-NF at pH 1 and pH 7.4 due to the restriction of CUR in the core of nanofibers and solubility improvement shown in phase solubility diagram, respectively. Improved antioxidant activity of cCUR/HPβCD-IC-sPLA-NF in methanol:water (1:1) is related with the solubility enhancement achieved in water based system. The slow reaction of cCUR/HPβCD-IC-sPLA-NF in methanol is associated with the shell inhibiting the quick release of CUR. On the other hand, cCUR/HPβCD-IC-sPLA-NF exhibited slightly higher rate of antioxidant activity than PLA-CUR-NF in methanol:water (1:1) owing to the enhanced solubility. To conclude, slow release of CUR was achieved by core-shell nanofiber structure and inclusion complexation of CUR with HPβCD provides high solubility. Briefly, electrospinning of core-shell nanofibers with CD-IC core could offer slow release of drugs as well as solubility enhancement for hydrophobic drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel Applications for Oxalate-Phosphate-Amine Metal-Organic-Frameworks (OPA-MOFs): Can an Iron-Based OPA-MOF Be Used as Slow-Release Fertilizer?

PubMed Central

Anstoetz, Manuela; Rose, Terry J.; Clark, Malcolm W.; Yee, Lachlan H.; Raymond, Carolyn A.; Vancov, Tony

2015-01-01

A porous iron-based oxalate-phosphate-amine metal-organic framework material (OPA-MOF) was investigated as a microbially-induced slow-release nitrogen (N) and phosphorus (P) fertilizer. Seedling growth, grain yields, nutrient uptake of wheat plants, and soil dynamics in incubated soil, were investigated using OPA-MOF vs standard P (triple-superphosphate) and N (urea) fertilizers in an acidic Ferralsol at two application rates (equivalent 120 and 40 kg N ha-1). While urea hydrolysis in the OPA-MOF treatment was rapid, conversion of ammonium to nitrate was significantly inhibited compared to urea treatment. Reduced wheat growth in OPA-MOF treatments was not caused by N-deficiency, but by limited P-bioavailability. Two likely reasons were slow P-mobilisation from the OPA-MOF or rapid P-binding in the acid soil. P-uptake and yield in OPA-MOF treatments were significantly higher than in nil-P controls, but significantly lower than in conventionally-fertilised plants. OPA-MOF showed potential as enhanced efficiency N fertilizer. However, as P-bioavailability was insufficient to meet plant demands, further work should determine if P-availability may be enhanced in alkaline soils, or whether central ions other than Fe, forming the inorganic metal-P framework in the MOF, may act as a more effective P-source in acid soils. PMID:26633174

Novel Applications for Oxalate-Phosphate-Amine Metal-Organic-Frameworks (OPA-MOFs): Can an Iron-Based OPA-MOF Be Used as Slow-Release Fertilizer?

PubMed

Anstoetz, Manuela; Rose, Terry J; Clark, Malcolm W; Yee, Lachlan H; Raymond, Carolyn A; Vancov, Tony

2015-01-01

A porous iron-based oxalate-phosphate-amine metal-organic framework material (OPA-MOF) was investigated as a microbially-induced slow-release nitrogen (N) and phosphorus (P) fertilizer. Seedling growth, grain yields, nutrient uptake of wheat plants, and soil dynamics in incubated soil, were investigated using OPA-MOF vs standard P (triple-superphosphate) and N (urea) fertilizers in an acidic Ferralsol at two application rates (equivalent 120 and 40 kg N ha(-1)). While urea hydrolysis in the OPA-MOF treatment was rapid, conversion of ammonium to nitrate was significantly inhibited compared to urea treatment. Reduced wheat growth in OPA-MOF treatments was not caused by N-deficiency, but by limited P-bioavailability. Two likely reasons were slow P-mobilisation from the OPA-MOF or rapid P-binding in the acid soil. P-uptake and yield in OPA-MOF treatments were significantly higher than in nil-P controls, but significantly lower than in conventionally-fertilised plants. OPA-MOF showed potential as enhanced efficiency N fertilizer. However, as P-bioavailability was insufficient to meet plant demands, further work should determine if P-availability may be enhanced in alkaline soils, or whether central ions other than Fe, forming the inorganic metal-P framework in the MOF, may act as a more effective P-source in acid soils.

Telotristat

MedlinePlus

... by carcinoid tumors (slow-growing tumors that release natural substances that can cause symptoms like diarrhea) in ... works by blocking the formation of a certain natural substance in the body that is released by ...

Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.

PubMed

Zhang, Yulong; Dong, Rui; Park, Yujin; Bohner, Marc; Zhang, Xinli; Ting, Kang; Soo, Chia; Wu, Benjamin M

2016-09-10

NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. Copyright © 2016 Elsevier B.V. All rights reserved.

Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis.

PubMed

Hellström, Per M; Hendolin, Panu; Kaihovaara, Pertti; Kronberg, Leif; Meierjohann, Axel; Millerhovf, Anders; Paloheimo, Lea; Sundelin, Heidi; Syrjänen, Kari; Webb, Dominic-Luc; Salaspuro, Mikko

2017-02-01

Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 ± 2687 μmol/L at 40 min and peak MTCA level 196 ± 98 μmol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.

Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction

PubMed Central

Projahn, Delia; Simsekyilmaz, Sakine; Singh, Smriti; Kanzler, Isabella; Kramp, Birgit K; Langer, Marcella; Burlacu, Alexandrina; Bernhagen, Jürgen; Klee, Doris; Zernecke, Alma; Hackeng, Tilman M; Groll, Jürgen; Weber, Christian; Liehn, Elisa A; Koenen, Rory R

2014-01-01

Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies. PMID:24512349

Inositol 1,4,5-trisphosphate-sensitive Ca2+ release in rat fast- and slow-twitch skinned muscle fibres.

PubMed

Talon, S; Huchet-Cadiou, C; Léoty, C

1999-11-01

Inositol 1,4,5-trisphosphate (InsP3), an intracellular messenger, induces Ca2+ release in various types of cells, particularly smooth muscle cells. Its role in skeletal muscle, however, is controversial. The present study shows that the application of InsP3 to rat slow- and fast-twitch saponin-skinned fibres induced contractile responses that were not related to an effect of InsP3 on the properties of the contractile proteins. The amplitude of the contractures was dependent upon the Ca(2+)-loading period, and was larger in slow- than in fast-twitch muscle. In both types of skeletal muscle, these responses, unlike caffeine contractures, were not inhibited by ryanodine (100 microM), but were abolished by heparin (20 micrograms.ml-1). In soleus muscle, the concentration of heparin required to inhibit the response by 50% (IC50) was 5.7 micrograms.ml-1, a similar value to that obtained previously in smooth muscle. Furthermore, the results show that in slow-twitch muscle, the InsP3 contractures have a "bell-shaped" dependency on the intracellular Ca2+ concentration. These results show that InsP3 receptors should be present in skeletal muscle. Thus, it is possible that InsP3 participates in the regulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle, particularly in slow-twitch fibres.

Effect of slow energy releasing on divergent detonation of Insensitive High Explosives

NASA Astrophysics Data System (ADS)

Hu, Xiaomian; Pan, Hao; Huang, Yong; Wu, Zihui

2014-03-01

There exists a slow energy releasing (SER) process in the slow reaction zone located behind the detonation wave due to the carbon cluster in the detonation products of Insensitive High Explosives (IHEs), and the process will affect the divergent detonation wave's propagation and the driving process of the explosives. To study the potential effect, a new artificial burn model including the SER process based on the programmed burn model is proposed in the paper. Quasi-steady analysis of the new model indicates that the nonlinearity of the detonation speed as a function of front curvature owes to the significant change of the reaction rate and the reaction zone length at the sonic state. What's more, in simulating the detonation of IHE JB-9014, the new model including the slow reaction can predict a slower jump-off velocity, in good agreement with the result of the test.

Evaluating vertical concentration profile of carbon source released from slow-releasing carbon source tablets and in situ biological nitrate denitrification activity

NASA Astrophysics Data System (ADS)

Yeum, Y.; HAN, K.; Yoon, J.; Lee, J. H.; Song, K.; Kang, J. H.; Park, C. W.; Kwon, S.; Kim, Y.

2017-12-01

Slow-releasing carbon source tablets were manufactured during the design of a small-scale in situ biological denitrification system to reduce high-strength nitrate (> 30 mg N/L) from a point source such as livestock complexes. Two types of slow-releasing tablets, precipitating tablet (PT, apparent density of 2.0 g/mL) and floating tablet (FT), were prepared to achieve a vertically even distribution of carbon source (CS) in a well and an aquifer. Hydroxypropyl methylcellulose (HPMC) was used to control the release rate, and microcrystalline cellulose pH 101 (MCC 101) was added as a binder. The #8 sand was used as a precipitation agent for the PTs, and the floating agents for the FTs were calcium carbonate and citric acid. FTs floated within 30 min. and remained in water because of the buoyance from carbon dioxide, which formed during the acid-base reaction between citric acid and calcium carbonate. The longevities of PTs with 300 mg of HPMC and FTs with 400 mg of HPMC were 25.4 days and 37.3 days, respectively. We assessed vertical CS profile in a continuous flowing physical aquifer model (release test, RT) and its efficiency on biological nitrate denitrification (denitrification test, DT). During the RT, PTs, FTs and a tracer (as 1 mg rhodamine B/L) were initially injected into a well of physical aquifer model (PAM). Concentrations of CS and the tracer were monitored along the streamline in the PAM to evaluate vertical profile of CS. During the DT, the same experiment was performed as RT, except continuous injection of solution containing 30 mg N/L into the PAM to evaluate biological denitrification activity. As a result of RT, temporal profiles of CS were similar at 3 different depths of monitoring wells. These results suggest that simultaneous addition of PT and FT be suitable for achieving a vertically even distribution of the CS in the injection well and an aquifer. In DT, similar profile of CS was detected in the injection well, and nitrate was biologically denitrified at downstream of the injection well. In conclusion, addition of PT and FT into a well under natural gradient condition may be an effective means for remediating high-strength nitrate in groundwater.

Ion release, fluoride charge of and adhesion of an orthodontic cement paste containing microcapsules.

PubMed

Burbank, Brant D; Slater, Michael; Kava, Alyssa; Doyle, James; McHale, William A; Latta, Mark A; Gross, Stephen M

2016-02-01

Dental materials capable of releasing calcium, phosphate and fluoride are of great interest for remineralization. Microencapsulated aqueous solutions of these ions in orthodontic cement demonstrate slow, sustained release by passive diffusion through a permeable membrane without the need for dissolution or etching of fillers. The potential to charge a dental material formulated with microencapsulated water with fluoride by toothbrushing with over the counter toothpaste and the effect of microcapsules on cement adhesion to enamel was determined. Orthodontic cements that contained microcapsules with water and controls without microcapsules were brushed with over-the-counter toothpaste and fluoride release was measured. Adhesion measurements were performed loading orthodontic brackets to failure. Cements that contained microencapsulated solutions of 5.0M Ca(NO3)2, 0.8M NaF, 6.0MK2HPO4 or a mixture of all three were prepared. Ion release profiles were measured as a function of time. A greater fluoride charge and re-release from toothbrushing was demonstrated compared to a control with no microcapsules. Adhesion of an orthodontic cement that contained microencapsulated remineralizing agents was 8.5±2.5MPa compared to the control without microcapsules which was of 8.3±1.7MPa. Sustained release of fluoride, calcium and phosphate ions from cement formulated with microencapsulated remineralizing agents was demonstrated. Orthodontic cements with microcapsules show a release of bioavailable fluoride, calcium, and phosphate ions near the tooth surface while having the ability to charge with fluoride and not effect the adhesion of the material to enamel. Incorporation of microcapsules in dental materials is promising for promoting remineralization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release.

PubMed

Rehman, Fozia; Rahim, Abdur; Airoldi, Claudio; Volpe, Pedro L O

2016-02-01

Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2m(2)g(-1) and pore volume was reduced from 1.98 to 0.89cm(3)g(-1), when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer-Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8h, while comparatively high release rates were observed in simulated intestinal (pH6.8) and simulated body fluids (pH7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system. Copyright © 2015 Elsevier B.V. All rights reserved.

NextGen Flight Deck Surface Trajectory-Based Operations (STBO): Contingency Holds

NASA Technical Reports Server (NTRS)

Bakowski, Deborah Lee; Hooey, Becky Lee; Foyle, David C.; Wolter, Cynthia A.; Cheng, Lara W. S.

2013-01-01

The purpose of this pilot-in-the-loop taxi simulation was to investigate a NextGen Surface Trajectory-Based Operations (STBO) concept called "contingency holds." The contingency-hold concept parses a taxi route into segments, allowing an air traffic control (ATC) surface traffic management (STM) system to hold an aircraft when necessary for safety. Under nominal conditions, if the intersection or active runway crossing is clear, the hold is removed, allowing the aircraft to continue taxiing without slowing, thus improving taxi efficiency, while minimizing the excessive brake use, fuel burn, and emissions associated with stop-and-go taxi. However, when a potential traffic conflict exists, the hold remains in place as a fail-safe mechanism. In this departure operations simulation, the taxi clearance included a required time of arrival (RTA) to a specified intersection. The flight deck was equipped with speed-guidance avionics to aid the pilot in safely meeting the RTA. On two trials, the contingency hold was not released, and pilots were required to stop. On two trials the contingency hold was released 15 sec prior to the RTA, and on two trials the contingency hold was released 30 sec prior to the RTA. When the hold remained in place, all pilots complied with the hold. Results also showed that when the hold was released at 15-sec or 30-sec prior to the RTA, the 30-sec release allowed pilots to maintain nominal taxi speed, thus supporting continuous traffic flow; whereas, the 15-sec release did not. The contingency-hold concept, with at least a 30-sec release, allows pilots to improve taxiing efficiency by reducing braking, slowing, and stopping, but still maintains safety in that no pilots "busted" the clearance holds. Overall, the evidence suggests that the contingency-hold concept is a viable concept for optimizing efficiency while maintaining safety.

RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro.

PubMed

Xing, James Z; Lu, Lei; Unsworth, Larry D; Major, Paul W; Doschak, Michael R; Kaipatur, Neelambar R

2017-02-01

To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of the recombinant receptor activator of NF-kB ligand; (RANKL) and to characterize the release kinetics and bioactivity of the released RANKL. Various concentrations of fluorescently-labelled RANKL protein were added to NF-hydrogels, composed of Acetyl-(Arg-Ala-Asp-Ala) 4 -CONH 2 [(RADA) 4 ] of different concentrations, to investigate the resulting in vitro release rates. The nano-structures of NF-hydrogel, with and without RANKL, were determined using atomic force microscopy (AFM). Released RANKL was further analyzed for changes in secondary and tertiary structure using CD spectroscopy and fluorescent emission spectroscopy, respectively. Bioactivity of released RANKL protein was determined using NFATc1 gene expression and tartrate resistant acid phosphatase (TRAP) activity of osteoclast cells as biomarkers. NF-hydrogel concentration dependent sustained release of RANKL protein was measured at concentrations between 0.5 and 2%(w/v). NF-hydrogel at 2%(w/v) concentration exhibited a sustained and slow-release of RANKL protein up to 48h. Secondary and tertiary structure analyses confirmed no changes to the RANKL protein released from NF-hydrogel in comparison to native RANKL. The results of NFATc1 gene mRNA expression and TRAP activities of osteoclast, showed that the release process did not affect the bioactivity of released RANKL. This novel study is the first of its kind to attempt in vitro characterization of NF-hydrogel based delivery of RANKL protein to induce osteoclastogenesis. We have shown the self-assembling NF-hydrogel peptide system is amenable to the sustained and controlled release of RANKL locally; that could in turn increase local concentration of RANKL to induce osteoclastogenesis, for application to the controlled mobilization of tooth movement in orthodontic procedures. Orthodontic tooth movement (OTM) occurs through controlled application of light forces to teeth, facilitating the required changes in the surrounding alveolar bone through the process of bone remodelling. The RANKL system regulates alveolar bone remodelling and controls root resorption during OTM. The use of exogenous RANKL to accelerate OTM has not been attempted to date because large quantities of RANKL for systemic therapy may subsequently cause serious systemic loss of skeletal bone. The controlled and sustained local release of RANKL from a carrier matrix could maximize its therapeutic benefit whilst minimizing systemic side effects. In this study a NF-hydrogel was used for sustained and controlled release of RANKL and the release kinetics and biofunctionality of the released RANKL was characterized. Our results provide fundamental insight for further investigating the role of RANKL NF-hydrogel release systems for inducing osteoclastogenesis in vivo. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biomimetic synthesis of hybrid hydroxyapatite nanoparticles using nanogel template for controlled release of bovine serum albumin.

PubMed

Qin, Jinli; Zhong, Zhenyu; Ma, Jun

2016-05-01

A biomimetic method was used to prepare hybrid hydroxyapatite (HAP) nanoparticles with chitosan/polyacrylic acid (CS-PAA) nanogel. The morphology, structure, crystallinity, thermal properties and biocompatibility of the obtained hybrid nanogel-HAP nanoparticles have been characterized. In addition, bovine serum albumin (BSA) was used as a model protein to study the loading and release behaviors of the hybrid nanogel-HAP nanoparticles. The results indicated that the obtained HAP nanoparticles were agglomerated and the nanogel could regulate the formation of HAP. When the nanogel concentration decreased, different HAP crystal shapes and agglomerate structures were obtained. The loading amount of BSA reached 67.6 mg/g for the hybrid nanoparticles when the mineral content was 90.4%, which decreased when the nanogel concentration increased. The release profile of BSA was sustained in neutral buffer. Meanwhile, an initial burst release was found at pH 4.5 due to the desorption of BSA from the surface, followed by a slow release. The hemolysis percentage of the hybrid nanoparticles was close to the negative control, and these particles were non-toxic to bone marrow stromal stem cells. The results suggest that these hybrid nanogel-HAP nanoparticles are promising candidate materials for biocompatible drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Bio-based Interpenetrating Network Polymer Composites from Locust Sawdust as Coating Material for Environmentally Friendly Controlled-Release Urea Fertilizers.

PubMed

Zhang, Shugang; Yang, Yuechao; Gao, Bin; Wan, Yongshan; Li, Yuncong C; Zhao, Chenhao

2016-07-20

A novel polymer-coated nitrogen (N) fertilizer was developed using bio-based polyurethane (PU) derived from liquefied locust sawdust as the coating material. The bio-based PU was successfully coated on the surface of the urea fertilizer prills to form polymer-coated urea (PCU) fertilizer for controlled N release. Epoxy resin (EP) was also used to further modify the bio-based PU to synthesize the interpenetrating network (IPN), enhancing the slow-release properties of the PCU. The N release characteristics of the EP-modified PCU (EMPCU) in water were determine at 25 °C and compared to that of PCU and EP-coated urea (ECU). The results showed that the EP modification reduced the N release rate and increased the longevity of the fertilizer coated with bio-based PU. A corn growth study was conducted to further evaluate the filed application of the EMPCU. In comparison to commercial PCU and conventional urea fertilizer, EMPCU was more effective and increased the yield and total dry matter accumulation of the corn. Findings from this work indicated that bio-based PU derived from sawdust can be used as coating materials for PCU, particularly after EP modification. The resulting EMPCU was more environmentally friendly and cost-effective than conventional urea fertilizers coated by EP.

Clustering of Ca2+ transients in interstitial cells of Cajal defines slow wave duration

PubMed Central

Drumm, Bernard T.; Hennig, Grant W.; Battersby, Matthew J.; Sung, Tae Sik

2017-01-01

Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca2+-activated Cl− channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca2+ regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca2+ transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca2+ sensor, GCaMP3, in ICC. Ca2+ transients in ICC-MY display a complex firing pattern caused by localized Ca2+ release events arising from multiple sites in cell somata and processes. Ca2+ transients are clustered within the time course of slow waves but fire asynchronously during these clusters. The durations of Ca2+ transient clusters (CTCs) correspond to slow wave durations (plateau phase). Simultaneous imaging and intracellular electrical recordings revealed that the upstroke depolarization of slow waves precedes clusters of Ca2+ transients. Summation of CTCs results in relatively uniform Ca2+ responses from one slow wave to another. These Ca2+ transients are caused by Ca2+ release from intracellular stores and depend on ryanodine receptors as well as amplification from IP3 receptors. Reduced extracellular Ca2+ concentrations and T-type Ca2+ channel blockers decreased the number of firing sites and firing probability of Ca2+ transients. In summary, the fundamental electrical events of small intestinal muscles generated by ICC-MY depend on asynchronous firing of Ca2+ transients from multiple intracellular release sites. These events are organized into clusters by Ca2+ influx through T-type Ca2+ channels to sustain activation of ANO1 channels and generate the plateau phase of slow waves. PMID:28592421

Masking Release in Children and Adults With Hearing Loss When Using Amplification

PubMed Central

McCreery, Ryan; Kopun, Judy; Lewis, Dawna; Alexander, Joshua; Stelmachowicz, Patricia

2016-01-01

Purpose This study compared masking release for adults and children with normal hearing and hearing loss. For the participants with hearing loss, masking release using simulated hearing aid amplification with 2 different compression speeds (slow, fast) was compared. Method Sentence recognition in unmodulated noise was compared with recognition in modulated noise (masking release). Recognition was measured for participants with hearing loss using individualized amplification via the hearing-aid simulator. Results Adults with hearing loss showed greater masking release than the children with hearing loss. Average masking release was small (1 dB) and did not depend on hearing status. Masking release was comparable for slow and fast compression. Conclusions The use of amplification in this study contrasts with previous studies that did not use amplification. The results suggest that when differences in audibility are reduced, participants with hearing loss may be able to take advantage of dips in the noise levels, similar to participants with normal hearing. Although children required a more favorable signal-to-noise ratio than adults for both unmodulated and modulated noise, masking release was not statistically different. However, the ability to detect a difference may have been limited by the small amount of masking release observed. PMID:26540194

Dehydration of subducting slow-spread oceanic lithosphere in the Lesser Antilles.

PubMed

Paulatto, Michele; Laigle, Mireille; Galve, Audrey; Charvis, Philippe; Sapin, Martine; Bayrakci, Gaye; Evain, Mikael; Kopp, Heidrun

2017-07-10

Subducting slabs carry water into the mantle and are a major gateway in the global geochemical water cycle. Fluid transport and release can be constrained with seismological data. Here we use joint active-source/local-earthquake seismic tomography to derive unprecedented constraints on multi-stage fluid release from subducting slow-spread oceanic lithosphere. We image the low P-wave velocity crustal layer on the slab top and show that it disappears beneath 60-100 km depth, marking the depth of dehydration metamorphism and eclogitization. Clustering of seismicity at 120-160 km depth suggests that the slab's mantle dehydrates beneath the volcanic arc, and may be the main source of fluids triggering arc magma generation. Lateral variations in seismic properties on the slab surface suggest that serpentinized peridotite exhumed in tectonized slow-spread crust near fracture zones may increase water transport to sub-arc depths. This results in heterogeneous water release and directly impacts earthquakes generation and mantle wedge dynamics.

Dehydration of subducting slow-spread oceanic lithosphere in the Lesser Antilles

PubMed Central

Paulatto, Michele; Laigle, Mireille; Galve, Audrey; Charvis, Philippe; Sapin, Martine; Bayrakci, Gaye; Evain, Mikael; Kopp, Heidrun

2017-01-01

Subducting slabs carry water into the mantle and are a major gateway in the global geochemical water cycle. Fluid transport and release can be constrained with seismological data. Here we use joint active-source/local-earthquake seismic tomography to derive unprecedented constraints on multi-stage fluid release from subducting slow-spread oceanic lithosphere. We image the low P-wave velocity crustal layer on the slab top and show that it disappears beneath 60–100 km depth, marking the depth of dehydration metamorphism and eclogitization. Clustering of seismicity at 120–160 km depth suggests that the slab’s mantle dehydrates beneath the volcanic arc, and may be the main source of fluids triggering arc magma generation. Lateral variations in seismic properties on the slab surface suggest that serpentinized peridotite exhumed in tectonized slow-spread crust near fracture zones may increase water transport to sub-arc depths. This results in heterogeneous water release and directly impacts earthquakes generation and mantle wedge dynamics. PMID:28691714

Agronomic Effectiveness of Granulated and Powdered P-Exchanged Mg-Al LDH Relative to Struvite and MAP.

PubMed

Everaert, Maarten; Degryse, Fien; McLaughlin, Mike J; De Vos, Dirk; Smolders, Erik

2017-08-16

Layered double hydroxides (LDHs) used to recover P from wastewater have recently been proposed as new slow-release fertilizers. Here, the use of P-exchanged Mg-Al LDHs as powdered or granulated fertilizer is explored and compared with monoammonium phosphate (MAP), a fully water-soluble fertilizer, and with struvite, a recycled phosphate fertilizer with lower solubility. First, these three fertilizers were compared in a 100-day incubation experiment using P diffusion visualization and chemical analysis to assess P release from either granules or powdered fertilizer in three different soils. By the end of the incubation, 74-90% of P remained within the LDH granule, confirming a slow release. Second, a pot experiment was performed with wheat (Triticum aestivum) in an acid and a calcareous soil. The granular treatment resulted in a considerably higher P uptake for MAP compared to LDH and struvite. For the powder treatments, the P uptake was less than for granular MAP and was largely unaffected by the chemical form. The LDHs and struvite showed a lower agronomic effectiveness than granular MAP, but the benefits of their use in P recycling, potential residual value, and environmental benefits may render these slow-release fertilizers attractive.

Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

PubMed

Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

2015-12-30

The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms. Copyright © 2015. Published by Elsevier B.V.

Using slow-release permanganate candles to remediate PAH-contaminated water.

PubMed

Rauscher, Lindy; Sakulthaew, Chainarong; Comfort, Steve

2012-11-30

Surface waters impacted by urban runoff in metropolitan areas are becoming increasingly contaminated with polycyclic aromatic hydrocarbons (PAHs). Slow-release oxidant candles (paraffin-KMnO(4)) are a relatively new technology being used to treat contaminated groundwater and could potentially be used to treat urban runoff. Given that these candles only release permanganate when submerged, the ephemeral nature of runoff events would influence when the permanganate is released for treating PAHs. Our objective was to determine if slow-release permanganate candles could be used to degrade and mineralize PAHs. Batch experiments quantified PAH degradation rates in the presence of the oxidant candles. Results showed most of the 16 PAHs tested were degraded within 2-4 h. Using (14)C-labled phenanthrene and benzo(a)pyrene, we demonstrated that the wax matrix of the candle initially adsorbs the PAH, but then releases the PAH back into solution as transformed, more water soluble products. While permanganate was unable to mineralize the PAHs (i.e., convert to CO(2)), we found that the permanganate-treated PAHs were much more biodegradable in soil microcosms. To test the concept of using candles to treat PAHs in multiple runoff events, we used a flow-through system where urban runoff water was pumped over a miniature candle in repetitive wet-dry, 24-h cycles. Results showed that the candle was robust in removing PAHs by repeatedly releasing permanganate and degrading the PAHs. These results provide proof-of-concept that permanganate candles could potentially provide a low-cost, low-maintenance approach to remediating PAH-contaminated water. Copyright © 2012 Elsevier B.V. All rights reserved.

[An experimental study on a slow-release complex with rifampicin-polylactic-co-glycolic acid-calcium 
phosphate cement].

PubMed

Wu, Jianhuang; Ding, Zhou; Lei, Qing; Li, Miao; Liang, Yan; Lu, Tao

2016-09-28

To prepare the slow-release complex with rifampicin (RFP)-polylactic-co-glycolic acid (PLGA)-calcium phosphate cement (CPC) (RFP-PLGA-CPC complex), and to study its physical and chemical properties and drug release properties in vitro.
 The emulsification-solvent evaporation method was adopted to prepare rifampicin polylactic acid-glycolic acid (RFP-PLGA) slow-release microspheres, which were divided into 3 groups: a calcium phosphate bone cement group (CPC group), a CPC embedded with RFP group (RFP-CPC group), and a PLGA slow-release microspheres carrying RFP and the self-curing CPC group (RFP- PLGA-CPC complex group). The solidification time and porosity of materials were determined. The drug release experiments in vitro were carried out to observe the compressive strength, the change of section morphology before and after drug release. 
 The CPC group showed the shortest solidification time, while the RFP-PLGA-CPC complex group had the longest one. There was statistical difference in the porosity between the CPC group and the RFP-CPC group (P<0.05); Compared to the RFP-PLGA-CPC complex group, the porosity in the CPC group and the RFP-CPC group were significantly changed (both P<0.01). There was significant difference in the compressive strength between the RFP- PLGA-CPC complex group and the CPC group (P<0.01), while there was significant difference in the compressive strength between the RFP-CPC group and the CPC group (3 days: P<0.05; 30 and 60 days: P<0.01). The change of the compressive strength in the CPC was not significant in the whole process of degradation. The sizes of PLGA microspheres were uniform, with the particle size between 100-150 μm. The microspheres were spheres or spheroids, and their surface was smooth without the attached impurities. There was no significant change in the section gap in the CPC group after soaking for 3 to 60 days. The microstructure change in the RFP-CPC group was small, and the cross section was formed by small particles. The pores of section in the RFP-PLGA-CPC complex group increased obviously, and PLGA microspheres gradually disappeared until the 60th day when there were only empty cavities left. The RFP-PLGA-CPC complex group had no obvious drugs sudden release, and the cumulative drug release rate was nearly 95% in the 60 days. The linear fitting was conducted for the drug release behavior of the complex, which was in accordance with zero order kinetics equation F=0.168×t.
 The porosity of RFP-PLGA-CPC complex is significantly higher than that of CPC, and it can keep slow release of the effective anti-tuberculosis drugs and maintain a certain mechanical strength for a long time.

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

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

Kumar, Rajiv, E-mail: r.kumar@neu.edu; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Belz, Jodi

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter,more » were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.« less

Elimination of Cigarette Smoke-derived Acetaldehyde in Saliva by Slow-release L-Cysteine Lozenge Is a Potential New Method to Assist Smoking Cessation. A Randomised, Double-blind, Placebo-controlled Intervention.

PubMed

Syrjänen, Kari; Salminen, Johanna; Aresvuo, Ulla; Hendolin, Panu; Paloheimo, Lea; Eklund, Carita; Salaspuro, Mikko; Suovaniemi, Osmo

2016-05-01

Harmans are condensation products of acetaldehyde and biogenic amines in saliva. Like other monoamine oxidase inhibitors, harmans help maintain behavioral sensitization to nicotine and mediate the addictive potential of cigarette smoke-derived acetaldehyde. The aim of this study was to test the hypothesis that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium™ lozenge; Biohit Oyj, Helsinki, Finland) blocks the formation of harmans and eliminates acetaldehyde-enhanced nicotine addiction in smokers. A double-blind, randomized, placebo-controlled trial comparing Acetium lozenges and placebo in smoking intervention was undertaken. A cohort of 423 cigarette smokers were randomly allocated to intervention (n=212) and placebo arms (n=211). Smoking-related data were recorded by questionnaires, together with nicotine dependence testing by Fagerström scale. The participants used a smoking diary to record the daily number of cigarettes, test lozenges and sensations of smoking. The data were analyzed separately for point prevalence of abstinence and prolonged abstinence endpoints. Altogether, 110 study participants completed the trial per protocol, 234 had minor violations, and the rest (n=79) were lost to follow-up. During the 6-month trial, 65 participants quit smoking; 38 (17.9%) in the intervention arm and 27 (12.8%) in the placebo arm [odds ratio (OR)=1.48; 95% confidence intervals (CI)=0.87-2.54; p=0.143]. Success in the per protocol group was better (42.9% vs. 31.1%, respectively; OR=1.65, 95% CI=0.75-3.62; p=0.205) than in the modified intention-to-treat group: 13.5% vs. 7.4% (p=0.128). If the efficacy of Acetium lozenge can be confirmed in an adequately powered study, this new approach would represent a major breakthrough in smoking quit intervention because slow-release L-cysteine is non-toxic with no side-effects or limitations of use. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Desorption kinetics of hydrophobic organic chemicals from sediment to water: a review of data and models.

PubMed

Birdwell, Justin; Cook, Robert L; Thibodeaux, Louis J

2007-03-01

Resuspension of contaminated sediment can lead to the release of toxic compounds to surface waters where they are more bioavailable and mobile. Because the timeframe of particle resettling during such events is shorter than that needed to reach equilibrium, a kinetic approach is required for modeling the release process. Due to the current inability of common theoretical approaches to predict site-specific release rates, empirical algorithms incorporating the phenomenological assumption of biphasic, or fast and slow, release dominate the descriptions of nonpolar organic chemical release in the literature. Two first-order rate constants and one fraction are sufficient to characterize practically all of the data sets studied. These rate constants were compared to theoretical model parameters and functionalities, including chemical properties of the contaminants and physical properties of the sorbents, to determine if the trends incorporated into the hindered diffusion model are consistent with the parameters used in curve fitting. The results did not correspond to the parameter dependence of the hindered diffusion model. No trend in desorption rate constants, for either fast or slow release, was observed to be dependent on K(OC) or aqueous solubility for six and seven orders of magnitude, respectively. The same was observed for aqueous diffusivity and sediment fraction organic carbon. The distribution of kinetic rate constant values was approximately log-normal, ranging from 0.1 to 50 d(-1) for the fast release (average approximately 5 d(-1)) and 0.0001 to 0.1 d(-1) for the slow release (average approximately 0.03 d(-1)). The implications of these findings with regard to laboratory studies, theoretical desorption process mechanisms, and water quality modeling needs are presented and discussed.

In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

PubMed

Zhang, J; Wang, Q; Wang, A

2010-02-01

In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

Are fluoride releasing dental materials clinically effective on caries control?

PubMed

Cury, Jaime Aparecido; de Oliveira, Branca Heloisa; dos Santos, Ana Paula Pires; Tenuta, Livia Maria Andaló

2016-03-01

(1) To describe caries lesions development and the role of fluoride in controlling disease progression; (2) to evaluate whether the use of fluoride-releasing pit and fissure sealants, bonding orthodontic agents and restorative materials, in comparison to a non-fluoride releasing material, reduces caries incidence in children or adults, and (3) to discuss how the anti-caries properties of these materials have been evaluated in vitro and in situ. The search was performed on the Cochrane Database of Systematic Reviews and on Medline via Pubmed. Caries is a biofilm-sugar dependent disease and as such it provokes progressive destruction of mineral structure of any dental surface - intact, sealed or restored - where biofilm remains accumulated and is regularly exposed to sugar. The mechanism of action of fluoride released from dental materials on caries is similar to that of fluoride found in dentifrices or other vehicles of fluoride delivery. Fluoride-releasing materials are unable to interfere with the formation of biofilm on dental surfaces adjacent to them or to inhibit acid production by dental biofilms. However, the fluoride released slows down the progression of caries lesions in tooth surfaces adjacent to dental materials. This effect has been clearly shown by in vitro and in situ studies but not in randomized clinical trials. The anti-caries effect of fluoride releasing materials is still not based on clinical evidence, and, in addition, it can be overwhelmed by fluoride delivered from dentifrices. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

The Mechanics of Transient Fault Slip and Slow Earthquakes

NASA Astrophysics Data System (ADS)

Marone, C.; Leeman, J.; Scuderi, M.; Saffer, D. M.; Collettini, C.

2015-12-01

Earthquakes are understood as frictional stick-slip instabilities in which stored elastic energy is released suddenly, driving catastrophic failure. In normal (fast) earthquakes the rupture zone expands at a rate dictated by elastic wave speeds, a few km/s, and fault slip rates reach 1-10 m/s. However, tectonic faults also fail in slow earthquakes with rupture durations of months and fault slip speeds of ~100 micron/s or less. We know very little about the mechanics of slow earthquakes. What determines the rupture propagation velocity in slow earthquakes and in other forms of quasi-dynamic rupture? What processes limit stress drop and fault slip speed in slow earthquakes? Existing lab studies provide some help via observations of complex forms of stick-slip, creep-slip, or, in a few cases, slow slip. However, these are mainly anecdotal and rarely include examples of repetitive slow slip or systematic measurements that could be used to isolate the underlying mechanisms. Numerical studies based on rate and state friction also shed light on transiently accelerating slip, showing that slow slip can occur if: 1) fault rheology involves a change in friction rate dependence (a-b) with velocity or unusually large values of the frictional weakening distance Dc, or 2) fault zone elastic stiffness equals the critical frictional weakening rate kc = (b-a)/Dc. Recent laboratory work shows that the latter can occur much more commonly that previously thought. We document the complete spectrum of stick-slip behaviors from transient slow slip to fast stick-slip for a narrow range of conditions around k/kc = 1.0. Slow slip occurs near the threshold between stable and unstable failure, controlled by the interplay of fault zone frictional properties, normal stress, and elastic stiffness of the surrounding rock. Our results provide a generic mechanism for slow earthquakes, consistent with the wide range of conditions for which slow slip has been observed.

A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

PubMed

Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

2002-07-01

In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

Cation Exchange Strategy for the Encapsulation of a Photoactive CO-Releasing Organometallic Molecule into Anionic Porous Frameworks.

PubMed

Carmona, Francisco J; Rojas, Sara; Sánchez, Purificación; Jeremias, Hélia; Marques, Ana R; Romão, Carlos C; Choquesillo-Lazarte, Duane; Navarro, Jorge A R; Maldonado, Carmen R; Barea, Elisa

2016-07-05

The encapsulation of the photoactive, nontoxic, water-soluble, and air-stable cationic CORM [Mn(tacn)(CO)3]Br (tacn = 1,4,7-triazacyclononane) in different inorganic porous matrixes, namely, the metalorganic framework bio-MOF-1, (NH2(CH3)2)2[Zn8(adeninate)4(BPDC)6]·8DMF·11H2O (BPDC = 4,4'-biphenyldicarboxylate), and the functionalized mesoporous silicas MCM-41-SO3H and SBA-15-SO3H, is achieved by a cation exchange strategy. The CO release from these loaded materials, under simulated physiological conditions, is triggered by visible light. The results show that the silica matrixes, which are unaltered under physiological conditions, slow the kinetics of CO release, allowing a more controlled CO supply. In contrast, bio-MOF-1 instability leads to the complete leaching of the CORM. Nevertheless, the degradation of the MOF matrix gives rise to an enhanced CO release rate, which is related to the presence of free adenine in the solution.

Formulating nanoparticles by flash nanoprecipitation for drug delivery and sustained release

NASA Astrophysics Data System (ADS)

Liu, Ying

This dissertation provides a fundamental understanding of the process for generating nanoparticles with controlled size distribution and of predicting nanoparticle stability for drug delivery and sustained release. We developed and characterized a novel technology to generate organic and inorganic nanoparticles protected by biocompatible and biodegradable polymers with precisely controlled size and size distribution. Computational fluid mechanics (CFD) together with experimental results provided details of the micromixing in the mixer. The particle size dependence on Reynolds number and supersaturation was illustrated. The study of the fundamental mass transfer phenomena leading to Ostwald ripening enables quantitative prediction of the time evolution of nanoparticles with monodistribution and relatively broader multi-distribution using beta-carotene and polystyrene-b-poly(ethylene oxide) (PS-b-PEO) as a model system. Negatively charged latex particles were used to exam the attachment of the diblock copolymer, PS-b-PEO, on the surface. The stability provided by the Columbic repulsion was replaced by steric stabilization. The attachment of the block copolymers on the surface of the colloids depends on the flow field, i.e. Reynolds number, of the mixing process. The slow degradation of poly(epsilon-caprolactone) (PCL) and poly(gamma-methyl-epsilon-caprolactone) (PMCL) was demonstrated. The slow degradation ensures long-term stability and long-term blood circulation of the polymeric nanoparticles. As a practical application, we formulate the anti-tuberculosis drug, rifampicin, into nanoparticles by conjugation to other hydrophobic molecules (such as vitamin E, PCL and 2-ethylhexyl vinyl ether) by pH sensitive cleavable chemical bonds to increase the drug loading, return stability of the nanoparticle suspension, and control drug release. The in vitro release profiles were provided by using HPLC and E.coli growth inhibition on LB agar plates. The prodrug nanoparticle suspensions were spray dried to form low density porous micro-particles for the purpose of aerosol drug delivery. The simultaneous encapsulation of imaging agents and therapeutic agents provides a method for studying the fate of nanoparticles and for medical imaging with treatment. As another example, bifenthrin nanoparticle suspensions with various stabilizers were formulated. The pesticide, bifenthrin, was used to test whether nanoparticles provided an advantage in increasing the effectiveness of pesticide formulations. Larvae mortality with the application of nanoparticle suspension was about 2.5 times of the mortality with the application of bifenthrin mineral oil solution. Nanoparticles at very low bifenthrin concentration showed sustained release for fourteen days.

Effect of a controlled-release albendazole capsule on parasitism and productivity of sheep.

PubMed

Corba, J; Krupicer, I; Legény, J; Juris, P; Veselý, L

1991-11-01

The efficacy of intraruminal albendazole (ABZ) capsules (Profitril-Captec) and the effect of treatment on productivity were studied in 300 ewes infected with gastrointestinal nematodes and the trematode Dicrocoelium dendriticum. Coprological tests revealed that treated animals remained negative for 10 weeks after the administration of capsules. Contamination of pasture with nematode larvae was significantly reduced during the whole experiment. Necropsy of 14 animals (seven treated and seven untreated) showed 96.9-99.2% efficacy against the nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis, while efficacy was 88.5% against D. dendriticum. During the 6 month pasture season (May-October 1989), treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls. Our study confirms the reliability of the ABZ slow-release capsules over 90 days and the positive effect of treatment on nematode contamination of pasture and ewe productivity.

NONOates regulate KCl cotransporter-1 and -3 mRNA expression in vascular smooth muscle cells.

PubMed

Di Fulvio, Mauricio; Lauf, Peter K; Shah, Shalin; Adragna, Norma C

2003-05-01

Nitric oxide (NO) donors regulate KCl cotransport (KCC) activity and cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in sheep erythrocytes and in primary cultures of rat vascular smooth muscle cells (VSMCs), respectively. In this study, we used NONOates as rapid and slow NO releasers to provide direct evidence implicating NO as a regulator of KCC3 gene expression at the mRNA level. In addition, we used the expression of KCC3 mRNA to further investigate the mechanism of action of these NO donors at the cellular level. Treatment of VSMCs with rapid NO releasers, like NOC-5 and NOC-9, as well as with the direct NO-independent soluble guanylyl cyclase (sGC) stimulator YC-1, acutely increased KCC3 mRNA expression in a concentration- and time-dependent manner. The slow NO releaser NOC-18 had no effect on KCC3 gene expression. A specific NO scavenger completely prevented the NONOate-induced KCC3 mRNA expression. Inhibition of sGC with LY-83583 blocked the NONOate- and YC-1-induced KCC3 mRNA expression. This study shows that in primary cultures of rat VSMCs, the fast NO releasers NOC-9 and NOC-5, but not the slow NO releaser NOC-18, acutely upregulate KCC3 mRNA expression in a NO/sGC-dependent manner.

Electrodeposition to construct free-standing chitosan/layered double hydroxides hydro-membrane for electrically triggered protein release.

PubMed

Zhao, Pengkun; Zhao, Yanan; Xiao, Ling; Deng, Hongbing; Du, Yumin; Chen, Yun; Shi, Xiaowen

2017-10-01

In this study, we report the electrodeposition of a chitosan/layered double hydroxides (LDHs) hydro-membrane for protein release triggered by an electrical signal. The electrodeposition was performed in a chitosan and insulin loaded LDHs suspension in the absence of salt. A free-standing chitosan/LDHs hydro-membrane was generated on the electrode with improved mechanical properties, which is dramatically different from the weak hydrogel deposited in the presence of salt. The amount of LDHs in the hydro-membrane affects the optical transmittance and multilayered structure of the hybrid membrane. Compared to the weak chitosan/LDHs hydrogel, the hydro-membrane has a higher insulin loading capacity and the release of insulin is relatively slow. By biasing electrical potentials to the hydro-membrane, the release behavior of insulin can be adjusted accordingly. In addition, the chitosan/LDHs hydro-membrane showed no toxicity to cells. Our results provide a facile method to construct a chitosan/LDHs hybrid multilayered hydro-membrane and suggest the great potential of the hydro-membrane in controlled protein release. Copyright © 2017 Elsevier B.V. All rights reserved.

Photo-crosslinked Biodegradable Elastomers for Controlled Nitric Oxide Delivery

PubMed Central

Wang, Ying; Kibbe, Melina R.; Ameer, Guillermo A.

2013-01-01

The delivery of nitric oxide (NO) has important applications in medicine, especially for procedures that involve the vasculature. We report photo-curable biodegradable poly(diol citrate) elastomers capable of slow release of NO. A methacrylated poly(diol citrate) macromonomer was prepared by polycondensation of citric acid with 1, 8-octanediol or 1, 12-dodecanediol followed by functionalization with 2-aminoethyl methacrylate. A miscible NO donor, diazeniumdiolated N, N-diethyldiethylenetriamine, was synthesized and incorporated into the polymer matrix. An elastomeric network was obtained via photo-polymerization of macromonomers upon UV irradiation within three minutes. Films and tubes of the NO-releasing crosslinked macromonomers exhibited strong tensile strength and radial compressive strength, respectively. They also exhibited cell compatibility and biodegradability in vitro. Sustained NO release under physiological conditions was achieved for at least one week. NO release enhanced the proliferation of human umbilical vein endothelial cells but inhibited the proliferation of human aortic smooth muscle cells. Photo-polymerizable NO-releasing materials provide a new approach for the localized and sustained delivery of NO to treat thrombosis and restenosis in the vasculature. PMID:24707352

Two Ca current components of the receptor current in the electroreceptors of the marine catfish Plotosus.

PubMed

Sugawara, Y

1989-02-01

In the isolated sensory epithelium of the Plotosus electroreceptor, the receptor current has been dissected into inward Ca current, ICa, and superimposed outward transient of Ca-gated K current, IK(Ca). In control saline (170 mM/liter Na), with IK(Ca) abolished by K blockers, ICa declined in two successive exponential phases with voltage-dependent time constants. Double-pulse experiments revealed that the test ICa was partially depressed by prepulses, maximally near voltage levels for the control ICa maximum, which suggests current-dependent inactivation. In low Na saline (80 mM/liter), ICa declined in a single phase with time constants similar to those of the slower phase in control saline. The test ICa was then unaffected by prepulses. The implied presence of two Ca current components, the fast and slow ICa's, were further examined. In control saline, the PSP externally recorded from the afferent nerve showed a fast peak and a slow tonic phase. The double-pulse experiments revealed that IK(Ca) and the peak PSP were similarly depressed, i.e., secondarily to inactivation of the peak current. The steady inward current, however, was unaffected by prolonged prepulses that were stepped to 0 mV, the in situ DC level. Therefore, the fast ICa seems to initiate IK(Ca) and phasic release of transmitter, which serves for phasic receptor responses. The slow ICa may provide persistent active current, which has been shown to maintain tonic receptor operation.

Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers.

PubMed

Cavallaro, Giuseppe; Lazzara, Giuseppe; Lisuzzo, Lorenzo; Milioto, Stefana; Parisi, Filippo

2018-08-10

Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of the PNIPAAM/halloysite based material. In particular, diclofenac release was slowed down above the LCST for PNIPAAM-co-MA/halloysite. Opposite trends occurred for halloysite functionalized with PNIPAAM at the outer surface. This work represents a further step toward the opportunity to extend and control the delivery conditions of active species, which represent a key point in technological applications.

Slow crack growth in glass in combined mode I and mode II loading

NASA Technical Reports Server (NTRS)

Shetty, D. K.; Rosenfield, A. R.

1991-01-01

Slow crack growth in soda-lime glass under combined mode I and mode II loading was investigated in precracked disk specimens in which pure mode I, pure mode II, and various combinations of mode I and mode II were achieved by loading in diametral compression at selected angles with respect to symmetric radial cracks. It is shown that slow crack growth under these conditions can be described by a simple exponential relationship with elastic strain energy release rate as the effective crack-driving force parameter. It is possible to interpret this equation in terms of theoretical models that treat subcritical crack growth as a thermally activated bond-rupture process with an activation energy dependent on the environment, and the elastic energy release rate as the crack-driving force parameter.

Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Jin, Erlei

2011-12-01

Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

Biogenic nanosilica blended by nanofibrillated cellulose as support for slow-release of tebuconazole

NASA Astrophysics Data System (ADS)

Mattos, Bruno D.; Magalhães, Washington L. E.

2016-09-01

Despite the potential application of nanotechnology in the agricultural sector, it is not as competitive as other industrial sectors because these approaches do not demonstrate a sufficient economic return to counterbalance the high production costs. For biocidal purposes, the reduction of the initial costs can be addressed if biogenic nanosilica and nanofibrillated cellulose were used to prepare nanocomposite for further utilization as support for slow-release of tebuconazole. Infrared spectroscopy and thermogravimetric analysis revealed that biocide was entrapped in the cellulose/silica nanocomposites network. The scanning electron microscopy and X-ray microtomography evaluation showed the nanocomposite's microstructure based on irregular shape nanosilica blended by nanofibrillated cellulose in a randomly organized network. Elemental mapping images showed the tebuconazole better dispersed in the composite blended with lower content of cellulose. The nanofibrillated cellulose played an important role in the release rate of the biocide mainly at short-term periods. At 15 days of immersion, the pure biocide had 95 % release compared with 30-45 % release of the tebuconazole loaded in the nanocomposites.

Characterization and optimization of GMO-based gels with long term release for intraarticular administration.

PubMed

Réeff, J; Gaignaux, A; Goole, J; Siepmann, J; Siepmann, F; Jerome, C; Thomassin, J M; De Vriese, C; Amighi, K

2013-07-15

Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release. Copyright © 2013. Published by Elsevier B.V.

Statistical optimization of controlled release microspheres containing cetirizine hydrochloride as a model for water soluble drugs.

PubMed

El-Say, Khalid M; El-Helw, Abdel-Rahim M; Ahmed, Osama A A; Hosny, Khaled M; Ahmed, Tarek A; Kharshoum, Rasha M; Fahmy, Usama A; Alsawahli, Majed

2015-01-01

The purpose was to improve the encapsulation efficiency of cetirizine hydrochloride (CTZ) microspheres as a model for water soluble drugs and control its release by applying response surface methodology. A 3(3) Box-Behnken design was used to determine the effect of drug/polymer ratio (X1), surfactant concentration (X2) and stirring speed (X3), on the mean particle size (Y1), percentage encapsulation efficiency (Y2) and cumulative percent drug released for 12 h (Y3). Emulsion solvent evaporation (ESE) technique was applied utilizing Eudragit RS100 as coating polymer and span 80 as surfactant. All formulations were evaluated for micromeritic properties and morphologically characterized by scanning electron microscopy (SEM). The relative bioavailability of the optimized microspheres was compared with CTZ marketed product after oral administration on healthy human volunteers using a double blind, randomized, cross-over design. The results revealed that the mean particle sizes of the microspheres ranged from 62 to 348 µm and the efficiency of entrapment ranged from 36.3% to 70.1%. The optimized CTZ microspheres exhibited a slow and controlled release over 12 h. The pharmacokinetic data of optimized CTZ microspheres showed prolonged tmax, decreased Cmax and AUC0-∞ value of 3309 ± 211 ng h/ml indicating improved relative bioavailability by 169.4% compared with marketed tablets.

Winter-injury following horticultural treatments to overcome juvenility in citrus seedlings

USDA-ARS?s Scientific Manuscript database

Citrus seedling juvenility delays new hybrid evaluation, slows cultivar release, and slows introgression of new traits. A horticultural program reported to overcome citrus juvenility was tested at the Whitmore Citrus Research Foundation farm (Lake County), using replicated Hirado Buntan x Clementine...

Masking Release in Children and Adults with Hearing Loss When Using Amplification

ERIC Educational Resources Information Center

Brennan, Marc; McCreery, Ryan; Kopun, Judy; Lewis, Dawna; Alexander, Joshua; Stelmachowicz, Patricia

2016-01-01

Purpose: This study compared masking release for adults and children with normal hearing and hearing loss. For the participants with hearing loss, masking release using simulated hearing aid amplification with 2 different compression speeds (slow, fast) was compared. Method: Sentence recognition in unmodulated noise was compared with recognition…

Injectable Silica–Permanganate Gel as a Slow-Release MnO 4 - Source for Groundwater Remediation. Rheological Properties and Release Dynamics

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

Yang, Shuo; Oostrom, Martinus; Truex, Michael J.

2016-01-12

Injectable slow-release permanganate gel (ISRPG), formed by mixing KMnO 4 solution with fumed silica powder, may have a potential application in remediating chlorinated solvent plumes in groundwater. A series of batch, column, and flow cell experiments has been completed to test the gel behavior under a variety of conditions. The experiments have provided information on ISRPG rheology, permanganate (MnO 4 - ) release dynamics and distribution, and trichloroethene (TCE) degradation by ISRPG-released oxidant. The gel possesses remarkable shear thinning characteristics, resulting in a relative low viscosity during mixing, and facilitating its subsurface injection and distribution. Batch tests revealed that MnOmore » 4 - was diffused out from ISRPG into water while the gel did not dissolve or disperse into water but maintained its initial shape. Column experiments showed that MnO 4 - release from ISRPG lasted considerably longer than the release from aqueous solution. TCE degradation by ISRPG-released MnO 4 - was much more effective than that when MnO 4 - was delivered using aqueous solution injection. In two-dimensional flow cell experiments, it was demonstrated that ISRPG slowly released a long-lasting low concentration MnO 4 - plume sufficient for remediation and sustainable in an aquifer for a long period of time.« less

Super water-absorbing new material from chitosan, EDTA and urea.

PubMed

Narayanan, Abathodharanan; Dhamodharan, Raghavachari

2015-12-10

A new, super water-absorbing, material is synthesized by the reaction between chitosan, EDTA and urea and named as CHEDUR. CHEDUR is probably formed through the crosslinking of chitosan molecules (CH) with the EDTA-urea (EDUR) adduct that is formed during the reaction. CHEDUR as well as the other products formed in control reactions are characterized extensively. CHEDUR exhibits a very high water uptake capacity when compared with chitosan, chitosan-EDTA adduct, as well as a commercial diaper material. A systematic study was done to find the optimum composition as well as reaction conditions for maximum water absorbing capacity. CHEDUR can play a vital role in applications that demand the rapid absorption and slow release of water such as agriculture, as a three in one new material for the slow release of urea, water and other metal ions that can be attached through the EDTA component. The other potential advantage of CHEDUR is that it can be expected to degrade in soil based on its chitosan backbone. The new material with rapid and high water uptake could also find potential applications as biodegradable active ingredient of the diaper material. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulation of release kinetics by plasma polymerization of ampicillin-loaded β-TCP ceramics

NASA Astrophysics Data System (ADS)

Labay, C.; Buxadera-Palomero, J.; Avilés, M.; Canal, C.; Ginebra, M. P.

2016-08-01

Beta-tricalcium phosphate (β-TCP) bioceramics are employed in bone repair surgery. Their local implantation in bone defects puts them in the limelight as potential materials for local drug delivery. However, obtaining suitable release patterns fitting the required therapeutics is a challenge. Here, plasma polymerization of ampicillin-loaded β-TCP is studied for the design of a novel antibiotic delivery system. Polyethylene glycol-like (PEG-like) coating of β-TCP by low pressure plasma polymerization was performed using diglyme as precursor, and nanometric PEG-like layers were obtained by simple and double plasma polymerization processes. A significant increase in hydrophobicity, and the presence of plasma polymer was visible on the surface by SEM and quantified by XPS. As a main consequence of the plasma polymerisation, the release kinetics were successfully modified, avoiding burst release, and slowing down the initial rate of release leading to a 4.5 h delay in reaching the same antibiotic release percentage, whilst conservation of the activity of the antibiotic was simultaneously maintained. Thus, plasma polymerisation on the surface of bioceramics may be a good strategy to design controlled drug delivery matrices for local bone therapies.

Slow slip events and seismic tremor at circum-Pacific subduction zones

NASA Astrophysics Data System (ADS)

Schwartz, Susan Y.; Rokosky, Juliana M.

2007-09-01

It has been known for a long time that slip accompanying earthquakes accounts for only a fraction of plate tectonic displacements. However, only recently has a fuller spectrum of strain release processes, including normal, slow, and silent earthquakes (or slow slip events) and continuous and episodic slip, been observed and generated by numerical simulations of the earthquake cycle. Despite a profusion of observations and modeling studies the physical mechanism of slow slip events remains elusive. The concurrence of seismic tremor with slow slip episodes in Cascadia and southwestern Japan provides insight into the process of slow slip. A perceived similarity between subduction zone and volcanic tremor has led to suggestions that slow slip involves fluid migration on or near the plate interface. Alternatively, evidence is accumulating to support the notion that tremor results from shear failure during slow slip. Global observations of the location, spatial extent, magnitude, duration, slip rate, and periodicity of these aseismic slip transients indicate significant variation that may be exploited to better understand their generation. Most slow slip events occur just downdip of the seismogenic zone, consistent with rate- and state-dependent frictional modeling that requires unstable to stable transitional properties for slow slip generation. At a few convergent margins the occurrence of slow slip events within the seismogenic zone makes it highly likely that transitions in frictional properties exist there and are the loci of slow slip nucleation. Slow slip events perturb the surrounding stress field and may either increase or relieve stress on a fault, bringing it closer to or farther from earthquake failure, respectively. This paper presents a review of slow slip events and related seismic tremor observed at plate boundaries worldwide, with a focus on circum-Pacific subduction zones. Trends in global observations of slow slip events suggest that (1) slow slip is a common phenomena observed at almost all subduction zones with instrumentation capable of recording it, (2) different frictional properties likely control fast versus slow slip, (3) the depth range of slow slip may be related to the thermal properties of the plate interface, and (4) the equivalent seismic moment of slow slip events is proportional to their duration (Moατ), different from the Moατ3 scaling observed for earthquakes.

Slow Release of Plant Volatiles Using Sol-Gel Dispensers.

PubMed

Bian, L; Sun, X L; Cai, X M; Chen, Z M

2014-12-01

The black citrus aphid, also known as the tea aphid, (Toxoptera aurantii Boyer) attacks economically important crops, including tea (Camellia sinensis (L.) O. Kuntze). In the current study, silica sol-gel formulations were screened to find one that could carry and release C. sinensis plant volatiles to lure black citrus aphids in a greenhouse. The common plant volatile trans-2-hexen-1-al was used as a model molecule to screen for suitable sol-gel formulations. A zNose (Electronic Sensor Technology, Newbury Park, CA) transportable gas chromatograph was used to continuously monitor the volatile emissions. A sol-gel formulation containing tetramethyl orthosilicate and methyltrimethoxysilane in an 8:2 (vol:vol) ratio was selected to develop a slow-release dispenser. The half-life of trans-2-hexen-1-al in the sol-gel dispenser increased slightly with the volume of this compound in the dispenser. Ten different volatiles were tested in the sol-gel dispenser. Alcohols of 6-10 carbons had the longest half-lives (3.01-3.77 d), while esters of 6-12 carbons had the shortest (1.53-2.28 d). Release of these volatiles from the dispensers could not be detected by the zNose after 16 d (cis-3-hexenyl acetate) to 26 d (3,7-dimethylocta-1,6-dien-3-ol). In greenhouse experiments, trans-2-hexen-1-al and cis-3-hexen-1-ol released from the sol-gel dispensers attracted aphids for ≍17 d, and release of these volatiles could not be detected by the zNose after ≍24 d. The sol-gel dispensers performed adequately for the slow release of plant volatiles to trap aphids in the greenhouse. © 2014 Entomological Society of America.

Platelet-derived Growth-factor-releasing Aligned Collagen-nanoparticle Fibers Promote the Proliferation and Tenogenic Differentiation of Adipose-derived Stem Cells

DTIC Science & Technology

2013-11-27

lar to the slow axis appear yellow [19]. To observe the morphology of aligned collagen fibril, fibers were dehydrated via graded series of ethanols (70...Invitrogen) displayed prolifer- ating cell numbers. 2.5. Effect of aligned collagen–NP fibers on cell morphology and proliferation (7 days’ culture) A...loaded with PDGF than in the well with fibers that contained only empty NPs (control). 3.5. ADSCs cell proliferation and morphology on aligned collagen–NP

Indirect coupling of phosphate release to de novo tension generation during muscle contraction.

PubMed Central

Davis, J S; Rodgers, M E

1995-01-01

A key question in muscle contraction is how tension generation is coupled to the chemistry of the actomyosin ATPase. Biochemical and mechanochemical experiments link tension generation to a change in structure associated with phosphate release. Length-jump and temperature-jump experiments, on the other hand, implicate phase 2slow, a significantly faster, markedly strain-sensitive kinetic process in tension generation. We use a laser temperature jump to probe the kinetics and mechanism of tension generation in skinned rabbit psoas fibers--an appropriate method since both phosphate release and phase 2slow are readily perturbed by temperature. Kinetics characteristic of the structural change associated with phosphate release are observed only when phosphate is added to fibers. When present, it causes a reduction in fiber tension; otherwise, no force is generated when it is perturbed. We therefore exclude this step from tension generation. The kinetics of de novo tension generation by the temperature-jump equivalent of phase 2slow appear unaffected by phosphate binding. We therefore propose that phosphate release is indirectly coupled to de novo tension generation via a steady-state flux through an irreversible step. We conclude that tension generation occurs in the absence of chemical change as the result of an entropy-driven transition between strongly bound crossbridges in the actomyosin-ADP state. The mechanism resembles the operation of a clock, with phosphate release providing the energy to tension the spring, and the irreversible step functions as the escapement mechanism, which is followed in turn by tension generation as the movement of the hands. Images Fig. 6 PMID:7479824

Slow glucose release property of enzyme-synthesized highly branched maltodextrins differs among starch sources.

PubMed

Kittisuban, Phatcharee; Lee, Byung-Hoo; Suphantharika, Manop; Hamaker, Bruce R

2014-07-17

Seven types of starch (waxy corn, normal corn, waxy rice, normal rice, waxy potato, normal potato, and tapioca) were selected to produce slowly digestible maltodextrins by enzymatic modification using a previously developed procedure. Branching enzyme (BE) alone and in combination with β-amylase (BA) were used to increase the amount of α-1,6 branching points, which are slowly hydrolyzed by mucosal α-glucosidases in the small intestine. The enzymatic treatments of all starches resulted in a reduction of the debranched linear chain length distribution and weight-average molecular weight. After α-amylolysis of the enzymatically synthesized-maltodextrins, the proportion of branched α-limit dextrins increased, and consequently a reduction in rate of glucose release by rat intestinal α-glucosidases in vitro. Among the samples, enzyme-modified waxy starches had a more pronounced effect on an increase in the slow digestion property than normal starches. These enzyme-modified maltodextrins show potential as novel functional foods by slowing digestion rate to attain extended glucose release. Copyright © 2014 Elsevier Ltd. All rights reserved.

Distinguishing splanchnic nerve and chromaffin cell stimulation in mouse adrenal slices with fast-scan cyclic voltammetry

PubMed Central

Walsh, Paul L.; Petrovic, Jelena

2011-01-01

Electrical stimulation is an indispensible tool in studying electrically excitable tissues in neurobiology and neuroendocrinology. In this work, the consequences of high-intensity electrical stimulation on the release of catecholamines from adrenal gland slices were examined with fast-scan cyclic voltammetry at carbon fiber microelectrodes. A biphasic signal, consisting of a fast and slow phase, was observed when electrical stimulations typically used in tissue slices (10 Hz, 350 μA biphasic, 2.0 ms/phase pulse width) were applied to bipolar tungsten-stimulating electrodes. This signal was found to be stimulation dependent, and the slow phase of the signal was abolished when smaller (≤250 μA) and shorter (1 ms/phase) stimulations were used. The slow phase of the biphasic signal was found to be tetrodotoxin and hexamethonium independent, while the fast phase was greatly reduced using these pharmacological agents. Two different types of calcium responses were observed, where the fast phase was abolished by perfusion with a low-calcium buffer while both the fast and slow phases could be modulated when Ca2+ was completely excluded from the solution using EGTA. Perfusion with nifedipine resulted in the reduction of the slow catecholamine release to 29% of the original signal, while the fast phase was only decreased to 74% of predrug values. From these results, it was determined that high-intensity stimulations of the adrenal medulla result in depolarizing not only the splanchnic nerves, but also the chromaffin cells themselves resulting in a biphasic catecholamine release. PMID:21048165

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission.

PubMed

Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

2017-02-15

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT 2A and 5-HT 1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT 1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission. Copyright © 2017 Sengupta et al.

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission

PubMed Central

Bannerman, David M.

2017-01-01

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10–20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission. PMID:28087766

A detailed view of microparticle formation by in-process monitoring of the glass transition temperature.

PubMed

Vay, Kerstin; Frieß, Wolfgang; Scheler, Stefan

2012-06-01

Biodegradable poly(D,L-lactide-co-glycolide) microspheres were prepared by a well-controlled emulsion solvent extraction/evaporation process. The objective of this study was to investigate how drug release can be modified by changing the morphology of the polymer matrix. The matrix structure was controlled by the preparation temperature which was varied between 10 and 35 °C, thus changing the 4 weeks release pattern from almost linear kinetics to a sigmoidal profile with a distinct lag phase and furthermore decreasing the encapsulation efficiency. By monitoring the glass transition temperature during the extraction process, it was shown that the preparation temperature determines the particle morphology by influencing the time span in which the polymer chains were mobile and flexible during the extraction process. Further factors determining drug release were found to be the molecular weight of the polymer and the rate of solvent removal. The latter, however, has also influence on the encapsulation efficiency with slow removal causing a higher drug loss. A secondary modification of the outer particle structure could be achieved by ethanolic post-treatment of the particles, which caused an extension of the lag phase and subsequently an accelerated drug release. Copyright © 2012. Published by Elsevier B.V.

Hollow polycaprolactone composite fibers for controlled magnetic responsive antifungal drug release.

PubMed

Wang, Baolin; Zheng, Hongxia; Chang, Ming-Wei; Ahmad, Zeeshan; Li, Jing-Song

2016-09-01

Hollow magnetic fibers for trigger based drug release were synthesized using one-step co-axial electrospinning (COX-ES). This was achieved by encapsulating the antifungal active 'ketoconazole' (KCZ) and iron oxide (Fe3O4) nanoparticles (NPs) in composite form within the core shell polymeric matrix material (polycaprolactone, PCL) during the COX-ES process. Dimethyl silicone oil was used as the inner core (liquid) of co-flowing solutions, which subsequently perfused out of the two-phase electrospun microstructures to form hollow fibers. Resulting drug-loaded magnetic hollow fibers were characterized using optical microscopy, scanning electron microscopy and Fourier Transform Infra-Red. The tensile strength and magnetization properties of composite fibers were also assessed. KCZ drug concentration in electrospinning solutions strongly influenced resulting fiber morphology, drug loading efficiency and release. Expedited drug release during a slow-sustained phase was demonstrated through the application of an auxiliary magnetic field. Variations in tensile strength (∼1.3-6.3MPa) were due to composite fiber components compromising polymer chain integrity. In-vitro cell studies (using human cervical carcinoma cell lines) demonstrated fiber biocompatibility. The present study demonstrates the potential application of magnetic hollow fibers for controlled treatment of fungal infections and antimicrobial indications. Copyright © 2016 Elsevier B.V. All rights reserved.

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo.

PubMed

Santos, Daniel; Giudetti, Guido; Micera, Silvestro; Navarro, Xavier; Del Valle, Jaume

2016-04-01

Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

A new slow darkening pinto bean with improved agronomic performance: Registration of ‘ND-Palomino’

USDA-ARS?s Scientific Manuscript database

ND-Palomino slow darkening pinto is a new cultivar jointly developed by the United States Department of Agriculture, Agricultural Research Service (USDA-ARS), and North Dakota State University (NDSU) and released by the North Dakota Agricultural Experimental Station (NDAES). ND-Palomino has shown co...

Xylan-Modified-Based Hydrogels with Temperature/pH Dual Sensitivity and Controllable Drug Delivery Behavior

PubMed Central

Kong, Wei-Qing; Gao, Cun-Dian; Hu, Shu-Feng; Ren, Jun-Li; Zhao, Li-Hong; Sun, Run-Cang

2017-01-01

Among the natural macromolecules potentially used as the scaffold material in hydrogels, xylan has aroused great interest in many fields because of its biocompatibility, low toxicity, and biodegradability. In this work, new pH and thermoresponsive hydrogels were prepared by the cross-linking polymerization of maleic anhydride-modified xylan (MAHX) with N-isopropylacrylamide (NIPAm) and acrylic acid (AA) under UV irradiation to form MAHX-g-P(NIPAm-co-AA) hydrogels. The pore volume, the mechanical properties, and the release rate for drugs of hydrogels could be controlled by the degree of substitution of MAHX. These hydrogels were characterized by swelling ability, lower critical solution temperature (LCST), Fourier-transform infrared (FTIR), and SEM. Furthermore, the cumulative release rate was investigated for acetylsalicylic acid and theophylline, as well as the cytocompatibility MAHX-based hydrogels. Results showed that MAHX-based hydrogels exhibited excellent swelling–deswelling properties, uniform porous structure, and the temperature/pH dual sensitivity. In vitro, the cumulative release rate of acetylsalicylic acid for MAHX-based hydrogels was higher than that for theophylline, and in the gastrointestinal sustained drug release study, the acetylsalicylic acid release rate was extremely slow during the initial 3 h in the gastric fluid (24.26%), and then the cumulative release rate reached to 90.5% after sustained release for 5 h in simulated intestinal fluid. The cytotoxicity experiment demonstrated that MAHX-based hydrogels could promote cell proliferation and had satisfactory biocompatibility with NIH3T3 cells. These results indicated that MAHX-based hydrogels, as new drug carriers, had favorable behavior for intestinal-targeted drug delivery. PMID:28772664

Marine structure derived calcium phosphate-polymer biocomposites for local antibiotic delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L; Milthorpe, Bruce

2015-01-20

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.

Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery

PubMed Central

Macha, Innocent J.; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L.; Milthorpe, Bruce

2015-01-01

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery. PMID:25608725

Effects of pH, Temperature, Dissolved Oxygen, and Flow Rate on Phosphorus Release Processes at the Sediment and Water Interface in Storm Sewer

PubMed Central

Li, Haiyan; Li, Mingyi; Zhang, Xiaoran

2013-01-01

The effects of pH, temperature, dissolved oxygen (DO), and flow rate on the phosphorus (P) release processes at the sediment and water interface in rainwater pipes were investigated. The sampling was conducted in a residential storm sewer of North Li Shi Road in Xi Cheng District of Beijing on August 3, 2011. The release rate of P increased with the increase of pH from 8 to 10. High temperature is favorable for the release of P. The concentration of total phosphorus (TP) in the overlying water increased as the concentration of DO decreased. With the increase of flow rate from 0.7 m s−1 to 1.1 m s−1, the concentration of TP in the overlying water increased and then tends to be stable. Among all the factors examined in the present study, the flow rate is the primary influence factor on P release. The cumulative amount of P release increased with the process of pipeline runoff in the rainfall events with high intensities and shorter durations. Feasible measures such as best management practices and low-impact development can be conducted to control the P release on urban sediments by slowing down the flow rate. PMID:24349823

Slow release of NO by microporous titanosilicate ETS-4.

PubMed

Pinto, Moisés L; Rocha, João; Gomes, José R B; Pires, João

2011-04-27

A novel approach to designing nitric oxide (NO) storage and releasing microporous agents based on very stable, zeolite-type silicates possessing framework unsaturated transition-metal centers has been proposed. This idea has been illustrated with ETS-4 [Na(9)Si(12)Ti(5)O(38)(OH)·xH(2)O], a titanosilicate that displays excellent NO adsorption capacity and a slow releasing kinetics. The performance of these materials has been compared to the performance of titanosilicate ETS-10, [(Na,K)(2)Si(5)TiO(13)·xH(2)O], of benchmark zeolites mordenite and CaA, and of natural and pillared clays. DFT periodic calculations have shown that the presence of water in the pores of ETS-4 promotes the NO adsorption at the unsaturated (pentacoordinated) Ti(4+) framework ions.

The 2012 Mw5.6 earthquake in Sofia seismogenic zone - is it a slow earthquake

NASA Astrophysics Data System (ADS)

Raykova, Plamena; Solakov, Dimcho; Slavcheva, Krasimira; Simeonova, Stela; Aleksandrova, Irena

2017-04-01

Recently our understanding of tectonic faulting has been shaken by the discoveries of seismic tremor, low frequency earthquakes, slow slip events, and other models of fault slip. These phenomenas represent models of failure that were thought to be non-existent and theoretically impossible only a few years ago. Slow earthquakes are seismic phenomena in which the rupture of geological faults in the earth's crust occurs gradually without creating strong tremors. Despite the growing number of observations of slow earthquakes their origin remains unresolved. Studies show that the duration of slow earthquakes ranges from a few seconds to a few hundred seconds. The regular earthquakes with which most people are familiar release a burst of built-up stress in seconds, slow earthquakes release energy in ways that do little damage. This study focus on the characteristics of the Mw5.6 earthquake occurred in Sofia seismic zone on May 22nd, 2012. The Sofia area is the most populated, industrial and cultural region of Bulgaria that faces considerable earthquake risk. The Sofia seismic zone is located in South-western Bulgaria - the area with pronounce tectonic activity and proved crustal movement. In 19th century the city of Sofia (situated in the centre of the Sofia seismic zone) has experienced two strong earthquakes with epicentral intensity of 10 MSK. During the 20th century the strongest event occurred in the vicinity of the city of Sofia is the 1917 earthquake with MS=5.3 (I0=7-8 MSK64).The 2012 quake occurs in an area characterized by a long quiescence (of 95 years) for moderate events. Moreover, a reduced number of small earthquakes have also been registered in the recent past. The Mw5.6 earthquake is largely felt on the territory of Bulgaria and neighbouring countries. No casualties and severe injuries have been reported. Mostly moderate damages were observed in the cities of Pernik and Sofia and their surroundings. These observations could be assumed indicative for a very low rupture velocity. The low rupture velocity can mean slow-faulting, which brings to slow release of accumulated seismic energy. The slow release energy does principally little to moderate damages. Additionally wave form of the earthquake shows low frequency content of P-waves (the maximum P-wave is at 1.19 Hz) and the specific P- wave displacement spectral is characterise with not expressed spectrum plateau and corner frequency. These and other signs suggest us to the conclusion, that the 2012 Mw5.6 earthquake can be considered as types of slow earthquake, like a low frequency quake. The study is based on data from Bulgarian seismological network (NOTSSI), the local network (LSN) deployed around Kozloduy NPP and System of Accelerographs for Seismic Monitoring of Equipment and Structures (SASMES) installed in the Kozloduy NPP. NOTSSI jointly with LSN and SASMES provide reliable information for multiple studies on seismicity in regional scale.

Is the S-Web the Secret to Observed Heliospheric Particle Distributions?

NASA Astrophysics Data System (ADS)

Higginson, A. K.; Antiochos, S. K.; DeVore, C. R.; Daldorff, L. K. S.; Wyper, P. F.; Ukhorskiy, A. Y.; Sorathia, K.

2017-12-01

Particle transport in the heliosphere remains an unsolved problem across energy regimes. Observations of slow solar wind show that plasma escapes from the closed-field corona, but ends up far away from the heliospheric current sheet, even though the release mechanisms are expected to occur at the HCS. Similarly, some impulsive SEP events have extreme longitudinal extents of 100 degrees or more. Recent theoretical and numerical work has shown that interchange reconnection near a coronal-hole corridor can release plasma from originally closed magnetic field lines into a large swath spread across the heliosphere, forming what is known as an S-Web arc. This is a promising mechanism for explaining both the slow solar wind, with its large latitudinal extent, and impulsive SEP particles, with their large longitudinal extent. Here we compute, for the first time, the dynamics of the S-Web when the photospheric driver is applied over a large portion of the solar surface compared to the scale of the driving. We examine the time scales for the interchange reconnection and compute the angular extent of the plasma released, in the context of understanding both the slow solar wind and flare-accelerated SEPs. We will make predictions for Solar Orbiter and Parker Solar Probe and discuss how these new measurements will help to both pinpoint the source of the slow solar wind and illuminate the transport mechanisms of wide-spread impulsive SEP events.

Safe and efficient pH sensitive tumor targeting modified liposomes with minimal cytotoxicity.

PubMed

Wang, Lilin; Geng, Di; Su, Haijia

2014-11-01

Incorporating the pH-sensitivity of octylamine grafted poly aspartic acid (PASP) with the biocompatibility of liposomes, a novel pH sensitive drug delivery system, octylamine-graft-PASP (PASP-g-C8) modified liposomes (OPLPs), was obtained. Since hydrophobic chains have been grafted into PASP backbones, the octylamine chain could act as the "anchor" to implant onto liposomes. The structure of PASP-g-C8, involving long-chain and hydrophobic anchors can significantly enhance the stability of the drug carrier. The shortcoming of single PASP chain modified liposomes (PLPs), that cannot sustain a slow and controlled release especially in a physiological pH solution (resembling normal tissues of pH 7.4) is thus overcome. Drug release experiments were carried out and the result showed that OPLPs sustained a slow and steady release in comparison with PLPs in the physiological pH 7.4 environment. However, OPLPs can provide a fast release in subacid environment (pH 5.0 of resembled tumor tissues). The results of diameter analysis and zeta potential demonstrated that OPLPs presented a larger diameter and higher electronegativity. Furthermore, in the "chain-anchor" structure of PASP-g-C8, the degree of substitution (DS) of the "anchor" is a remarkable factor to alter the pH-sensitivity of OPLPs. The in vitro tumor inhibition and cell toxicity studies revealed that tumor cells treated with OPLPs survived only 35.0% after 48 h whereas normal cells survived 100% in the same condition. The pH sensitive OPLPs are promising tumor targeting drug delivery with high tumor inhibition and insignificant cytotoxicity. Copyright © 2014. Published by Elsevier B.V.

Development of a slow non-viral DNA release system from PDLLA scaffolds fabricated using a supercritical CO2 technique.

PubMed

Heyde, Mieke; Partridge, Kris A; Howdle, Steven M; Oreffo, Richard O C; Garnett, Martin C; Shakesheff, Kevin M

2007-10-15

Polyamidoamine polymers (PAA) comprising methylene-bisacrylamide/dimethylethylene-diamine monomers were synthesized, complexed with DNA and incorporated into porous P(DL)LA scaffolds by using a supercritical CO(2) (scCO(2)) technique. Scaffolds were made in a dry state consequently there was a need to lyophilize the complexes. A statistically significant reduction of the transfection efficiency was observed in the absence of trehalose when compared to the original complex after freeze-drying. Increasing concentrations (0-10% w/v) of trehalose were added to the complex prior to freeze-drying. Structure dependent differences in DNA binding were evaluated by gel electrophoresis and thermal transition analysis. TEM and PCS showed aggregate formation after freeze-drying without trehalose. Scaffolds were characterized by pore sizes of 173 +/- 73 microm and a porosity of 71%. The transfection potential of the released DNA was investigated by seeding scaffolds with A549 cells and following firefly luciferase as a marker gene after 48 h exposure. Low but continuous levels of transfection were observed for PAA complexes during a 60-day study. Complexes made with Lipofectaminetrade mark gave initially higher levels of DNA release but no further expression was seen after 40 days. Uncomplexed DNA showed background levels of transfection. Culturing cells on 3D scaffolds showed a benefit in retention of transfection activity with time compared to 2D controls. Transfection levels could be increased when cells were grown in OptiMEM. This study demonstrated that PAA/DNA complexes incorporated into a P(DL)LA scaffold made by using scCO(2) processing exhibited a slow release and extended gene expression profile. Copyright 2007 Wiley Periodicals, Inc.

Levonorgestrel-releasing intrauterine device in the treatment of abnormal uterine bleeding: a 6- and 12-month morphological and clinical follow-up.

PubMed

Palmara, Vittorio; Sturlese, Emanuele; Villari, Daniela; Giacobbe, Valentina; Retto, Annalisa; Santoro, Giuseppe

2013-08-01

Abnormal uterine bleeding is defined as any alteration in the pattern or volume of menstrual blood flow, and it is preferably treated using hysterectomy, endometrial destruction or the levonorgestrel-releasing intrauterine system (Mirena(®) ). Recently, it has been demonstrated that studies of Mirena(®) were generally small and consequently imprecise. Our study was aimed at assessing the effects of a slow-release levonorgestrel (20 μg/day) intrauterine device in fertile and postmenopausal women experiencing abnormal uterine bleeding that did not respond to traditional medical management. A total of 40 women, of whom 24 were of reproductive capacity and 16 were postmenopausal, were enrolled in the trial. Removal of the intrauterine device was required for only 2 of the 24 fertile women and for only 3 of the 16 postmenopausal women. After 6 and 12 months of treatment, the remaining women were clinically evaluated and underwent ultrasound and hysteroscopy using biopsy specimens as a control. The EuroQol Group EQ-5D questionnaire was used for evaluation of quality of life. The device showed good tolerability and efficacy. It resulted in a reduction in the endometrial mucosal thickness with a regression of bleeding and collateral effects, which were more evident after 12 months of treatment. A positive effect of the device on the woman's quality of life was demonstrated. The slow-release levonorgestrel intrauterine device may be a valid therapeutic tool for treating basic symptomatology and increasing quality of life in women with abnormal uterine bleeding. © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Shift in Mass Transfer of Wastewater Contaminants from Microplastics in the Presence of Dissolved Substances.

PubMed

Seidensticker, Sven; Zarfl, Christiane; Cirpka, Olaf A; Fellenberg, Greta; Grathwohl, Peter

2017-11-07

In aqueous environments, hydrophobic organic contaminants are often associated with particles. Besides natural particles, microplastics have raised public concern. The release of pollutants from such particles depends on mass transfer, either in an aqueous boundary layer or by intraparticle diffusion. Which of these mechanisms controls the mass-transfer kinetics depends on partition coefficients, particle size, boundary conditions, and time. We have developed a semianalytical model accounting for both processes and performed batch experiments on the desorption kinetics of typical wastewater pollutants (phenanthrene, tonalide, and benzophenone) at different dissolved-organic-matter concentrations, which change the overall partitioning between microplastics and water. Initially, mass transfer is externally dominated, while finally, intraparticle diffusion controls release kinetics. Under boundary conditions typical for batch experiments (finite bath), desorption accelerates with increasing partition coefficients for intraparticle diffusion, while it becomes independent of partition coefficients if film diffusion prevails. On the contrary, under field conditions (infinite bath), the pollutant release controlled by intraparticle diffusion is not affected by partitioning of the compound while external mass transfer slows down with increasing sorption. Our results clearly demonstrate that sorption/desorption time scales observed in batch experiments may not be transferred to field conditions without an appropriate model accounting for both the mass-transfer mechanisms and the specific boundary conditions at hand.

Factors Affecting the Design of Slow Release Formulations of Herbicides Based on Clay-Surfactant Systems. A Methodological Approach

PubMed Central

Galán-Jiménez, María del Carmen; Mishael, Yael-Golda; Nir, Shlomo; Morillo, Esmeralda; Undabeytia, Tomás

2013-01-01

A search for clay-surfactant based formulations with high percentage of the active ingredient, which can yield slow release of active molecules is described. The active ingredients were the herbicides metribuzin (MZ), mesotrione (MS) and flurtamone (FL), whose solubilities were examined in the presence of four commercial surfactants; (i) neutral: two berols (B048, B266) and an alkylpolyglucoside (AG6202); (ii) cationic: an ethoxylated amine (ET/15). Significant percent of active ingredient (a.i.) in the clay/surfactant/herbicide formulations could be achieved only when most of the surfactant was added as micelles. MZ and FL were well solubilized by berols, whereas MS by ET/15. Sorption of surfactants on the clay mineral sepiolite occurred mostly by sorption of micelles, and the loadings exceeded the CEC. Higher loadings were determined for B266 and ET/15. The sorption of surfactants was modeled by using the Langmuir-Scatchard equation which permitted the determination of binding coefficients that could be used for further predictions of the sorbed amounts of surfactants under a wide range of clay/surfactant ratios. A possibility was tested of designing clay-surfactant based formulations of certain herbicides by assuming the same ratio between herbicides and surfactants in the formulations as for herbicides incorporated in micelles in solution. Calculations indicated that satisfactory FL formulations could not be synthesized. The experimental fractions of herbicides in the formulations were in agreement with the predicted ones for MS and MZ. The validity of this approach was confirmed in in vitro release tests that showed a slowing down of the release of a.i. from the designed formulations relative to the technical products. Soil dissipation studies with MS formulations also showed improved bioactivity of the clay-surfactant formulation relative to the commercial one. This methodological approach can be extended to other clay-surfactant systems for encapsulation and slow release of target molecules of interest. PMID:23527087

Biocompatibility and antifibrotic effect of UV-cross-linked hyaluronate as a release-system for tranilast after trabeculectomy in a rabbit model--a pilot study.

PubMed

Spitzer, Martin S; Sat, Macarena; Schramm, Charlotte; Schnichels, Sven; Schultheiss, Maximilian; Yoeruek, Efdal; Dzhelebov, Dimitar; Szurman, Peter

2012-06-01

To analyze the release kinetics and the clinical and histological effects of UV-cross-linked hyaluronic acid as a release-system for the transforming growth factor β-2 antagonist tranilast with anti-phlogistic properties on intraocular pressure after trabeculectomy in an aggressive scarring animal model. Hyaluronate acid was UV-cross linked and loaded with tranilast. The release of tranilast into a buffered salt solution was assessed spectrophotometrically. Glaucoma filtration surgery, similar to that performed in clinical practice, was performed on chinchilla rabbits. The rabbits were divided in 3 groups. (Group A: trabeculectomy alone, group B: trabeculectomy with a cross-linked hyaluronic acid gel preparation and group C: trabeculectomy with cross-linked hyaluronic gel preparation mixed with tranilast). Antifibrotic efficacy was established by clinical response and histologic examination. The cross-linked gels released tranilast for up to 26 h. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. Both the gel preparation alone and the gel preparation mixed with tranilast were well tolerated in vivo. No adverse effects such as inflammation, corneal toxicity or blurring of the optical media were observed. The intraocular pressure reached preoperative levels within 9 days after surgery in control animals and group B, but remained significantly reduced (p = 0.00016) in the group with tranilast until day 22. The data of this pilot study suggest that the intraoperative application of UV-crossed linked hyaluronic acid used as a slow release system for tranilast may improve the surgical outcome of glaucoma filtration surgery.

Effect of food characteristics, storage conditions, and electron beam irradiation on active agent release from polyamide-coated LDPE films.

PubMed

Han, J; Castell-Perez, M E; Moreira, R G

2008-03-01

We investigated the effect of electron beam irradiation, storage conditions, and model food pH on the release characteristics of trans-cinnamaldehyde incorporated into polyamide-coated low-density polyethylene (LDPE) films. Active agent release rate on irradiated films (up to 20.0 kGy) decreased by 69% compared with the nonirradiated controls, from 0.252 to 0.086 microg/mL/h. Storage temperature (4, 21, and 35 degrees C) and pH (4, 7, and 10) of the food simulant solutions (10% aqueous ethanol) affected the release rate of trans-cinnamaldehyde. As expected, antimicrobial release rate decreased to 0.013 microg/mL/h at the refrigerated temperature (4 degrees C) compared to the higher temperatures (0.029 and 0.035 microg/mL/h at 21 and 35 degrees C). The fastest release rate occurred when exposed to the acidic food simulant solution (pH 4). In aqueous solution, trans-cinnamaldehyde was highly unstable to ionizing radiation, with loss in concentration from 24.50 to 1.36 microg/mL after exposure to 2.0 kGy. Fourier transform infrared (FTIR) analysis revealed that exposure to ionizing radiation up to 10.0 kGy did not affect the structural conformation of LDPE/polyamide films and the trans-cinnamaldehyde in the films, though it induced changes in the functional group of trans-cinnamaldehyde when dose increased up to 20.0 kGy. Studies with a radiation-stable compound (naphthalene) showed that ionizing radiation induced the crosslinking in polymer networks of LDPE/polyamide film and caused slow and gradual release of the compound. This study demonstrated that irradiation serves as a controlling factor for release of active compounds, with potential applications in the development of antimicrobial packaging systems.

Water- and Fertilizer-Integrated Hydrogel Derived from the Polymerization of Acrylic Acid and Urea as a Slow-Release N Fertilizer and Water Retention in Agriculture.

PubMed

Cheng, Dongdong; Liu, Yan; Yang, Guiting; Zhang, Aiping

2018-05-31

To reduce the preparation cost of superabsorbent and improve the N release rate at the same time, a novel low-cost superabsorbent (SA) with the function of N slow release was prepared by chemical synthesis with neutralized acrylic acid (AA), urea, potassium persulfate (KPS), and N, N'-methylenebis(acrylamide) (MBA). The order of influence factors on the water absorbency property was determined by an orthogonal L 18 (3) 7 experiment. On the basis of the optimization results of the orthogonal experiment, the effects of a single factor on the water absorption were investigated, and the highest water absorbency (909 g/g) was achieved for the conditions of 1.0 mol urea/mol AA ratio, 100% of AA neutralized, K + , 1.5% KPS to AA mass fraction, 0.02% MBA to AA mass fraction, 45 °C reaction temperature, and 4.0 h reaction time. The optimal sample was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Swelling behaviors of the superabsorbent were investigated in distilled water and various soil and salt solutions. The water-release kinetics of SA in different negative pressures and soils were systematically investigated. Additionally, the maize seed germination in various types of soil with different amounts of SA was proposed, and the N could release 3.71% after being incubated in distilled water for 40 days. After 192 h, the relative water content of SA-treated sandy loam, loam, and paddy soil were 42, 56, and 45%, respectively. All of the results in this work showed that SA had good water retention and slow N-release properties, which are expected to have potential applications in sustainable modern agriculture.

Moderate Cortical Cooling Eliminates Thalamocortical Silent States during Slow Oscillation.

PubMed

Sheroziya, Maxim; Timofeev, Igor

2015-09-23

Reduction in temperature depolarizes neurons by a partial closure of potassium channels but decreases the vesicle release probability within synapses. Compared with cooling, neuromodulators produce qualitatively similar effects on intrinsic neuronal properties and synapses in the cortex. We used this similarity of neuronal action in ketamine-xylazine-anesthetized mice and non-anesthetized mice to manipulate the thalamocortical activity. We recorded cortical electroencephalogram/local field potential (LFP) activity and intracellular activities from the somatosensory thalamus in control conditions, during cortical cooling and on rewarming. In the deeply anesthetized mice, moderate cortical cooling was characterized by reversible disruption of the thalamocortical slow-wave pattern rhythmicity and the appearance of fast LFP spikes, with frequencies ranging from 6 to 9 Hz. These LFP spikes were correlated with the rhythmic IPSP activities recorded within the thalamic ventral posterior medial neurons and with depolarizing events in the posterior nucleus neurons. Similar cooling of the cortex during light anesthesia rapidly and reversibly eliminated thalamocortical silent states and evoked thalamocortical persistent activity; conversely, mild heating increased thalamocortical slow-wave rhythmicity. In the non-anesthetized head-restrained mice, cooling also prevented the generation of thalamocortical silent states. We conclude that moderate cortical cooling might be used to manipulate slow-wave network activity and induce neuromodulator-independent transition to activated states. Significance statement: In this study, we demonstrate that moderate local cortical cooling of lightly anesthetized or naturally sleeping mice disrupts thalamocortical slow oscillation and induces the activated local field potential pattern. Mild heating has the opposite effect; it increases the rhythmicity of thalamocortical slow oscillation. Our results demonstrate that slow oscillation can be influenced by manipulations to the properties of cortical neurons without changes in neuromodulation. Copyright © 2015 the authors 0270-6474/15/3513006-14$15.00/0.

Extending Time Profile of Morphine-Induced Analgesia Using a Chitosan-Based Molecular Imprinted Polymer Nanogel.

PubMed

Hassanzadeh, Marjan; Ghaemy, Mousa; Ahmadi, Shamseddin

2016-10-01

Chitosan-based molecular imprinted polymer (CS-MIP) nanogel is prepared in the presence of morphine template, fully characterized and used as a new vehicle to extend duration of morphine analgesic effect in Naval Medical Research Institute mice. The CS-MIP nanogel with ≈25 nm size range exhibits 98% loading efficiency, and in vitro release studies show an initial burst followed by an extended slow release of morphine. In order to study the feasibility of CS-MIP nanogel as morphine carrier, 20 mice are divided into two groups randomly and received subcutaneous injection of morphine-loaded CS-MIP and morphine (10 mg kg -1 ) dissolved in physiologic saline. Those received injection of morphine-loaded CS-MIP show slower and long lasting release of morphine with 193 min effective time of 50% (ET50) analgesia compared to 120 min ET50 in mice received morphine dissolved in physiologic saline. These results suggest that CS-MIP nanogel can be a possible strategy as morphine carrier for controlled release and extension of its analgesic efficacy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of the release rate of magnesium ions in multiple emulsions (water-in-oil-in-water) containing BSA on the resulting physical properties and microstructure of soy protein gel.

PubMed

Zhu, Qiaomei; Zhao, Ling; Zhang, Hui; Saito, Masayoshi; Yin, Lijun

2017-04-01

The objective of present study was to prepare multiple water-in-oil-in-water (W/O/W) emulsions that exhibit different release rates of magnesium ions; and assess their utility as coagulants in improving tofu quality. W/O/W emulsions containing bovine serum albumin (BSA) and magnesium chloride (MgCl 2 ) were developed for controlled release applications. An increasing BSA concentration led to an increase in viscosity and droplet size of W/O/W double emulsions, as well as a decreased release rate of encapsulated Mg 2+ from emulsions. The gelation process of soy protein was simulated by conducting dynamic viscoelastic measurements. The rate constant (k) and saturated storage modulus (G' sat ) values of soy protein gel decreased as BSA concentration increased, suggesting that BSA could slow the release of magnesium ions from double emulsions. Confocal laser scanning microscopy (CLSM) results showed that increased concentration of BSA created a more homogeneous microstructure of soy protein gels with smaller pores within the gel network structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effects of dynamic compressive loading on biodegradable implants of 50-50% polylactic Acid-polyglycolic Acid.

PubMed

Thompson, D E; Agrawal, C M; Athanasiou, K

1996-01-01

Biodegradable implants that release growth factors or other bioactive agents in a controlled manner are investigated to enhance the repair of musculoskeletal tissues. In this study, the in vitro release characteristics and mechanical properties of a 50:50 polylactic acid/polyglycolic acid two phase implant were examined over a 6-week period under no-load conditions or under a cyclic compressive load, such as that experienced when walking slowly during rehabilitation. The results demonstrated that a cyclic compressive load significantly slows the decrease of molecular chain size during the first week, significantly increases protein release for the first 2-3 weeks, and significantly stiffens the implant for the first 3 weeks. It was also shown that protein release is initially high and steadily decreases with time until the molecular weight declines to about 20% of its original value (approximately 4 weeks). Once this threshold is reached, increased protein release, surface deformation, and mass loss occurs. This study also showed that dynamic loading and the environment in which an implant is placed affect its biodegradation. Therefore, it may be essential that in vitro degradation studies of these or similar implants include a dynamic functional environment.

Endothelialization of sirolimus-eluting stents with slow and extended drug release in the porcine overstretch model.

PubMed

Frey, Daniela; Billinger, Michael; Meier, Pascal; Beslac, Olgica; Grossenbacher, Raphael; Hänni, Beat; Hess, Otto M

2008-12-01

Vascular healing of intracoronary stents has been shown to be delayed in drug-eluting stents (DES) due to the cytotoxic compounds on the stent surface that prevent stent ingrowth and endothelialization. The lack of endothelialization explains the occurrence of late and very late stent thrombosis in DES. In 11 house swines (body weight 38-45 kg), 3 stents were implanted randomly into the 3 large epicardial coronary arteries, namely a bare-metal stent (BMS), a sirolimus-eluting stent with slow-release (SES) and a SES with extended-release (SESXR). Stent length was 18 mm, and stent diameter 3 mm. All stents were of identical design. Animals were followed for 3 (n = 3), 7 (n = 4) and 14 (n = 4) days, respectively. One animal died before implantation due to hyperthermia. On the day of explantation, the animals were euthanized and endothelialization was tested by scanning electron microscopy after drying and sputtering the samples. Endothelial coverage was determined semiquantitatively by 2 observers. Endothelialization was more rapid with BMS and SESXR than SES at 3 and 14 days. At 7 days there were no significant differences between the 2 SES. Endothelialization of intracoronary stents is faster with BMS and SESXR at 3 days than with SES. These differences persist at 14 days, suggesting delayed vascular healing with the slow-release SES.

TRANSPORT, FATE AND RISK IMPLICATIONS OF ENVIRONMENTALLY ACCEPTABLE ENDPOINT DECISIONS

EPA Science Inventory

The second and third year project goals are the following: Continue to develop and finalize the expected source zone module incorporating slow release and finalize the contaminated soil screening model. Chemical rate of release data will be obtained and used with t...

Micronization increases vitamin E carrying and releasing abilities of insoluble fiber.

PubMed

Hsu, Pang-Kuei; Chien, Po-Jung; Chau, Chi-Fai

2008-03-26

This study was to investigate the effects of micronization on vitamin-carrying capacity and slow-release ability of carambola (starfruit) insoluble fiber (IF) and cellulose using in vitro and in vivomodels. Upon micronization, carambola IF (8.1 microm) underwent structural changes to expose more functional groups in the fiber matrix and to exhibit higher oil-holding capacity ( approximately 20.4-fold). Micronized fibers in forms of fiber-vitamin composites, particularly the micronized carambola IF-vitamin composite, were capable of carrying vitamin E (alpha-tocopherol) up to 9.6-fold over their unmicronized forms and releasing nutrient gradually. Animal studies demonstrated that the adminstration of micronized carambola IF-vitamin composite could maintain the plasma vitamin E of rats at relatively higher levels (2.1-3.6-fold of the initial values) for at least 5 h. The results suggested that micronized fibers, particularly the micronized carambola IF, could be exploited as potential nutrient carriers in food applications and also be used to produce slow-release formulations.

Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells.

PubMed

Nahire, Rahul; Haldar, Manas K; Paul, Shirshendu; Ambre, Avinash H; Meghnani, Varsha; Layek, Buddhadev; Katti, Kalpana S; Gange, Kara N; Singh, Jagdish; Sarkar, Kausik; Mallik, Sanku

2014-08-01

Although liposomes are widely used as carriers of drugs and imaging agents, they suffer from a lack of stability and the slow release of the encapsulated contents at the targeted site. Polymersomes (vesicles of amphiphilic polymers) are considerably more stable compared to liposomes; however, they also demonstrate a slow release for the encapsulated contents, limiting their efficacy as a drug-delivery tool. As a solution, we prepared and characterized echogenic polymersomes, which are programmed to release the encapsulated drugs rapidly when incubated with cytosolic concentrations of glutathione. These vesicles encapsulated air bubbles inside and efficiently reflected diagnostic-frequency ultrasound. Folate-targeted polymersomes showed an enhanced uptake by breast and pancreatic-cancer cells in a monolayer as well as in three-dimensional spheroid cultures. Polymersomes encapsulated with the anticancer drugs gemcitabine and doxorubicin showed significant cytotoxicity to these cells. With further improvements, these vesicles hold the promise to serve as multifunctional nanocarriers, offering a triggered release as well as diagnostic ultrasound imaging. Copyright © 2014 Elsevier Ltd. All rights reserved.

Load and Pi control flux through the branched kinetic cycle of myosin V.

PubMed

Kad, Neil M; Trybus, Kathleen M; Warshaw, David M

2008-06-20

Myosin V is a processive actin-based motor protein that takes multiple 36-nm steps to deliver intracellular cargo to its destination. In the laser trap, applied load slows myosin V heavy meromyosin stepping and increases the probability of backsteps. In the presence of 40 mm phosphate (P(i)), both forward and backward steps become less load-dependent. From these data, we infer that P(i) release commits myosin V to undergo a highly load-dependent transition from a state in which ADP is bound to both heads and its lead head trapped in a pre-powerstroke conformation. Increasing the residence time in this state by applying load increases the probability of backstepping or detachment. The kinetics of detachment indicate that myosin V can detach from actin at two distinct points in the cycle, one of which is turned off by the presence of P(i). We propose a branched kinetic model to explain these data. Our model includes P(i) release prior to the most load-dependent step in the cycle, implying that P(i) release and load both act as checkpoints that control the flux through two parallel pathways.

Efficacy of a slow-release imidacloprid (10%)/flumethrin (4.5%) collar for the prevention of canine leishmaniosis

PubMed Central

2014-01-01

Background The efficacy of a slow-release insecticidal and repellent collar containing 10% imidacloprid and 4.5% flumethrin (Seresto, Bayer Animal Health) in preventing Leishmania infantum infection was evaluated in a large population of dogs living in a hyper-endemic area of Sicily (Italy). Methods A total of 219 dogs, negative for L. infantum were enrolled in a multicentre, controlled study. Dogs were divided into two homogeneous groups, defined as G1 (n = 102) and G2 (n = 117). Before the start of the sand fly season, dogs in G1 were treated with the collar while animals in G2 were left untreated, serving as negative controls. Dogs were serially sampled on day D90, D180, D210 and D300 in order to assess Leishmania infection by IFAT, PCR on skin (D210-D300) and bone marrow (D300) and cytology on bone marrow aspirate (D300). Results Three dogs (2.9%) in G1 and 41 (40.2%) in G2 became positive for L. infantum in at least one of the diagnostic tests employed in the study. The number of seropositive dogs in G2 increased in the course of the study from 15 (D90) to 41 (D300), with some of them also positive in other diagnostic tests. Eight (19.6%) of the seropositive dogs in G2 showed an increase in antibody titers ranging from 1:160 to 1:1,280. At the last follow-up, some of dogs in G2 displayed overt clinical signs suggestive of leishmaniosis. The mean incidence density rate at the final follow-up was 4.0% for G1 and 60.7% for G2, leading to a mean efficacy of the collar in protecting dogs at both sites of 93.4%. Conclusions The slow-release collar tested in this study was shown to be safe and highly effective in preventing L. infantum infection in a large population of dogs. Protection conferred by a single collar (up to eight months) spanned an entire sand fly season in a hyper-endemic area of southern Italy. The regular use of collars, at least during the sand fly season, may represent a reliable and sustainable strategy for the prevention of leishmaniosis in dogs living in or travelling to an endemic area. PMID:25023573

A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

PubMed Central

Guo, Jun; Ge, Jian-long; Hao, Mei; Sun, Zhi-cheng; Wu, Xin-sheng; Zhu, Jian-bing; Wang, Wei; Yao, Pan-tong; Lin, Wei; Xue, Lei

2015-01-01

Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP), and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles. PMID:25825223

Revealing the cluster of slow transients behind a large slow slip event.

PubMed

Frank, William B; Rousset, Baptiste; Lasserre, Cécile; Campillo, Michel

2018-05-01

Capable of reaching similar magnitudes to large megathrust earthquakes [ M w (moment magnitude) > 7], slow slip events play a major role in accommodating tectonic motion on plate boundaries through predominantly aseismic rupture. We demonstrate here that large slow slip events are a cluster of short-duration slow transients. Using a dense catalog of low-frequency earthquakes as a guide, we investigate the M w 7.5 slow slip event that occurred in 2006 along the subduction interface 40 km beneath Guerrero, Mexico. We show that while the long-period surface displacement, as recorded by Global Positioning System, suggests a 6-month duration, the motion in the direction of tectonic release only sporadically occurs over 55 days, and its surface signature is attenuated by rapid relocking of the plate interface. Our proposed description of slow slip as a cluster of slow transients forces us to re-evaluate our understanding of the physics and scaling of slow earthquakes.

Oil-Water Interface Templating of Mesoporous Macroscale Structures

PubMed

Schacht; Huo; Voigt-Martin; Stucky; Schuth

1996-08-09

Ordered mesostructured porous silicas that are also macroscopically structured were created by control of the interface on two different length scales simultaneously. Micellar arrays controlled the nanometer-scale assembly, and at the static boundary between an aqueous phase and an organic phase, control was achieved on the micrometer to centimeter scale. Acid-prepared mesostructures of silica were made with the p6, Pm3n, and the P63/mmc structures in the form of porous fibers 50 to 1000 micrometers in length, hollow spheres with diameters of 1 to 100 micrometers, and thin sheets up to 10 centimeters in diameter and about 10 to 500 micrometers in thickness. These results might have implications for technical applications, such as slow drug-release systems or membranes, and in biomineralization, where many processes are also interface-controlled.

Light-induced spatial control of pH-jump reaction at smart gel interface.

PubMed

Techawanitchai, Prapatsorn; Ebara, Mitsuhiro; Idota, Naokazu; Aoyagi, Takao

2012-11-01

We proposed here a 'smart' control of an interface movement of proton diffusion in temperature- and pH-responsive hydrogels using a light-induced spatial pH-jump reaction. A photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (NBA) was integrated into poly(N-isopropylacrylamide-o-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm)) hydrogels. NBA-integrated hydrogels demonstrated quick release of proton upon UV irradiation, allowing the pH inside the gel to decrease below the pK(a) of P(NIPAAm-co-CIPAAm) within a minute. The NBA-integrated gel was shown to shrink rapidly upon UV irradiation without polymer "skin layer" formation due to a uniform decrease of pH inside the gel. Spatial control of gel shrinking was also created by irradiating UV light to a limited region of the gel through a photomask. The interface of proton diffusion ("active interface") gradually moved toward non-illuminated area. The apparent position of "active interface", however, did not change remarkably above the LCST, while protons continuously diffused outward direction. This is because the "active interface" also moved inward direction as gel shrank above the LCST. As a result, slow movement of the apparent interface was observed. The NBA-integrated gel was also successfully employed for the controlled release of an entrapped dextran in a light controlled manner. This system is highly promising as smart platforms for triggered and programmed transportation of drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Stabilization of Tetanus Toxoid Encapsulated in PLGA Microspheres

PubMed Central

Jiang, Wenlei; Schwendeman, Steven P.

2014-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT) in PLGA microspheres. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: 1) protein aggregation mediated by formaldehyde and 2) acid-induced protein unfolding and epitope damage. Further, we systemically identified excipients which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA. PMID:18710256

Uniaxial strain of cultured mouse and rat cardiomyocyte strands slows conduction more when its axis is parallel to impulse propagation than when it is perpendicular.

PubMed

Buccarello, A; Azzarito, M; Michoud, F; Lacour, S P; Kucera, J P

2018-05-01

Cardiac tissue deformation can modify tissue resistance, membrane capacitance and ion currents and hence cause arrhythmogenic slow conduction. Our aim was to investigate whether uniaxial strain causes different changes in conduction velocity (θ) when the principal strain axis is parallel vs perpendicular to impulse propagation. Cardiomyocyte strands were cultured on stretchable custom microelectrode arrays, and θ was determined during steady-state pacing. Uniaxial strain (5%) with principal axis parallel (orthodromic) or perpendicular (paradromic) to propagation was applied for 1 minute and controlled by imaging a grid of markers. The results were analysed in terms of cable theory. Both types of strain induced immediate changes of θ upon application and release. In material coordinates, orthodromic strain decreased θ significantly more (P < .001) than paradromic strain (2.2 ± 0.5% vs 1.0 ± 0.2% in n = 8 mouse cardiomyocyte cultures, 2.3 ± 0.4% vs 0.9 ± 0.5% in n = 4 rat cardiomyocyte cultures, respectively). The larger effect of orthodromic strain can be explained by the increase in axial myoplasmic resistance, which is not altered by paradromic strain. Thus, changes in tissue resistance substantially contributed to the changes of θ during strain, in addition to other influences (eg stretch-activated channels). Besides these immediate effects, the application of strain also consistently initiated a slow progressive decrease in θ and a slow recovery of θ upon release. Changes in cardiac conduction velocity caused by acute stretch do not only depend on the magnitude of strain but also on its orientation relative to impulse propagation. This dependence is due to different effects on tissue resistance. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Chest compression release velocity: Association with survival and favorable neurologic outcome after out-of-hospital cardiac arrest.

PubMed

Kovacs, Alexander; Vadeboncoeur, Tyler F; Stolz, Uwe; Spaite, Daniel W; Irisawa, Taro; Silver, Annemarie; Bobrow, Bentley J

2015-07-01

We evaluated the association between chest compression release velocity (CCRV) and outcomes after out-of-hospital cardiac arrest (OHCA). CPR quality was measured using a defibrillator with accelerometer-based technology (E Series, ZOLL Medical) during OHCA resuscitations by 2 EMS agencies in Arizona between 10/2008 and 06/2013. All non-EMS-witnessed adult (≥ 18 years) arrests of presumed cardiac etiology were included. The association between mean CCRV (assessed as an appropriate measure of central tendency) and both survival to hospital discharge and neurologic outcome (Cerebral Performance Category score = 1 or 2) was analyzed using multivariable logistic regression to control for known and potential confounders and multiple imputation to account for missing data. 981 OHCAs (median age 68 years, 65% male, 11% survival to discharge) were analyzed with 232 (24%) missing CPR quality data. All-rhythms survival varied significantly with CCRV [fast (≥ 400 mm/s) = 18/79 (23%); moderate (300-399.9 mm/s) = 50/416 (12%); slow (<300 mm/s) 17/255 (7%); p < 0.001], as did favorable neurologic outcome [fast = 14/79 (18%); moderate = 43/415 (10%); slow = 11/255 (4%); p < 0.001]. Fast CCRV was associated with increased survival compared to slow [adjusted odds ratio (aOR) 4.17 (95% CI: 1.61, 10.82) and moderate CCRV [aOR 3.08 (1.39, 6.83)]. Fast CCRV was also associated with improved favorable neurologic outcome compared to slow [4.51 (1.57, 12.98)]. There was a 5.2% increase in the adjusted odds of survival for each 10mm/s increase in CCRV [aOR 1.052 (1.001, 1.105)]. CCRV was independently associated with improved survival and favorable neurologic outcome at hospital discharge after adult OHCA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Brivaracetam augments short-term depression and slows vesicle recycling.

PubMed

Yang, Xiaofeng; Bognar, Joseph; He, Tianyu; Mohammed, Mouhari; Niespodziany, Isabelle; Wolff, Christian; Esguerra, Manuel; Rothman, Steven M; Dubinsky, Janet M

2015-12-01

Brivaracetam (BRV) decreases seizure activity in a number of epilepsy models and binds to the synaptic vesicle glycoprotein 2A (SV2A) with a higher affinity than the antiepileptic drug levetiracetam (LEV). Experiments were performed to determine if BRV acted similarly to LEV to induce or augment short-term depression (STD) under high-frequency neuronal stimulation and slow synaptic vesicle recycling. Electrophysiologic field excitatory postsynaptic potential (fEPSP) recordings were made from CA1 synapses in rat hippocampal slices loaded with BRV or LEV during intrinsic activity or with BRV actively loaded during hypertonic stimulation. STD was examined in response to 5 or 40 Hz stimulus trains. Presynaptic release of FM1-43 was visualized using two-photon microscopy to assess drug effects upon synaptic vesicle mobilization. When hippocampal slices were incubated in 0.1-30 μm BRV or 30 μm-1 mm LEV for 3 h, the relative CA1 field EPSPs decreased over the course of a high-frequency train of stimuli more than for control slices. This STD was frequency- and concentration-dependent, with BRV being 100-fold more potent than LEV. The extent of STD depended on the length of the incubation time for both drugs. Pretreatment with LEV occluded the effects of BRV. Repeated hypertonic sucrose treatments and train stimulation successfully unloaded BRV from recycling vesicles and reversed BRVs effects on STD, as previously reported for LEV. At their maximal concentrations, BRV slowed FM1-43 release to a greater extent than in slices loaded with LEV during prolonged stimulation. BRV, similar to LEV, entered into recycling synaptic vesicles and produced a frequency-dependent decrement of synaptic transmission at 100-fold lower concentrations than LEV. In addition, BRV slowed synaptic vesicle mobilization more effectively than LEV, suggesting that these drugs may modify multiple functions of the synaptic vesicle protein SV2A to curb synaptic transmission and limit epileptic activity. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Release rates of methylcyclohexenone and verbenone from bubble cap and bead releasers under field conditions suitable for the management of bark beetles in California, Oregon, and Alaska.

Treesearch

Edward H. Holsten; Warren Webb; Patrick J. Shea; Richard A. Werner

2002-01-01

Devices releasing antiaggregation pheromones, such as MCH (3-methyl-2-cyclohexen-1-one) and verbenone (4-methylene-6,6-dimethylbicyclo(3.1.1)hept-2-ene), are used experimentally to manipulate destructive populations of bark beetles. Two slow release devices, bubble caps attached to boles of trees and granular beads placed on the ground, were tested in forests of...

Nitrogen release from urea with different coatings.

PubMed

Campos, Odirley R; Mattiello, Edson Marcio; Cantarutti, Reinaldo Bertola; Vergütz, Leonardus

2018-01-01

Coatings or urease inhibitors are designed to reduce losses of ammonia [NH 3(g) ] from urea fertilizers. However, nitrogen (N) release and its effects on soil solution have not previously been evaluated under standardized conditions in soils. In this study, the urea fertilizers were incubated in chambers filled with sandy loam soil, adapted for the collection of NH 3(g) and soil solution by centrifugation. In the fast-release N fertilizers, around 93% and 100% of urea-N applied was recovered within the first hours of incubation. In contrast, in the slow-release N fertilizers, less than 40% of urea-N applied, was recovered at 19 days of incubation. The maximum N release from the fertilizers followed the order: UP1 (106%) ≈ UNBPT (102%) ≈ urea (93%) > USP2 (57%) ≈ USP3 (57%) > USP4 (31%) ≈ USP5 (18%). NH 3(g) volatilization accounted for only 3% of the applied N in the slow-release fertilizers, which corresponded to about 88% less than the NH 3(g) loss from prilled urea. This study demonstrated distinct N release patterns, which changed the N dynamics in the soil. Some coatings effectively delayed urea release from granules and reduced NH 3(g) gas losses, while other were not efficient. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

[Advances in the treatment of acromegaly].

PubMed

Krysiak, Robert; Okopień, Bogusław; Marek, Bogdan

2008-01-01

Acromegaly is a slow developing chronic debilitating disease caused by a growth hormone (GH)-producing pituitary adenoma. The clinical consequences of acromegaly result both from excess GH secretion and from mass effect of the pituitary tumour. The disease is associated with increased morbidity and mortality compared to normal population. Currently available therapies for acromegaly are transsphenoidal surgery, radiotherapy and medical therapy. The last includes dopamine agonists, slow release formulation of somatostatin analogues and pegvisomant, a GH-receptor antagonist. All these forms of treatment attempt to control the disease by reducing GH secretion from the tumour and inhibiting the growth of adenoma. The decision concerning the choice of therapy should depend on age, the severity of acromegaly and the presence of its complications and should also consider the dangers associated with each treatment. This review paper summarizes the contemporary treatment of acromegaly with special emphasis on their established benefits and risks.

Short- and long-term releases of fluorocarbons from disposal of polyurethane foam waste.

PubMed

Kjeldsen, Peter; Scheutz, Charlotte

2003-11-01

Several halocarbons having very high global warming or ozone depletion potentials have been used as a blowing agent (BA) for insulation foam in home appliances, such as refrigerators and freezers. Many appliances are shredded after the end of their useful life. Release experiments carried out in the laboratory on insulation foam blown with the blowing agents CFC-11, HCFC-141b, HCF-134fa, and HFC-245fa revealed that not all blowing agents are released during a 6-week period following the shredding process. The experiments confirmed the hypothesis that the release could be divided into three segments: By shredding foam panels, a proportion of the closed cells is either split or damaged to a degree allowing for a sudden release of the contained atmosphere in the cell (the instantaneous release). Cells adjacent to the cut surface may be only slightly damaged by tiny cracks or holes allowing a relative slow release of the BA to the surroundings (the short-term release). A significant portion of the cells in the foam particle will be unaffected and only allows release governed by slow diffusion through the PUR cell wall (the long-term release). The magnitude of the releases is for all three types highly dependent on how fine the foam is shredded. The residual blowing agent remaining after the 6-week period may be very slowly released if the integrity of the foam particles with respect to diffusion properties is kept after disposal of the foam waste on landfills. It is shown by setting up a national model simulating the BA releases following decommissioning of used domestic refrigerators/freezers in the United States that the release patterns are highly dependent on how the appliances are shredded.

Characterization of temperature and pH-responsive poly-N-isopropylacrylamide-co-polymer nanoparticles for the release of antimicrobials

NASA Astrophysics Data System (ADS)

Hill, Laura E.; Gomes, Carmen L.

2014-09-01

Chitosan and alginate are both pH-responsive biopolymers extracted from crustacean exoskeletons and brown algae, respectively. Poly-N-isopropylacrylamide (PNIPAAM) is a hydrogel that becomes hydrophobic at a lower-critical solution temperature. This study sought to combine pH- and temperature-responsive polymers via crosslinking, in order to create a dual-stimuli responsive polymer for hydrophobic antimicrobial compounds delivery, improving their antimicrobial effects. Cinnamon bark extract (CBE) was used as a model for hydrophobic antimicrobial. Two co-polymers were synthesized to create two nanoparticles types: chitosan-co-PNIPAAM and alginate-co-PNIPAAM. Nanoparticles were formed from the resulting co-polymers using a self-assembly top-down process followed by glutaraldehyde or calcium chloride crosslinking. These nanoparticles were then used as controlled delivery vehicles for CBE, whose rapid release could be triggered by specific external stimuli. For the same pH and temperature conditions, the chitosan-co-PNIPAAM nanoparticles were significantly more potent bacterial inhibitors against both pathogens and also exhibited a faster CBE release over time as well as slightly higher entrapment efficiency. The alginate-co-PNIPAAM nanoparticles were significantly smaller and exhibited a slow, gradual release over a long time period. Although both nanoparticles were able to effectively inhibit pathogen growth at lower (P < 0.05) concentration than free CBE, the chitosan-co-PNIPAAM nanoparticles were more effective in delivering a natural antimicrobial with controlled release against foodborne pathogens.

Impact of slow-release Bacillus sphaericus granules on mosquito populations followed in a tropical urban environment.

PubMed

Skovmand, Ole; Ouedraogo, Thierry D A; Sanogo, Edith; Samuelsen, Helle; Toé, Lea P; Baldet, Thierry

2009-01-01

A floating, slow-release, granular formulation of Bacillus sphaericus (Neide) was used to control mosquito larvae in two suburban areas of two tropical cities: Ouagadougou and Bobo-Dioulasso, Burkina Faso. A circular area of 2 km2, diameter 1,600 m, was treated in each city using a similar, smaller area 1 km away as an untreated control. Mosquito captures were made in houses in four concentric circles, from the periphery to the center; each circle was 50 m in width. Mosquitoes were captured in CDC light traps or from human landings. More than 95% of the mosquitoes were Culex quinquefasciatus (Say) (Diptera: Culicidae). The human landing catches provided twice as many mosquitoes as did the CDC traps/night/house. The treatments resulted in important reductions relative to the control area and to preintervention captures. The reduction was more prominent in the inner circle (up to 90%) than in the outer circle (50-70%), presumably because of the impact of immigrating mosquitoes from nontreated breeding sites around the intervention area. This effect was more pronounced for light trap catches than from human landings. The impact of treatment was also measured as the mean ratio of mosquito density in the two outer circles to that of the two inner circles. This ratio was approximately 1:1 before the intervention and reached 1:0.43 during the intervention. This comparison does not depend on the assumption that, in the absence of intervention, the mosquito population development in the two areas would have been identical, but does depend on the homogeneity of the intervention area. The study showed that it is possible to organize mosquito control in a tropical, urban environment by forming and rapidly training teams of young people to carry out the mosquito control mostly using a biopesticide that can be applied without any tools except an iron bar to lift lids on some cesspits.

DNA repair phenotype and dietary antioxidant supplementation.

PubMed

Guarnieri, Serena; Loft, Steffen; Riso, Patrizia; Porrini, Marisa; Risom, Lotte; Poulsen, Henrik E; Dragsted, Lars O; Møller, Peter

2008-05-01

Phytochemicals may protect cellular DNA by direct antioxidant effect or modulation of the DNA repair activity. We investigated the repair activity towards oxidised DNA in human mononuclear blood cells (MNBC) in two placebo-controlled antioxidant intervention studies as follows: (1) well-nourished subjects who ingested 600 g fruits and vegetables, or tablets containing the equivalent amount of vitamins and minerals, for 24 d; (2) poorly nourished male smokers who ingested 500 mg vitamin C/d as slow- or plain-release formulations together with 182 mg vitamin E/d for 4 weeks. The mean baseline levels of DNA repair incisions were 65.2 (95 % CI 60.4, 70.0) and 86.1 (95 % CI 76.2, 99.9) among the male smokers and well-nourished subjects, respectively. The male smokers also had high baseline levels of oxidised guanines in MNBC. After supplementation, only the male smokers supplemented with slow-release vitamin C tablets had increased DNA repair activity (27 (95 % CI 12, 41) % higher incision activity). These subjects also benefited from the supplementation by reduced levels of oxidised guanines in MNBC. In conclusion, nutritional status, DNA repair activity and DNA damage are linked, and beneficial effects of antioxidants might only be observed among poorly nourished subjects with high levels of oxidised DNA damage and low repair activity.

Measuring hydrophobic micropore volumes in geosorbents from trichloroethylene desorption data.

PubMed

Cheng, Hefa; Reinhard, Martin

2006-06-01

Hydrophobic micropores can play a significant role in controlling the long-term release of organic contaminants from geosorbents. We describe a technique for quantifying the total and the hydrophobic mineral micropore volumes based on the mass of trichloroethylene (TCE) sorbed in the slow-releasing pores under dry and wet conditions, respectively. Micropore desorption models were used to differentiate the fast- and slow-desorbing fractions in desorption profiles. The micropore environment in which organic molecules were sorbed in the presence of water was probed by studying the transformation of a water-reactive compound (2,2-dichloropropane or 2,2-DCP). For sediment from an alluvial aquifer, the total and hydrophobic micropore volumes estimated using this technique were 4.65 microL/g and 0.027 microL/g (0.58% of total), respectively. In microporous silica gel A, a hydrophobic micropore volume of 0.038 microL/g (0.035% of reported total) was measured. The dehydrohalogenation rate of 2,2-DCP sorbed in hydrophobic micropores of the sediment was slower than that reported in bulk water, indicating an environment of low water activity. The results suggest that hydrolyzable organic contaminants sorbed in hydrophobic micropores react slower than in bulk water, consistent with the reported persistence of reactive contaminants in natural soils.

Slow-release oral morphine for opioid maintenance treatment: a systematic review

PubMed Central

Jegu, Jeremie; Gallini, Adeline; Soler, Pauline; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse

2011-01-01

This review article summarizes the results of all available clinical trials considering the use of slow-release oral morphine (SROM) for opioid maintenance treatment (OMT). All studies published up to October 2010 and assessing SROM for OMT in adult patients are included. Three independent reviewers assessed the selected articles using a standardized checklist. Study design, study length and number of subjects included were recorded. Data about retention rate (proportion of participants remaining under maintenance treatment at the end of the study), quality of life, withdrawal symptoms, craving, additional drug consumption, driving capacity and adverse events were collected. We identified 13 articles corresponding to nine clinical trials considering the use of SROM for OMT. Among them, only one was a randomized trial and one was a controlled not randomized trial. All other studies were uncontrolled. Retention rates were good (from 80.6 to 95%) with SROM maintenance, but similar retention rates were obtained with methadone. Most of the studies showed that quality of life, withdrawal symptoms, craving and additional drug consumption improved with SROM. However, there was no comparison with other maintenance drugs. As most of the studies assessing SROM efficacy were uncontrolled, there is no definite evidence that SROM is an effective alternative to methadone for OMT. PMID:21265874

Toxicity and Metabolism of Layered Double Hydroxide Intercalated with Levodopa in a Parkinson’s Disease Model

PubMed Central

Kura, Aminu Umar; Ain, Nooraini Mohd; Hussein, Mohd Zobir; Fakurazi, Sharida; Hussein-Al-Ali, Samer Hasan

2014-01-01

Layered hydroxide nanoparticles are generally biocompatible, and less toxic than most inorganic nanoparticles, making them an acceptable alternative drug delivery system. Due to growing concern over animal welfare and the expense of in vivo experiments both the public and the government are interested to find alternatives to animal testing. The toxicity potential of zinc aluminum layered hydroxide (ZAL) nanocomposite containing anti-Parkinsonian agent may be determined using a PC 12 cell model. ZAL nanocomposite demonstrated a decreased cytotoxic effect when compared to levodopa on PC12 cells with more than 80% cell viability at 100 μg/mL compared to less than 20% cell viability in a direct levodopa exposure. Neither levodopa-loaded nanocomposite nor the un-intercalated nanocomposite disturbed the cytoskeletal structure of the neurogenic cells at their IC50 concentration. Levodopa metabolite (HVA) released from the nanocomposite demonstrated the slow sustained and controlled release character of layered hydroxide nanoparticles unlike the burst uptake and release system shown with pure levodopa treatment. PMID:24722565

Ordered DNA-Surfactant Hybrid Nanospheres Triggered by Magnetic Cationic Surfactants for Photon- and Magneto-Manipulated Drug Delivery and Release.

PubMed

Xu, Lu; Wang, Yitong; Wei, Guangcheng; Feng, Lei; Dong, Shuli; Hao, Jingcheng

2015-12-14

Here we construct for the first time ordered surfactant-DNA hybrid nanospheres of double-strand (ds) DNA and cationic surfactants with magnetic counterion, [FeCl3Br](-). The specificity of the magnetic cationic surfactants that can compact DNA at high concentrations makes it possible for building ordered nanospheres through aggregation, fusion, and coagulation. Cationic surfactants with conventional Br(-) cannot produce spheres under the same condition because they lose the DNA compaction ability. When a light-responsive magnetic cationic surfactant is used to produce nanospheres, a dual-controllable drug-delivery platform can be built simply by the applications of external magnetic force and alternative UV and visible light. These nanospheres obtain high drug absorption efficiency, slow release property, and good biocompatibility. There is potential for effective magnetic-field-based targeted drug delivery, followed by photocontrollable drug release. We deduce that our results might be of great interest for making new functional nucleic-acid-based nanomachines and be envisioned to find applications in nanotechnology and biochemistry.

Cellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release

PubMed Central

2015-01-01

A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl–]), an ionic liquid, was used as the sole solvent, and because the [BMIm+Cl–] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds. PMID:25548871

Monoamine Release during Unihemispheric Sleep and Unihemispheric Waking in the Fur Seal

PubMed Central

Lyamin, Oleg I.; Lapierre, Jennifer L.; Kosenko, Peter O.; Kodama, Tohru; Bhagwandin, Adhil; Korneva, Svetlana M.; Peever, John H.; Mukhametov, Lev M.; Siegel, Jerome M.

2016-01-01

Study Objectives: Our understanding of the role of neurotransmitters in the control of the electroencephalogram (EEG) has been entirely based on studies of animals with bilateral sleep. The study of animals with unihemispheric sleep presents the opportunity of separating the neurochemical substrates of waking and sleep EEG from the systemic, bilateral correlates of sleep and waking states. Methods: The release of histamine (HI), norepinephrine (NE), and serotonin (5HT) in cortical and subcortical areas (hypothalamus, thalamus and caudate nucleus) was measured in unrestrained northern fur seals (Callorhinus ursinus) using in vivo microdialysis, in combination with, polygraphic recording of EEG, electrooculogram, and neck electromyogram. Results: The pattern of cortical and subcortical HI, NE, and 5HT release in fur seals is similar during bilaterally symmetrical states: highest in active waking, reduced in quiet waking and bilateral slow wave sleep, and lowest in rapid eye movement (REM) sleep. Cortical and subcortical HI, NE, and 5HT release in seals is highly elevated during certain waking stimuli and behaviors, such as being sprayed with water and feeding. However, in contrast to acetylcholine (ACh), which we have previously studied, the release of HI, NE, and 5HT during unihemispheric sleep is not lateralized in the fur seal. Conclusions: Among the studied neurotransmitters most strongly implicated in waking control, only ACh release is asymmetric in unihemispheric sleep and waking, being greatly increased on the activated side of the brain. Commentary: A commentary on this article appears in this issue on page 491. Citation: Lyamin OI, Lapierre JL, Kosenko PO, Kodama T, Bhagwandin A, Korneva SM, Peever JH, Mukhametov LM, Siegel JM. Monoamine release during unihemispheric sleep and unihemispheric waking in the fur seal. SLEEP 2016;39(3):625–636. PMID:26715233

Encapsulation of anticancer drug copper bis(8-hydroxyquinoline) in hydroxyapatite for pH-sensitive targeted delivery and slow release.

PubMed

Weerasuriya, D R K; Wijesinghe, W P S L; Rajapakse, R M G

2017-02-01

There is a conspicuous progress in increasing anticancer drug delivery through the utilization of nanoparticles (NPs) as drug delivery agents. Hydroxyapatite (HA) gives improved clinical effectiveness of drugs by reducing systemic toxicity and broadening the spectrum of drug delivery since it is biocompatible and it can be targeted towards tumor cells. Herein, investigation of the potential of enhancing controlled drug release of the template model drug, copper bis-(8-hydroxyquinoline), by encapsulating it in hollow hydroxyapatite nano-carriers, is presented. Hydroxyapatite nanoparticles are synthesized by following four different routes to optimize its efficacy of drug loading. Copper bis-(8-hydroxyquinoline) is encapsulated by Method (a) which was effected by stirring the model drug and porous HA NPs in colloidal solution and Method (b) which was done during synthesis of hydroxyapatite nanoparticles in a solution of the model drug. In synthesizing nanoporous HA NPs, calcium carbonate is used as a template to create voids in HA. In each method, Ca/P ratio was ensured to be kept at 1.67:1. Appealing results are reported for the encapsulated product which was prepared by Method (a2). Method (a) was done at three different molar ratios of PO 4 3- :CO 3 2- and best result was obtained for that utilized 2.003:1 molar ratio (Method (a2).). It produced 98.67% of encapsulation efficiency and 2.9522mg/g of drug loading capacity. Release kinetics was studied at a range of pH values; the lower the pH of the medium the higher is the drug release. For instance, when considering the product which exhibited high encapsulation efficiency and high drug loading capacity, at pH3.5 during the first 8h it elicited about 13% of release, at pH5.0 about 8% release while at pH6.0 it was just 2.5%. During the 24-hour span, pH3.5 exhibited about 23.8%, at pH5.0 approximately 9% with an increasing trend of release and at pH6.0 showed a value just above 2.5%. As such, acidity of the cancerous cells can be made use to increase the drug slow-release kinetics at the vicinity of the cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Development and dissolution studies of bisphosphonate (clodronate)-containing hydroxyapatite-polylactic acid biocomposites for slow drug delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Shimmon, Ronald; Ben-Nissan, Besim; Milthorpe, Bruce

2017-06-01

An increase in clinical demand on the controlled release of bisphosphonates (BPs) due to complications associated with systemic administration, has been the current driving force on the development of BP drug-release systems. Bisphosphonates have the ability to bind to divalent metal ions, such as Ca 2+ , in bone mineral and prevent bone resorption by influencing the apoptosis of osteoclasts. Localized delivery using biodegradable materials, such as polylactic acid (PLA) and hydroxyapatite (HAp), which are ideal in this approach, have been used in this study to investigate the dissolution of clodronate (non-nitrogen-containing bisphosphonate) in a new release system. The effects of coral structure-derived HAp and the release kinetics of the composites were evaluated. The release kinetics of clodronate from PLA-BP and PLA-HAp-BP systems seemed to follow the power law model described by Korsmeyer-Peppas. Drug release was quantified by 31 P-NMR with detection and quantification limits of 9.2 and 30.7 mM, respectively. The results suggest that these biocomposite systems could be tuned to release clodronate for both relatively short and prolonged period of time. In addition to drug delivery, the degradation of HAp supplies both Ca 2+ and phosphate ions that can help in bone mineralization. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Biodegradable, elastomeric coatings with controlled anti-proliferative agent release for magnesium-based cardiovascular stents.

PubMed

Gu, Xinzhu; Mao, Zhongwei; Ye, Sang-Ho; Koo, Youngmi; Yun, Yeoheung; Tiasha, Tarannum R; Shanov, Vesselin; Wagner, William R

2016-08-01

Vascular stent design continues to evolve to further improve the efficacy and minimize the risks associated with these devices. Drug-eluting coatings have been widely adopted and, more recently, biodegradable stents have been the focus of extensive evaluation. In this report, biodegradable elastomeric polyurethanes were synthesized and applied as drug-eluting coatings for a relatively new class of degradable vascular stents based on Mg. The dynamic degradation behavior, hemocompatibility and drug release were investigated for poly(carbonate urethane) urea (PCUU) and poly(ester urethane) urea (PEUU) coated magnesium alloy (AZ31) stents. Poly(lactic-co-glycolic acid) (PLGA) coated and bare stents were employed as control groups. The PCUU coating effectively slowed the Mg alloy corrosion in dynamic degradation testing compared to PEUU-coated, PLGA-coated and bare Mg alloy stents. This was confirmed by electron microscopy, energy-dispersive x-ray spectroscopy and magnesium ion release experiments. PCUU-coating of AZ31 was also associated with significantly reduced platelet adhesion in acute blood contact testing. Rat vascular smooth muscle cell (rSMC) proliferation was successfully inhibited when paclitaxel was released from pre-loaded PCUU coatings. The corrosion retardation, low thrombogenicity, drug loading capacity, and high elasticity make PCUU an attractive option for drug eluting coating on biodegradable metallic cardiovascular stents. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a CO2 -releasing coformulation based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae.

PubMed

Vemmer, Marina; Schumann, Mario; Beitzen-Heineke, Wilhelm; French, Bryan W; Vidal, Stefan; Patel, Anant V

2016-11-01

CO 2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO 2 -emitting formulations need to be developed. The aim of the present work was to develop a slow-release bead system in order to bridge the gap between application and hatching of western corn rootworm larvae. We compared different Ca-alginate beads containing Saccharomyces cerevisiae for their potential to release CO 2 over a period of several weeks. The addition of starch improved CO 2 release, resulting in significantly higher CO 2 concentrations in soil for at least 4 weeks. The missing amylase activity was compensated for either by microorganisms present in the soil or by coencapsulation of Beauveria bassiana. Formulations containing S. cerevisiae, starch and B. bassiana were attractive for western corn rootworm larvae within the first 4 h following exposure; however, when considering the whole testing period, the maize root systems remained more attractive for the larvae. Coencapsulation of S. cerevisiae, starch and B. bassiana is a promising approach for the development of attractive formulations for soil applications. For biological control strategies, the attractiveness needs to be increased by phagostimuli to extend contact between larvae and the entomopathogenic fungus growing out of these formulations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Development and agronomical validation of new fertilizer compositions of high bioavailability and reduced potential nutrient losses.

PubMed

Erro, Javier; Urrutia, Oscar; San Francisco, Sara; Garcia-Mina, Jose M

2007-09-19

To optimize the economical cost of each unit of fertilizer applied and to reduce the environmental contamination caused by nutrient losses, the development of highly efficient granulated fertilizers is of great importance. This study proposes a strategy that consists of developing specific fertilizers having nutrient release patterns that are dependent on plant activity in the rhizosphere. This type of fertilizer is named "rhizosphere-controlled fertilizer" (RCF fertilizer). This fertilizer is based on the introduction of an organomineral matrix composed of metal [Mg (Ca is also possible), Zn (Fe and other metals are also possible)]-humic phosphates. The presence of this matrix modifies the nutrient release pattern of the fertilizer. In this way there are two main nutrient fractions: (i) a water-soluble fraction or "starter" fraction and (ii) a "rhizosphere-controlled" fraction insoluble in water but soluble by the action of the rhizospheric acids released by plants and microorganisms. This study shows the chemical and structural characterization of the organomineral matrix, as well as its efficiency in slowing the nutrient release rate of the RCF fertilizer, principally with respect to P and N. It is demonstrated how these properties of the matrix were also reflected in the significant reduction in both ammonia volatilization and N leaching in a pot system consisting of wheat plants cultivated in a calcareous soil and fertilized with a RCF fertilizer.

Observed rate of ionization in shaped-charge releases of barium in the ionosphere

NASA Technical Reports Server (NTRS)

Hallinan, Thomas J.

1988-01-01

Data from 36 Ba shaped-charge releases carried out at an angle of less than 25 deg to the magnetic field, by the technique of Wescott et al. (1972) and Michel (1974), were examined for evidence of a sustained rate of ionization in excess of that attributable to sunlight. In four of the experiments, the time constant for the decay of the neutrals was measured using an ultrasensitive color TV camera and was found to have a value of about 30 sec, consistent with slow (solar) ionization. Although the qualitative appearance of most jets was found to be consistent with a slow process of ionization, some releases produced a thin confined jet that was suggestive of rapid ionization. Two of these jets were analyzed in detail, but no evidence of anomalous ionization was produced. The data obtained in this work agree with the geometrical predictions of the Swift model.

Use of slow-release fertilizer and biopolymers for stimulating hydrocarbon biodegradation in oil-contaminated beach sediments.

PubMed

Xu, Ran; Yong, Li Ching; Lim, Yong Giak; Obbard, Jeffrey Philip

2005-01-01

Nutrient concentration and hydrocarbon bioavailability are key factors affecting biodegradation rates of oil in contaminated beach sediments. The effect of a slow-release fertilizer, Osmocote, as well as two biopolymers, chitin and chitosan, on the bioremediation of oil-spiked beach sediments was investigated using an open irrigation system over a 56-day period under laboratory conditions. Osmocote was effective in sustaining a high level of nutrients in leached sediments, as well as elevated levels of microbial activity and rates of hydrocarbon biodegradation. Chitin was more biodegradable than chitosan and gradually released nitrogen into the sediment. The addition of chitin or chitosan to the Osmocote amended sediments enhanced biodegradation rates of the alkanes relative to the presence of Osmocote alone, where chitosan was more effective than chitin due to its greater oil sorption capacity. Furthermore, chitosan significantly enhanced the biodegradation rates of all target polycyclic aromatic hydrocarbons.

Study on encapsulation of chlorine dioxide in gelatin microsphere for reducing release rate

PubMed Central

Ci, Ying; Wang, Lin; Guo, Yanchuan; Sun, Ruixue; Wang, Xijie; Li, Jinyou

2015-01-01

Objective: This study aims to explore the effects of encapsulation of chlorine dioxide in a hydrophilic biodegradable polymer gelatin to reduce its release rate. Methods: An emulsification-coacervation method was adopted. The characterizations of chlorine dioxide-gelatin microspheres were described. Using UV-vis spectrophotometer the λmax of chlorine dioxide was observed at 358 nm. The particle size and distribution of chlorine oxide-gelatin microspheres was measured by a dynamic light scattering (DLS) method, the diameter was (1400~1900) nm. The entrapment of chlorine dioxide-gelatin microspheres was confirmed by IR. The surface morphology, size, and shape of chlorine dioxide-gelatin microspheres were analyzed using Scanning electron microscope (SEM). Results: It showed that the encapsulated microspheres size was around 2000 nm with uniform distribution. The percentage entrapment of chlorine dioxide in the encapsulated samples was about 80~85%. A slow release study of chlorine dioxide from the encapsulated biopolymer (gelatin) in air was also carried out, which showed continuous release up to ten days. Conclusions: It can be concluded that it is possible to make a slow release formulation of ClO2 by entrapped in a hydrophilic biodegradable polymer gelatin. ClO2-gelatin microspheres can stable release low concentration ClO2 gas over an extended period. PMID:26550151

Slow-release Permanganate Gel (SRP-G) for Groundwater Remediation: Spreading, Gelation, and Release in Porous and Low-Permeability Media

NASA Astrophysics Data System (ADS)

Lee, E. S.; Hastings, J.; Kim, Y.

2015-12-01

Dense nonaqueous phase liquids (DNAPLs) like trichloroethylene (TCE) serve as the most common form of groundwater pollution in the world. Pore-plugging by the solid oxidation product MnO2 and limited lateral dispersion of the oxidant are two common problems with existing in-situ chemical oxidation (ISCO) schemes that could be alleviated through the development of a delayed gelation method for oxidant delivery. The objective of the current study was to further develop and optimize slow-release permanganate gel (SRP-G), a solution comprising colloidal silica and KMnO4, as a novel low-cost treatment option for large and dilute TCE plumes in groundwater. Batch tests showed that gelation could be delayed through manipulation of KMnO4 concentration, pH, and silica particle size of the SRP-G solution. In flow-through columns and flow-tanks filled with saturated sands, silica concentration had little effect on the gelation lag stage and release rate, but increasing silica concentration was associated with increasing release duration. When compared to a pure KMnO4 solution, visual observations and [MnO4-] measurements from flow tank tests demonstrated that the SRP-G prolonged the release duration and enhanced lateral spreading of the oxidant.

Importance of dual delivery systems for bone tissue engineering.

PubMed

Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

2016-03-10

Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantifying Ca2+ release and inactivation of Ca2+ release in fast- and slow-twitch muscles.

PubMed

Barclay, C J

2012-12-01

The aims of this study were to quantify the Ca(2+) release underlying twitch contractions of mammalian fast- and slow-twitch muscle and to comprehensively describe the transient inactivation of Ca(2+) release following a stimulus. Experiments were performed using bundles of fibres from mouse extensor digitorum longus (EDL) and soleus muscles. Ca(2+) release was quantified from the amount of ATP used to remove Ca(2+) from the myoplasm following stimulation. ATP turnover by crossbridges was blocked pharmacologically (N-benzyl-p-toluenesulphonamide for EDL, blebbistatin for soleus) and muscle heat production was used as an index of Ca(2+) pump ATP turnover. At 20°C, Ca(2+) release in response to a single stimulus was 34 and 84 μmol (kg muscle)(-1) for soleus and EDL, respectively, and increased with temperature (30°C: soleus, 61 μmol kg(-1); EDL, 168 μmol kg(-1)). Delivery of another stimulus within 100 ms of the first produced a smaller Ca(2+) release. The maximum magnitude of the decrease in Ca(2+) release was greater in EDL than soleus. Ca(2+) release recovered with an exponential time course which was faster in EDL (mean time constant at 20°C, 32.1 ms) than soleus (65.6 ms) and faster at 30°C than at 20°C. The amounts of Ca(2+) released and crossbridge cycles performed are consistent with a scheme in which Ca(2+) binding to troponin-C allowed an average of ∼1.7 crossbridge cycles in the two muscles.

Quantifying Ca2+ release and inactivation of Ca2+ release in fast- and slow-twitch muscles

PubMed Central

Barclay, C J

2012-01-01

The aims of this study were to quantify the Ca2+ release underlying twitch contractions of mammalian fast- and slow-twitch muscle and to comprehensively describe the transient inactivation of Ca2+ release following a stimulus. Experiments were performed using bundles of fibres from mouse extensor digitorum longus (EDL) and soleus muscles. Ca2+ release was quantified from the amount of ATP used to remove Ca2+ from the myoplasm following stimulation. ATP turnover by crossbridges was blocked pharmacologically (N-benzyl-p-toluenesulphonamide for EDL, blebbistatin for soleus) and muscle heat production was used as an index of Ca2+ pump ATP turnover. At 20°C, Ca2+ release in response to a single stimulus was 34 and 84 μmol (kg muscle)−1 for soleus and EDL, respectively, and increased with temperature (30°C: soleus, 61 μmol kg−1; EDL, 168 μmol kg−1). Delivery of another stimulus within 100 ms of the first produced a smaller Ca2+ release. The maximum magnitude of the decrease in Ca2+ release was greater in EDL than soleus. Ca2+ release recovered with an exponential time course which was faster in EDL (mean time constant at 20°C, 32.1 ms) than soleus (65.6 ms) and faster at 30°C than at 20°C. The amounts of Ca2+ released and crossbridge cycles performed are consistent with a scheme in which Ca2+ binding to troponin-C allowed an average of ∼1.7 crossbridge cycles in the two muscles. PMID:23027818

Ca2+ release by inositol-trisphosphorothioate in isolated triads of rabbit skeletal muscle.

PubMed Central

Valdivia, C; Valdivia, H H; Potter, B V; Coronado, R

1990-01-01

The effectiveness of the nonmetabolizable second messenger analogue DL-myo-inositol 1,4,5-trisphosphorothioate (IPS3) described by Cooke, A. M., R. Gigg, and B. V. L. Potter, (1987b. Jour. Chem. Soc. Chem. Commun. 1525-1526.) was examined in triads purified from rabbit skeletal muscle. A Ca2+ electrode uptake-release assay was used to determine the size and sensitivity of the IPS3-releasable pool of Ca2+ in isolated triads. Uptake was initiated by 1 mM MgATP, pCa 5.8, pH 7.5 Release was initiated when the free Ca2+ had lowered to pCa approximately 7. We found that 5-25 microM myo-inositol 1,4,5-trisphosphate (IP3), and separately IPS3, consistently released 5-20% of the Ca2+ pool actively loaded into triads. Single channel recording was used to determine if ryanodine receptor Ca2+ release channels were affected by IPS3 at the same myoplasmic Ca2+ and IPS3 concentrations. Open probability of ryanodine receptor Ca2+ release channels was monitored in triads fused to bilayers over long periods (200 s) in the absence and following addition of 30 microM IPS3 to the same channel. At myoplasmic pCa approximately 7, IPS3 had no effect in the absence of MgATP (Po = 0.0094 +/- 0.001 in control and Po = 0.01 +/- 0.006 after IPS3) and slightly increased activity in the presence of 1 mM MgATP (Po = 0.024 +/- 0.03 in control and Po = 0.05 +/- 0.03 after IPS3). Equally small effects were observed at higher myoplasmic Ca2+. The onset of channel activation by IPS3 or IP3 was slow, on the time scale 20-60 s. We suggest that in isolated triads of rabbit skeletal muscle, IP3-induced release of stored Ca2+ is probably not mediated by the opening of Ca2+ release channels. PMID:2168221

Controls on Nitrous Oxide Emissions from the Hyporheic Zones of Streams.

PubMed

Quick, Annika M; Reeder, W Jeffery; Farrell, Tiffany B; Tonina, Daniele; Feris, Kevin P; Benner, Shawn G

2016-11-01

The magnitude and mechanisms of nitrous oxide (N 2 O) release from rivers and streams are actively debated. The complex interactions of hydrodynamic and biogeochemical controls on emissions of this important greenhouse gas preclude prediction of when and where N 2 O emissions will be significant. We present observations from column and large-scale flume experiments supporting an integrative model of N 2 O emissions from stream sediments. Our results show a distinct, replicable, pattern of nitrous oxide generation and consumption dictated by subsurface (hyporheic) residence times and biological nitrogen reduction rates. Within this model, N 2 O emission from stream sediments requires subsurface residence times (and microbially mediated reduction rates) be sufficiently long (and fast reacting) to produce N 2 O by nitrate reduction but also sufficiently short (or slow reacting) to limit N 2 O conversion to dinitrogen gas. Most subsurface exchange will not result in N 2 O emissions; only specific, intermediate, residence times (reaction rates) will both produce and release N 2 O to the stream. We also confirm previous observations that elevated nitrate and declining organic carbon reactivity increase N 2 O production, highlighting the importance of associated reaction rates in controlling N 2 O accumulation. Combined, these observations help constrain when N 2 O release will occur, providing a predictive link between stream geomorphology, hydrodynamics, and N 2 O emissions.

Contrasting guest binding interaction of cucurbit[7-8]urils with neutral red dye: controlled exchange of multiple guests.

PubMed

Shaikh, Mhejabeen; Choudhury, Sharmistha Dutta; Mohanty, Jyotirmayee; Bhasikuttan, Achikanath C; Pal, Haridas

2010-07-14

Interactions among macrocyclic hosts and dyes/drugs have been explored extensively for their direct usage in controlled uptake and release of large number of potential drug molecules. In this paper we report the non-covalent interaction of cucurbit[8]uril macrocycle (CB8) with a biologically important dye, neutral red, by absorption and fluorescence spectroscopy. A comparative analysis with the complexation behaviour of the dye with CB7, the lower homologue of CB8, indicates contrasting guest binding behaviour with significant changes in the photophysical characteristics of the dye. While CB7 interaction leads to a 1 ratio 1 stoichiometry resulting in approximately 6 fold enhancement in the fluorescence emission of the dye, CB8 displays signatures for a 1 ratio 2 host-guest stoichiometry with drastic reduction in the fluorescence emission. Apart from the evaluation of approximately 2 unit shift in the protolytic equilibrium on complexation (pK(a) shift), the measurements with tryptophan established a selective guest exchange to favour a co-localized dimer inside the CB8 cavity. In a protein medium (BSA), the 1 ratio 2 complex was converted to a 1 ratio 1 ratio 1 CB8-NRH(+)-BSA complex. The finding that NRH(+) can be transferred from CB8 to BSA, even though the binding constant for NRH(+)-CB8 is much higher than NRH(+)-BSA, is projected for a controlled slow release of NRH(+) towards BSA. Since the release and activity of drugs can be controlled by regulating the protolytic equilibrium, the macromolecular encapsulation and release of NRH(+) demonstrated here provide information relevant to host-guest based drug delivery systems and its applications.

Recovery from Short Term Intense Exercise: Its Relation to Capillary Supply and Lactate Release,

DTIC Science & Technology

1982-01-01

accumulate at a higher rate in fast twitch (FT or Type II) than in slow twitch (ST or Type I) fibers of exercised muscles . Lactate form- ed and accumulated...is made up by a high percentage of FT fibers than can be expected in a " slow twitch " muscle . Moreover, the over-all metabolic profile of the ST fiber...local muscular fatigue. Eur. J. Appl. Physiol. 38, 9-15 (1978b) Baldwin, K.M., Tipton, C.M.: Work and metabolic patterns of fast and slow twitch

Lyophilized Silk Fibroin Hydrogels for the Sustained Local Delivery of Therapeutic Monoclonal Antibodies

PubMed Central

Guziewicz, Nicholas; Best, Annie; Perez-Ramirez, Bernardo; Kaplan, David L.

2011-01-01

The development of sustained delivery systems compatible with protein therapeutics continues to be a significant unmet need. A lyophilized silk fibroin hydrogel matrix (lyogel) for the sustained release of pharmaceutically relevant monoclonal antibodies is described. Sonication of silk fibroin prior to antibody incorporation avoids exposing the antibody to the sol-gel transition inducing shear stress. Fourier Transform Infrared (FTIR) analysis showed no change in silk structural composition between hydrogel and lyogel or with increasing silk fibroin concentration. Antibody release from hydrogels occurred rapidly over 10 days regardless of silk concentration. Upon lyophilization, sustained antibody release was observed over 38 days from lyogels containing 6.2% (w/w) silk fibroin and above. In 3.2% (w/w) silk lyogels, antibody release was comparable to hydrogels. Swelling properties of lyogels followed a similar threshold behavior. Lyogels at 3.2% (w/w) silk recovered approximately 90% of their fluid mass upon rehydration, while approximately 50% fluid recovery was observed at 6.2% (w/w) silk and above. Antibody release was primarily governed by hydrophobic/hydrophilic silk-antibody interactions and secondarily altered by the hydration resistance of the lyogel. Hydration resistance was controlled by altering β-sheet (crystalline) density of the matrix. The antibody released from lyogels maintained biological activity. Silk lyogels offer an advantage as a delivery matrix over other hydrogel materials for the slow release of the loaded protein, making lyogels suitable for long-term sustained release applications. PMID:21216004

Graphene-based active slow surface plasmon polaritons

PubMed Central

Lu, Hua; Zeng, Chao; Zhang, Qiming; Liu, Xueming; Hossain, Md Muntasir; Reineck, Philipp; Gu, Min

2015-01-01

Finding new ways to control and slow down the group velocity of light in media remains a major challenge in the field of optics. For the design of plasmonic slow light structures, graphene represents an attractive alternative to metals due to its strong field confinement, comparably low ohmic loss and versatile tunability. Here we propose a novel nanostructure consisting of a monolayer graphene on a silicon based graded grating structure. An external gate voltage is applied to graphene and silicon, which are separated by a spacer layer of silica. Theoretical and numerical results demonstrate that the structure exhibits an ultra-high slowdown factor above 450 for the propagation of surface plasmon polaritons (SPPs) excited in graphene, which also enables the spatially resolved trapping of light. Slowdown and trapping occur in the mid-infrared wavelength region within a bandwidth of ~2.1 μm and on a length scale less than 1/6 of the operating wavelength. The slowdown factor can be precisely tuned simply by adjusting the external gate voltage, offering a dynamic pathway for the release of trapped SPPs at room temperature. The presented results will enable the development of highly tunable optoelectronic devices such as plasmonic switches and buffers. PMID:25676462

Slow-Release Fertilizers For Plants

NASA Technical Reports Server (NTRS)

Ming, Douglas W.; Golden, D. C.

1995-01-01

Synthetic mineral provides growing plants with nutrients, including micronutrients. Dissolves slowly in moist soil or in hydroponic solution, releasing constituents. Mineral synthetic apatite into which nutrients calcium, phosphorous, iron, manganese, copper, zinc, molybdenum, chlorine, boron, and sulfur incorporated in form of various salts. Each pellet has homogeneous inorganic composition. Composition readily adjusted to meet precise needs of plant.

Thirty-year assessment of released, overtopped white oaks

Treesearch

C. Miller; S. Grayson; A. Houser; W. Clatterbuck; K. Kuers

2011-01-01

White oak (Quercus alba L.) is a slow-growing species that is often overtopped in the mixed upland hardwood forests of the Cumberland Plateau. Forest managers have concerns about the potential economic value of releasing overtopped white oaks to become valuable crop trees. This study follows the growth and development of 104 overtopped white oaks...

Modulation of the formation and release of bovine SRS-A in vitro by several anti-anaphylactic drugs.

PubMed

Burka, J F; Eyre, P

1975-01-01

Slow-reacting substance of anaphylaxis (SRS-A) is released immunologically from bovine lung in vitro. Various drugs known to protect calves and other animals during anaphylaxis were tested to investigate their modulation of the formation and release of SRS-A. The anti-inflammatory drugs, meclofenamate and aspirin, potentiated SRS-A release. Chlorphenesin and diethylcarbamazine citrate at high concentrations both inhibited SRS-A release. Two new anti-anaphylactic drugs, PR-D-92-EA and M&B 22,948, were particularly effective in inhibiting SRS-A release at low concentrations. The possible modes of actions of these drugs are discussed.

Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

PubMed Central

Garcia, Bonnie G.; Neely, M. Diana

2010-01-01

Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion–induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease. PMID:20118184

Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway

PubMed Central

Zhong, Cheng; Feng, Jun; Lin, Xiangjin; Bao, Qi

2017-01-01

Graphene oxide (GO) has been used as a delivery vehicle for small molecule drugs and nucleotides. To further investigate GO as a smart biomaterial for the controlled release of cargo molecules, we hypothesized that GO may be an appropriate delivery vehicle because it releases bone morphogenetic protein 2 (BMP2). GO characterization indicated that the size distribution of the GO flakes ranged from 81.1 nm to 45,749.7 nm, with an approximate thickness of 2 nm. After BMP2 adsorption onto GO, Fourier-transformed infrared spectroscopy (FTIR) and thermal gravimetric analysis were performed. Compared to GO, BMP2-GO did not induce significant changes in the characteristics of the materials. GO continuously released BMP2 for at least 40 days. Bone marrow stem cells (BMSCs) and chondrocytes were treated with BMP2-GO in interleukin-1 media and assessed in terms of cell viability, flow cytometric characterization, and expression of particular mRNA. Compared to GO, BMP2-GO did not induce any significant changes in biocompatibility. We treated osteoarthritic rats with BMP2 and BMP2-GO, which showed significant differences in Osteoarthritis Research Society International (OARSI) scores (P<0.05). Quantitative assessment revealed significant differences compared to that using BMP2 and BMP2-GO (P<0.05). These findings indicate that GO may be potentially used to control the release of carrier materials. The combination of BMP2 and GO slowed the progression of NF-κB-activated degenerative changes in osteoarthritis. Therefore, we infer that our BMP2-GO strategy could alleviate the NF-κB pathway by inducing continuous BMP2 release. PMID:28243085

Effects of N Fertilizer Sources and Tillage Practices on NH3 Volatilization, Grain Yield, and N Use Efficiency of Rice Fields in Central China

PubMed Central

Liu, Tianqi; Huang, Jinfeng; Chai, Kaibin; Cao, Cougui; Li, Chengfang

2018-01-01

Tillage practices and nitrogen (N) sources are important factors affecting rice production. Few studies, however, have examined the interactions between tillage practices and N fertilizer sources on NH3 volatilization, nitrogen use efficiency (NUE), and rice grain yield. This study aimed to investigate the effects of N fertilizer sources (no N fertilizer, inorganic N fertilizer, organic N fertilizer alone, organic N fertilizer plus inorganic N fertilizer, and slow-release N fertilizer plus inorganic N fertilizer) and tillage practices (no-tillage [NT] and conventional intensive tillage [CT]) on NH3 flux, grain yield, and NUE in the rice field of central China. N sources significantly affected NH3 volatilization, as the cumulative volatilization from the treatments of inorganic N fertilizer, organic N fertilizer, organic N fertilizer plus inorganic N fertilizer, slow-release N fertilizer plus inorganic N fertilizer was 4.19, 2.13, 3.42, and 2.23 folds in 2013, and 2.49, 1.68, 2.08, and 1.85 folds in 2014 compared with that under no N fertilizer treatment, respectively. The organic N fertilizer treatment had the lowest grain yield and NUE among all N fertilizer treatments, while slow-release N fertilizer plus inorganic N fertilizer treatment led to relatively higher grain yield and the greatest N use efficiency. Moreover, NT only markedly increased NH3 volatilization from basal fertilizer by 10–14% in average compared with CT, but had no obvious effects on total volatilization during the whole seasons. Tillage practices had no significant effects on grain yield and NUE. Our study suggested that the combination of slow-release N fertilizer plus inorganic N fertilizer and NT might be a sustainable method for mitigating greenhouse gas and NH3 emissions and improving grain yield and NUE in paddy fields of central China. PMID:29623086

Electrospray-assisted encapsulation of caffeine in alginate microhydrogels.

PubMed

Nikoo, Alireza Mehregan; Kadkhodaee, Rassoul; Ghorani, Behrouz; Razzaq, Hussam; Tucker, Nick

2018-05-02

One of the major challenges with microencapsulation and delivery of low molecular weight bioactive compounds is their diffusional loss during storage and process conditions as well as under gastric conditions. In an attempt to slow down the release rate of core material, electrospray fabricated calcium alginate microhydrogels were coated with low molecular weight and high molecular weight chitosans. Caffeine as a hydrophilic model compound was used due to its several advantages on human behavior especially increasing consciousness. Mathematical modeling of the caffeine release by fitting the data with Korsmeyer-Peppas model showed that Fick's diffusion law could be the prevalent mechanism of the release. Electrostatic interaction between alginate and chitosan (particularly in the presence of 1% low molecular weight chitosan) provided an effective barrier against caffeine release and significantly reduced swelling of particles compared to control samples. The results of this study demonstrated that calcium alginate microhydrogels coated by chitosan could be used for encapsulation of low molecular compounds. However, more complementary research must be done in this field. In addition, electrospray, by producing monodisperse particles, would be as an alternative method for fabrication of microparticles based on natural polymers. Copyright © 2018. Published by Elsevier B.V.

The pH-dependent and enzymatic release of cytarabine from hydrophilic polymer conjugates.

PubMed

Pola, R; Janoušková, O; Etrych, T

2016-10-20

Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropa-noyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl-phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine. The enzymatic release of cytarabine from the conjugate containing a GFLG spacer utilizing cathepsin B was verified. In addition to enzymolysis, the pH-dependent hydrolysis of cytarabine from both copolymers was also confirmed. Approximately 40 % and 20 % of the drug was released by spontaneous hydrolysis at pH 7.4 within 72 h from the polymer conjugates with the GFLG and beta-Ala spacers, respectively. At pH 6.0, the spontaneous hydrolysis slowed down, and less than 10 % of the drug was liberated within 72 h. The results of the cytotoxicity evaluation of the polymer conjugates in vitro against various cell lines showed that the cytotoxicity of the polymer conjugates is approximately three times lower in comparison to free cytarabine.

Dopamine and serotonin: influences on male sexual behavior.

PubMed

Hull, Elaine M; Muschamp, John W; Sato, Satoru

2004-11-15

Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.

Antibacterial Surgical Silk Sutures Using a High-Performance Slow-Release Carrier Coating System.

PubMed

Chen, Xiaojie; Hou, Dandan; Wang, Lu; Zhang, Qian; Zou, Jiahan; Sun, Gang

2015-10-14

Sutures are a vital part for surgical operation, and suture-associated surgical site infections are an important issue of postoperative care. Antibacterial sutures have been proved to reduce challenging complications caused by bacterial infections. In recent decades, triclosan-free sutures have been on their way to commercialization. Alternative antibacterial substances are becoming relevant to processing surgical suture materials. Most of the antibacterial substances are loaded directly on sutures by dipping or coating methods. The aim of this study was to optimize novel antibacterial braided silk sutures based on levofloxacin hydrochloride and poly(ε-caprolactone) by two different processing sequences, to achieve suture materials with slow-release antibacterial efficacy and ideal physical and handling properties. Silk strands were processed into sutures on a circular braiding machine, and antibacterial treatment was introduced alternatively before or after braiding by two-dipping-two-rolling method (M1 group and M2 group). The antibacterial activity and durability against Staphylococcus aureus and Escherichia coli were tested. Drug release profiles were measured in phosphate buffer with different pH values, and release kinetics model was built to analyze the sustained drug release mechanism between the interface of biomaterials and the in vitro aqueous environment. Knot-pull tensile strength, thread-to-thread friction, and bending stiffness were determined to evaluate physical and handling properties of sutures. All coated sutures showed continuous antibacterial efficacy and slow drug release features for more than 5 days. Besides, treated sutures fulfilled U.S. Pharmacopoeia required knot-pull tensile strength. The thread-to-thread friction and bending stiffness for the M1 group changed slightly when compared with those of uncoated ones. However, physical and handling characteristics of the M2 group tend to approach those of monofilament ones. The novel suture showed acceptable in vitro cytotoxicity according to ISO 10993-5. Generally speaking, all coated sutures show potential in acting as antibacterial suture materials, and M1 group is proved to have a higher prospect for clinical applications.

A facile approach toward transition metal oxide hierarchical structures and their lithium storage properties.

PubMed

Zhang, Cuimiao; Chen, Jing; Zeng, Yi; Rui, Xianhong; Zhu, Jixin; Zhang, Wenyu; Xu, Chen; Lim, Tuti Mariana; Hng, Huey Hoon; Yan, Qingyu

2012-06-21

A simple, non-template, non-surfactant and environmentally friendly hydrothermal method is presented based on the controlled release of the reactants into the reaction solvents to induce slow nucleation and growth of three-dimensional hierarchical nanostructures of transition metal oxides. This method is a general approach, which can be used to prepare Co(3)O(4), CuO, and Ni(OH)(2)/NiO. These metal oxides with hierarchical nanostructures can be used as anode materials for lithium-ion batteries with good Li storage performance, e.g. high specific capacities and stable cyclability.

A bionanohybrid ZnAl-NADS ecological pesticide as a treatment for soft rot disease in potato (Solanum tuberosum L.).

PubMed

Morales-Irigoyen, Erika Elizabeth; de Las Mercedes Gómez-Y-Gómez, Yolanda; Flores-Moreno, Jorge Luis; Franco-Hernández, Marina Olivia

2017-09-18

Pectobacterium carotovorum (Pc) is a phytopathogenic strain that causes soft rot disease in potato (Solanum tuberosum L.), resulting in postharvest losses. Chemical control is effective for managing this disease, but overdoses cause adverse effects. Because farmers insist on using chemical agents for crop protection, it is necessary to develop more effective pesticides in which the active compound released can be regulated. In this context, we proposed the synthesis of ZnAl-NADS, in which nalidixic acid sodium salt (NADS) is linked to a ZnAl-NO 3 layered double hydroxide (LDH) host as a nanocarrier. XRD, FT-IR, and SEM analyses confirmed the successful intercalation of NADS into the interplanar LDH space. The drug release profile indicated that the maximum release was completed in 70 or 170 min for free NADS (alone) or for NADS released from ZnAl-NADS, respectively. This slow release was attributed to strong electrostatic interactions between the drug and the anion exchanger. A modulated release is preferable to the action of the bulk NADS, showing increased effectiveness and minimizing the amount of the chemical available to pollute the soil and the water. The fitting data from modified Freundlich and parabolic diffusion models explain the release behavior of the NADS, suggesting that the drug released from ZnAl-NADS bionanohybrid was carried out from the interlamellar sites, according to the ion exchange diffusion process also involving intraparticle diffusion (coeffect). ZnAl-NADS was tested in vitro against Escherichia coli (Ec) and Pc and exhibited bacteriostatic and biocidal effects at 0.025 and 0.075 mg mL -1 , respectively. ZnAl-NADS was also tested in vivo as an ecological pesticide for combating potato soft rot and was found to delay typical disease symptoms. In conclusion, ZnAl-NADS can potentially be used to control pests, infestation, and plant disease.

Novel sustained-release dosage forms of proteins using polyglycerol esters of fatty acids.

PubMed

Yamagata, Y; Iga, K; Ogawa, Y

2000-02-03

In order to develop a novel delivery system for proteins based on polyglycerol esters of fatty acids (PGEFs), we studied a model system using interferon-alpha (IFN-alpha) as the test protein. A cylindrical matrix was prepared by a heat extrusion technique using a lyophilized powder of the protein and 11 different types of synthetic PGEFs, which varied in degree of glycerol polymerization (di- and tetra-), chain length of fatty acids (myristate, palmitate and stearate) and degree of fatty acid esterification (mono-, di- and tri-). In an in-vitro release study using an enzyme-linked immunosorbent assay (ELISA) as a detection method, the matrices prepared from a monoglyceride (used for comparison) and from diglycerol esters exhibited a biphasic release pattern with a large initial burst followed by slow release. In contrast, the matrices prepared from tetraglycerol esters showed a steady rate of release without a large initial burst. In an in vivo release study, initial bursts of IFN-alpha release were, also, dramatically reduced when the matrices were prepared from the tetraglycerol esters of palmitate and stearate, and the mean residence time (MRT) of IFN-alpha was prolonged, whereas the matrices prepared from monoglyceride and from diglycerol esters showed large initial bursts of IFN-alpha release. Since the release rates from the matrices prepared from the tetraglycerol esters of palmitate and stearate were governed by Jander's equation modified for a cylindrical matrix, the release from those matrices was concluded to be a diffusion-controlled process. The bioavailability of IFN-alpha after implantation of the matrix formulation prepared using all types of PGEFs, except for tetraglycerol triesters, was almost equivalent to that after injection of IFN-alpha solution; consequently, IFN-alpha in these matrices appears to remain stable during the release period.

Calcium regulates vesicle replenishment at the cone ribbon synapse

PubMed Central

Babai, Norbert; Bartoletti, Theodore M.; Thoreson, Wallace B.

2010-01-01

Cones release glutamate-filled vesicles continuously in darkness and changing illumination modulates this release. Because sustained release in darkness is governed by vesicle replenishment rates, we analyzed how cone membrane potential regulates replenishment. Synaptic release from cones was measured by recording post-synaptic currents in Ambystoma tigrinum horizontal or OFF bipolar cells evoked by depolarization of simultaneously voltage-clamped cones. We measured replenishment after attaining a steady-state between vesicle release and replenishment using trains of test pulses. Increasing Ca2+ currents (ICa) by changing the test step from −30 to −10 mV increased replenishment. Lengthening −30 mV test pulses to match the Ca2+ influx during 25 ms test pulses to −10 mV produced similar replenishment rates. Reducing Ca2+ driving force by using test steps to +30 mV slowed replenishment. Using UV flashes to reverse inhibition of ICa by nifedipine accelerated replenishment. Increasing [Ca2+]i by flash photolysis of caged Ca2+ also accelerated replenishment. Replenishment, but not the initial burst of release, was enhanced by using an intracellular Ca2+ buffer of 0.5 mM EGTA rather than 5 mM EGTA, and diminished by 1 mM BAPTA. This suggests that although release and replenishment and release exhibited similar Ca2+-dependencies, release sites are <200 nm from Ca2+ channels but replenishment sites are >200 nm away. Membrane potential thus regulates replenishment by controlling Ca2+ influx, principally by effects on replenishment mechanisms but also by altering releasable pool size. This in turn provides a mechanism for converting changes in light intensity into changes in sustained release at the cone ribbon synapse. PMID:21106825

Effects of atropine on refractive development, dopamine release, and slow retinal potentials in the chick.

PubMed

Schwahn, H N; Kaymak, H; Schaeffel, F

2000-01-01

Atropine has previously been found to suppress visually induced myopia both in animals and humans. The mechanism of its action is unclear. We have studied its retinal effects in an in vitro preparation, using the retina-pigment epithelium-choroid complex of the chick eye. In vivo, deprivation myopia was induced by translucent goggles. Atropine solution was injected into the vitreous at two-day intervals. Dopamine release from the retina following atropine injection in vivo and from the in vitro retina preparation was quantified by HPLC-EC. In vitro preparations of the isolated chick retina-pigment epithelium-choroid were superfused with atropine. Light-induced potentials (local ERG), slow standing potentials from the retinal pigment epithelium/neural retina, and extracellular potassium concentrations were recorded. In line with previous findings, intravitreal injections of atropine (25 microg, 250 microg) reduced deprivation myopia in a dose-dependent manner. Atropine increased the release of the neurotransmitter dopamine into the superfusate in vitro at 100-500 microM and into the vitreous in vivo at 250 microg. Before an increase was measured in the vitreous, the retinal dopamine content was elevated. In concentrations equivalent to the intravitreal concentration to suppress myopia in vivo (200-800 microM), atropine induced spreading depression (SD) in the in vitro preparation. In contrast, muscarinic agonists, acetylcholine and pilocarpine, did not induce SD. Atropine reduced the ERG b- and d-wave, led to damped oscillations of RPE potentials, and reversed the ERG c-wave. Atropine suppressed myopia only at doses at which severe nonspecific side effects were observed in the retina. Atropine seems to intrude massively into the vital functions of the retina as indicated by the occurrence of SD. We conclude that atropine, by inducing SD, boosts neurotransmitter release from cellular stores, which may cancel out a presumed retinal signal that controls eye growth and through this, myopia.

Lipid transfer in oil-in-water isasome emulsions: influence of arrested dynamics of the emulsion droplets entrapped in a hydrogel.

PubMed

Iglesias, Guillermo Ramón; Pirolt, Franz; Sadeghpour, Amin; Tomšič, Matija; Glatter, Otto

2013-12-17

The transfer kinetics of lipids between internally self-assembled droplets of O/W emulsions is studied. The droplets (isasomes) consist of various liquid-crystalline phases or W/O microemulsions stabilized by a polymeric stabilizer F127. The various internal phases were identified by the relative peak positions in the small-angle X-ray scattering (SAXS) curves. An arrested system composed of isasomes embedded in a gel matrix actually provides an additional possibility to control these systems in terms of the release of various host molecules. These experiments have been applied to examine the kinetics of the internal phase reorganization imposed by the lipids' release and uptake by the droplets embedded in a κ-carrageenan (KC) hydrogel network. Increasing the concentration of the gelling agent slows down the transfer from one droplet to the other through the aqueous phase. We examined the region where the free diffusion is stopped. i.e., the point where the system changes from the ergodic to the nonergodic state and the kinetics is essentially slowed down. This effect can be balanced by the addition of small amounts of free polymeric stabilizer, which speeds up the kinetics. This is even possible in the case of highly arrested dynamics of the emulsion droplets, as found for the highest KC hydrogel concentrations forming nonergodic systems.

Effect of fertilizer formulation and bioaugmentation on biodegradation and leaching of crude oils and refined products in soils.

PubMed

Coulon, F; Brassington, K J; Bazin, R; Linnet, P E; Thomas, K A; Mitchell, T R; Lethbridge, G; Smith, J W N; Pollarda, S J T

2012-09-01

The effects of soil characteristics and oil types as well as the efficacy of two fertilizer formulations and three bioaugmentation packages in improving the bioremediation of oil-contaminated soils were assessed as a means of ex situ treatment selection and optimization through seven laboratory microcosm studies. The influence of bioremediation on leaching of oil from the soil was also investigated. The studies demonstrated the benefits ofbiostimulation to overcome nutrient limitation, as most of the soils were nutrient depleted. The application of both liquid and pelleted slow-release N and P fertilizers increased both the hydrocarbon biodegradation rates (by a factor of 1.4 to 2.9) and the percentage of hydrocarbon mass degraded (by > 30% after 12 weeks and 80% after 37 weeks), when compared with the unamended soils. Slow-release fertilizers can be particularly useful when multiple liquid applications are not practical or cost-effective. Bioaugmentation products containing inoculum plus fertilizer also increased biodegradation by 20% to 37% compared with unamended biotic controls; however, there was no clear evidence of additional benefits due to the inocula, compared with fertilizer alone. Therefore biostimulation is seen as the most cost-effective bioremediation strategy for contaminated soils with the levels of crude oil and refined products used in this study. However, site-specific considerations remain essential for establishing the treatability of oil-contaminated soils.

Sorption and vapor transmission properties of uncompressed and compressed microcellular starch foam.

PubMed

Glenn, Gregory M; Klamczynski, Artur P; Takeoka, Gary; Orts, William J; Wood, Delilah; Widmaier, Robert

2002-11-20

Microcellular starch foams (MCFs) are made by a solvent-exchange process and consist of a porous matrix with pores generally ranging from approximately 2 microm to submicrometer size. MCF may potentially be useful as a slow-release agent for volatile compounds because of its ability to sorb chemicals from the atmosphere and to absorb liquids into its porous structure, and because it can be compressed to form a starch plastic. MCF made of high-amylose corn and wheat starches was prepared with or without 2% (w/w) silicone oil (SO) or palmitic acid (PA). The MCF was loaded with 1% of various volatile compounds with vapor pressures ranging from 0.02 to 28 mm. The MCF depressed the vapor pressure from 0.37 to 37% compared to a control containing no MCF. Incorporating SO or PA in the matrix of the MCF had little effect on sorption of volatiles. Compressing MCF at 1.4, 6.9, and 69 MPa made a starch plastic with varying porosity. The vapor transmission rate of various volatile compounds through MCF was positively correlated to the vapor pressure of the test compound but was inversely proportional to the compression force used to form the starch plastic. The results indicate that uncompressed and compressed MCFs could be effective slow-release agents for a variety of volatile compounds, especially if used together.

Slow Sodium: An Oral Slowly Released Sodium Chloride Preparation

PubMed Central

Clarkson, E. M.; Curtis, J. R.; Jewkes, R. J.; Jones, B. E.; Luck, V. A.; de Wardener, H. E.; Phillips, N.

1971-01-01

The use of a slowly released oral preparation of sodium chloride is described. It was given to patients and athletes to treat or prevent acute and chronic sodium chloride deficiency. Gastrointestinal side effects were not encountered after the ingestion of up to 500 mEq in one day or 200 mEq in 10 minutes. PMID:5569979

Ponderosa pine needle length: an early indicator of release treatment effectiveness

Treesearch

Philip M. McDonald; Carl N. Skinner; Gary O. Fiddler

1992-01-01

Growth responses of ponderosa pine seedlings range from fast to slow after release and often demonstrate the effectiveness of the prescribed treatments. Although several morphological parameters have have identified as being sensitive to competition, no link to future growth and treatment effectiveness has been made. Shrubs and grasses in four 1- to 3-year-old...

Oral, Slow-Release Ivermectin: Biting Back at Malaria Vectors.

PubMed

Chaccour, Carlos J; Rabinovich, N Regina

2017-03-01

Bellinger and colleagues offer an elegant twist for a promising new tool against malaria. This formulation is designed to release ivermectin, a mosquito-killing drug for 10 days after a single oral dose. This could reduce the vector population and serve as a complementary tool for malaria elimination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Field and laboratory investigations of inactivation of viruses (PRD1 and MS2) attached to iron oxide-coated quartz san

USGS Publications Warehouse

Ryan, Joseph N.; Harvey, Ronald W.; Metge, David W.; Elimelech, Menachem; Navigato, Theresa; Pieper, Ann P.

2002-01-01

Field and laboratory experiments were conducted to investigate inactivation of viruses attached to mineral surfaces. In a natural gradient transport field experiment, bacteriophage PRD1, radiolabeled with 32P, was injected into a ferric oxyhydroxide-coated sand aquifer with bromide and linear alkylbenzene sulfonates. In a zone of the aquifer contaminated by secondary sewage infiltration, small fractions of infective and 32P-labeled PRD1 broke through with the bromide tracer, followed by the slow release of 84% of the 32P activity and only 0.011% of the infective PRD1. In the laboratory experiments, the inactivation of PRD1, labeled with 35S (protein capsid), and MS2, dual radiolabeled with 35S (protein capsid) and 32P (nucleic acid), was monitored in the presence of groundwater and sediment from the contaminated zone of the field site. Release of infective viruses decreased at a much faster rate than release of the radiolabels, indicating that attached viruses were undergoing surface inactivation. Disparities between 32P and35S release suggest that the inactivated viruses were released in a disintegrated state. Comparison of estimated solution and surface inactivation rates indicates solution inactivation is ∼3 times as fast as surface inactivation. The actual rate of surface inactivation may be substantially underestimated owing to slow release of inactivated viruses.

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

Gu, Lina; He, Xiaomei; Wu, Zhenyu, E-mail: zhenyuwuhn@sina.com

Highlights: • Mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite composite was synthesized by a simple, efficient and environmental friendly method. • The prepared material had a large surface area, high pore volume, and good magnetic separability. • DOX-loaded Fe{sub 3}O{sub 4}/hydroxyapatite composite exhibited surprising slow drug release behavior and pH-dependent behavior. - Abstract: In this contribution, we introduced a simple, efficient, and green method of preparing a mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite (HA) composite. The as-prepared material had a large surface area, high pore volume, and good magnetic separability, which made it suitable for targeted drug delivery systems. The chemotherapeutic agent doxorubicin (DOX) wasmore » used to investigate the drug release behavior of Fe{sub 3}O{sub 4}/HA composite. The drug release profiles displayed a little burst effect and pH-dependent behavior. The release rate of DOX at pH 5.8 was larger than that at pH 7.4, which could be attributed to DOX protonation in acid medium. In addition, the released DOX concentrations remained at 0.83 and 1.39 μg/ml at pH 7.4 and 5.8, respectively, which indicated slow, steady, and safe release rates. Therefore, the as-prepared Fe{sub 3}O{sub 4}/hydroxyapatite composite could be an efficient platform for targeted anticancer drug delivery.« less

Activity-dependent release of tissue plasminogen activator from the dendritic spines of hippocampal neurons revealed by live-cell imaging.

PubMed

Lochner, Janis E; Honigman, Leah S; Grant, Wilmon F; Gessford, Sarah K; Hansen, Alexis B; Silverman, Michael A; Scalettar, Bethe A

2006-05-01

Tissue plasminogen activator (tPA) has been implicated in a variety of important cellular functions, including learning-related synaptic plasticity and potentiating N-methyl-D-aspartate (NMDA) receptor-dependent signaling. These findings suggest that tPA may localize to, and undergo activity-dependent secretion from, synapses; however, conclusive data supporting these hypotheses have remained elusive. To elucidate these issues, we studied the distribution, dynamics, and depolarization-induced secretion of tPA in hippocampal neurons, using fluorescent chimeras of tPA. We found that tPA resides in dense-core granules (DCGs) that traffic to postsynaptic dendritic spines and that can remain in spines for extended periods. We also found that depolarization induced by high potassium levels elicits a slow, partial exocytotic release of tPA from DCGs in spines that is dependent on extracellular Ca(+2) concentrations. This slow, partial release demonstrates that exocytosis occurs via a mechanism, such as fuse-pinch-linger, that allows partial release and reuse of DCG cargo and suggests a mechanism that hippocampal neurons may rely upon to avoid depleting tPA at active synapses. Our results also demonstrate release of tPA at a site that facilitates interaction with NMDA-type glutamate receptors, and they provide direct confirmation of fundamental hypotheses about tPA localization and release that bear on its neuromodulatory functions, for example, in learning and memory.

One-pot synthesis and lubricity of fluorescent carbon dots applied on PCL-PEG-PCL hydrogel.

PubMed

Guo, Junde; Mei, Tangjie; Li, Yue; Hafezi, Mahshid; Lu, Hailin; Li, Jianhui; Dong, Guangneng

2018-06-12

This work presents a method for one-pot synthesis of N-doped nanometer-size carbon dots, which can be assembled with thermosensitive poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) hydrogel to achieve slow-release lubricity. The typical property of this green production was studied by fourier transform infrared (FT-IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscope (TEM). The photoluminescence of composite PCEC/CDs hydrogel and its released solutions were characterized by ultraviolet spectrum, and the rheological properties were tested by rotary rheometer. Tribological performance of the released solution from composite PCEC/CDs hydrogel was obtained to compare with PBS and pure CDs solution. The experimental results reveal that the CDs contain the chemical groups of N-H, C-OH/C-O-C and -COOH, etc. In addition, the diameter of the CDs is in the range of 6~8 nm. The phase transition behavior of PCEC/CDs hydrogel can be still kept and its viscoelasticity hydrogel is improved by approximatively 7%. Furthermore, friction coefficient of the released solution from composite PCEC/CDs hydrogel decreases by about 70% than that of PBS. Besides, the wear condition can be improved by a lubricating transfer film formed by released CDs. This novel strategy for slow-release application is valuable for drug delivery and bio-tribology.

Unified law of evolution of experimental gouge-filled fault for fast and slow slip events at slider frictional experiments

NASA Astrophysics Data System (ADS)

Ostapchuk, Alexey; Saltykov, Nikolay

2017-04-01

Excessive tectonic stresses accumulated in the area of rock discontinuity are released while a process of slip along preexisting faults. Spectrum of slip modes includes not only creeps and regular earthquakes but also some transitional regimes - slow-slip events, low-frequency and very low-frequency earthquakes. However, there is still no agreement in Geophysics community if such fast and slow events have mutual nature [Peng, Gomberg, 2010] or they present different physical phenomena [Ide et al., 2007]. Models of nucleation and evolution of fault slip events could be evolved by laboratory experiments in which regularities of shear deformation of gouge-filled fault are investigated. In the course of the work we studied deformation regularities of experimental fault by slider frictional experiments for development of unified law of evolution of fault and revelation of its parameters responsible for deformation mode realization. The experiments were conducted as a classic slider-model experiment, in which block under normal and shear stresses moves along interface. The volume between two rough surfaces was filled by thin layer of granular matter. Shear force was applied by a spring which deformed with a constant rate. In such experiments elastic energy was accumulated in the spring, and regularities of its releases were determined by regularities of frictional behaviour of experimental fault. A full spectrum of slip modes was simulated in laboratory experiments. Slight change of gouge characteristics (granule shape, content of clay), viscosity of interstitial fluid and level of normal stress make it possible to obtained gradual transformation of the slip modes from steady sliding and slow slip to regular stick-slip, with various amplitude of 'coseismic' displacement. Using method of asymptotic analogies we have shown that different slip modes can be specified in term of single formalism and preparation of different slip modes have uniform evolution law. It is shown that shear stiffness of experimental fault is the parameter, which control realization of certain slip modes. It is worth to be mentioned that different serious of transformation is characterized by functional dependences, which have general view and differ only in normalization factors. Findings authenticate that slow and fast slip events have mutual nature. Determination of fault stiffness and testing of fault gouge allow to estimate intensity of seismic events. The reported study was funded by RFBR according to the research project № 16-05-00694.

Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan.

PubMed

Li, Ze; Xiong, Fangfang; He, Jintian; Dai, Xiaojing; Wang, Gaizhen

2016-12-01

In the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen was released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg. Copyright © 2016. Published by Elsevier B.V.

Nanostructured nanoparticles of self-assembled lipid pro-drugs as a route to improved chemotherapeutic agents.

PubMed

Sagnella, Sharon M; Gong, Xiaojuan; Moghaddam, Minoo J; Conn, Charlotte E; Kimpton, Kathleen; Waddington, Lynne J; Krodkiewska, Irena; Drummond, Calum J

2011-03-01

We demonstrate that oral delivery of self-assembled nanostructured nanoparticles consisting of 5-fluorouracil (5-FU) lipid prodrugs results in a highly effective, target-activated, chemotherapeutic agent, and offers significantly enhanced efficacy over a commercially available alternative that does not self-assemble. The lipid prodrug nanoparticles have been found to significantly slow the growth of a highly aggressive mouse 4T1 breast tumour, and essentially halt the growth of a human MDA-MB-231 breast tumour in mouse xenografts. Systemic toxicity is avoided as prodrug activation requires a three-step, enzymatic conversion to 5-FU, with the third step occurring preferentially at the tumour site. Additionally, differences in the lipid prodrug chemical structure and internal nanostructure of the nanoparticle dictate the enzymatic conversion rate and can be used to control sustained release profiles. Thus, we have developed novel oral nanomedicines that combine sustained release properties with target-selective activation.

Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.

PubMed

Halassa, Michael M; Florian, Cedrick; Fellin, Tommaso; Munoz, James R; Lee, So-Young; Abel, Ted; Haydon, Philip G; Frank, Marcos G

2009-01-29

Astrocytes modulate neuronal activity by releasing chemical transmitters via a process termed gliotransmission. The role of this process in the control of behavior is unknown. Since one outcome of SNARE-dependent gliotransmission is the regulation of extracellular adenosine and because adenosine promotes sleep, we genetically inhibited the release of gliotransmitters and asked if astrocytes play an unsuspected role in sleep regulation. Inhibiting gliotransmission attenuated the accumulation of sleep pressure, assessed by measuring the slow wave activity of the EEG during NREM sleep, and prevented cognitive deficits associated with sleep loss. Since the sleep-suppressing effects of the A1 receptor antagonist CPT were prevented following inhibition of gliotransmission and because intracerebroventricular delivery of CPT to wild-type mice mimicked the transgenic phenotype, we conclude that astrocytes modulate the accumulation of sleep pressure and its cognitive consequences through a pathway involving A1 receptors.

Surface-deacetylated chitin nanofibers reinforced with a sulfobutyl ether β-cyclodextrin gel loaded with prednisolone as potential therapy for inflammatory bowel disease.

PubMed

Tabuchi, Ryo; Anraku, Makoto; Iohara, Daisuke; Ishiguro, Takako; Ifuku, Shinsuke; Nagae, Tomone; Uekama, Kaneto; Okazaki, Shoko; Takeshita, Keizo; Otagiri, Masaki; Hirayama, Fumitoshi

2017-10-15

Surface-deacetylated chitin nanofibers (SDACNFs) reinforced with a sulfobutyl ether β-cyclodextrin (SBE-β-CD) (NFs-CDs) gel were developed to obtain a controlled release carrier of prednisolone (PD) for the treatment of colitis. PD was released slowly from the gel at both pH 1.2 and 6.8. The in vitro slow release of PD from the NFs-CDs gel was reflected in the in vivo absorption of the drug after oral administration to rats. These results suggest that a simple gel composed of a mixture of SDACNFs and SBE-β-CD has the potential for use in the controlled release of PD. We also evaluated the therapeutic effects of the NFs-CDs gel containing PD on dextran sulfate sodium (DSS)-induced colitis model mice. The administration of the NFs-CDs gel at intervals of 3days from the beginning of the DSS treatment resulted in a significant improvement, not only in colitis symptoms but also histopathological changes in colon tissue. In addition, the therapeutic effects of the NFs-CDs gel on colitis can be attributed to decreased levels of neutrophil infiltration and the development of oxidative stress. These efficacy profiles of the NFs-CDs gel containing PD suggest that it has the potential for use in the treatment of, not only colitis, but also a variety of other disorders associated with inflammation and oxidative injuries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Delayed photolysis of liposomes: a strategy for the precision timing of bolus drug release using ex-vivo photochemical sensitization

NASA Astrophysics Data System (ADS)

Kozikowski, Raymond T.; Sorg, Brian S.

2012-03-01

Chemotherapy is a standard treatment for metastatic cancer. However drug toxicity limits the dosage that can safely be used, thus reducing treatment efficacy. Drug carrier particles, like liposomes, can help reduce toxicity by shielding normal tissue from drug and selectively depositing drug in tumors. Over years of development, liposomes have been optimized to avoid uptake by the Reticuloendothelial System (RES) as well as effectively retain their drug content during circulation. As a result, liposomes release drug passively, by slow leakage, but this uncontrolled drug release can limit treatment efficacy as it can be difficult to achieve therapeutic concentrations of drug at tumor sites even with tumor-specific accumulation of the carriers. Lipid membranes can be photochemically lysed by both Type I (photosensitizer-substrate) and Type II (photosensitizer-oxygen) reactions. It has been demonstrated in red blood cells (RBCs) in vitro that these photolysis reactions can occur in two distinct steps: a light-initiated reaction followed by a thermally-initiated reaction. These separable activation steps allow for the delay of photohemolysis in a controlled manner using the irradiation energy, temperature and photosensitizer concentration. In this work we have translated this technique from RBCs to liposomal nanoparticles. To that end, we present in vitro data demonstrating this delayed bolus release from liposomes, as well as the ability to control the timing of this event. Further, we demonstrate for the first time the improved delivery of bioavailable cargo selectively to target sites in vivo.

Anticancer nanodelivery system with controlled release property based on protocatechuate–zinc layered hydroxide nanohybrid

PubMed Central

Barahuie, Farahnaz; Hussein, Mohd Zobir; Abd Gani, Shafinaz; Fakurazi, Sharida; Zainal, Zulkarnain

2014-01-01

Background We characterize a novel nanocomposite that acts as an efficient anticancer agent. Methods This nanocomposite consists of zinc layered hydroxide intercalated with protocatechuate (an anionic form of protocatechuic acid), that has been synthesized using a direct method with zinc oxide and protocatechuic acid as precursors. Results The resulting protocatechuic acid nanocomposite (PAN) showed a basal spacing of 12.7 Å, indicating that protocatechuate was intercalated in a monolayer arrangement, with an angle of 54° from the Z-axis between the interlayers of the zinc layered hydroxide, and an estimated drug loading of about 35.7%. PAN exhibited the properties of a mesoporous type material, with greatly enhanced thermal stability of protocatechuate as compared to its free counterpart. The presence of protocatechuate in the interlayers of the zinc layered hydroxide was further supported by Fourier transform infrared spectroscopy. Protocatechuate was released from PAN in a slow and sustained manner. This mechanism of release was well represented by a pseudo-second order kinetics model. PAN has shown increased cytotoxicity compared to the free form of protocatechuic acid in all cancer cell lines tested. Tumor growth suppression was extensive, particularly in HepG2 and HT29 cell lines. Conclusion PAN is suitable for use as a controlled release formulation, and our in vitro evidence indicates that PAN is an effective anticancer agent. PAN may have potential as a chemotherapeutic drug for human cancer. PMID:25061291

Porous starch-based drug delivery systems processed by a microwave route.

PubMed

Malafaya, P B; Elvira, C; Gallardo, A; San Román, J; Reis, R L

2001-01-01

Abstract-A new simple processing route to produce starch-based porous materials was developed based on a microwave baking methodology. This innovative processing route was used to obtain non-loaded controls and loaded drug delivery carriers, incorporating a non-steroid anti-inflammatory agent. This bioactive agent was selected as model drug with expectations that the developed methodology might be used for other drugs and growth factors. The prepared systems were characterized by 1H and 13C NMR spectroscopy which allow the study of the interactions between the starch-based materials and the processing components, i.e, the blowing agents. The porosity of the prepared materials was estimated by measuring their apparent density and studied by comparing drug-loaded and non-loaded carriers. The behaviour of the porous structures, while immersed in aqueous media, was studied in terms of swelling and degradation, being intimately related to their porosity. Finally, in vitro drug release studies were performed showing a clear burst effect, followed by a slow controlled release of the drug over several days (up to 10 days).

Stabilization of tetanus toxoid encapsulated in PLGA microspheres.

PubMed

Jiang, Wenlei; Schwendeman, Steven P

2008-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine based on PLGA microspheres have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT), in the polymer. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: (1) protein aggregation mediated by formaldehyde and (2) acid-induced protein unfolding and epitope damage. Further, we systematically identified excipients, which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA.

Development and characterization of colloidal silica-based slow-release permanganate gel (SRP-G): laboratory investigations.

PubMed

Lee, Eung Seok; Gupta, Neha

2014-08-01

Slow-release permanganate (MnO4(-)) gel (SRP-G) is a hyper-saline KMnO4 solution that can be used for treating large, dilute, or deep plumes of chlorinated solvents in groundwater. Ideally, the SRP-G injected into aquifers will slowly gelate to form MnO4(-) gel in situ, and the gel will slowly releases MnO4(-). Objectives of this study were to develop SRP-G using colloidal silica as gelling solution, characterize its gelation and release kinetics, and delineate its dynamics in a saturated sandy media. The SRP-G exhibited a two-phase increase in viscosity: a lag phase characterized by little increase in viscosity followed by a short gelation phase. Gelation lag times of SRP-G solutions increased (from 0.5h to 13d) with decreasing KMnO4 concentrations (from 25 to 8 g L(-1)). Permanganate release from gelated SRP-G increased with increasing KMnO4 concentrations, and was characterized as asymptotic release with initial peak (0.9-2.2 mg min(-1)) followed by more attenuated release. Gelation lag times of SRP-G flowing in sands (linear velocity=2.1md(-1)) increased (1, 3, and 6h) with decreasing KMnO4 concentrations (25.0, 23.0, and 22.9 g L(-1)). Permanganate release from gelated SRP-Gs continued for up to 3d and was characterized as asymptotic release with an initial peak release (∼1.2 g min(-1)) followed by more attenuated release over 70h. Dilution of SRP-G by dispersion in porous media affects gelation and release kinetics. Increasing the silica concentration in the SRP-G may facilitate gelation and extend the duration of MnO4(-) release from emplaced SRP-G in porous media. Copyright © 2014. Published by Elsevier Ltd.

Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation.

PubMed

Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek; Tilser, Ivan; Holecek, Milan

2008-02-01

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40-60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs-Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL.

Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation

PubMed Central

Muthny, Tomas; Kovarik, Miroslav; Sispera, Ludek; Tilser, Ivan; Holecek, Milan

2008-01-01

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40–60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty-four hours later SOL and EDL were dissected and incubated in modified Krebs–Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin-like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine-induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL. PMID:18197871

Alginate coated chitosan nanogel for the controlled topical delivery of Silver sulfadiazine.

PubMed

El-Feky, Gina S; El-Banna, Sally T; El-Bahy, G S; Abdelrazek, E M; Kamal, Mustafa

2017-12-01

Burn wounds environment favors the growth of micro-organisms causing delay in wound healing. The traditional treatment with antimicrobial creams offer inaccurate doses. The aim of the present study is to formulate and evaluate different silver sulfadiazine loaded nanogel formulations. A factorial design experiment was used for the identification of critical process parameters and for the optimization of the respective process conditions. The prepared drug loaded nanogels were characterized for their particle size, zeta potential, entrapment efficiency and swelling index in order to demonstrate their physicochemical properties, in addition, FTIR, TEM, SEM and in vitro release were used for characterization. The release profile of all tested nanogels showed an initial burst followed by a slow and continuous release rate. An optimum nanogel formulation was predicted by the JMP ® software according to the stated prediction expressions and was composed of 0.4% sodium alginate (ALG) and 0.414% Silver sulfadiazine (SSD). The optimized formulation showed higher therapeutic efficacy in vivo when compared to market product. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phosphorus release from dairy manure, the manure-derived biochar, and their amended soil: effects of phosphorus nature and soil property.

PubMed

Liang, Yuan; Cao, Xinde; Zhao, Ling; Xu, Xiaoyun; Harris, Willie

2014-07-01

Land application of animal manure often risks excessive phosphorus (P) release into the surrounding water. The aim of this study was to convert the dairy manure into biochar, followed by their application into soil, and then to investigate P release from the manure and its derived biochar as well as from the manure- and biochar-amended soil. The results showed that P release was reduced when the manure was converted into biochar due to formation of less-soluble whitlockite [(Ca, Mg)(PO)]. The cumulative P released from biochar over 240 h was 0.26 g kg, a 76% reduction of that from the manure (1.07 g kg). The kinetic release of P from the manure was determined by the fast desorption process and was better fitted to Elovich equation, whereas P release from biochar was initially controlled by the diffusion process and then by slow but steady dissolution of (Ca,Mg)(PO), following the parabolic diffusion and linear models, respectively. When the manure or biochar was incorporated into the soil, P release in the CaCl and simulated acid rain water extraction from biochar-amended soil was consistently lower than that from the manure-amended soil during 210-d incubation. The lower P release in the biochar-amended soil was determined by stable P form (Ca, Mg)(PO) in the biochar itself, but less from the soil property effect. Results indicated that initial high P release from manure can be mitigated by converting the manure into biochar. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Subjective and Objective Effects of Fast and Slow Compression on the Perception of Reverberant Speech in Listeners with Hearing Loss

ERIC Educational Resources Information Center

Shi, Lu-Feng; Doherty, Karen A.

2008-01-01

Purpose: The purpose of the current study was to assess the effect of fast and slow attack/release times (ATs/RTs) on aided perception of reverberant speech in quiet. Method: Thirty listeners with mild-to-moderate sensorineural hearing loss were tested monaurally with a commercial hearing aid programmed in 3 AT/RT settings: linear, fast (AT = 9…

Subduction and dehydration of slow-spread oceanic lithosphere

NASA Astrophysics Data System (ADS)

Paulatto, M.; Laigle, M.; Galve, A.; Charvis, P.

2016-12-01

Water transported by subducting slabs affects the dynamics of subduction zones and is a major gateway in the global geochemical water cycle. During subduction much of the water stored in the slab is released via pore fluid escape and through metamorphic reactions that depend on the thermal regime. The most notable are eclogitization of hydrated basalt and gabbro and breakdown of serpentinite. Most constraints to date have been obtained at Pacific subduction zones, and have contributed to a model of slab dehydration applicable to normal fast-spread oceanic lithosphere with a mafic crust. Slow-spread crust however, is heterogeneous in thickness and composition and has a different water distribution than fast-spread crust. We use P-wave traveltimes from several active source seismic experiments and P- and S-wave traveltimes from shallow and intermediate depth (< 160 km) local earthquakes recorded on a vast amphibious array of OBSs and land seismometers to recover the 3D Vp and Vp/Vs structure of the central Lesser Antilles subduction zone from the surface to 160 km depth. This slab was formed by slow accretion at the Mid-Atlantic ridge and represents the global slow accretion rate end-member. We image the dipping low-Vp layer at the top of the slab corresponding to the hydrated slab crust penetrating to about 100 km depth. High Vp/Vs ratio on the slab top and in the forearc crust is interpreted as evidence of elevated fluid content either as free fluids or as bound water in hydrated minerals. A local minimum in Vp is observed on the slab top at 50 km depth, and forms an elongated trench-parallel anomaly. This anomaly is interrupted at the projection of the Marathon fracture zone. We suggest that this is the result of lateral variations in slab crust composition from normal mafic oceanic crust to tectonized oceanic crust consisting to a large extent of serpentinized peridotite near the fracture zone. Slab regions with normal mafic oceanic crust likely undergo eclogitization, resulting in voluminous water release over a narrow depth range. Serpentinized ultramafic crust, in contrast, may release water at a more constant rate. We infer that subduction of slow-spread lithosphere may result in heterogeneous water transport and release at subduction zones with implications for seismicity, magma generation and the geochemical budget.

How Well Does the S-Web Theory Predict In-Situ Observations of the Slow Solar Wind?

NASA Astrophysics Data System (ADS)

Young, A. K.; Antiochos, S. K.; Linker, J.; Zurbuchen, T.

2014-12-01

The S-Web theory provides a physical explanation for the origin and properties of the slow solar wind, particularly its composition. The theory proposes that magnetic reconnection along topologically complex boundaries between open and closed magnetic fields on the sun releases plasma from closed magnetic field regions into the solar wind at latitudes away from the heliospheric current sheet. Such a wind would have elevated charge states compared to the fast wind and an elemental composition resembling the closed-field corona. This theory is currently being tested using time-dependent, high-resolution, MHD simulations, however comparisons to in-situ observations play an essential role in testing and understanding slow-wind release mechanisms. In order to determine the relationship between S-Web signatures and the observed, slow solar wind, we compare plasma data from the ACE and Ulysses spacecraft to solutions from the steady-state models created at Predictive Science, Inc., which use observed magnetic field distributions on the sun as a lower boundary condition. We discuss the S-Web theory in light of our results and the significance of the S-Web for interpreting current and future solar wind observations. This work was supported, in part, by the NASA TR&T and SR&T programs.

Utilization of coal fly ash as a slow-release granular medium for soil improvement.

PubMed

Yoo, Jeong Gun; Jo, Young Min

2003-01-01

This work proposes a new potential application of waste coal fly ash as a K fertilizer support. Fly ash was reacted with KOH to facilitate the impregnation of K as well as to enhance the bonding force. In particular, the applied process resulted in a significant slow-releasing characteristic of fertilizer elements. To examine the effect of K impregnation, a few detailed leaching tests were carried out in terms of process variables such as reaction time and temperature, sintering time and temperature, and KOH concentration. The current experiment presented an optimum preparation condition that is competitive with conventional commercial fertilizers. The manufactured ash fertilizers inhibited release of the K elements. It was also found through the continuous leaching test with pure water that the ash fertilizer had excellent moisture absorbability. However, the effects of some trace elements in fly ash on soil health and crop productivity as well as environmental considerations need to be established with long-term studies.

Structure-dependent water transport across nanopores of carbon nanotubes: toward selective gating upon temperature regulation.

PubMed

Zhao, Kuiwen; Wu, Huiying

2015-04-28

Determining water structure in nanopores and its influence on water transport behaviour is of great importance for understanding and regulating the transport across nanopores. Here we report an ultrafast-slow flow transition phenomenon for water transport across nanopores of carbon nanotubes owing to the change in water structure in nanopores induced by temperature. By performing extensive molecular dynamics simulations, we show the dependence of water transport behaviours on water structures. Our results indicate that owing to the change in water structure in nanopores, water flux across nanopores with certain pore sizes decreases sharply (nearly 3 orders of magnitude) with the decreasing temperature. This phenomenon is very sensitive to the pore size. The threshold temperatures for the occurrence of the ultrafast-slow flow transition for water transport are also determined for various pore sizes. These findings suggest a novel protocol for selective gating of water and proton conduction across nanopores and temperature-controlled drug release.

Reversible solvatomagnetic switching in a single-ion magnet from an entatic state.

PubMed

Vallejo, J; Pardo, E; Viciano-Chumillas, M; Castro, I; Amorós, P; Déniz, M; Ruiz-Pérez, C; Yuste-Vivas, C; Krzystek, J; Julve, M; Lloret, F; Cano, J

2017-05-01

A vast impact on molecular nanoscience can be achieved using simple transition metal complexes as dynamic chemical systems to perform specific and selective tasks under the control of an external stimulus that switches "ON" and "OFF" their electronic properties. While the interest in single-ion magnets (SIMs) lies in their potential applications in information storage and quantum computing, the switching of their slow magnetic relaxation associated with host-guest processes is insufficiently explored. Herein, we report a unique example of a mononuclear cobalt(ii) complex in which geometrical constraints are the cause of easy and reversible water coordination and its release. As a result, a reversible and selective colour and SIM behaviour switch occurs between a "slow-relaxing" deep red anhydrous material (compound 1 ) and its "fast-relaxing" orange hydrated form (compound 2 ). The combination of this optical and magnetic switching in this new class of vapochromic and thermochromic SIMs offers fascinating possibilities for designing multifunctional molecular materials.

Renal effects of nifedipine in healthy normotensive volunteers. Effects of dose, formulation, duration of treatment, and chlorothiazide coadministration.

PubMed

Adebayo, G I; Coker, H A; Fagbure, F

1988-01-01

Renal effects of nifedipine were assessed in 3 groups of healthy normotensive volunteers. In the first group (N = 10), a single 20-mg dose of the slow-release formulation caused an increase in 8-h sodium excretion (P less than 0.025) and urine volume (P less than 0.005). Natriuresis (P less than 0.05) and diuresis (P less than 0.05) were still evident after 1 wk of pretreatment, but were significantly attenuated (P less than 0.05), in each case, compared to levels after a single dose. Natriuresis and diuresis after 2 wk of intake were indistinguishable from control levels. In another group of 8, a single 10 mg dose of the conventional formulation (capsule) effected natriuresis (P less than 0.01) and diuresis (P less than 0.001) similar to those associated with intake of a single 20-mg dose of the slow-release formulation. Natriuresis and diuresis associated with a 20-mg single dose of the conventional formulation were not different from control but were less than those following intake of the 10-mg dose (P less than 0.025 in each case). In the third group of 6, nifedipine, though weaker than chlorothiazide, promoted natriuresis (P less than 0.025) and diuresis (P less than 0.025) of the thiazide without augmenting its kaliuresis. In all the groups, there were no changes in creatinine clearance, and nifedipine did not alter kaliuresis. It is suggested that natriuretic and diuretic effects of nifedipine in healthy normotensive individuals are dependent on the dose employed, the formulation used, and the duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Vector control in leishmaniasis.

PubMed

Kishore, K; Kumar, V; Kesari, S; Dinesh, D S; Kumar, A J; Das, P; Bhattacharya, S K

2006-03-01

Indoor residual spraying is a simple and cost effective method of controlling endophilic vectors and DDT remains the insecticide of choice for the control of leishmaniasis. However resistance to insecticide is likely to become more widespread in the population especially in those areas in which insecticide has been used for years. In this context use of slow release emulsified suspension (SRES) may be the best substitute. In this review spraying frequencies of DDT and new schedule of spray have been discussed. Role of biological control and environment management in the control of leishmaniasis has been emphasized. Allethrin (coil) 0.1 and 1.6 per cent prallethrin (liquid) have been found to be effective repellents against Phlebotomus argentipes, the vector of Indian kalaazar. Insecticide impregnated bednets is another area which requires further research on priority basis for the control of leishmaniasis. Role of satellite remote sensing for early prediction of disease by identifying the sandflygenic conditions cannot be undermined. In future synthetic pheromons can be exploited in the control of leishmaniasis.

Prolonged nerve block by microencapsulated bupivacaine prevents acute postoperative pain in rats.

PubMed

Ohri, Rachit; Blaskovich, Phillip; Wang, Jeffrey Chi-Fei; Pham, Lan; Nichols, Gary; Hildebrand, William; Costa, Daniel; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary

2012-01-01

To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed. Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls. Bupivacaine was released in vitro at a relatively constant rate over a period of ≈ 72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours. Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.

Supramolecular binding and release of sulfide and hydrosulfide anions in water.

PubMed

Vázquez, J; Sindelar, V

2018-06-05

Hydrogen sulfide (H2S) has become an important target for research due to its physiological properties as well as its potential applications in medicine. In this work, supramolecular binding of sulfide (S2-) and hydrosulfide (HS-) anions in water is presented for the first time. Bambusurils were used to slow down the release of these anions in water.

Glucose and lactate as metabolic constraints on presynaptic transmission at an excitatory synapse.

PubMed

Lucas, Sarah J; Michel, Christophe B; Marra, Vincenzo; Smalley, Joshua L; Hennig, Matthias H; Graham, Bruce P; Forsythe, Ian D

2018-05-01

Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission. Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic transmission through a reduction in the number of functional synaptic vesicle release sites and a slowing of vesicle pool replenishment, without a consistent change in release probability. Metabolic function is compromised in many pathological conditions (e.g. stroke, traumatic brain injury and neurodegeneration). Knowledge of how synaptic transmission is constrained by metabolic stress, especially during intense brain activity, will provide insights to improve cognition following pathological insults. The synapse has high energy demands, which increase during intense activity. Presynaptic ATP production depends on substrate availability and usage will increase during activity, which in turn could influence transmitter release and information transmission. We investigated transmitter release at the mouse calyx of Held synapse using glucose or lactate (10, 1 or 0 mm) as the extracellular substrates while inducing metabolic stress. High-frequency stimulation (HFS) and recovery paradigms evoked trains of EPSCs monitored under voltage-clamp. Whilst postsynaptic intracellular ATP was stabilised by diffusion from the patch pipette, depletion of glucose increased EPSC depression during HFS and impaired subsequent recovery. Computational modelling of these data demonstrated a reduction in the number of functional release sites and slowed vesicle pool replenishment during metabolic stress, with little change in release probability. Directly depleting presynaptic terminal ATP impaired transmitter release in an analogous manner to glucose depletion. In the absence of glucose, presynaptic terminal metabolism could utilise lactate from the aCSF and this was blocked by inhibition of monocarboxylate transporters (MCTs). MCT inhibitors significantly suppressed transmission in low glucose, implying that lactate is a presynaptic substrate. Additionally, block of glycogenolysis accelerated synaptic transmission failure in the absence of extracellular glucose, consistent with supplemental supply of lactate by local astrocytes. We conclude that both glucose and lactate support presynaptic metabolism and that limited availability, exacerbated by high-intensity firing, constrains presynaptic ATP, impeding transmission through a reduction in functional presynaptic release sites as vesicle recycling slows when ATP levels are low. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Neuronal plasticity and thalamocortical sleep and waking oscillations

PubMed Central

Timofeev, Igor

2011-01-01

Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma. PMID:21854960

Comprehensive study of the drug delivery properties of poly(l-lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice.

PubMed

Shalgunov, Vladimir; Zaytseva-Zotova, Daria; Zintchenko, Arkadi; Levada, Tatiana; Shilov, Yuri; Andreyev, Dmitry; Dzhumashev, Dzhangar; Metelkin, Evgeny; Urusova, Alexandra; Demin, Oleg; McDonnell, Kevin; Troiano, Greg; Zale, Stephen; Safarovа, Elmira

2017-09-10

Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice. Nanoparticle formulations differed by surface PEG coverage and by release kinetics of the encapsulated model active pharmaceutical ingredient (API). Increase in PEG coverage prolonged nanoparticle circulation half-life up to ~20h in rats and ~10h in mice and decreased retention in liver, spleen and lungs. Circulation half-life of the encapsulated API grew monotonously as the release rate slowed down. Plasma and tissue pharmacokinetics was dose-linear for inactive nanoparticles, but markedly dose-dependent for the model therapeutic formulation, presumably because of the toxic effects of released API. A mathematical model of API distribution calibrated on the data for inactive nanoparticles and conventional API form correctly predicted the distribution of the model therapeutic formulation at the lowest investigated dose, but for higher doses the toxic action of the released API had to be explicitly modelled. Our results provide a coherent illustration of the ability of controllable-release PLA-PEG nanoparticles to serve as an effective drug delivery platform to alter API biodistribution. They also underscore the importance of physiological effects of released drug in determining the biodistribution of therapeutic drug formulations at doses approaching tolerability limits. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

NASA Astrophysics Data System (ADS)

Valenti, G.; La Carta, S.; Mazzotti, G.; Rapisarda, M.; Perna, S.; Di Gesù, R.; Giorgini, L.; Carbone, D.; Recca, G.; Rizzarelli, P.

2016-05-01

Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient's compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye's diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10-60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy (1H-NMR, 13C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic models allowed to deduce that release of BDP is controlled over time from PMMA-b-PHEMA 53/47. In particular, PMMA-b-PHEMA 53/47 showed the best release profile to achieve the therapeutic reference dose of 3 µg/die, employed in treatment of posterior eye disease, up to four months. Accordingly, PMMA-b-PHEMA 53/47 has been tested to prepare ocular inserts. Ocular inserts with different shape and the same area of polymer films have been obtained using silicon moulds made by a 3D printer.

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

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

Valenti, G.; La Carta, S.; Rapisarda, M.

Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient’s compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site.more » Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye’s diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10–60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy ({sup 1}H-NMR, {sup 13}C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic models allowed to deduce that release of BDP is controlled over time from PMMA-b-PHEMA 53/47. In particular, PMMA-b-PHEMA 53/47 showed the best release profile to achieve the therapeutic reference dose of 3 µg/die, employed in treatment of posterior eye disease, up to four months. Accordingly, PMMA-b-PHEMA 53/47 has been tested to prepare ocular inserts. Ocular inserts with different shape and the same area of polymer films have been obtained using silicon moulds made by a 3D printer.« less

Octreotide Injection

MedlinePlus

... to decrease the amount of growth hormone (a natural substance) produced by people with acromegaly (condition in ... by carcinoid tumors (slow-growing tumors that release natural substances that can cause symptoms) and vasoactive intestinal ...

Liraglutide Injection

MedlinePlus

... called incretin mimetics. It works by helping the pancreas to release the right amount of insulin when ... suicide, changes in behavior, pancreatitis (inflammation of the pancreas); severe stomach problems, including gastroparesis (slowed movement of ...

Dulaglutide Injection

MedlinePlus

... called incretin mimetics. It works by helping the pancreas to release the right amount of insulin when ... or have ever had pancreatitis (inflammation of the pancreas); severe stomach problems, including gastroparesis (slowed movement of ...

Albiglutide Injection

MedlinePlus

... called incretin mimetics. It works by helping the pancreas to release the right amount of insulin when ... or have ever had pancreatitis (inflammation of the pancreas); severe stomach problems, including gastroparesis (slowed movement of ...

Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.

PubMed

Asberg, A; Midtvedt, K; Vassbotn, T; Hartmann, A

2001-07-01

The prevalence of hypertension in renal transplant recipients is high but the pathophysiology is poorly defined. Impaired endothelial function may be a factor of major importance. The present study addresses the effects of long-term treatment with either lisinopril or slow-release nifedipine on microvascular function and plasma endothelin in renal transplant recipients on cyclosporin A (CsA). Seventy-five hypertensive renal transplant recipients were double-blind randomized to receive slow-release nifedipine (NIF, n=40) or lisinopril (LIS, n=35). Ten normotensive, age-matched recipients served as controls. All patients received CsA-based immunosuppressive therapy including prednisolone and azathioprine. Microvascular function was assessed in the forearm skin vasculature, using laser Doppler flowmetry in combination with post-occlusive reactive hyperaemia and endothelial-dependent function during local acetylcholine (ACh) stimulation. The analysis of microvascular function (AUC(rh)) showed that nifedipine-treated patients had significantly lower responses compared with lisinopril-treated patients (20+/-17 and 43+/-20 AU x min respectively, P=0.0016). Endothelial function was borderline significantly lower in the NIF group compared with the LIS group (640+/-345 and 817+/-404 AU x min respectively, P=0.056). The responses in the LIS group were comparable with those in non-hypertensive controls (AUC(rh) was 37+/-16 and AUC(ACh) was 994+/-566 AU x min). Plasma endothelin-1 concentrations were significantly higher in the NIF group compared with the LIS group (0.44+/-0.19 vs. 0.34+/-0.10 fmol/ml respectively, P=0.048), and were 0.29+/-0.09 fmol/ml in the control patients. AUC(ACh) was associated with plasma endothelin-1 (P=0.0053), while AUC(rh) was not (P=0.080). The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvascular function in hypertensive renal transplant recipients on CsA. The beneficial microvascular effect may be mediated in part by an endothelin-1-associated effect on the endothelium.

Nicorandil Versus Nitroglycerin for Symptomatic Relief of Angina in Patients With Slow Coronary Flow Phenomenon: A Randomized Clinical Trial.

PubMed

Sani, Hashem Danesh; Eshraghi, Ali; Nezafati, Mohammad Hassan; Vojdanparast, Mohammad; Shahri, Bahram; Nezafati, Pouya

2015-07-01

Patients with the coronary slow flow phenomenon frequently experience angina episodes. The present study aimed to compare the efficacy of nicorandil versus nitroglycerin for alleviation of angina symptoms in slow flow patients. In a single-center, single-blind, parallel-design, comparator-controlled, randomized clinical trial (NCT02254252), 54 patients with slow flow and normal or near-normal coronary angiography who presented with frequent angina episodes were randomly assigned to 1-month treatment with nicorandil 10 mg, 2 times a day (n = 27) or sustained-release glyceryltrinitrate 6.4 mg 2 times a day (n =27). Frequency of angina episodes, pain intensity, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were assessed at baseline and after 1 month of treatment. In all, 25 patients in the nicorandil arm and 24 patients in the nitroglycerin arm were analyzed. After 1 month, patients treated with nicorandil had fewer angina episodes (adjusted mean number of episodes per week, nicorandil versus nitroglycerin; 1.68 ± 0.15 vs 2.29 ± 0.15, P = .007, effect size = 14.6%). Patients also reported greater reductions in pain intensity with nicorandil versus nitroglycerin (adjusted mean of self-reported pain score; 3.03 ± 0.29 vs 3.89 ± 0.30, P = .046, effect size = 8.4%). A significantly higher proportion of patients in the nicorandil arm were categorized in CCS class I (76% vs 33.3%, P = .004) or class II (16.0% vs 45.8%, P = .032). In slow flow patients, nicorandil provides better symptomatic relief of angina than nitroglycerin. © The Author(s) 2015.

Urea encapsulation in modified starch matrix for nutrients retention

NASA Astrophysics Data System (ADS)

Naz, Muhammad Yasin; Sulaiman, Shaharin Anwar; Ariff, Mohd. Hazwan Bin Mohd.; Ariwahjoedi, Bambang

2014-10-01

It has been estimated that 20-70% of the used urea goes to the environment via leaching, nitrification and volatilization which not only harms the environment but also reduces the urea efficiency. By coating the urea granules, the farmers can achieve high urea performance through controlling the excess release of nitrogen. Up until now, different materials have been tested for nutrients retention. However, most of them are either expensive or unfriendly to the environment. Being cheap and biodegradable materials, the starches may also be used to coat the urea fertilizer for controlling the nutrients release. However, the pure starches do not meet the standards set by many industrial processes due to their slow tacking and too low viscosities and should be modified for getting smooth, compact and mechanically stronger coatings. In these studies, the tapioca starch was modified by reacting it with urea and different masses of borax. The prepared solutions were used to coat the urea granules of 3.45 mm average diameter. Different volumes (1, 1.5 and 2 mL) of each solution were used to coat 30 g of urea fluidized above the minimum level of fluidization. It was noticed that the coating thickness, percent coating, dissolution rate and percent release follow an increasing trend with an increase of solution volume; however, some random results were obtained while investigating the solution volume effects on the percent release. It was seen that the nutrients percent release over time increases with an increase in solution volume from 1 to 1.5 mL and thereafter reaches to a steady state. It confirms that the 1.5 mL of solution for 30 g urea samples will give the optimized coating results.

Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti

PubMed Central

Schmidt, Tom L.; Barton, Nicholas H.; Rašić, Gordana; Turley, Andrew P.; Montgomery, Brian L.; Iturbe-Ormaetxe, Inaki; Cook, Peter E.; Ryan, Peter A.; Ritchie, Scott A.; Hoffmann, Ary A.; O’Neill, Scott L.

2017-01-01

Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100–200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation. PMID:28557993

Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti.

PubMed

Schmidt, Tom L; Barton, Nicholas H; Rašić, Gordana; Turley, Andrew P; Montgomery, Brian L; Iturbe-Ormaetxe, Inaki; Cook, Peter E; Ryan, Peter A; Ritchie, Scott A; Hoffmann, Ary A; O'Neill, Scott L; Turelli, Michael

2017-05-01

Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100-200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation.

Microwave-assisted microemulsion technique for production of miconazole nitrate- and econazole nitrate-loaded solid lipid nanoparticles.

PubMed

Shah, Rohan M; Eldridge, Daniel S; Palombo, Enzo A; Harding, Ian H

2017-08-01

The microwave-assisted production of solid lipid nanoparticles (SLNs) is a novel technique reported recently by our group. The small particle size, solid nature and use of physiologically well-tolerated lipid materials make SLNs an interesting and potentially efficacious drug carrier. The main purpose of this research work was to investigate the suitability of microwave-assisted microemulsion technique to encapsulate selected ionic drug substances such as miconazole nitrate and econazole nitrate. The microwave-produced SLNs had a small size (250-300nm), low polydispersity (<0.20), high encapsulation efficiency (72-87%) and loading capacity (3.6-4.3%). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies suggested reduced crystallinity of stearic acid in SLNs. The release studies demonstrated a slow, sustained but incomplete release of drugs (<60% after 24h) from microwave-produced SLNs. Data fitting of drug release data revealed that the release of both drugs from microwave-produced SLNs was governed by non-Fickian diffusion indicating that drug release was both diffusion- and dissolution- controlled. Anti-fungal efficacy of drug-loaded SLNs was evaluated on C. albicans. The cell viability studies showed that cytotoxicity of SLNs was concentration-dependent. These encouraging results suggest that the microwave-assisted procedure is suitable for encapsulation of ionic drugs and that microwave-produced SLNs can act as potential carriers of antifungal drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitochondrial alkaline pH-responsive drug release mediated by Celastrol loaded glycolipid-like micelles for cancer therapy.

PubMed

Tan, Yanan; Zhu, Yun; Zhao, Yue; Wen, Lijuan; Meng, Tingting; Liu, Xuan; Yang, Xiqin; Dai, Suhuan; Yuan, Hong; Hu, Fuqiang

2018-02-01

Mitochondria, crucial regulators of inducing tumor cells apoptosis, can be treated as the prime target for tumor therapy. The selective and responsive release of proapoptotic therapeutics into mitochondria may notably improve antitumor efficiency. Herein, (4-Carboxybutyl) triphenylphosphonium bromide (CTPP), a lipophilic cation, was conjugated with glucolipid-like conjugates (CSOSA) to produce mitochondria-targeted conjugates (CTPP-CSOSA). Loading with weakly acidic drug Celastrol (Cela), CTPP-CSOSA/Cela micelles could selectively respond to mitochondrial alkaline pH (pH 8.0), controlled by the weaker interaction between hydrophobic core of micelles and Cela with higher solubility at pH 8.0. However, there was a slow drug release behavior at pH 7.4 and pH 5.0. It illustrated that CTPP-CSOSA/Cela could realize mitochondrial fast drug release, and decrease drug leakage in the cytoplasm and lysosome. CTPP-CSOSA/Cela highly enhanced ROS levels, which further induced mitochondria membrane potential decreasing and more Cytochrome C releasing into cytoplasm, then promoted tumor cells apoptosis notably. In vivo, CTPP-CSOSA had an enhanced accumulation in tumor tissue, compared with CSOSA. Moreover, the tumor-inhibition rate of CTPP-CSOSA/Cela was 80.17%, which was significantly higher than CSOSA/Cela (58.35%) and Cela (54.89%). Thus, CTPP-CSOSA/Cela micelles with mitochondrial targeting and alkaline pH-responsive release capability could provide a new strategy for tumor therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two-stage controlled release system possesses excellent initial and long-term efficacy.

PubMed

Luo, Jian; Jing, Tong-Fang; Zhang, Da-Xia; Zhang, Xian-Peng; Li, Beixing; Liu, Feng

2018-05-24

In this work, a series of polyurea-based lambda-cyhalothrin-loaded microcapsules (MCs) with three different size distributions (average diameters of 1.35 μm, MC-S; 5.13 μm, MC-M; and 21.48 μm, MC-L) were prepared and characterized. The results indicated that MCs with a smaller particle size distribution had a faster release rate and excellent initial efficacy against pests. MC-L had a remarkably slow incipient release rate, outstanding photostability and better later-stage efficacy than that of the other tested MCs. The results clarified that the diameter distribution of MCs is the key factor in determining the release property and bioactivity of the MC formulations. Subsequently, the binary mixture MC formulations of MC(+M), MC(S+L) and MC(M+L) were obtained by mixing MC-S, MC-M or MC-L at 1:1 to establish a two-stage release system utilized for foliar application situations. Greenhouse and field experiments showed that MC(S+L) provided an optimal efficacy, and its effective duration was much longer than that of the emulsifiable concentrate (EC) group. Therefore, the release system established in this study was simple and workable for regulating the initial and long-term efficacy by adjusting the particle size distribution; in addition, this system has potential applications in other fields such as drug delivery devices. Copyright © 2018 Elsevier B.V. All rights reserved.

Development and characterization of different black raspberry confection matrices designed for delivery of phytochemicals.

PubMed

Gu, Junnan; Ahn-Jarvis, Jennifer H; Vodovotz, Yael

2015-03-01

Three forms of confections containing black raspberries (BRB) powder were developed to provide controlled release of phytochemicals for oral disease prevention. Our objective was to investigate the impact of varying confection matrices on the release rate of BRB phytochemicals. Confections were developed and prepared. Textural properties of confections were analyzed, compared and correlated with the release rate of phytochemicals from BRB confections with in vitro dissolution test. In the results, BRB content reached 22% in hard candy and pectin-based confections and 40% in starch-based confections, respectively. Pectin- and starch-based confections retained >93% of its original anthocyanins after processing while hard candy had 59%. Starch confections showed higher G' in rheological analysis and higher hardness but lower cohesiveness and springiness in textural profile analysis than pectin confections (P < 0.05). The confection types showed different microstructure with scanning electronic microscopy (SEM). Corresponding to their physicochemical properties, confections showed fast (hard candy), intermediate (pectin confections), and slow (starch confections) release rates with a final releasing time of 90, 150, and 540 min in dissolution studies. Three confections were rated between neither like nor dislike to like slightly (n = 60). Pectin confections had the highest overall acceptance (like slightly) and 62% of subjects rated this type of confection as the most liked ones. These results indicate that delivery matrix could modulate the phytochemical release rate from BRB confection and also influence sensory preference. © 2015 Institute of Food Technologists®

United States Department of Agriculture-Agricultural Research Service research on biological control of arthropods.

PubMed

Hopper, Keith R

2003-01-01

During 1999-2001, ARS scientists published over 100 papers on more than 30 species of insect pest and 60 species of predator and parasitoid. These papers address issues crucial to the three strategies of biological control: conservation, augmentation and introduction. Conservation biological control includes both conserving extant populations of natural enemies by using relatively non-toxic pesticides and increasing the abundance of natural enemies in crops by providing or improving refuges for population growth and dispersal into crops. ARS scientists have been very active in determining the effects of pesticides on beneficial arthropods and in studying movement of natural enemies from refuges into crops. Augmentation involves repeated releases of natural enemies in the field, which can be inoculative or inundative. Inoculative releases are used to initiate self-propagating populations at times or in places where they would be slow to colonize. ARS scientists have studied augmentative biological control of a variety of pest insects. The targets are mostly pests in annual crops or other ephemeral habitats, where self-reproducing populations of natural enemies are not sufficiently abundant early enough to keep pest populations in check. ARS research in augmentative biological control centers on methods for rearing large numbers of healthy, effective natural enemies and for releasing them where and when they are needed at a cost less than the value of the reduction in damage to the crop. ARS scientists have researched various aspects of introductions of exotic biological control agents against a diversity of pest insects. The major issues in biological control introductions are accurate identification and adequate systematics of both natural enemies and target pests, exploration for natural enemies, predicting the success of candidates for introduction and the likelihood of non-target impacts, quarantine and rearing methods, and post-introduction evaluation of establishment, control and non-target impacts. ARS scientists have published research on several general issues in biological control. Among the most important are the mechanisms affecting mate- and host-finding and host specificity.

Areas prone to slow slip events impede earthquake rupture propagation and promote afterslip.

PubMed

Rolandone, Frederique; Nocquet, Jean-Mathieu; Mothes, Patricia A; Jarrin, Paul; Vallée, Martin; Cubas, Nadaya; Hernandez, Stephen; Plain, Morgan; Vaca, Sandro; Font, Yvonne

2018-01-01

At subduction zones, transient aseismic slip occurs either as afterslip following a large earthquake or as episodic slow slip events during the interseismic period. Afterslip and slow slip events are usually considered as distinct processes occurring on separate fault areas governed by different frictional properties. Continuous GPS (Global Positioning System) measurements following the 2016 M w (moment magnitude) 7.8 Ecuador earthquake reveal that large and rapid afterslip developed at discrete areas of the megathrust that had previously hosted slow slip events. Regardless of whether they were locked or not before the earthquake, these areas appear to persistently release stress by aseismic slip throughout the earthquake cycle and outline the seismic rupture, an observation potentially leading to a better anticipation of future large earthquakes.

Areas prone to slow slip events impede earthquake rupture propagation and promote afterslip

PubMed Central

Rolandone, Frederique; Nocquet, Jean-Mathieu; Mothes, Patricia A.; Jarrin, Paul; Vallée, Martin; Cubas, Nadaya; Hernandez, Stephen; Plain, Morgan; Vaca, Sandro; Font, Yvonne

2018-01-01

At subduction zones, transient aseismic slip occurs either as afterslip following a large earthquake or as episodic slow slip events during the interseismic period. Afterslip and slow slip events are usually considered as distinct processes occurring on separate fault areas governed by different frictional properties. Continuous GPS (Global Positioning System) measurements following the 2016 Mw (moment magnitude) 7.8 Ecuador earthquake reveal that large and rapid afterslip developed at discrete areas of the megathrust that had previously hosted slow slip events. Regardless of whether they were locked or not before the earthquake, these areas appear to persistently release stress by aseismic slip throughout the earthquake cycle and outline the seismic rupture, an observation potentially leading to a better anticipation of future large earthquakes. PMID:29404404

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

Otto, H.; Marti, T.; Holz, M.

Photocycle and flash-induced proton release and uptake were investigated for bacteriorhodopsin mutants in which Asp-85 was replaced by Ala, Asn, or Glu; Asp-212 was replaced by Asn or Glu; Asp-115 was replaced by Ala, Asn, or Glu; Asp-96 was replaced by Ala, Asn, or Glu; and Arg-82 was replaced by Ala or Gln in dimyristoylphosphatidylcholine/3-((3-cholamidopropyl)dimethylammonio)-1- propanesulfonate micelles at pH 7.3. In the Asp-85----Ala and Asp-85----Asn mutants, the absence of the charged carboxyl group leads to a blue chromophore at 600 and 595 nm, respectively, and lowers the pK of the Schiff base deprotonation to 8.2 and 7, respectively, suggesting amore » role for Asp-85 as counterion to the Schiff base. The early part of the photocycles of the Asp-85----Ala and Asp-85----Asn mutants is strongly perturbed; the formation of a weak M-like intermediate is slowed down about 100-fold over wild type. In both mutants, proton release is also slower but clearly precedes the rise of M. The amplitude of the early reversed photovoltage component in the Asp-85----Asn mutant is very large, and the net charge displacement is close to zero, indicating proton release and uptake on the cytoplasmic side of the membrane. The data suggest an obligatory role for Asp-85 in the efficient deprotonation of the Schiff base and in the proton release phase, probably as proton acceptor. In the Asp-212----Asn mutant, the rise of the absorbance change at 410 nm is slowed down to 220 microsecond, its amplitude is small, and the release of protons is delayed to 1.9 ms. The absorbance changes at 650 nm indicate perturbations in the early time range with a slow K intermediate. Thus Asp-212 also participates in the early events of charge translocation and deprotonation of the Schiff base.« less

Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from metal-organic frameworks Cu-BTC.

PubMed

Lucena, Flávia Raquel Santos; de Araújo, Larissa C C; Rodrigues, Maria do D; da Silva, Teresinha G; Pereira, Valéria R A; Militão, Gardênia C G; Fontes, Danilo A F; Rolim-Neto, Pedro J; da Silva, Fausthon F; Nascimento, Silene C

2013-10-01

This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48 hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Novel Strategy of Using Methyl Esters as Slow Release Methanol Source during Lipase Expression by mut+ Pichia pastoris X33

PubMed Central

Kumari, Arti; Gupta, Rani

2014-01-01

One of the major issues with heterologous production of proteins in Pichia pastoris X33 under AOX1 promoter is repeated methanol induction. To obviate repeated methanol induction, methyl esters were used as a slow release source of methanol in lipase expressing mut+ recombinant. Experimental design was based on the strategy that in presence of lipase, methyl esters can be hydrolysed to release their products as methanol and fatty acid. Hence, upon break down of methyl esters by lipase, first methanol will be used as a carbon source and inducer. Then P. pastoris can switch over to fatty acid as a carbon source for multiplication and biomass maintenance till further induction by methyl esters. We validated this strategy using recombinant P. pastoris expressing Lip A, Lip C from Trichosporon asahii and Lip11 from Yarrowia lipolytica. We found that the optimum lipase yield under repeated methanol induction after 120 h was 32866 U/L, 28271 U/L and 21978 U/L for Lip C, Lip A and Lip 11 respectively. In addition, we found that a single dose of methyl ester supported higher production than repeated methanol induction. Among various methyl esters tested, methyl oleate (0.5%) caused 1.2 fold higher yield for LipA and LipC and 1.4 fold for Lip11 after 120 h of induction. Sequential utilization of methanol and oleic acid by P. pastoris was observed and was supported by differential peroxisome proliferation studies by transmission electron microscopy. Our study identifies a novel strategy of using methyl esters as slow release methanol source during lipase expression. PMID:25170843

A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous secretion of multiple cardiotherapeutic cytokines and improves cardiac function in a rapid-pacing-induced model of canine heart failure.

PubMed

Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Nakatani, Satoshi; Sakai, Yoshiki; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

2013-08-01

Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM. ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area. Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Self-assembly of model graft copolymers of agarose and weak polyelectrolyte-based amphiphilic diblock copolymers: controlled drug release and degradation.

PubMed

Muppalla, Ravikumar; Jewrajka, Suresh K; Prasad, Kamalesh

2013-06-01

Polysaccharide-based copolymers are promising biomaterials due to their biocompatibility and biodegradability. For potential biomedical applications the copolymer as a whole and all the degraded species must be biocompatible and easily removable from the system. In this regards, new model pH-responsive seaweed agarose (Agr) grafted with weak polyelectrolyte-based well-defined amphiphilic block copolymers ca. poly[(methyl methacrylate)-b-(2-dimethylamino)ethyl methacrylate)] (PMMA-b-PDMA) were designed and synthesized to study the self-assembly, degradation, and in vitro hydrophobic/hydrophilic drug release behavior. The graft copolymer solutions display extremely low critical micelle concentration (CMC) and form pH responsive stable micelles. The degradation study of the graft copolymer reveals that the entire degraded components are well soluble/dispersible in water due to formation of mixed micelles. The micelles are also strongly adsorbed on the mica surface owing to electrostatic interaction. One application of the graft copolymer micelles is that it can entrap both hydrophilic and poorly water soluble hydrophobic drugs effectively and exhibit slow release kinetics. The release kinetics of both the hydrophilic and poorly water soluble hydrophobic drugs change with pH as well as with the composition of the graft copolymer. Copyright © 2012 Wiley Periodicals, Inc.

Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision.

PubMed

Ohri, Rachit; Wang, Jeffrey Chi-Fei; Blaskovich, Phillip D; Pham, Lan N; Costa, Daniel S; Nichols, Gary A; Hildebrand, William P; Scarborough, Nelson L; Herman, Clifford J; Strichartz, Gary R

2013-09-01

Acute postoperative pain causes physiological deficits and slows recovery. Reduction of such pain by local anesthetics that are delivered for several days postoperatively is a desirable clinical objective, which is approached by a new formulation and applied in animal studies reported here. We subcutaneously injected a new formulation of poly-lactic-co-glycolic acid polymer microspheres, which provides steady drug release for 96+ hours into rats at the dorsal region 2 hours before surgery. A single 1.2-cm-long skin incision was followed by blunt dissection of skin away from the underlying fascia, and closed by 2 sutures, followed by 14 days of testing. Microspheres containing 5, 10, 20, and 40 mg bupivacaine were injected locally 2 hours before surgery; bupivacaine-free microspheres were the vehicle control, and bupivacaine HCl solution (0.5%), the positive control. Mechanical sensitivity was determined by the frequency of local muscle contractions to repeated pokes with nylon monofilaments (von Frey hairs) exerting 4 and 15 g forces, testing, respectively, allodynia and hyperalgesia, and by pinprick. Injection of bupivacaine microspheres (40 mg drug) into intact skin reduced responses to 15 g von Frey hairs for 6 hours and to pinprick for 36 hours. Respective reductions from bupivacaine HCl lasted for 3 and 2 hours. Skin incision and dissection alone caused mechanical allodynia and hyperalgesia for 14 days. Microspheres containing 20 or 40 mg bupivacaine suppressed postoperative hypersensitivity for up to 3 days, reduced integrated allodynia (area under curve of response versus time) over postoperative days 1 to 5 by 51% ± 20% (mean ± SE) and 78% ± 12%, and reduced integrated hyperalgesia by 55% ± 13% and 64% ± 11%, for the respective doses. Five and ten milligrams bupivacaine in microspheres and the 0.5% bupivacaine solution were ineffective in reducing postoperative hypersensitivity, as were 40 mg bupivacaine microspheres injected contralateral to the incision. Significant suppression of postoperative pain by the slow-release bupivacaine preparation outlasts its anesthetic action on intact skin. These findings demonstrate preventive analgesia and indicate the importance of acute processes in the development of chronic postoperative pain.

On factors controlling precursor slip fronts in the laboratory and their relation to slow slip events in nature

NASA Astrophysics Data System (ADS)

Selvadurai, Paul A.; Glaser, Steven D.; Parker, Jessica M.

2017-03-01

Spatial variations in frictional properties on natural faults are believed to be a factor influencing the presence of slow slip events (SSEs). This effect was tested on a laboratory frictional interface between two polymethyl methacrylate (PMMA) bodies. We studied the evolution of slip and slip rates that varied systematically based on the application of both high and low normal stress (σ0=0.8 or 0.4 MPa) and the far-field loading rate (VLP). A spontaneous, frictional rupture expanded from the central, weaker, and more compliant section of the fault that had fewer asperities. Slow rupture propagated at speeds Vslow˜0.8 to 26 mm s-1 with slip rates from 0.01 to 0.2 μm s-1, resulting in stress drops around 100 kPa. During certain nucleation sequences, the fault experienced a partial stress drop, referred to as precursor detachment fronts in tribology. Only at the higher level of normal stress did these fronts exist, and the slip and slip rates mimicked the moment and moment release rates during the 2013-2014 Boso SSE in Japan. The laboratory detachment fronts showed rupture propagation speeds Vslow/VR∈ (5 to 172) × 10-7 and stress drops ˜ 100 kPa, which both scaled to the aforementioned SSE. Distributions of asperities, measured using a pressure sensitive film, increased in complexity with additional normal stress—an increase in normal stress caused added complexity by increasing both the mean size and standard deviation of asperity distributions, and this appeared to control the presence of the detachment front.

Permeability evolution associated to creep and episodic slow slip of a fault affecting clay formations: Results from the FS fault activation experiment in Mt Terri (Switzerland).

NASA Astrophysics Data System (ADS)

Guglielmi, Y.; Nussbaum, C.; Birkholzer, J. T.; De Barros, L.; Cappa, F.

2017-12-01

There is a large spectrum of fault slow rupture processes such as stable creep and slow slip that radiate no or little seismic energy, and which relationships to normal earthquakes and fault permeability variations are enigmatic. Here we present measurements of a fault slow rupture, permeability variation and seismicity induced by fluid-injection in a fault affecting the Opalinus clay (Mt Terri URL, Switzerland) at a depth of 300 m. We observe multiple dilatant slow slip events ( 0.1-to-30 microm/s) associated with factor-of-1000 increase of permeability, and terminated by a magnitude -2.5 main seismic event associated with a swarm of very small magnitude ones. Using fully coupled numerical modeling, we calculate that the short term velocity strengthening behavior observed experimentally at laboratory scale is overcome by longer slip weakening that may be favored by slip induced dilation. Two monitoring points set across the fault allow estimating that, at the onset of the seismicity, the radius of the fault patch invaded by pressurized fluid is 9-to-11m which is in good accordance with a fault instability triggering when the dimensions of the critical slip distance are overcome. We then observe that the long term slip weakening is associated to an exponential permeability increase caused by a cumulated effective normal stress drop of about 3.4MPa which controls the successive slip activation of multiple fracture planes inducing a 0.1MPa shear stress drop in the fault zone. Therefore, our data suggest that the induced earthquake that terminated the rupture sequence may have represented enough dynamic stress release to arrest the fault permeability increase, suggesting the high sensitivity of the slow rupture processes to the structural heterogeneity of the fault zone hydromechanical properties.

A Citizen's Guide to Solidification and Stabilization

EPA Pesticide Factsheets

This guide describes how solidification and stabilization refer to a group of cleanup methods that prevent or slow the release of harmful chemicals from wastes, such as contaminated soil, sediment, and sludge.

A short term quality control tool for biodegradable microspheres.

PubMed

D'Souza, Susan; Faraj, Jabar A; Dorati, Rossella; DeLuca, Patrick P

2014-06-01

Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C.

Controlled release of D-glucose from starch granules containing 29% free D-glucose and Eudragit L100-55 as a binding and coating agent.

PubMed

Kim, Yeon-Kye; Mukerjea, Rupendra; Robyt, John F

2010-05-27

Waxy maize starch (100% amylopectin) granules were modified by reaction of the granules with glucoamylase in a minimum amount of water to give 29% (w/w) D-glucose inside the granules [Kim, Y.-K.; Robyt, J. F. Carbohydr. Res.1999, 318, 129-134]. These granules were made into beads by dropping an ethanol slurry of starch and different amounts of Eudragit L100-55 in a constant ratio of 100:1 from a pipette onto Whatman 3MM filter paper. The starch beads were air dried and then repeatedly sprayed 0-12 times with 2.0% (w/v) Eudragit L100-55 in ethanol, with drying between each spraying, to coat the surface of the starch beads, giving different amounts of Eudragit L100-55 coating. Seven different kinds of beads, with different amounts of Eudragit L100-55 binding and coating agent, were obtained. The rates of release of D-glucose into water from the seven kinds of beads were inversely proportional to the amount of binding and coating agent. Bead type I, which was without any binding and coating gave a fast 100% release of D-glucose in 30 min. Beads II and III also gave a fast 100% release in 60 min and 90 min, respectively. Bead IV gave a near linear release of 97% D-glucose in 150 min; Bead V gave a 50% release in 120 min followed by the remaining 50% in 60 min; and Beads VI and VII gave a slow release of 10% and 4%, respectively, from 0 to 120 min, followed by a rapid 100% release from 120 to 180 min. (c) 2010 Elsevier Ltd. All rights reserved.

Influence of Carbopol 71G-NF on the release of dextromethorphan hydrobromide from extended-release matrix tablets.

PubMed

Fayed, Mohamed H; Mahrous, Gamal M; Ibrahim, Mohamed A; Sakr, Adel

2013-01-01

The objective of this study was to evaluate the potential of Carbopol(®) 71G-NF on the release of dextromethorphan hydrobromide (DM) from matrix tablets in comparison with hydroxypropyl methylcellulose (HPMC(®) K15M) and Eudragit(®) L100-55 polymers. Controlled release DM matrix tablets were prepared using Carbopol 71G-NF, HPMC K15M, and Eudragit L100-55 at different drug to polymer ratios by direct compression technique. The mechanical properties of the tablets as tested by crushing strength and friability tests were improved as the concentration of Carbopol, HPMC, and Eudragit increased. However, Carbopol-based tablets showed a significantly (P<0.05) higher crushing strength and a lower friability than HPMC and Eudragit tablets. No significant differences in weight uniformity and thickness values were observed between the different formulations. It was also found that Carbopol significantly (P<0.05) delayed the release of DM in comparison with HPMC K15M and Eudragit L100-55. A combination of HPMC K15M and Eudragit L100-55 in a 1:1 ratio at 20 and 30% significantly (P<0.05) delayed the release of DM than Eudragit L100-55 alone. Moreover, blends of Carbopol and HPMC at a 1:1 ratio at the 10, 20, and 30% total polymer concentration were investigated. The blend of Carbopol and HPMC at 10% level significantly (P<0.05) slowed the release of DM than Carbopol or HPMC alone, whereas blends at 20 and 30% level significantly (P<0.05) delayed the release of DM compared with HPMC or Carbopol alone. The results with these polymer blends showed that it was possible to reduce the total amount of polymers when used as a combination in formulation.

Ultrathin ZnSe nanowires: one-pot synthesis via a heat-triggered precursor slow releasing route, controllable Mn doping and application in UV and near-visible light detection.

PubMed

Li, Dong; Xing, Guanjie; Tang, Shilin; Li, Xiaohong; Fan, Louzhen; Li, Yunchao

2017-10-12

We report herein a heat-triggered precursor slow releasing route for the one-pot synthesis of ultrathin ZnSe nanowires (NWs), which relies on the gradual dissolving of Se powder into oleylamine containing a soluble Zn precursor under heating. This route allows the reaction system to maintain a high monomer concentration throughout the entire reaction process, thus enabling the generation of ZnSe NWs with diameter down to 2.1 nm and length approaching 400 nm. The size-dependent optical properties and band-edge energy levels of the ZnSe NWs were then explored in depth by UV-visible spectroscopy and cyclic voltammetry, respectively. Considering their unique absorption properties, these NWs were specially utilized for fabricating photoelectrochemical-type photodetectors (PDs). Impressively, the PDs based on the ZnSe NWs with diameters of 2.1 and 4.5 nm exhibited excellent responses to UVA and near-visible light, respectively: both possessed ultrahigh on/off ratios (5150 for UVA and 4213 for near-visible light) and ultrawide linear response ranges (from 2.0 to 9000 μW cm -2 for UVA and 5.0 to 8000 μW cm -2 for near-visible light). Furthermore, these ZnSe NWs were selectively doped with various amounts of Mn 2+ to tune their emission properties. As a result, ZnSe NW film-based photochromic cards were creatively developed for visually detecting UVA and near-visible radiation.

Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses

PubMed Central

Silver, R Angus; Momiyama, Akiko; Cull-Candy, Stuart G

1998-01-01

EPSCs were recorded under whole-cell voltage clamp at room temperature from Purkinje cells in slices of cerebellum from 12- to 14-day-old rats. EPSCs from individual climbing fibre (CF) inputs were identified on the basis of their large size, paired-pulse depression and all-or-none appearance in response to a graded stimulus. Synaptic transmission was investigated over a wide range of experimentally imposed release probabilities by analysing fluctuations in the peak of the EPSC. Release probability was manipulated by altering the extracellular [Ca2+] and [Mg2+]. Quantal parameters were estimated from plots of coefficient of variation (CV) or variance against mean conductance by fitting a multinomial model that incorporated both spatial variation in quantal size and non-uniform release probability. This ‘multiple-probability fluctuation’ (MPF) analysis gave an estimate of 510 ± 50 for the number of functional release sites (N) and a quantal size (q) of 0.5 ± 0.03 nS (n = 6). Control experiments, and simulations examining the effects of non-uniform release probability, indicate that MPF analysis provides a reliable estimate of quantal parameters. Direct measurement of quantal amplitudes in the presence of 5 mm Sr2+, which gave asynchronous release, yielded distributions with a mean quantal size of 0.55 ± 0.01 nS and a CV of 0.37 ± 0.01 (n = 4). Similar estimates of q were obtained in 2 mm Ca2+ when release probability was lowered with the calcium channel blocker Cd2+. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1 μm) reduced both the evoked current and the quantal size (estimated with MPF analysis) to a similar degree, but did not affect the estimate of N. We used MPF analysis to identify those quantal parameters that change during frequency-dependent depression at climbing fibre-Purkinje cell synaptic connections. At low stimulation frequencies, the mean release probability (P¯r) was unusually high (0.90 ± 0.03 at 0.033 Hz, n = 5), but as the frequency of stimulation was increased, pr fell dramatically (0.02 ± 0.01 at 10 Hz, n = 4) with no apparent change in either q or N. This indicates that the observed 50-fold depression in EPSC amplitude is presynaptic in origin. Presynaptic frequency-dependent depression was investigated with double-pulse and multiple-pulse protocols. EPSC recovery, following simultaneous release at practically all sites, was slow, being well fitted by the sum of two exponential functions (time constants of 0.35 ± 0.09 and 3.2 ± 0.4 s, n = 5). EPSC recovery following sustained stimulation was even slower. We propose that presynaptic depression at CF synapses reflects a slow recovery of release probability following release of each quantum of transmitter. The large number of functional release sites, relatively large quantal size, and unusual dynamics of transmitter release at the CF synapse appear specialized to ensure highly reliable olivocerebellar transmission at low frequencies but to limit transmission at higher frequencies. PMID:9660900

Evaluation of ceftiofur–PHBV microparticles in rats

PubMed Central

Vilos, Cristian; Constandil, Luis; Rodas, Paula I; Cantin, Mario; Zepeda, Katherine; Herrera, Natalia; Velasquez, Luis A

2014-01-01

Despite the high number of antibiotics used for the treatment of infectious disease in animals, the development of slow release formulations presents a significant challenge, particularly in using novel biomaterials with low cost. In this report, we studied the pharmacokinetics, toxicity, and therapeutic activity of ceftiofur–PHBV (ceftiofur–poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) in rats. The pharmacokinetic study demonstrated a sustained release of ceftiofur into the bloodstream, with detectable levels over the minimum inhibitory concentration for at least 17 days after a single intramuscular injection of ceftiofur–PHBV (10 mg/kg weight). In addition, the toxicological evaluation of biochemical, hematological, and coagulation blood parameters at the therapeutic dose demonstrated the safety of ceftiofur–PHBV, with no adverse effects. In addition, ceftiofur–PHBV exhibited a therapeutic effect for a longer time period than the nonencapsulated ceftiofur in rats challenged with Salmonella Typhimurium. The slow release of ceftiofur from the ceftiofur–PHBV, its low toxicity in the blood parameters evaluated, and the efficacy in the rats infected with Salmonella Typhimurium make ceftiofur–PHBV a strong candidate for biotechnological applications in the veterinary industry. PMID:24936127

A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma.

PubMed

Xie, Hui; Tian, Shengtao; Yu, Haipeng; Yang, Xueling; Liu, Jia; Wang, Huaming; Feng, Fan; Guo, Zhi

2018-01-01

Radiofrequency ablation (RFA) is the foremost treatment option for advanced hepatocellular carcinoma (HCC), however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial-mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects. In this study, we prepared an apatinib microcrystal formulation (Apa-MS) that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors. It was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial-mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment. Based on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC.

Influence of acidic and alkaline waste solution properties on uranium migration in subsurface sediments.

PubMed

Szecsody, Jim E; Truex, Mike J; Qafoku, Nikolla P; Wellman, Dawn M; Resch, Tom; Zhong, Lirong

2013-08-01

This study shows that acidic and alkaline wastes co-disposed with uranium into subsurface sediments have significant impact on changes in uranium retardation, concentration, and mass during downward migration. For uranium co-disposal with acidic wastes, significant rapid (i.e., hours) carbonate and slow (i.e., 100 s of hours) clay dissolution resulted, releasing significant sediment-associated uranium, but the extent of uranium release and mobility change was controlled by the acid mass added relative to the sediment proton adsorption capacity. Mineral dissolution in acidic solutions (pH2) resulted in a rapid (<10 h) increase in aqueous carbonate (with Ca(2+), Mg(2+)) and phosphate and a slow (100 s of hours) increase in silica, Al(3+), and K(+), likely from 2:1 clay dissolution. Infiltration of uranium with a strong acid resulted in significant shallow uranium mineral dissolution and deeper uranium precipitation (likely as phosphates and carbonates) with downward uranium migration of three times greater mass at a faster velocity relative to uranium infiltration in pH neutral groundwater. In contrast, mineral dissolution in an alkaline environment (pH13) resulted in a rapid (<10h) increase in carbonate, followed by a slow (10 s to 100 s of hours) increase in silica concentration, likely from montmorillonite, muscovite, and kaolinite dissolution. Infiltration of uranium with a strong base resulted in not only uranium-silicate precipitation (presumed Na-boltwoodite) but also desorption of natural uranium on the sediment due to the high ionic strength solution, or 60% greater mass with greater retardation compared with groundwater. Overall, these results show that acidic or alkaline co-contaminant disposal with uranium can result in complex depth- and time-dependent changes in uranium dissolution/precipitation reactions and uranium sorption, which alter the uranium migration mass, concentration, and velocity. Copyright © 2013 Elsevier B.V. All rights reserved.

Early release improves long-term growth and development of direct-seeded nuttall oak saplings

Treesearch

James S. Meadows; Robert L. Johnson; Roger M. Krinard

2015-01-01

Early growth of bottomland oaks is typically slow, and many oaks eventually become overtopped by trees of other species. Removal of these larger competitors in a young stand might improve growth of the oaks and lead to more free-to-grow oaks as the stand matures. Release treatments were applied in 1980 to an 11-year-old, direct-seeded Nuttall oak (Quercus texana Buckl...

Fluoride mechanisms.

PubMed

ten Cate, J M; van Loveren, C

1999-10-01

This article discusses fluoride mechanisms in relation to dental caries. The authors specifically address firmly bound versus loosely bound fluoride; different fluoride active ingredients; fluoride and demineralization and remineralization; fluoride slow-release devices and F-releasing dental materials; antimicrobial effects of fluoride; the uptake of fluoride by oral bacteria; inhibition of enolase, protein-intruding ATPase and sugar transport; the various aspects of plaque as it relates to fluoride; and the rational use of fluoride.

Sustained release of hepatocyte growth factor by cationic self-assembling peptide/heparin hybrid hydrogel improves β-cell survival and function through modulating inflammatory response

PubMed Central

Liu, Shuyun; Zhang, Lanlan; Cheng, Jingqiu; Lu, Yanrong; Liu, Jingping

2016-01-01

Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated. Cationic KLD1R and KLD2R self-assembled to nanofiber hydrogel, which showed higher binding affinity for Hep and HGF because of electrostatic interaction. Slow release of HGF from cationic SAP/Hep gel is a two-step mechanism involving binding affinity with Hep and molecular diffusion. In vitro and in vivo results showed that HGF-loaded KLD2R/Hep gel promoted β-cell survival and insulin secretion, and inhibited cell apoptosis, cytokine release, T-cell infiltration, and activation of NFκB/p38 MAPK pathways in β-cells. This study suggested that SAP/Hep gel is a promising carrier for local delivery of bioactive proteins in islet transplantation. PMID:27729786

Comparison of PAH Biodegradation and Desorption Kinetics During Bioremediation of Aged Petroleum Hydrocarbon Contaminated Soils

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

Huesemann, Michael H.; Hausmann, Tom S.; Fortman, Timothy J.

It is commonly assumed that mass-transfer limitations are the cause for slow and incomplete biodegradation of PAHs in aged soils. In order to test this hypothesis, the biodegradation rate and the abiotic release rate were measured and compared for selected PAHs in three different soils. It was found that PAH biodegradation was not mass-transfer limited during slurry bioremediation of an aged loamy soil. By contrast, PAH biodegradation rates were much larger than abiotic release rates in kaolinite clay indicating that sorbed-phase PAHs can apparently be biodegraded directly from mineral surfaces without prior desorption or dissolution into the aqueous phase. Amore » comparison of PAH biodegradation rates and abiotic release rates at termination of the slurry bioremediation treatment revealed that abiotic release rates are much larger than the respective biodegradation rates. In addition, it was found that the number of hydrocarbon degraders decreased by four orders of magnitude during the bioremediation treatment. It can therefore be concluded that the slow and incomplete biodegradation of PAHs is not caused by mass-transfer limitations but rather by microbial factors. Consequently, the residual PAHs that remain after extensive bioremediation treatment are still bioavailable and for that reason could pose a greater risk to environmental receptors than previously thought.« less

The Role of Neurotrophins in Neurotransmitter Release

PubMed Central

Tyler, William J.; Perrett, Stephen P.; Pozzo-Miller, Lucas D.

2009-01-01

The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by “fine-tuning” synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as “kiss-and-run.” By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system. PMID:12467374

The role of neurotrophins in neurotransmitter release.

PubMed

Tyler, William J; Perrett, Stephen P; Pozzo-Miller, Lucas D

2002-12-01

The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by "fine-tuning" synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as "kiss-and-run." By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system.

Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

NASA Astrophysics Data System (ADS)

Milne, Peter J.; Gautier, Sandrine; Parel, Jean-Marie A.; Jallet, Valerie

1997-05-01

The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

Opposing effects of different soil organic matter fractions on crop yields.

PubMed

Wood, Stephen A; Sokol, Noah; Bell, Colin W; Bradford, Mark A; Naeem, Shahid; Wallenstein, Matthew D; Palm, Cheryl A

2016-10-01

Soil organic matter is critical to sustainable agriculture because it provides nutrients to crops as it decomposes and increases nutrient- and water-holding capacity when built up. Fast- and slow-cycling fractions of soil organic matter can have different impacts on crop production because fast-cycling fractions rapidly release nutrients for short-term plant growth and slow-cycling fractions bind nutrients that mineralize slowly and build up water-holding capacity. We explored the controls on these fractions in a tropical agroecosystem and their relationship to crop yields. We performed physical fractionation of soil organic matter from 48 farms and plots in western Kenya. We found that fast-cycling, particulate organic matter was positively related to crop yields, but did not have a strong effect, while slower-cycling, mineral-associated organic matter was negatively related to yields. Our finding that slower-cycling organic matter was negatively related to yield points to a need to revise the view that stabilization of organic matter positively impacts food security. Our results support a new paradigm that different soil organic matter fractions are controlled by different mechanisms, potentially leading to different relationships with management outcomes, like crop yield. Effectively managing soils for sustainable agriculture requires quantifying the effects of specific organic matter fractions on these outcomes. © 2016 by the Ecological Society of America.

Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes.

PubMed

Duggan, A W; Schaible, H G; Hope, P J; Lang, C W

1992-05-08

Antibody microprobes bearing antibodies to the C-terminus of substance P (SP) were used to measure release of immunoreactive (ir) SP in the dorsal horn of barbiturate anaesthetized spinal cats. Electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve produced a relatively localised release of ir SP in the superficial dorsal horn. Prior microinjection of the peptidase inhibitors kelatorphan and enalaprilat in the dorsal horn resulted in ir SP being detected over the whole of the dorsal horn and the overlying dorsal column. This pattern had previously been observed with evoked release of ir neurokinin A and supports the proposal that a slow degradation results in a neuropeptide accessing many sites remote from sites of release.

Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety.

PubMed

Bulling, M T; Wing, L M; Burns, R J

1991-08-01

Twenty patients with moderately severe Parkinson's disease entered an open study of the efficacy and safety of a slow release preparation containing levodopa 200 mg and carbidopa 50 mg per tablet ('Sinemet CR4'). Following an initial four week baseline stabilisation period on conventional 'Sinemet' tablets, the patients were transferred to 'Sinemet CR4' and observed at intervals over the next 12 months. Fifteen patients completed the full year observation period. When compared with the baseline period, treatment with 'Sinemet CR4' was associated with longer periods of functional improvement and less fluctuation of response following each dose. The median (range) dose frequency was reduced from three (three-12) to two (two-seven) times daily (p less than 0.001) on 'Sinemet CR4' although median (range) total daily dose of levodopa was increased from 700 (375-2525) to 800 (400-2800) mg without any increase in adverse effects. Three patients developed peripheral neuropathy while receiving Sinemet CR4, but the association with this therapy is unclear. Overall 'Sinemet CR4' allowed a longer dosage interval and provided more stable control of disease manifestations than conventional 'Sinemet'.

Probability of brittle failure

NASA Technical Reports Server (NTRS)

Kim, A.; Bosnyak, C. P.; Chudnovsky, A.

1991-01-01

A methodology was developed for collecting statistically representative data for crack initiation and arrest from small number of test specimens. An epoxy (based on bisphenol A diglycidyl ether and polyglycol extended diglycyl ether and cured with diethylene triamine) is selected as a model material. A compact tension specimen with displacement controlled loading is used to observe multiple crack initiation and arrests. The energy release rate at crack initiation is significantly higher than that at a crack arrest, as has been observed elsewhere. The difference between these energy release rates is found to depend on specimen size (scale effect), and is quantitatively related to the fracture surface morphology. The scale effect, similar to that in statistical strength theory, is usually attributed to the statistics of defects which control the fracture process. Triangular shaped ripples (deltoids) are formed on the fracture surface during the slow subcritical crack growth, prior to the smooth mirror-like surface characteristic of fast cracks. The deltoids are complementary on the two crack faces which excludes any inelastic deformation from consideration. Presence of defects is also suggested by the observed scale effect. However, there are no defects at the deltoid apexes detectable down to the 0.1 micron level.

Comparative studies on osmosis based encapsulation of sodium diclofenac in porcine and outdated human erythrocyte ghosts.

PubMed

Bukara, Katarina; Drvenica, Ivana; Ilić, Vesna; Stančić, Ana; Mišić, Danijela; Vasić, Borislav; Gajić, Radoš; Vučetić, Dušan; Kiekens, Filip; Bugarski, Branko

2016-12-20

The objective of our study was to develop controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process. Copyright © 2016 Elsevier B.V. All rights reserved.

Complex coacervation of collagen hydrolysate extracted from leather solid wastes and chitosan for controlled release of lavender oil.

PubMed

Ocak, Buğra

2012-06-15

In the world, approximately 600,000 metric tonnes of chromium-containing solid wastes are generated by the leather industry each year. Environmental concerns and escalating landfill costs are becoming increasingly serious problems to the leather industry and seeking solutions to these problems is a prime concern in much research today. In this study, solid collagen-based protein hydrolysate was isolated from chromium-tanned leather wastes and its chemical properties were determined. Microcapsules of collagen hydrolysate (CH) - chitosan (C) crosslinked with glutaraldehyde (GA) containing Lavender oil (LO) were prepared by complex coacervation method. The effects of various processing parameters, including the CH to C ratio, LO content, and GA, on the oil load (%), oil content (%), encapsulation efficiency (%) and release rate of LO from microcapsules were investigated. As the ratio of C present in the CH/C mixture and crosslinking density increased, the release rate of LO from microcapsules slowed down. Optical and scanning electron microscopy images illustrated that the LO microcapsules were spherical in shape. Fourier transform infrared spectroscopy (FTIR) studies confirmed that there was no significant interaction between CH/C complex and LO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Shallow very-low-frequency earthquakes accompany slow slip events in the Nankai subduction zone.

PubMed

Nakano, Masaru; Hori, Takane; Araki, Eiichiro; Kodaira, Shuichi; Ide, Satoshi

2018-03-14

Recent studies of slow earthquakes along plate boundaries have shown that tectonic tremor, low-frequency earthquakes, very-low-frequency events (VLFEs), and slow-slip events (SSEs) often accompany each other and appear to share common source faults. However, the source processes of slow events occurring in the shallow part of plate boundaries are not well known because seismic observations have been limited to land-based stations, which offer poor resolution beneath offshore plate boundaries. Here we use data obtained from seafloor observation networks in the Nankai trough, southwest of Japan, to investigate shallow VLFEs in detail. Coincident with the VLFE activity, signals indicative of shallow SSEs were detected by geodetic observations at seafloor borehole observatories in the same region. We find that the shallow VLFEs and SSEs share common source regions and almost identical time histories of moment release. We conclude that these slow events arise from the same fault slip and that VLFEs represent relatively high-frequency fluctuations of slip during SSEs.

Efficacy of slow-release tags impregnated with aggregation-attachment pheromone and deltamethrin for control of Amblyomma variegatum on St. Kitts, West Indies.

PubMed

Kelly, Patrick J; Lucas, Helene M; Randolph, Craig M; Ackerson, Kate; Blackburn, Jason K; Dark, Michael J

2014-04-14

Amblyomma variegatum is an important cause of morbidity, mortality and economic losses in Africa and the West Indies. Attempts to control and/or eradicate the tick from the Caribbean have largely been unsuccessful because of difficulties relating to the biology of the three-host tick and problems with applying acaricides on a regular basis to free-ranging domestic ruminants. While plastic collars impregnated with insecticides are widely and effectively used in companion animals to control external parasites there is little information on this technology in ruminants. Over 21 months we tested the efficacy of slow-release plastic tags impregnated with deltamethrin (7%) and aggregation-attachment pheromones (DPITs) in controlling A. variegatum on free-ranging cattle on two farms on St. Kitts. The tags were replaced every three months or when found to be lost. On sentinel animals fitted with tags containing only aggregation-attachment pheromones there were an average of 23.1 ticks per semi-monthly visit although this number varied considerably, peaking in the dry season around May and being lowest in August to October during the wet season. Significantly fewer ticks (3.5 on average) were found on cattle with DPITs at each visit (P < 0.001). Although the DIPTs provided good control (92% on average), they did not significantly reduce A. variegatum in the environment with tick numbers on sentinels being higher in the second year of the study, despite up to 44% of animals being fitted with DPITs. The tags were economical, costing 0.2% of the 1% flumethrin pour-on treatment widely recommended for A. variegatum control in the Caribbean. The major problem encountered was that 38% of tail tags were lost before they were due for replacement every three months. Our study has shown that DPITs are cheap to produce, easy to place, only require handling of animals every three months, and are very effective in protecting cattle from A. variegatum. Before DPITs can be considered for eradication programs the problems needing to be addressed include loss of tail tags, particularly in thick vegetation, and the optimum number of animals that must be treated to reduce numbers of ticks in the environment.

Slow-Releasing Oxygen Source

EPA Science Inventory

Subsurface pollution is an environmental issue of great concern in the United States and around the world. Bioremediation has proven to be an effective and environmentally preferable treatment for biodegradable pollutants, such as methyl tertiary butyl ether, toluene, ethylbenze...

Selective expression of the type 3 isoform of ryanodine receptor Ca{sup 2+} release channel (RyR3) in a subset of slow fibers in diaphragm and cephalic muscles of adult rabbits

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

Conti, Antonio; Reggiani, Carlo; Sorrentino, Vincenzo

2005-11-11

The expression pattern of the RyR3 isoform of Ca{sup 2+} release channels was analysed by Western blot in neonatal and adult rabbit skeletal muscles. The results obtained show that the expression of the RyR3 isoform is developmentally regulated. In fact, RyR3 expression was detected in all muscles analysed at 2 and 15 days after birth while, in adult animals, it was restricted to a subset of muscles that includes diaphragm, masseter, pterygoideus, digastricus, and tongue. Interestingly, all of these muscles share a common embryonic origin being derived from the somitomeres or from the cephalic region of the embryo. Immunofluorescence analysismore » of rabbit skeletal muscle cross-sections showed that RyR3 staining was detected in all fibers of neonatal muscles. In contrast, in those adult muscles expressing RyR3 only a fraction of fibers was labelled. Staining of these muscles with antibodies against fast and slow myosins revealed a close correlation between expression of RyR3 and fibers expressing slow myosin isoform.« less

Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition

PubMed Central

Collins, Kevin M; Bode, Addys; Fernandez, Robert W; Tanis, Jessica E; Brewer, Jacob C; Creamer, Matthew S; Koelle, Michael R

2016-01-01

Like many behaviors, Caenorhabditis elegans egg laying alternates between inactive and active states. To understand how the underlying neural circuit turns the behavior on and off, we optically recorded circuit activity in behaving animals while manipulating circuit function using mutations, optogenetics, and drugs. In the active state, the circuit shows rhythmic activity phased with the body bends of locomotion. The serotonergic HSN command neurons initiate the active state, but accumulation of unlaid eggs also promotes the active state independent of the HSNs. The cholinergic VC motor neurons slow locomotion during egg-laying muscle contraction and egg release. The uv1 neuroendocrine cells mechanically sense passage of eggs through the vulva and release tyramine to inhibit egg laying, in part via the LGC-55 tyramine-gated Cl- channel on the HSNs. Our results identify discrete signals that entrain or detach the circuit from the locomotion central pattern generator to produce active and inactive states. DOI: http://dx.doi.org/10.7554/eLife.21126.001 PMID:27849154

Drug-loaded erythrocytes: on the road toward marketing approval

PubMed Central

Bourgeaux, Vanessa; Lanao, José M; Bax, Bridget E; Godfrin, Yann

2016-01-01

Erythrocyte drug encapsulation is one of the most promising therapeutic alternative approaches for the administration of toxic or rapidly cleared drugs. Drug-loaded erythrocytes can operate through one of the three main mechanisms of action: extension of circulation half-life (bioreactor), slow drug release, or specific organ targeting. Although the clinical development of erythrocyte carriers is confronted with regulatory and development process challenges, industrial development is expanding. The manufacture of this type of product can be either centralized or bedside based, and different procedures are employed for the encapsulation of therapeutic agents. The major challenges for successful industrialization include production scalability, process validation, and quality control of the released therapeutic agents. Advantages and drawbacks of the different manufacturing processes as well as success key points of clinical development are discussed. Several entrapment technologies based on osmotic methods have been industrialized. Companies have already achieved many of the critical clinical stages, thus providing the opportunity in the future to cover a wide range of diseases for which effective therapies are not currently available. PMID:26929599

Fate of 90Sr and U(VI) in Dounreay sediments following saline inundation and erosion.

PubMed

Eagling, Jane; Worsfold, Paul J; Blake, William H; Keith-Roach, Miranda J

2013-08-01

There is concern that sea level rise associated with projected climate change will lead to the inundation, flooding and erosion of soils and sediments contaminated with radionuclides at coastal nuclear sites, such as Dounreay (UK), with seawater. Here batch and column experiments were designed to simulate these scenarios and sequential extractions were used to identify the key radionuclide solid phase associations. Strontium was exchangeable and was mobilised rapidly by ion exchange with seawater Mg(2+) in both batch and column experiments. In contrast, U was more strongly bound to the sediments and mobilisation was initially limited by the influence of the sediment on the pH of the water. Release was only observed when the pH increased above 6.9, suggesting that the formation of soluble U(VI)-carbonate species was important. Under dynamic flow conditions, long term release was significant (47%), but controlled by slow desorption kinetics from a range of binding sites. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biocompatible and biodegradable fibrinogen microspheres for tumor-targeted doxorubicin delivery

PubMed Central

Joo, Jae Yeon; Park, Gil Yong; An, Seong Soo A

2015-01-01

In the development of effective drug delivery carriers, many researchers have focused on the usage of nontoxic and biocompatible materials and surface modification with targeting molecules for tumor-specific drug delivery. Fibrinogen (Fbg), an abundant glycoprotein in plasma, could be a potential candidate for developing drug carriers because of its biocompatibility and tumor-targeting property via arginine–glycine–aspartate (RGD) peptide sequences. Doxorubicin (DOX), a chemotherapeutic agent, was covalently conjugated to Fbg, and the microspheres were prepared. Acid-labile and non-cleavable linkers were used for the conjugation of DOX to Fbg, resulting in an acid-triggered drug release under a mild acidic condition and a slow-controlled drug release, respectively. In vitro cytotoxicity tests confirmed low cytotoxicity in normal cells and high antitumor effect toward cancer cells. In addition, it was discovered that a longer linker could make the binding of cells to Fbg drug carriers easier. Therefore, DOX–linker–Fbg microspheres could be a suitable drug carrier for safer and effective drug delivery. PMID:26366073

HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

PubMed

Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

2015-03-18

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

HDL-Mimetic PLGA Nanoparticle To Target Atherosclerosis Plaque Macrophages

PubMed Central

Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J.; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J M

2015-01-01

High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA–HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA–HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers. PMID:25650634

Drug-loaded erythrocytes: on the road toward marketing approval.

PubMed

Bourgeaux, Vanessa; Lanao, José M; Bax, Bridget E; Godfrin, Yann

2016-01-01

Erythrocyte drug encapsulation is one of the most promising therapeutic alternative approaches for the administration of toxic or rapidly cleared drugs. Drug-loaded erythrocytes can operate through one of the three main mechanisms of action: extension of circulation half-life (bioreactor), slow drug release, or specific organ targeting. Although the clinical development of erythrocyte carriers is confronted with regulatory and development process challenges, industrial development is expanding. The manufacture of this type of product can be either centralized or bedside based, and different procedures are employed for the encapsulation of therapeutic agents. The major challenges for successful industrialization include production scalability, process validation, and quality control of the released therapeutic agents. Advantages and drawbacks of the different manufacturing processes as well as success key points of clinical development are discussed. Several entrapment technologies based on osmotic methods have been industrialized. Companies have already achieved many of the critical clinical stages, thus providing the opportunity in the future to cover a wide range of diseases for which effective therapies are not currently available.

Alginate-hydroxypropylcellulose hydrogel microbeads for alkaline phosphatase encapsulation.

PubMed

Karewicz, A; Zasada, K; Bielska, D; Douglas, T E L; Jansen, J A; Leeuwenburgh, S C G; Nowakowska, M

2014-01-01

There is a growing interest in using proteins as therapeutics agents. Unfortunately, they suffer from limited stability and bioavailability. We aimed to develop a new delivery system for proteins. ALP, a model protein, was successfully encapsulated in the physically cross-linked sodium alginate/hydroxypropylcellulose (ALG-HPC) hydrogel microparticles. The obtained objects had regular, spherical shape and a diameter of ∼4 µm, as confirmed by optical microscopy and SEM analysis. The properties of the obtained microbeads could be controlled by temperature and additional coating or crosslinking procedures. The slow, sustained release of ALP in its active form with no initial burst effect was observed for chitosan-coated microspheres at pH = 7.4 and 37 °C. Activity of ALP released from ALG/HPC microspheres was confirmed by the occurance of effectively induced mineralization. SEM and AFM images revealed formation of the interpenetrated three-dimensional network of mineral, originating from the microbeads' surfaces. FTIR and XRD analyses confirmed formation of hydroxyapatite.

Exploring a new jellyfish collagen in the production of microparticles for protein delivery.

PubMed

Calejo, M Teresa; Almeida, António J; Fernandes, Ana I

2012-01-01

A microparticulate protein delivery system was developed using collagen, from the medusa Catostylus tagi, as a polymeric matrix. Collagen microparticles (CMPs) were produced by an emulsification-gelation-solvent extraction method and a high loading efficiency was found for the entrapment of lysozyme and α-lactalbumin. CMPs were cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The uncross-linked CMPs were spherical, rough-surfaced, presenting an estimated median size of 28 µm by laser diffraction. Upon cross-linking, particle size (9.5 µm) and size distribution were reduced. CMPs showed a moderate hydrophobic behaviour and a positive surface charge. Cross-linking also resulted in greater stability in water, allowing a slow release, as shown by in vitro experiments. The assessment of lysozyme's biological activity showed that the protein remained active throughout the encapsulation and cross-linking processes. In summary, the work herein described shows the potential use of a marine collagen in the production of microparticles for the controlled release of therapeutic proteins.

Nanostructured nanoparticles of self-assembled lipid pro-drugs as a route to improved chemotherapeutic agents

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

Sagnella, Sharon M.; Gong, Xiaojuan; Moghaddam, Minoo J.

2014-09-24

We demonstrate that oral delivery of self-assembled nanostructured nanoparticles consisting of 5-fluorouracil (5-FU) lipid prodrugs results in a highly effective, target-activated, chemotherapeutic agent, and offers significantly enhanced efficacy over a commercially available alternative that does not self-assemble. The lipid prodrug nanoparticles have been found to significantly slow the growth of a highly aggressive mouse 4T1 breast tumour, and essentially halt the growth of a human MDA-MB-231 breast tumour in mouse xenografts. Systemic toxicity is avoided as prodrug activation requires a three-step, enzymatic conversion to 5-FU, with the third step occurring preferentially at the tumour site. Additionally, differences in the lipidmore » prodrug chemical structure and internal nanostructure of the nanoparticle dictate the enzymatic conversion rate and can be used to control sustained release profiles. Thus, we have developed novel oral nanomedicines that combine sustained release properties with target-selective activation.« less

Analysis of slow depolarizing potential in frog taste cell induced by parasympathetic efferent stimulation under hypoxia.

PubMed

Sato, Toshihide; Nishishita, Kazushisa; Okada, Yukio; Toda, Kazuo

2007-05-01

Strong electrical stimulation (ES) of the frog glossopharyngeal (GP) efferent nerve induced slow depolarizing potentials (DPs) in taste cells under hypoxia. This study aimed to elucidate whether the slow DPs were postsynaptically induced in taste cells. After a block of parasympathetic nerve (PSN) ganglia by tubocurarine, ES of GP nerve never induced slow DPs in the taste cells, so slow DPs were induced by PSN. When Ca(2+) in the blood plasma under hypoxia was decreased to approximately 0.5 mM, the slow DPs reduced in amplitude and lengthened in latency. Increasing the normal Ca(2+) to approximately 20 mM increased the amplitude of slow DPs and shortened the latency. Addition of Cd(2+) to the plasma greatly reduced the amplitude of slow DPs and lengthened the latency. These data suggest that the slow DPs depend on Ca(2+) and Cd(2+) concentration at the presynaptic PSN terminals of taste disk. Antagonists, [D-Arg(1), D-Trp(7,9), Leu(11)]-substance P and L-703 606, of neurotransmitter substance P neurokinin(1) receptor completely blocked the slow DPs. Intravenous application of substance P induced a DP of approximately 7 mV and a reduction of membrane resistance of approximately 48% in taste cells. A nonselective cation channel antagonist, flufenamic acid, completely blocked the slow DPs. These findings suggest that the slow DPs are postsynaptically initiated in frog taste cells under hypoxia by opening nonselective cation channels on the postsynaptic membrane after substance P is probably released from the presynaptic PSN axon terminals.

Polyanionic carbohydrate doxorubicin–dextran nanocomplex as a delivery system for anticancer drugs: in vitro analysis and evaluations

PubMed Central

Yousefpour, Parisa; Atyabi, Fatemeh; Farahani, Ebrahim Vashegani; Sakhtianchi, Ramin; Dinarvand, Rassoul

2011-01-01

This study deals with the preparation and investigation of a nanoscale delivery system for the anticancer drug doxorubicin (DOX) using its complexation with polyanionic carbohydrate dextran sulfate (DS). Dynamic light scattering, SEM, and zeta potential determination were used to characterize nanocomplexes. DOX-DS complexation was studied in the presence of ethanol as a hydrogen-bond disrupting agent, NaCl as an electrostatic shielding agent, and chitosan as a positively charged polymer. Thermodynamics of DOX-DS interaction was studied using isothermal titration calorimetry (ITC). A dialysis method was applied to investigate the release profile of DOX from DOX-DS nanocomplexes. Spherical and smooth-surfaced DOX-DS nanocomplexes (250–500 nm) with negative zeta potential were formed at a DS/DOX (w/w) ratio of 0.4–0.6, with over 90% drug encapsulation efficiency. DOX when complexed with DS showed lower fluorescence emission and 480 nm absorbance plus a 15 nm bathometric shift in its visible absorbance spectrum. Electrostatic hydrogen bonding and π-π stacking interactions are the main contributing interactions in DOX-DS complexation. Thermal analysis of DOX-DS complexation by ITC revealed that each DOX molecule binds with 3 DS glycosyl monomers. Drug release profile of nanocomplexes showed a fast DOX release followed by a slow sustained release, leading to release of 32% of entrapped DOX within 15 days. DOX-DS nanocomplexes may serve as a drug delivery system with efficient drug encapsulation and also may be taken into consideration in designing DOX controlled-release systems. PMID:21796249

How the Binding of Human Transferrin Primes the Transferrin Receptor Potentiating Iron Release at Endosomal pH

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

B Eckenroth; A Steere; N Chasteen

2011-12-31

Delivery of iron to cells requires binding of two iron-containing human transferrin (hTF) molecules to the specific homodimeric transferrin receptor (TFR) on the cell surface. Through receptor-mediated endocytosis involving lower pH, salt, and an unidentified chelator, iron is rapidly released from hTF within the endosome. The crystal structure of a monoferric N-lobe hTF/TFR complex (3.22-{angstrom} resolution) features two binding motifs in the N lobe and one in the C lobe of hTF. Binding of Fe{sub N}hTF induces global and site-specific conformational changes within the TFR ectodomain. Specifically, movements at the TFR dimer interface appear to prime the TFR to undergomore » pH-induced movements that alter the hTF/TFR interaction. Iron release from each lobe then occurs by distinctly different mechanisms: Binding of His349 to the TFR (strengthened by protonation at low pH) controls iron release from the C lobe, whereas displacement of one N-lobe binding motif, in concert with the action of the dilysine trigger, elicits iron release from the N lobe. One binding motif in each lobe remains attached to the same {alpha}-helix in the TFR throughout the endocytic cycle. Collectively, the structure elucidates how the TFR accelerates iron release from the C lobe, slows it from the N lobe, and stabilizes binding of apohTF for return to the cell surface. Importantly, this structure provides new targets for mutagenesis studies to further understand and define this system.« less

Saquinavir Loaded Acetalated Dextran Microconfetti – a Long Acting Protease Inhibitor Injectable

PubMed Central

Collier, Michael A.; Gallovic, Matthew D.; Bachelder, Eric M.; Sykes, Craig D.; Kashuba, Angela; Ainslie, Kristy M.

2018-01-01

Purpose Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral injectables that deliver drug for months at a time have moved into late phase clinical trials. Unfortunately, these solid phase crystal formulations have inherent drawbacks in potential dose dumping and a greater likelihood for burst release of drug compared to polymeric formulations. Methods Using electrospinning, acetalated dextran scaffolds containing the protease inhibitor saquinavir were created. Grinding techniques were then used to process these scaffolds into injectables which are termed saquinavir microconfetti. Microconfetti was analyzed for in vitro and in vivo release kinetics. Results Highly saquinavir loaded acetalated dextran electrospun fibers were able to be formed and processed into saquinavir microconfetti while other polymers such as poly lactic-co-glycolic acid and polycaprolactone were unable to do so. Saquinavir microconfetti release kinetics were able to be tuned via drug loading and polymer degradation rates. In vivo, a single subcutaneous injection of saquinavir microconfetti released drug for greater than a week with large tissue retention. Conclusions Microconfetti is a uniquely tunable long acting injectable that would reduce the formation of adherence related HIV resistance. Our findings suggest that the injectable microconfetti delivery system could be used for long acting controlled release of saquinavir and other hydrophobic small molecule drugs. PMID:27154460

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging.

PubMed

Jayasinghe, Isuru D; Munro, Michelle; Baddeley, David; Launikonis, Bradley S; Soeller, Christian

2014-10-06

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging

PubMed Central

Jayasinghe, Isuru D.; Munro, Michelle; Baddeley, David; Launikonis, Bradley S.; Soeller, Christian

2014-01-01

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. PMID:25100314

Comparative Study on Two Different Methods for Determination of Hydraulic Conductivity of HeLa Cells During Freezing.

PubMed

Li, Lei; Gao, Cai; Zhao, Gang; Shu, Zhiquan; Cao, Yunxia; Gao, Dayong

2016-12-01

The measurement of hydraulic conductivity of the cell membrane is very important for optimizing the protocol of cryopreservation and cryosurgery. There are two different methods using differential scanning calorimetry (DSC) to measure the freezing response of cells and tissues. Devireddy et al. presented the slow-fast-slow (SFS) cooling method, in which the difference of the heat release during the freezing process between the osmotically active and inactive cells is used to obtain the cell membrane hydraulic conductivity and activation energy. Luo et al. simplified the procedure and introduced the single-slow (SS) cooling protocol, which requires only one cooling process although different cytocrits are required for the determination of the membrane transport properties. To the best of our knowledge, there is still a lack of comparison of experimental processes and requirements for experimental conditions between these two methods. This study made a systematic comparison between these two methods from the aforementioned aspects in detail. The SFS and SS cooling methods mentioned earlier were utilized to obtain the reference hydraulic conductivity (L pg ) and activation energy (E Lp ) of HeLa cells by fitting the model to DSC data. With the SFS method, it was determined that L pg  = 0.10 μm/(min·atm) and E Lp  = 22.9 kcal/mol; whereas the results obtained by the SS cooling method showed that L pg  = 0.10 μm/(min·atm) and E Lp  = 23.6 kcal/mol. The results indicated that the values of the water transport parameters measured by two methods were comparable. In other words, the two parameters can be obtained by comparing the heat releases between two slow cooling processes of the same sample according to the SFS method. However, the SS method required analyzing heat releases of samples with different cytocrits. Thus, more experimental time was required.

Controlling the strontium-doping in calcium phosphate microcapsules through yeast-regulated biomimetic mineralization.

PubMed

Huang, Miaojun; Li, Tianjie; Pan, Ting; Zhao, Naru; Yao, Yongchang; Zhai, Zhichen; Zhou, Jiaan; Du, Chang; Wang, Yingjun

2016-10-01

Yeast cells have controllable biosorption on metallic ions during metabolism. However, few studies were dedicated to using yeast-regulated biomimetic mineralization process to control the strontium-doped positions in calcium phosphate microcapsules. In this study, the yeast cells were allowed to pre-adsorb strontium ions metabolically and then served as sacrificing template for the precipitation and calcination of mineral shell. The pre-adsorption enabled the microorganism to enrich of strontium ions into the inner part of the microcapsules, which ensured a slow-release profile of the trace element from the microcapsule. The co-culture with human marrow stromal cells showed that gene expressions of alkaline phosphatase and Collagen-I were promoted. The promotion of osteogenic differentiation was further confirmed in the 3D culture of cell-material complexes. The strategy using living microorganism as 'smart doping apparatus' to control incorporation of trace element into calcium phosphate paved a pathway to new functional materials for hard tissue regeneration.

Release from the cone ribbon synapse under bright light conditions can be controlled by the opening of only a few Ca2+ channels

PubMed Central

Bartoletti, Theodore M.; Jackman, Skyler L.; Babai, Norbert; Mercer, Aaron J.; Kramer, Richard H.

2011-01-01

Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca2+ channels to open infrequently. To understand neurotransmission under these conditions, we determined the number of L-type Ca2+ channel openings necessary for vesicle fusion at the cone ribbon synapse. Ca2+ currents (ICa) were activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs) were recorded from horizontal cells in the salamander retina slice preparation. Ca2+ channel number and single-channel current amplitude were calculated by mean-variance analysis of ICa. Two different comparisons—one comparing average numbers of release events to average ICa amplitude and the other involving deconvolution of both EPSCs and simultaneously recorded cone ICa—suggested that fewer than three Ca2+ channel openings accompanied fusion of each vesicle at the peak of release during the first few milliseconds of stimulation. Opening fewer Ca2+ channels did not enhance fusion efficiency, suggesting that few unnecessary channel openings occurred during strong depolarization. We simulated release at the cone synapse, using empirically determined synaptic dimensions, vesicle pool size, Ca2+ dependence of release, Ca2+ channel number, and Ca2+ channel properties. The model replicated observations when a barrier was added to slow Ca2+ diffusion. Consistent with the presence of a diffusion barrier, dialyzing cones with diffusible Ca2+ buffers did not affect release efficiency. The tight clustering of Ca2+ channels, along with a high-Ca2+ affinity release mechanism and diffusion barrier, promotes a linear coupling between Ca2+ influx and vesicle fusion. This may improve detection of small light decrements when cones are hyperpolarized by bright light. PMID:21880934

Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets.

PubMed

Rekhi, G S; Nellore, R V; Hussain, A S; Tillman, L G; Malinowski, H J; Augsburger, L L

1999-06-02

The objective of this study, was to examine the influence of critical formulation and processing variables as described in the AAPS/FDA Workshop II report on scale-up of oral extended-release dosage forms, using a hydrophilic polymer hydroxypropyl methylcellulose (Methocel K100LV). A face-centered central composite design (26 runs+3 center points) was selected and the variables studied were: filler ratio (lactose:dicalcium phosphate (50:50)), polymer level (15/32.5/50%), magnesium stearate level (1/1.5/2%), lubricant blend time (2/6/10 min) and compression force (400/600/800 kg). Granulations (1.5 kg, 3000 units) were manufactured using a fluid-bed process, lubricated and tablets (100 mg metoprolol tartrate) were compressed on an instrumented Manesty D3B rotary tablet press. Dissolution tests were performed using USP apparatus 2, at 50 rpm in 900 ml phosphate buffer (pH 6.8). Responses studied included percent drug released at Q1 (1 h), Q4, Q6, Q12. Analysis of variance indicated that change in polymer level was the most significant factor affecting drug release. Increase in dicalcium phosphate level and compression force were found to affect the percent released at the later dissolution time points. Some interaction effects between the variables studied were also found to be statistically significant. The drug release mechanism was predominantly found to be Fickian diffusion controlled (n=0.46-0.59). Response surface plots and regression models were developed which adequately described the experimental space. Three formulations having slow-, medium- and fast-releasing dissolution profiles were identified for a future bioavailability/bioequivalency study. The results of this study provided the framework for further work involving both in vivo studies and scale-up.

Investigation of the Dissolution Profile of Gliclazide Modified-Release Tablets Using Different Apparatuses and Dissolution Conditions.

PubMed

Skripnik, K K S; Riekes, M K; Pezzini, B R; Cardoso, S G; Stulzer, H K

2017-07-01

In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.

Release from the cone ribbon synapse under bright light conditions can be controlled by the opening of only a few Ca(2+) channels.

PubMed

Bartoletti, Theodore M; Jackman, Skyler L; Babai, Norbert; Mercer, Aaron J; Kramer, Richard H; Thoreson, Wallace B

2011-12-01

Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca(2+) channels to open infrequently. To understand neurotransmission under these conditions, we determined the number of L-type Ca(2+) channel openings necessary for vesicle fusion at the cone ribbon synapse. Ca(2+) currents (I(Ca)) were activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs) were recorded from horizontal cells in the salamander retina slice preparation. Ca(2+) channel number and single-channel current amplitude were calculated by mean-variance analysis of I(Ca). Two different comparisons-one comparing average numbers of release events to average I(Ca) amplitude and the other involving deconvolution of both EPSCs and simultaneously recorded cone I(Ca)-suggested that fewer than three Ca(2+) channel openings accompanied fusion of each vesicle at the peak of release during the first few milliseconds of stimulation. Opening fewer Ca(2+) channels did not enhance fusion efficiency, suggesting that few unnecessary channel openings occurred during strong depolarization. We simulated release at the cone synapse, using empirically determined synaptic dimensions, vesicle pool size, Ca(2+) dependence of release, Ca(2+) channel number, and Ca(2+) channel properties. The model replicated observations when a barrier was added to slow Ca(2+) diffusion. Consistent with the presence of a diffusion barrier, dialyzing cones with diffusible Ca(2+) buffers did not affect release efficiency. The tight clustering of Ca(2+) channels, along with a high-Ca(2+) affinity release mechanism and diffusion barrier, promotes a linear coupling between Ca(2+) influx and vesicle fusion. This may improve detection of small light decrements when cones are hyperpolarized by bright light.

Tail-extension following the termination codon is critical for release of the nascent chain from membrane-bound ribosomes in a reticulocyte lysate cell-free system.

PubMed

Takahara, Michiyo; Sakaue, Haruka; Onishi, Yukiko; Yamagishi, Marifu; Kida, Yuichiro; Sakaguchi, Masao

2013-01-11

Nascent chain release from membrane-bound ribosomes by the termination codon was investigated using a cell-free translation system from rabbit supplemented with rough microsomal membrane vesicles. Chain release was extremely slow when mRNA ended with only the termination codon. Tail extension after the termination codon enhanced the release of the nascent chain. Release reached plateau levels with tail extension of 10 bases. This requirement was observed with all termination codons: TAA, TGA and TAG. Rapid release was also achieved by puromycin even in the absence of the extension. Efficient translation termination cannot be achieved in the presence of only a termination codon on the mRNA. Tail extension might be required for correct positioning of the termination codon in the ribosome and/or efficient recognition by release factors. Copyright © 2012. Published by Elsevier Inc.

Study on the behavior of heavy metals during thermal treatment of municipal solid waste (MSW) components.

PubMed

Yu, Jie; Sun, Lushi; Wang, Ben; Qiao, Yu; Xiang, Jun; Hu, Song; Yao, Hong

2016-01-01

Laboratory experiments were conducted to investigate the volatilization behavior of heavy metals during pyrolysis and combustion of municipal solid waste (MSW) components at different heating rates and temperatures. The waste fractions comprised waste paper (Paper), disposable chopstick (DC), garbage bag (GB), PVC plastic (PVC), and waste tire (Tire). Generally, the release trend of heavy metals from all MSW fractions in rapid-heating combustion was superior to that in low-heating combustion. Due to the different characteristics of MSW fractions, the behavior of heavy metals varied. Cd exhibited higher volatility than the rest of heavy metals. For Paper, DC, and PVC, the vaporization of Cd can reach as high as 75% at 500 °C in the rapid-heating combustion due to violent combustion, whereas a gradual increase was observed for Tire and GB. Zn and Pb showed a moderate volatilization in rapid-heating combustion, but their volatilities were depressed in slow-heating combustion. During thermal treatment, the additives such as kaolin and calcium can react or adsorb Pb and Zn forming stable metal compounds, thus decreasing their volatilities. The formation of stable compounds can be strengthened in slow-heating combustion. The volatility of Cu was comparatively low in both high and slow-heating combustion partially due to the existence of Al, Si, or Fe in residuals. Generally, in the reducing atmosphere, the volatility of Cd, Pb, and Zn was accelerated for Paper, DC, GB, and Tire due to the formation of elemental metal vapor. TG analysis also showed the reduction of metal oxides by chars forming elemental metal vapor. Cu2S was the dominant Cu species in reducing atmosphere below 900 °C, which was responsible for the low volatility of Cu. The addition of PVC in wastes may enhance the release of heavy metals, while GB and Tire may play an opposite effect. In controlling heavy metal emission, aluminosilicate- and calcium-based sorbents can be co-treated with fuels. Moreover, pyrolysis can be a better choice for treatment of solid waster in terms of controlling heavy metals. PVC and Tire should be separated and treated individually due to high possibility of heavy metal emission. This information may then serve as a guideline for the design of the subsequent gas cleaning plant, necessary to reduce the final emissions to the atmosphere to an acceptable level.

Development and characterization of surface engineered PPI dendrimers for targeted drug delivery.

PubMed

Kaur, Avleen; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N K

2017-05-01

In this study, we reported folate-conjugated polypropylene imine dendrimers (FA-PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH-sensitive drug release, selective targeting to cancer cells, and anticancer activity. In the in vitro drug release studies this nanoconjugate of MTX showed initial rapid release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. The ex vivo investigations with human breast cancer cell lines, MCF-7, showed enhanced cytotoxicity of MTX-FA-PPI with significantly enhanced intracellular uptake. The biofate of nanoconjugate was determined in Wistar rat where MTX-FA-PPI showed 37.79-fold increase in the concentration of MTX in liver after 24 h in comparison with free MTX formulation.

Wind turbine spoiler

DOEpatents

Sullivan, W.N.

An aerodynamic spoiler system for a vertical axis wind turbine includes spoilers on the blades initially stored near the rotor axis to minimize drag. A solenoid latch adjacent the central support tower releases the spoilers and centrifugal force causes the spoilers to move up the turbine blades away from the rotor axis, thereby producing a braking effect and actual slowing of the associated wind turbine, if desired. The spoiler system can also be used as an infinitely variable power control by regulated movement of the spoilers on the blades over the range between the undeployed and fully deployed positions. This is done by the use of a suitable powered reel and cable located at the rotor tower to move the spoilers.

Wind turbine spoiler

DOEpatents

Sullivan, William N.

1985-01-01

An aerodynamic spoiler system for a vertical axis wind turbine includes spoilers on the blades initially stored near the rotor axis to minimize drag. A solenoid latch adjacent the central support tower releases the spoilers and centrifugal force causes the spoilers to move up the turbine blades away from the rotor axis, thereby producing a braking effect and actual slowing of the associated wind turbine, if desired. The spoiler system can also be used as an infinitely variable power control by regulated movement of the spoilers on the blades over the range between the undeployed and fully deployed positions. This is done by the use of a suitable powered reel and cable located at the rotor tower to move the spoilers.

Adjunctive 5-hydroxytryptophan slow-release for treatment-resistant depression: Clinical and pre-clinical rationale

PubMed Central

Jacobsen, Jacob P.R.; Krystal, Andrew D.; Krishnan, K. Ranga R.; Caron, Marc G.

2017-01-01

Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need. Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP) safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; but, 5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics. A slow-release (SR) delivery mode would be predicted to overcome the pharmacokinetic limitations of 5-HTP, substantially enhance the pharmacological action, and transform 5-HTP into a clinically viable drug. Animal studies bear out this prediction. Thus, adjunct 5-HTP SR could be an important new treatment for TRD. Here we review the clinical and preclinical evidence. PMID:27692695

Fortified interpenetrating polymers – bacteria resistant coatings for medical devices† †Electronic supplementary information (ESI) available: Supporting figures and tables, and additional experimental procedures. See DOI: 10.1039/c6tb01110a Click here for additional data file.

PubMed Central

Venkateswaran, Seshasailam; Henrique Dos Santos, Orlando David; Scholefield, Emma; Lilienkampf, Annamaria; Gwynne, Peter J.; Swann, David G.; Dhaliwal, Kevin

2016-01-01

Infections arising from contaminated medical devices are a serious global issue, contributing to antibiotic resistance and imposing significant strain on healthcare systems. Since the majority of medical device-associated infections are biofilm related, efforts are being made to generate either bacteria-repellent or antibacterial coatings aimed at preventing bacterial colonisation. Here, we utilise a nanocapsule mediated slow release of a natural antimicrobial to improve the performance of a bacteria repellent polymer coating. Poly(lauryl acrylate) nanocapsules containing eugenol (4-allyl-2-methoxyphenol) were prepared and entrapped within a interpenetrating network designed to repel bacteria. When coated on a catheter and an endotracheal tube, this hemocompatible system allowed slow-release of eugenol, resulting in notable reduction in surface-bound Klebsiella pneumoniae and methicillin resistant Staphylococcus aureus. PMID:27746915

Thermonuclear plasma with autocatalytic thermomagnetic current amplification by nuclear reactions from fusion neutrons

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

Winterberg, F.

2006-03-15

It is proposed to use the neutrons released from a deuterium-tritium or deuterium-deuterium fusion reaction to drive thermomagnetic currents in a plasma corona surrounding the fusion plasma through the heating of the corona with nuclear reactions by the neutrons released in the fusion reaction. Because the neutron reaction cross sections are larger for slow neutrons, it is proposed to slow them down in a moderator separated from the hot plasma of the corona, giving the configuration a striking similarity to a heterogeneous nuclear fission reactor. While in a fission reactor the separation makes possible a growing neutron chain reaction, itmore » here makes possible the autocatalytic amplification of the thermomagnetic currents by an increase of the fusion reaction rate through a rise of the plasma pressure by the magnetic pressure of the thermomagnetic currents. This is expected to substantially increase the n{tau} product over its Lawson value.« less

Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

PubMed Central

Pankratov, Yuriy

2017-01-01

Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. PMID:28845311

Gonadotrophin-Releasing Hormone Agonists and Other Contraceptive Medications in Exotic Companion Animals.

PubMed

Schoemaker, Nico J

2018-05-01

The use of a gonadotrophin-releasing hormone agonist slow-release implant (GnRH A-SRI) has become increasingly popular as an alternative for surgical contraception in many species. Although these implants have proven to be very effective in some species (eg, ferrets, rats, chicken, psittacines, and iguanas), they have been found less effective in other species (eg, male guinea pigs and rabbits, veiled chameleons, slider turtles, and leopard geckos). This review provides an overview of the available literature on the effects of GnRH A-SRIs in companion exotic animals. Copyright © 2018 Elsevier Inc. All rights reserved.

Substitution of amino acids Asp-85, Asp-212, and Arg-82 in bacteriorhodopsin affects the proton release phase of the pump and the pK of the Schiff base.

PubMed

Otto, H; Marti, T; Holz, M; Mogi, T; Stern, L J; Engel, F; Khorana, H G; Heyn, M P

1990-02-01

Photocycle and flash-induced proton release and uptake were investigated for bacteriorhodopsin mutants in which Asp-85 was replaced by Ala, Asn, or Glu; Asp-212 was replaced by Asn or Glu; Asp-115 was replaced by Ala, Asn, or Glu; Asp-96 was replaced by Ala, Asn, or Glu; and Arg-82 was replaced by Ala or Gln in dimyristoylphosphatidylcholine/3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate micelles at pH 7.3. In the Asp-85----Ala and Asp-85----Asn mutants, the absence of the charged carboxyl group leads to a blue chromophore at 600 and 595 nm, respectively, and lowers the pK of the Schiff base deprotonation to 8.2 and 7, respectively, suggesting a role for Asp-85 as counterion to the Schiff base. The early part of the photocycles of the Asp-85----Ala and Asp-85----Asn mutants is strongly perturbed; the formation of a weak M-like intermediate is slowed down about 100-fold over wild type. In both mutants, proton release is also slower but clearly precedes the rise of M. The amplitude of the early (less than 0.2 microseconds) reversed photovoltage component in the Asp-85----Asn mutant is very large, and the net charge displacement is close to zero, indicating proton release and uptake on the cytoplasmic side of the membrane. The data suggest an obligatory role for Asp-85 in the efficient deprotonation of the Schiff base and in the proton release phase, probably as proton acceptor. In the Asp-212----Asn mutant, the rise of the absorbance change at 410 nm is slowed down to 220 microsecond, its amplitude is small, and the release of protons is delayed to 1.9 ms. The absorbance changes at 650 nm indicate perturbations in the early time range with a slow K intermediate. Thus Asp-212 also participates in the early events of charge translocation and deprotonation of the Schiff base. In the Arg-82----Gln mutant, no net transient proton release was observed, whereas, in the Arg-82----Ala mutant, uptake and release were reversed. The pK shift of the purple-to-blue transition in the Asp-85----Glu, Arg-82----Ala, and Arg-82----Gln mutants and the similarity in the photocycle and photoelectrical signals of the Asp-85----Ala, Asp-85----Asn, and Asp-212----Asn mutants suggest the interaction between Asp-85, Arg-82, Asp-212, and the Schiff base as essential for proton release.

Hydration of dicalcium silicate and diffusion through neo-formed calcium-silicate-hydrates at weathered surfaces control the long-term leaching behaviour of basic oxygen furnace (BOF) steelmaking slag.

PubMed

Stewart, Douglas I; Bray, Andrew W; Udoma, Gideon; Hobson, Andrew J; Mayes, William M; Rogerson, Mike; Burke, Ian T

2018-04-01

Alkalinity generation and toxic trace metal (such as vanadium) leaching from basic oxygen furnace (BOF) steel slag particles must be properly understood and managed by pre-conditioning if beneficial reuse of slag is to be maximised. Water leaching under aerated conditions was investigated using fresh BOF slag at three different particle sizes (0.5-1.0, 2-5 and 10 × 10 × 20 mm blocks) and a 6-month pre-weathered block. There were several distinct leaching stages observed over time associated with different phases controlling the solution chemistry: (1) free-lime (CaO) dissolution (days 0-2); (2) dicalcium silicate (Ca 2 SiO 4 ) dissolution (days 2-14) and (3) Ca-Si-H and CaCO 3 formation and subsequent dissolution (days 14-73). Experiments with the smallest size fraction resulted in the highest Ca, Si and V concentrations, highlighting the role of surface area in controlling initial leaching. After ~2 weeks, the solution Ca/Si ratio (0.7-0.9) evolved to equal those found within a Ca-Si-H phase that replaced dicalcium silicate and free-lime phases in a 30- to 150-μm altered surface region. V release was a two-stage process; initially, V was released by dicalcium silicate dissolution, but V also isomorphically substituted for Si into the neo-formed Ca-Si-H in the alteration zone. Therefore, on longer timescales, the release of V to solution was primarily controlled by considerably slower Ca-Si-H dissolution rates, which decreased the rate of V release by an order of magnitude. Overall, the results indicate that the BOF slag leaching mechanism evolves from a situation initially dominated by rapid hydration and dissolution of primary dicalcium silicate/free-lime phases, to a slow diffusion limited process controlled by the solubility of secondary Ca-Si-H and CaCO 3 phases that replace and cover more reactive primary slag phases at particle surfaces.

Robust, flexible, and bioadhesive free-standing films for the co-delivery of antibiotics and growth factors.

PubMed

Chen, Dongdong; Wu, Mingda; Chen, Jie; Zhang, Chunqiu; Pan, Tiezheng; Zhang, Bing; Tian, Huayu; Chen, Xuesi; Sun, Junqi

2014-11-25

Free-standing polymer films that adhere strongly to tissue and can codeliver multiple therapeutic agents in a controlled manner are useful as medical plasters. In this study, a bilayer polymer film comprising a drug reservoir layer and a supporting layer is fabricated by spin-coating poly(lactic-co-glycolic acid) (PLGA) on top of a layer-by-layer assembled film of poly(β-amino esters) (PAE), alginate sodium (ALG), and recombinant human basic fibroblast growth factor (bFGF). Apart from bFGF, the bilayer film can also load antibiotic drug ceftriaxone sodium (CTX) by a postdiffusion process. The PLGA supporting layer facilitates the direct peeling of the bilayer film from substrate to produce a robust and flexible free-standing film with excellent adhesion onto the human skin and porcine liver. The excellent adhesion of the bilayer film originates from the ALG component in the drug reservoir layer. CTX is quickly released by easily breaking its electrostatic interaction with the drug reservoir layer, whereas the sustained release of bFGF is due to the slow degradation of PAE component in the drug reservoir layer. Wounds can be synergetically treated by fast release of CTX to effectively eradicate invasive bacteria and by sustained release of bFGF to accelerate wound healing. Our results serve as a basis for designing multifunctional free-standing films with combination therapy for biomedical applications.

Controlled drug release on amine functionalized spherical MCM-41

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

Szegedi, Agnes, E-mail: szegedi@chemres.hu; Popova, Margarita; Goshev, Ivan

2012-10-15

MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin methodmore » and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41. - Graphical abstract: Determination of surface amino groups by ninhidrin method. Highlights: Black-Right-Pointing-Pointer Spherical MCM-41 modified by different amounts of APTES was studied. Black-Right-Pointing-Pointer Ibuprofen (IBU) adsorption and release characteristics was tested. Black-Right-Pointing-Pointer The ninhydrin reaction was used for the quantitative determination of amino groups. Black-Right-Pointing-Pointer Stoichiometric amount of APTES is enough for totally covering the surface with amino groups. Black-Right-Pointing-Pointer Good correlation was found between the amino content and IBU adsorption capacity.« less

Neurexin and Neuroligin Mediate Retrograde Synaptic Inhibition in C. elegans

PubMed Central

Hu, Zhitao; Hom, Sabrina; Kudze, Tambudzai; Tong, Xia-Jing; Choi, Seungwon; Aramuni, Gayane; Zhang, Weiqi; Kaplan, Joshua M.

2013-01-01

The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. We find that C. elegans Neurexin (NRX-1) and Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits neurotransmitter release at neuromuscular junctions. Retrograde signaling was induced in mutants lacking a muscle microRNA (miR-1) and was blocked in mutants lacking NLG-1 or NRX-1. Release was rapid and abbreviated when the retrograde signal was on whereas release was slow and prolonged when retrograde signaling was blocked. The retrograde signal adjusted release kinetics by inhibiting exocytosis of synaptic vesicles (SVs) that are distal to the site of calcium entry. Inhibition of release was mediated by increased pre-synaptic levels of Tomosyn, an inhibitor of SV fusion. PMID:22859820

Boron-Based Hydrogen Storage: Ternary Borides and Beyond

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

Vajo, John J.

DOE continues to seek reversible solid-state hydrogen materials with hydrogen densities of ≥11 wt% and ≥80 g/L that can deliver hydrogen and be recharged at moderate temperatures (≤100 °C) and pressures (≤100 bar) enabling incorporation into hydrogen storage systems suitable for transportation applications. Boron-based hydrogen storage materials have the potential to meet the density requirements given boron’s low atomic weight, high chemical valance, and versatile chemistry. However, the rates of hydrogen exchange in boron-based compounds are thus far much too slow for practical applications. Although contributing to the high hydrogen densities, the high valance of boron also leads to slowmore » rates of hydrogen exchange due to extensive boron-boron atom rearrangements during hydrogen cycling. This rearrangement often leads to multiple solid phases occurring over hydrogen release and recharge cycles. These phases must nucleate and react with each other across solid-solid phase boundaries leading to energy barriers that slow the rates of hydrogen exchange. This project sought to overcome the slow rates of hydrogen exchange in boron-based hydrogen storage materials by minimizing the number of solid phases and the boron atom rearrangement over a hydrogen release and recharge cycle. Two novel approaches were explored: 1) developing matched pairs of ternary borides and mixed-metal borohydrides that could exchange hydrogen with only one hydrogenated phase (the mixed-metal borohydride) and only one dehydrogenated phase (the ternary boride); and 2) developing boranes that could release hydrogen by being lithiated using lithium hydride with no boron-boron atom rearrangement.« less

Limited Dissolved Phosphorus Runoff Losses from Layered Double Hydroxide and Struvite Fertilizers in a Rainfall Simulation Study.

PubMed

Everaert, Maarten; da Silva, Rodrigo C; Degryse, Fien; McLaughlin, Mike J; Smolders, Erik

2018-03-01

The enrichment of P in surface waters has been linked to P runoff from agricultural fields amended with fertilizers. Novel slow-release mineral fertilizers, such as struvite and P-exchanged layered double hydroxides (LDHs), have received increasing attention for P recycling from waste streams, and these fertilizers may potentially reduce the risk of runoff losses. Here, a rainfall simulation experiment was performed to evaluate P runoff associated with the application of recycled slow-release fertilizers relative to that of a soluble fertilizer. Monoammonium phosphate (MAP), struvite, and LDH granular fertilizers were broadcasted at equal total P doses on soil packed in trays (5% slope) and covered with perennial ryegrass ( L.). Four rainfall simulation events of 30 min were performed at 1, 5, 15, and 30 d after the fertilizer application. Runoff water from the trays was collected, filtered, and analyzed for dissolved P. For the MAP treatment, P runoff losses were high in the first two rain events and leveled off in later rain events. In total, 42% of the applied P in the MAP treatment was lost due to runoff. In the slow-release fertilizer treatments, P runoff losses were limited to 1.9 (struvite) and 2.4% (LDH) of the applied doses and were more similar over the different rain events. The use of these novel P fertilizer forms could be beneficial in areas with a high risk of surface water eutrophication and a history of intensive fertilization. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Locating an atmospheric contamination source using slow manifolds

NASA Astrophysics Data System (ADS)

Tang, Wenbo; Haller, George; Baik, Jong-Jin; Ryu, Young-Hee

2009-04-01

Finite-size particle motion in fluids obeys the Maxey-Riley equations, which become singular in the limit of infinitesimally small particle size. Because of this singularity, finding the source of a dispersed set of small particles is a numerically ill-posed problem that leads to exponential blowup. Here we use recent results on the existence of a slow manifold in the Maxey-Riley equations to overcome this difficulty in source inversion. Specifically, we locate the source of particles by projecting their dispersed positions on a time-varying slow manifold, and by advecting them on the manifold in backward time. We use this technique to locate the source of a hypothetical anthrax release in an unsteady three-dimensional atmospheric wind field in an urban street canyon.

Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans.

PubMed

Wu, Tongzhi; Zhao, Beiyi R; Bound, Michelle J; Checklin, Helen L; Bellon, Max; Little, Tanya J; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

2012-01-01

Macronutrient "preloads" can stimulate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia. Ten healthy subjects were studied on 4 separate occasions each. A preload drink containing 40 g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before a (13)C-octanoic acid-labeled mashed potato meal. Blood glucose, plasma total GLP-1 and GIP, serum insulin, and gastric emptying were determined. Both glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P < 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1 response was greater after glucose, 3OMG, and TIM than after sucralose (P < 0.05), albeit later after TIM than the other preloads. The blood glucose and insulin responses in the first 30 min after the meal were greatest after glucose (each P < 0.05). Gastric emptying was slower after both 3OMG and TIM than after sucralose (each P < 0.05). In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910.

Dissociation of Laboratory-Synthesized Methane Hydrate in Coarse-Grained Sediments by Slow Depressurization

NASA Astrophysics Data System (ADS)

Phillips, S. C.; You, K.; Borgfeldt, T.; Meyer, D.; Dong, T.; Flemings, P. B.

2016-12-01

We performed four dissociation experiments in which experimentally-formed methane hydrate was dissociated via slow, stepwise depressurization, revealing in situ salinity conditions. Overall, these results suggest the occurrence of local pore water freshening around dissociating hydrate in which bulk equilibrium behavior is limited by salt diffusion. Depressurization was performed at a constant confining temperature over 1 to 3 weeks by releasing small volumes of methane gas from the top of a vertically-oriented sample into an inverted graduated cylinder. We identify three distinct regimes of depressurization based on pressure drop behavior: (1) release of free gas down to initial hydrate dissociation at 3.3 MPa in NaBr or 4.64 MPa in NaCl, (2) dissociation of methane hydrate characterized by a slow, logarithmic increase in pressure after each gas release and (3) residual free gas release. Initial hydrate dissociation in NaCl brine at 4.64 MPa corresponds to the phase boundary for hydrate in 9.6 wt% NaCl. In the NaCl experiment, pressure increases of 0.16 MPa while the sample was shut in over 3 days likely correspond to a recovery in salinity of 0.7 wt. %. Salt ions likely diffuse from brine ahead of the hydrate front, based on a length scale for diffusion of NaCl of 6.3 cm for 3 days. In this experiment dissociation at bulk equilibrium is expected to decline from 4.54 to 4.04 MPa; however actual dissociation during 73 gas releases over 15 days, results in a pressure drop from 4.64 to 3.25 MPa. Hydrate samples were formed by injection of methane gas at 1 ºC and 12.24 MPa within a cylinder packed with medium-grained quartz sand and initially saturated in a 7 wt% NaBr or NaCl solution. In two experiments in which the system was thoroughly leak tested, total methane consumed during formation and recovered during depressurization match within 7% indicating this approach to be relatively accurate for determining total methane in experimental or pressure core samples.

Characteristics of broadband slow earthquakes explained by a Brownian model

NASA Astrophysics Data System (ADS)

Ide, S.; Takeo, A.

2017-12-01

Brownian slow earthquake (BSE) model (Ide, 2008; 2010) is a stochastic model for the temporal change of seismic moment release by slow earthquakes, which can be considered as a broadband phenomena including tectonic tremors, low frequency earthquakes, and very low frequency (VLF) earthquakes in the seismological frequency range, and slow slip events in geodetic range. Although the concept of broadband slow earthquake may not have been widely accepted, most of recent observations are consistent with this concept. Then, we review the characteristics of slow earthquakes and how they are explained by BSE model. In BSE model, the characteristic size of slow earthquake source is represented by a random variable, changed by a Gaussian fluctuation added at every time step. The model also includes a time constant, which divides the model behavior into short- and long-time regimes. In nature, the time constant corresponds to the spatial limit of tremor/SSE zone. In the long-time regime, the seismic moment rate is constant, which explains the moment-duration scaling law (Ide et al., 2007). For a shorter duration, the moment rate increases with size, as often observed for VLF earthquakes (Ide et al., 2008). The ratio between seismic energy and seismic moment is constant, as shown in Japan, Cascadia, and Mexico (Maury et al., 2017). The moment rate spectrum has a section of -1 slope, limited by two frequencies corresponding to the above time constant and the time increment of the stochastic process. Such broadband spectra have been observed for slow earthquakes near the trench axis (Kaneko et al., 2017). This spectrum also explains why we can obtain VLF signals by stacking broadband seismograms relative to tremor occurrence (e.g., Takeo et al., 2010; Ide and Yabe, 2014). The fluctuation in BSE model can be non-Gaussian, as far as the variance is finite, as supported by the central limit theorem. Recent observations suggest that tremors and LFEs are spatially characteristic, rather than random (Rubin and Armbruster, 2013; Bostock et al., 2015). Since even spatially characteristic source must be activated randomly in time, moment release from these sources are compatible to the fluctuation in BSE model. Therefore, BSE model contains the model of Gomberg et al. (2016), which suggests that the cluster of LFEs makes VLF signals, as a special case.

SOLID OXYGEN SOURCE FOR BIOREMEDIATION IN SUBSURFACE SOILS

EPA Science Inventory

Sodium percarbonate was encapsulated in poly(vinylidene chloride) to determine its potential as a slow-release oxygen source for biodegradation of contaminan ts in subsurface soils. In laboratory studies under aqueous conditions, the encapsulated sodium percarbonate was estimate...

The National LUST Cleanup Backlog: A Study of Opportunities

EPA Pesticide Factsheets

To understand the makeup of UST releases remaining and why the pace of cleanups is slowing, EPA undertook a two-phase, data-driven analysis of the cleanups remaining as of 2006 (Phase 1) and 2009 (Phase 2).

SEQUESTRATION OF HYDROPHOBIC ORGANIC CONTAMINANTS BY GEOSORBENTS. (R822626)

EPA Science Inventory

The chemical interactions of hydrophobic organic contaminants (HOCs) with soils and sediments (geosorbents) may result in strong binding and slow subsequent release rates that significantly affect remediation rates and endpoints. The underlying physical and chemical phenomena ...

Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel

PubMed Central

Kim, Sungwon; Kim, Ji Young; Huh, Kang Moo; Acharya, Ghanshyam; Park, Kinam

2008-01-01

Hydrotropic polymers (HPs) and their micelles have been recently developed as vehicles for delivery of poorly water-soluble drugs, such as paclitaxel (PTX), by oral administration. The release of PTX from HP micelles, however, was slow and it took more than a day for complete release of the loaded PTX. Since the gastrointestinal (GI) transit time is known to be only several hours, pH-sensitive HP micelles were prepared for fast release of the loaded PTX responding to pH changes along the GI tract. Acrylic acid (AA) was introduced, as a release modulator, into HPs by copolymerization with 4-(2-vinylbenzyloxy)-N,N-(diethylnicotinamide) (VBODENA). The AA content was varied from 0% to 50 % (in the molar ratio to VBODENA). HPs spontaneously produced micelles in water, and their critical micelle concentrations (CMCs) ranged from 31 μg/mL to 86 μg/mL. Fluorescence probe study using pyrene showed that blank HP micelles possessed a good pH-sensitivity, which was clearly observed at relatively high AA contents and pH > 6. The pH sensitivity also affected the PTX loading property. Above pH 5, the PTX loading content and loading efficiency in HP micelles were significantly reduced. Although this may be primarily due to the AA moieties, other factors may include PTX degradation and polymer aggregation. The PTX release from HP micelles with more than 20% (mol) AA contents was completed within 12 h in a simulated intestinal fluid (SIF, pH=6.5). The HP micelles without any AA moiety showed very slow release profiles. In the simulated gastric fluid (SGF, pH=1.6), severe degradation of the released PTX was observed. The pH-dependent release of PTX from HP micelles can be used to increase the bioavailability of PTX upon oral delivery. PMID:18672013

Effects of slow-release urea and rumen-protected methionine and histidine on performance of dairy cows.

PubMed

Giallongo, F; Hristov, A N; Oh, J; Frederick, T; Weeks, H; Werner, J; Lapierre, H; Patton, R A; Gehman, A; Parys, C

2015-05-01

This experiment was conducted with the objective to investigate the effects of slow-release urea and rumen-protected (RP) Met and His supplementation of a metabolizable protein (MP)-deficient diet (according to NRC, 2001) on lactation performance of dairy cows. Sixty lactating Holstein cows were used in a 10-wk randomized complete block-design trial. Cows were fed a covariate diet for 2 wk and then assigned to one of the following treatments for an 8-wk experimental period: (1) MP-adequate diet [AMP; 107% of MP requirements, based on the National Research Council (NRC, 2001)]; (2) MP-deficient diet (DMP; 95% of MP requirements); (3) DMP supplemented with slow-release urea (DMPU); (4) DMPU supplemented with RPMet (DMPUM); and (5) DMPUM supplemented with RPHis (DMPUMH). Total-tract apparent digestibility of dry matter, organic matter, neutral detergent fiber, and crude protein, and urinary N and urea-N excretions were decreased by DMP, compared with AMP. Addition of slow-release urea to the DMP diet increased urinary urea-N excretion. Dry matter intake (DMI) and milk yield (on average 44.0±0.9kg/d) were not affected by treatments, except DMPUMH increased DMI and numerically increased milk yield, compared with DMPUM. Milk true protein concentration and yield were increased and milk fat concentration tended to be decreased by DMPUMH, compared with DMPUM. Cows gained less body weight on the DMP diet, compared with AMP. Plasma concentrations of His and Lys were not affected by treatments, whereas supplementation of RPMet increased plasma Met concentration. Plasma concentration of 3-methylhistidine was or tended to be higher for DMP compared with AMP and DMPU, respectively. Addition of RPHis to the DMPUM diet tended to increase plasma glucose and creatinine. In conclusion, feeding a 5% MP-deficient diet (according to NRC, 2001) did not decrease DMI and yields of milk and milk components, despite a reduction in nutrient digestibility. Supplementation of RPHis increased DMI and milk protein concentration and yield. These results are in line with our previous data and suggest that His may have a positive effect on voluntary feed intake and milk production and composition in high-yielding dairy cows fed MP-deficient diets. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A novel gel based on an ionic complex from a dendronized polymer and ciprofloxacin: Evaluation of its use for controlled topical drug release.

PubMed

García, Mónica C; Cuggino, Julio C; Rosset, Clarisa I; Páez, Paulina L; Strumia, Miriam C; Manzo, Ruben H; Alovero, Fabiana L; Alvarez Igarzabal, Cecilia I; Jimenez-Kairuz, Alvaro F

2016-12-01

The development and characterization of a novel, gel-type material based on a dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of its possible use for controlled drug release, are presented in this work. DP showed biocompatible and non-toxic behaviors in cultured cells, both of which are considered optimal properties for the design of a final material for biomedical applications. These results were encouraging for the use of the polymer loaded with CIP (as a drug model), under gel form, in the development of a new controlled-release system to be evaluated for topical administration. First, DP-CIP ionic complexes were obtained by an acid-base reaction using the high density of carboxylic acid groups of the DP and the amine groups of the CIP. The complexes obtained in the solid state were broadly characterized using FTIR spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques. Gels based on the DP-CIP complexes were easily prepared and presented excellent mechanical behaviors. In addition, optimal properties for application on mucosal membranes and skin were achieved due to their high biocompatibility and acute skin non-irritation. Slow and sustained release of CIP toward simulated physiological fluids was observed in the assays (in vitro), attributed to ion exchange phenomenon and to the drug reservoir effect. An in vitro bacterial growth inhibition assay showed significant CIP activity, corresponding to 38 and 58% of that exhibited by a CIP hydrochloride solution at similar CIP concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. However, CIP delivery was appropriate, both in terms of magnitude and velocity to allow for a bactericidal effect. In conclusion, the final product showed promising behavior, which could be exploited for the treatment of topical and mucosal opportunistic infections in human or veterinary applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Loading and release mechanisms of a biocide in polystyrene-block-poly(acrylic acid) block copolymer micelles.

PubMed

Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo G M

2008-07-24

The kinetics of loading of polystyrene197-block-poly(acrylic acid)47 (PS197-b-PAA47) micelles, suspended in water, with thiocyanomethylthiobenzothiazole biocide and its subsequent release were investigated. Loading of the micelles was found to be a two-step process. First, the surface of the PS core of the micelles is saturated with biocide, with a rate determined by the transfer of solid biocide to micelles during transient micelle-biocide contacts. Next, the biocide penetrates as a front into the micelles, lowering the Tg in the process (non-Fickian case II diffusion). The slow rate of release is governed by the height of the energy barrier that a biocide molecule must overcome to pass from PS into water, resulting in a uniform biocide concentration within the micelle, until Tg is increased to the point that diffusion inside the micelles becomes very slow. Maximum loading of biocide into micelles is approximately 30% (w/w) and is achieved in 1 h. From partition experiments, it can be concluded that the biocide has a similar preference for polystyrene as for ethylbenzene over water, implying that the maximum loading is governed by thermodynamics.

Potential mechanisms of cytosolic calcium modulation in interferon-gamma treated U937 cells

NASA Technical Reports Server (NTRS)

Klein, Jon B.; Mcleish, Kenneth R.; Sonnenfeld, Gerald; Dean, William L.

1987-01-01

The ability of interferon-gamma (IFN-gamma) to alter cytoplasmic Ca(2+) content in the monocytelike cell line U937 was investigated, using a slow Ca-channel blocker, diltiazem. In addition, the Ca-ATPase and the Ca-uptake activities were measured in isolated U937 membranes, together with the effect of inositol trisphosphate (IP3) upon the Ca(2+) release from Ca-loaded membranes. The addition of 50 U/ml INF-gamma to U937 cultures was found to increase internal Ca(2+) by about 100 percent within 3 min. The increase was significantly reduced by incubation in Ca-free buffer or by the addition of diltiazem. A crude membrane preparation from U937 cells was found to contain significant amounts of Ca-ATPase activity and to sequester Ca(2+) to a level of 8 nmol/mg in 30 sec; the addition of IP3 induced release of a portion of the sequestered Ca(2+) which was then resequestered. The results suggest that IFN-gamma causes an increase of cytoplasmic Ca(2+), in part, by the IP3-induced release from the internal storage sites and, in part, from the entry of extracellular Ca through slow channels.

Creation of a Long-Acting Nanoformulated 2′,3′-Dideoxy-3′-Thiacytidine

PubMed Central

Guo, Dongwei; Zhou, Tian; Araínga, Mariluz; Palandri, Diana; Gautam, Nagsen; Bronich, Tatiana; Alnouti, Yazen; McMillan, JoEllyn; Edagwa, Benson

2017-01-01

Background: Antiretroviral drug discovery and formulation design will facilitate viral clearance in infectious reservoirs. Although progress has been realized for selected hydrophobic integrase and nonnucleoside reverse transcriptase inhibitors, limited success has been seen to date with hydrophilic nucleosides. To overcome these limitations, hydrophobic long-acting drug nanoparticles were created for the commonly used nucleoside reverse transcriptase inhibitor, lamivudine (2′,3′-dideoxy-3′-thiacytidine, 3TC). Methods: A 2-step synthesis created a slow-release long-acting hydrophobic 3TC. Conjugation of 3TC to a fatty acid created a myristoylated prodrug which was encased into a folate-decorated poloxamer 407. Both in vitro antiretroviral efficacy in human monocyte-derived macrophages and pharmacokinetic profiles in mice were evaluated for the decorated nanoformulated drug. Results: A stable drug formulation was produced by poloxamer encasement that improved monocyte–macrophage uptake, antiretroviral activities, and drug pharmacokinetic profiles over native drug formulations. Conclusions: Sustained release of long-acting antiretroviral therapy is a new therapeutic frontier for HIV/AIDS. 3TC depot formation in monocyte-derived macrophages can be facilitated through stable subcellular internalization and slow drug release. PMID:27559685

Hunting for shallow slow-slip events at Cascadia

NASA Astrophysics Data System (ADS)

Tan, Y. J.; Bletery, Q.; Fan, W.; Janiszewski, H. A.; Lynch, E.; McCormack, K. A.; Phillips, N. J.; Rousset, B.; Seyler, C.; French, M. E.; Gaherty, J. B.; Regalla, C.

2017-12-01

The discovery of slow earthquakes at subduction zones is one of the major breakthroughs of Earth science in the last two decades. Slow earthquakes involve a wide spectrum of fault slip behaviors and seismic radiation patterns, such as tremor, low-frequency earthquakes, and slow-slip events. The last of these are particularly interesting due to their large moment releases accompanied by minimal ground shaking. Slow-slip events have been reported at various subduction zones ; most of these slow-slip events are located down-dip of the megathrust seismogenic zone, while a few up-dip cases have recently been observed at Nankai and New Zealand. Up-dip slow-slip events illuminate the structure of faulting environments and rupture mechanisms of tsunami earthquakes. Their possible presence and location at a particular subduction zone can help assess earthquake and tsunami hazard for that region. However, their typical location distant from the coast requires the development of techniques using offshore instrumentation. Here, we investigate the absolute pressure gauges (APG) of the Cascadia Initiative, a four year amphibious seismic experiment, to search for possible shallow up-dip slow-slip events in the Cascadia subduction zone. These instruments are collocated with ocean bottom seismometers (OBS) and located close to buoys and onshore GPS stations, offering the opportunity to investigate the utility of multiple datasets. Ultimately, we aim to develop a protocol to analyze APG data for offshore shallow slow-slip event detections and quantify uncertainties, with direct applications to understanding the up-dip subduction interface system in Cascadia.

Endocrine approaches to male fertility control.

PubMed

Knuth, U A; Nieschlag, E

1987-02-01

As in the female, gametogenesis in the male is under the control of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Their suppression should inhibit spermatogenesis. If a non-androgenic substance is used to suppress gonadotrophins, androgens must be supplemented to maintain virility, potency and metabolic processes. To avoid administration of several substances, testosterone and its esters were used to develop a male antifertility agent. Although azoospermia can be induced in a high proportion of men with administration of testosterone esters alone, this effect is not uniform. Even frequent injections with testosterone enanthate at weekly intervals fail to inhibit spermatogenesis in all participants. Combinations of gestagenic compounds with testosterone esters show a somewhat better effect, but again azoospermia is only achieved in around 50% of participants. LHRH analogues, although considered by many to offer a realistic potential for male fertility regulation, have not been proven to be successful for this purpose so far. Animal studies in monkeys and preliminary clinical trials demonstrate that agonistic analogues of LHRH have to be given continuously by pump or implant to achieve a pronounced effect on spermatogenesis. But even under these provisions, results in clinical trials have been worse than effects achieved with testosterone/gestagen combinations. Whether new antagonistic compounds offer a better potential awaits clinical trials. Studies in non-human primates demonstrate that testosterone by itself can maintain and initiate spermatogenesis. Based on these findings one could postulate an attenuating effect of high serum androgen levels after supplementation with available testosterone esters. Trials of alternative androgenic substances with slow-release characteristics and without high serum levels after single injections, like 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), tend to support this theory. With slow-release testosterone preparations under development by the WHO and more advanced delivery systems for LHRH analogues it is not unreasonable to speculate that an effective endocrine antifertility agent for the male will become available.

Dietary Slowly Digestible Starch Triggers the Gut-Brain Axis in Obese Rats with Accompanied Reduced Food Intake.

PubMed

Hasek, Like Y; Phillips, Robert J; Zhang, Genyi; Kinzig, Kimberly P; Kim, Choon Young; Powley, Terry L; Hamaker, Bruce R

2018-03-01

Slowly digestible starch (SDS), as a functional carbohydrate providing a slow and sustained glucose release, may be able to modulate food intake through activation of the gut-brain axis. Diet-induced obese rats were used to test the effect on feeding behavior of high-fat (HF) diets containing an SDS, fabricated to digest into the ileum, as compared to rapidly digestible starch (RDS). Ingestion of the HF-SDS diet over an 11-week period reduced daily food intake, through smaller meal size, to the same level as a lean body control group, while the group consuming the HF-RDS diet remained at a high food intake. Expression levels (mRNA) of the hypothalamic orexigenic neuropeptide Y (NPY) and Agouti-related peptide (AgRP) were significantly reduced, and the anorexigenic corticotropin-releasing hormone (CRH) was increased, in the HF-SDS fed group compared to the HF-RDS group, and to the level of the lean control group. SDS with digestion into the ileum reduced daily food intake and paralleled suppressed expression of appetite-stimulating neuropeptide genes associated with the gut-brain axis. This novel finding suggests further exploration involving a clinical study and potential development of SDS-based functional foods as an approach to obesity control. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of rats.

PubMed

Zold, Camila L; Ballion, Bérangère; Riquelme, Luis A; Gonon, François; Murer, M Gustavo

2007-04-01

There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

Development of a single-dose recombinant CAMP factor entrapping poly(lactide-co-glycolide) microspheres-based vaccine against Streptococcus agalactiae.

PubMed

Liu, Gang; Yin, Jinhua; Barkema, Herman W; Chen, Liben; Shahid, Muhammad; Szenci, Otto; De Buck, Jeroen; Kastelic, John P; Han, Bo

2017-03-01

Streptococcus agalactiae is an important contagious bovine mastitis pathogen. Although it is well controlled and even eradicated in most Northern European and North American dairy herds, the prevalence of this pathogen remains very high in China. However, research on development of a vaccine against S. agalactiae mastitis is scarce. The aims of the present study were to: (1) develop a single-dose vaccine against S. agalactiae based on poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) encapsulated CAMP factor, a conserved virulent protein encoded by S. agalactiae's cfb gene; and (2) evaluate its immunogenicity and protective efficacy in a mouse model. The cfb gene was cloned and expressed in a recombinant Escherichia coli strain Trans1-T1. The CAMP factor was tested to determine a safe dose range and then encapsulated in MS of PLGA (50:50) to assess its release pattern in vitro and immune reaction in vivo. Furthermore, a mouse model and a histopathological assay were developed to evaluate bacterial burden and vaccine efficacy. In the low dosage range (<100μg), CAMP factor had no obvious toxicity in mice. The release pattern in vitro was characterized by an initial burst release (44%), followed by a sustained and slower release over 7wk. In mice immunized with either pure CAMP factor protein or PLGA-CAMP, increased antibody titers were detected in the first 2wk, whereas only PLGA-CAMP immunization induced a sustained increase of antibody titers. In mice vaccinated with PLGA-CAMP, mortality and bacteria counts were lower (compared to a control group) after S. agalactiae challenge. Additionally, no pathological lesions were detected in the vaccinated group. Therefore, PLGA-CAMP conferred protective efficacy against S. agalactiae in our mouse model, indicating its potential as a vaccine against S. agalactiae mastitis. Furthermore, the slow-release kinetics of PLGA MS warranted optimism for development of a single-dose vaccine. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Repellent effects of Melaleuca alternifolia (tea tree) oil against cattle tick larvae (Rhipicephalus australis) when formulated as emulsions and in β-cyclodextrin inclusion complexes.

PubMed

Yim, Wei Tsun; Bhandari, Bhesh; Jackson, Louise; James, Peter

2016-07-30

Rhipicephalus australis (formerly Boophilus microplus) is a one host tick responsible for major economic loss in tropical and subtropical cattle production enterprises. Control is largely dependent on the application of acaricides but resistance has developed to most currently registered chemical groups. Repellent compounds that prevent initial attachment of tick larvae offer a potential alternative to control with chemical toxicants. The repellent effects of Melaleuca alternifolia oil (TTO) emulsions and two β-cyclodextrin complex formulations, a slow release form (SR) and a modified faster release form (FR), were examined in a series of laboratory studies. Emulsions containing 4% and 5% TTO applied to cattle hair in laboratory studies completely repelled ascending tick larvae for 24h whereas 2% and 3% formulations provided 80% protection. At 48h, 5% TTO provided 78% repellency but lower concentrations repelled less than 60% of larvae. In a study conducted over 15 days, 3% TTO emulsion applied to cattle hair provided close to 100% repellency for 2 days, but then protection fell to 23% by day 15. The FR formulation gave significantly greater repellency than the emulsion and the SR formulation from day 3 until the end of the study (P<0.05), providing almost complete repellency at day 3 (99.5%), then decreasing over the period of the study to 49% repellency at day 15. Proof of concept is established for the use of appropriately designed controlled-release formulations to extend the period of repellency provided by TTO against R. australis larvae. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanocomposite PAAm/methyl cellulose/montmorillonite hydrogel: evidence of synergistic effects for the slow release of fertilizers.

PubMed

Bortolin, Adriel; Aouada, Fauze A; Mattoso, Luiz H C; Ribeiro, Caue

2013-08-07

In this work, we synthesized a novel series of hydrogels composed of polyacrylamide (PAAm), methylcellulose (MC), and calcic montmorillonite (MMt) appropriate for the controlled release of fertilizers, where the components presented a synergistic effect, giving very high fertilizer loading in their structure. The synthesized hydrogel was characterized in relation to morphological, hydrophilic, spectroscopic, structural, thermal, and kinetic properties. After those characterizations, the application potential was verified through sorption and desorption studies of a nitrogenated fertilizer, urea (CO(NH2)2). The swelling degree results showed that the clay loading considerably reduces the water absorption capability; however, the hydrolysis process favored the urea adsorption in the hydrogel nanocomposites, increasing the load content according to the increase of the clay mass. The FTIR spectra indicated that there was incorporation of the clay with the polymeric matrix of the hydrogel and that incorporation increased the water absorption speed (indicated by the kinetic constant k). By an X-ray diffraction technique, good nanodispersion (intercalation) and exfoliation of the clay platelets in the hydrogel matrix were observed. Furthermore, the presence of the montmorillonite in the hydrogel caused the system to liberate the nutrient in a more controlled manner than that with the neat hydrogel in different pH ranges. In conclusion, excellent results were obtained for the controlled desorption of urea, highlighting the hydrolyzed hydrogels containing 50% calcic montmorillonite. This system presented the best desorption results, releasing larger amounts of nutrient and almost 200 times slower than pure urea, i.e., without hydrogel. The total values of nutrients present in the system show that this material is potentially viable for application in agriculture as a nutrient carrier vehicle.

Earthquake and tsunami forecasts: Relation of slow slip events to subsequent earthquake rupture

PubMed Central

Dixon, Timothy H.; Jiang, Yan; Malservisi, Rocco; McCaffrey, Robert; Voss, Nicholas; Protti, Marino; Gonzalez, Victor

2014-01-01

The 5 September 2012 Mw 7.6 earthquake on the Costa Rica subduction plate boundary followed a 62-y interseismic period. High-precision GPS recorded numerous slow slip events (SSEs) in the decade leading up to the earthquake, both up-dip and down-dip of seismic rupture. Deeper SSEs were larger than shallower ones and, if characteristic of the interseismic period, release most locking down-dip of the earthquake, limiting down-dip rupture and earthquake magnitude. Shallower SSEs were smaller, accounting for some but not all interseismic locking. One SSE occurred several months before the earthquake, but changes in Mohr–Coulomb failure stress were probably too small to trigger the earthquake. Because many SSEs have occurred without subsequent rupture, their individual predictive value is limited, but taken together they released a significant amount of accumulated interseismic strain before the earthquake, effectively defining the area of subsequent seismic rupture (rupture did not occur where slow slip was common). Because earthquake magnitude depends on rupture area, this has important implications for earthquake hazard assessment. Specifically, if this behavior is representative of future earthquake cycles and other subduction zones, it implies that monitoring SSEs, including shallow up-dip events that lie offshore, could lead to accurate forecasts of earthquake magnitude and tsunami potential. PMID:25404327

Earthquake and tsunami forecasts: relation of slow slip events to subsequent earthquake rupture.

PubMed

Dixon, Timothy H; Jiang, Yan; Malservisi, Rocco; McCaffrey, Robert; Voss, Nicholas; Protti, Marino; Gonzalez, Victor

2014-12-02

The 5 September 2012 M(w) 7.6 earthquake on the Costa Rica subduction plate boundary followed a 62-y interseismic period. High-precision GPS recorded numerous slow slip events (SSEs) in the decade leading up to the earthquake, both up-dip and down-dip of seismic rupture. Deeper SSEs were larger than shallower ones and, if characteristic of the interseismic period, release most locking down-dip of the earthquake, limiting down-dip rupture and earthquake magnitude. Shallower SSEs were smaller, accounting for some but not all interseismic locking. One SSE occurred several months before the earthquake, but changes in Mohr-Coulomb failure stress were probably too small to trigger the earthquake. Because many SSEs have occurred without subsequent rupture, their individual predictive value is limited, but taken together they released a significant amount of accumulated interseismic strain before the earthquake, effectively defining the area of subsequent seismic rupture (rupture did not occur where slow slip was common). Because earthquake magnitude depends on rupture area, this has important implications for earthquake hazard assessment. Specifically, if this behavior is representative of future earthquake cycles and other subduction zones, it implies that monitoring SSEs, including shallow up-dip events that lie offshore, could lead to accurate forecasts of earthquake magnitude and tsunami potential.

Functional effects of uridine triphosphate on human skinned skeletal muscle fibers.

PubMed

Vianna-Jorge, R; Oliveira, C F; Mounier, Y; Suarez-Kurtz, G

1998-02-01

Chemically skinned human skeletal muscle fibers were used to study the effects of uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+ uptake and release by the sarcoplasmic reticulum (SR). Total replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship to the left along the abcissae and increased maximum Ca(2+)-activated tension, both effects being larger in slow- than in fast-type fibers; (ii) markedly reduced Ca2+ uptake by the SR (evaluated by the caffeine-evoked tension) in both fiber types; (iii) had no effect on the rate of depletion of caffeine-sensitive Ca2+ stores during soaking in relaxing solutions; (iv) induced tension in slow- but not in fast-type fibers. The effects on the SR functional properties are consistent with the notion that UTP is a poor substitute for ATP as a substrate for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca(2+)-release channel. The UTP-induced tension in human slow-type fibers is attributed to effect(s) of the nucleotide on the tension-pCa relationship of the contractile machinery. The present data reveal important differences between the effects of UTP on human versus rat muscle fibers.

A large silent earthquake and the future rupture of the Guerrero seismic

NASA Astrophysics Data System (ADS)

Kostoglodov, V.; Lowry, A.; Singh, S.; Larson, K.; Santiago, J.; Franco, S.; Bilham, R.

2003-04-01

The largest global earthquakes typically occur at subduction zones, at the seismogenic boundary between two colliding tectonic plates. These earthquakes release elastic strains accumulated over many decades of plate motion. Forecasts of these events have large errors resulting from poor knowledge of the seismic cycle. The discovery of slow slip events or "silent earthquakes" in Japan, Alaska, Cascadia and Mexico provides a new glimmer of hope. In these subduction zones, the seismogenic part of the plate interface is loading not steadily as hitherto believed, but incrementally, partitioning the stress buildup with the slow slip events. If slow aseismic slip is limited to the region downdip of the future rupture zone, slip events may increase the stress at the base of the seismogenic region, incrementing it closer to failure. However if some aseismic slip occurs on the future rupture zone, the partitioning may significantly reduce the stress buildup rate (SBR) and delay a future large earthquake. Here we report characteristics of the largest slow earthquake observed to date (Mw 7.5), and its implications for future failure of the Guerrero seismic gap, Mexico. The silent earthquake began in October 2001 and lasted for 6-7 months. Slow slip produced measurable displacements over an area of 550x250 km2. Average slip on the interface was about 10 cm and the equivalent magnitude, Mw, was 7.5. A shallow subhorizontal configuration of the plate interface in Guererro is a controlling factor for the physical conditions favorable for such extensive slow slip. The total coupled zone in Guerrero is 120-170 km wide while the seismogenic, shallowest portion is only 50 km. This future rupture zone may slip contemporaneously with the deeper aseismic sleep, thereby reducing SBR. The slip partitioning between seismogenic and transition coupled zones may diminish SBR up to 50%. These two factors are probably responsible for a long (at least since 1911) quiet on the Guerrero seismic gap in Mexico. The discovery of silent earthquakes in Guerrero in 1972, 1979, 1998, and 2001-2002 calls for a reassessment of the seismic potential and careful seismotectonic monitoring of the seismic gaps in Mexico.

Reactor for producing large particles of materials from gases

NASA Technical Reports Server (NTRS)

Flagan, Richard C. (Inventor); Alam, Mohammed K. (Inventor)

1987-01-01

A method and apparatus is disclosed for producing large particles of material from gas, or gases, containing the material (e.g., silicon from silane) in a free-space reactor comprised of a tube (20) and controlled furnace (25). A hot gas is introduced in the center of the reactant gas through a nozzle (23) to heat a quantity of the reactant gas, or gases, to produce a controlled concentration of seed particles (24) which are entrained in the flow of reactant gas, or gases. The temperature profile (FIG. 4) of the furnace is controlled for such a slow, controlled rate of reaction that virtually all of the material released condenses on seed particles and new particles are not nucleated in the furnace. A separate reactor comprised of a tube (33) and furnace (30) may be used to form a seed aerosol which, after passing through a cooling section (34) is introduced in the main reactor tube (34) which includes a mixer (36) to mix the seed aerosol in a controlled concentration with the reactant gas or gases.

Essential oils nanoformulations for stored-product pest control - characterization and biological properties.

PubMed

Werdin González, Jorge Omar; Gutiérrez, María Mercedes; Ferrero, Adriana Alicia; Fernández Band, Beatriz

2014-04-01

The lethal and sublethal activity of poly(ethylene glycol) (PEG) nanoparticles containing essential oils (EO), also the physicochemical characterization, were determined against Tribolium castaneum and Rhizopertha dominica. The 10% ratio EO-PEG nanoparticles showed an average diameter<235 nm (PDI<0.280) and a loading efficacy>75%; after 6 month of storage their size did not change significantly and the amount of the EOs decreased 25%, approximately. Furthermore, during this period, no chemical derivates were observed. The EOs nanoparticles produced a notable increase of the residual contact toxicity apparently due to the slow and persistent release of the active terpenes. In addition, the nanoformulation enhanced the EO contact toxicity and altered the nutritional physiology of both stored product pest. The results indicated that these novel systems could be used in integrated pest management program for T. castaneum and R. dominica control. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantum memory with a controlled homogeneous splitting

NASA Astrophysics Data System (ADS)

Hétet, G.; Wilkowski, D.; Chanelière, T.

2013-04-01

We propose a quantum memory protocol where an input light field can be stored onto and released from a single ground state atomic ensemble by controlling dynamically the strength of an external static and homogeneous field. The technique relies on the adiabatic following of a polaritonic excitation onto a state for which the forward collective radiative emission is forbidden. The resemblance with the archetypal electromagnetically induced transparency is only formal because no ground state coherence-based slow-light propagation is considered here. As compared to the other grand category of protocols derived from the photon-echo technique, our approach only involves a homogeneous static field. We discuss two physical situations where the effect can be observed, and show that in the limit where the excited state lifetime is longer than the storage time; the protocols are perfectly efficient and noise free. We compare the technique with other quantum memories, and propose atomic systems where the experiment can be realized.

Characterization and mosquito repellent activity of citronella oil nanoemulsion.

PubMed

Sakulku, Usawadee; Nuchuchua, Onanong; Uawongyart, Napaporn; Puttipipatkhachorn, Satit; Soottitantawat, Apinan; Ruktanonchai, Uracha

2009-05-08

Encapsulated citronella oil nanoemulsion prepared by high pressure homogenization at varying amounts of surfactant and glycerol, was studied in terms of the droplet size, stability, release characteristics and in vivo mosquito protection. Transparent nanoemulsion can be obtained at optimal concentration of 2.5% surfactant and 100% glycerol. Physical appearance and the stability of the emulsion were greatly improved through an addition of glycerol, owing to its co-solvent and highly viscous property. The increasing emulsion droplet increased the oil retention. The release behavior could be attributed to the effect of droplet size and concentrations of surfactant and glycerol. By fitting to Higuchi's equation, an increase in glycerol and surfactant concentrations resulted in slow release of the oil. The release rate related well to the protection time where a decrease in release rate can prolong mosquito protection time.

Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.

PubMed

Zhang, Yalin; Kim, Min Soo; Jia, Baosen; Yan, Jingqi; Zuniga-Hertz, Juan Pablo; Han, Cheng; Cai, Dongsheng

2017-08-03

It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.

A novel antiproliferative drug coating for glaucoma drainage devices.

PubMed

Ponnusamy, Thiruselvam; Yu, Haini; John, Vijay T; Ayyala, Ramesh S; Blake, Diane A

2014-01-01

The implantation of a glaucoma drainage device (GDD) is often necessary for intractable cases of glaucoma. Currently, the success rate of GDD implants is relatively low because fibrosis that develops during the wound-healing process ultimately blocks fluid drainage. We describe herein a novel porous coating for Ahmed glaucoma valves based on biodegradable poly(lactic-co-glycolic acid) (PLGA). Thin films of PLGA were fabricated using a spin-coating technique. The procedure led to an asymmetric pore structure that was exploited to control the rate of dissolution. Double-layered porous films were constructed to achieve continuous drug release. A cell culture system was used to test the efficacy of these coatings. Double-layered films were manufactured to provide a burst of mitomycin C (MMC) release followed by a slow release of 5-fluorouracil (5-FU), which together prevented fibrosis over the most active period of postoperative wound healing (0 to 28 d). Double-layered films containing 5-FU only in the bottom layer showed a 3- to 5-day delay in drug release, followed by a sharp increase that continued for ~28 days. MMC was stable only when surface-loaded, and this drug was therefore surface-loaded onto the top PLGA layer to provide a continuous release of antifibrotics over the wound-healing period. The combined use of both MMC and 5-FU in a biodegradable device inhibits cell proliferation in a tissue culture model and has the potential to reduce fibrosis and increase the success rate of GDD implants. The design is simple and can be scaled for commercial production.

Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement.

PubMed

Tsao, Nadia H; Hall, Elizabeth A H

2017-11-14

Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been filled with a fluorescent acridium salt (lucigenin) as a model for a drug-loaded delivery vehicle. The uptake and delivery were studied and compared with similar microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively charged lucigenin was encapsulated through an electrostatic mechanism, following a Type I Langmuir isotherm as expected, but with an additional multilayer uptake that leads to a much higher loading for the SiPCL system (∼280 μg/2.4 × 10 9 microcapsules compared with ∼135 μg/2.4 × 10 9 microcapsules for S/M/S). Whereas the lucigenin release from the S/M/S bubbles and capsules loaded below the solubility limit is consistent with diffusion from a monolithic structure, the SiPCL structures show distinct release patterns; the Weibull function predicts a general trend for diffusion from normal Euclidean space at short times tending toward diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (T d ) increases from 1 to 2 days for the S/M/S and for the low concentration, loaded SiPCl vehicles to ∼10 days for the high loaded microcapsules. However, T d can be reduced on insonation to 2 days, indicating the potential to gain control over the local enhanced release with ultrasound. This was tested for a docetaxel model and its effect on C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC 50 in solution.

Development of an Injectable Slow-Release Metformin Formulation and Evaluation of Its Potential Antitumor Effects.

PubMed

Baldassari, Sara; Solari, Agnese; Zuccari, Guendalina; Drava, Giuliana; Pastorino, Sara; Fucile, Carmen; Marini, Valeria; Daga, Antonio; Pattarozzi, Alessandra; Ratto, Alessandra; Ferrari, Angelo; Mattioli, Francesca; Barbieri, Federica; Caviglioli, Gabriele; Florio, Tullio

2018-03-02

Metformin is an antidiabetic drug which possesses antiproliferative activity in cancer cells when administered at high doses, due to its unfavorable pharmacokinetics. The aim of this work was to develop a pharmacological tool for the release of metformin in proximity of the tumor, allowing high local concentrations, and to demonstrate the in vivo antitumor efficacy after a prolonged metformin exposition. A 1.2% w/w metformin thermoresponsive parenteral formulation based on poloxamers P407 and P124, injectable at room temperature and undergoing a sol-gel transition at body temperature, has been developed and optimized for rheological, thermal and release control properties; the formulation is easily scalable, and proved to be stable during a 1-month storage at 5 °C. Using NOD/SCID mice pseudo-orthotopically grafted with MDA-MB-231/luc + human breast cancer cells, we report that multiple administrations of 100 mg of the optimized metformin formulation close to the tumor site cause tissue accumulation of the drug at levels significantly higher than those observed in plasma, and enough to exert antiproliferative and pro-apoptotic activities. Our results demonstrate that this formulation is endowed with good stability, tolerability, thermal and rheological properties, representing a novel tool to be pursued in further investigations for adjuvant cancer treatment.

Delivery of S1P Receptor-Targeted Drugs via Biodegradable Polymer Scaffolds Enhances Bone Regeneration in a Critical Size Cranial Defect*

PubMed Central

Das, Anusuya; Tanner, Shaun; Barker, Daniel A.; Green, David; Botchwey, Edward A.

2014-01-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with microcomputed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. PMID:23640833

Delivery of S1P receptor-targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect.

PubMed

Das, Anusuya; Tanner, Shaun; Barker, Daniel A; Green, David; Botchwey, Edward A

2014-04-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro-computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. Copyright © 2013 Wiley Periodicals, Inc.

Geologic controls on movement of produced-water releases at US geological survey research Site A, Skiatook lake, Osage county, Oklahoma

USGS Publications Warehouse

Otton, J.K.; Zielinski, R.A.; Smith, B.D.; Abbott, M.M.

2007-01-01

Highly saline produced water was released from multiple sources during oil field operations from 1913 to 1973 at the USGS research Site A on Skiatook Lake in northeastern Oklahoma. Two pits, designed to hold produced water and oil, were major sources for release of these fluids at the site. Produced water spills from these and other features moved downslope following topography and downdip by percolating through permeable eolian sand and colluvium, underlying permeable sandstone, and, to a lesser extent, through shales and mudstones. Saline water penetrated progressively deeper units as it moved through the gently dipping bedrock to the north and NW. A large eroded salt scar north of the pits coincides with underlying fine-grained rocks that have retained substantial concentrations of salt, causing slow revegetation. Where not eroded, thick eolian sand or permeable sandstone bedrock is near the surface, and vegetation has been little affected or has reestablished itself after the introduced salt was flushed by precipitation. The extent of salt-contaminated bedrock extends well beyond existing surface salt scars. These results indicate that one of the legacies of surface salt spills can be a volume of subsurface salinization larger than the visible surface disturbance. ?? 2007.

The race between infection and immunity - how do pathogens set the pace?

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

Ribiero, Ruy M

2009-01-01

Infection is often referred to as a race between pathogen and immune response. This metaphor suggests that slower growing pathogens should be more easily controlled. However, a growing body ofevidence shows that many chronic infections are caused by failure to control slow growing pathogens. The slow growth of pathogens appears to directly affect the kinetics of the immune response. Compared with the response to fast growing pathogens, the T cell response to slow pathogens is delayed in its initiation, lymphocyte expansion is slow and the response often fails to clear the pathogen, leading to chronic infection. Understanding the 'rules ofthemore » race' for slow growing pathogens has important implications for vaccine design and immune control of many chronic infections.« less

Use of Additives in Bioremediation of Contaminated Groundwater and Soil

EPA Science Inventory

This chapter reviews application of additives used in bioremediation of chlorinated solvents and fuels for groundwater and soil remediation. Soluble carbon substrates are applicable to most site conditions except aquifers with very high or very low groundwater flow. Slow-release ...

Phenol esterase activity of porcine skin

USDA-ARS?s Scientific Manuscript database

The alkyl esters of plant-derived phenols may serve as slow-release sources for cutaneous delivery of antioxidants. The ability of skin esterases to hydrolyze phenolic esters was examined. Esters of tyrosol and hydroxytyrosol were prepared from decanoic and lipoic acids. Ferulic acid was esterified ...

Use of phosphorus to reduce blooms of the benthic diatom Didymosphenia geminata in an oligotrophic stream

USGS Publications Warehouse

James, Daniel A.; Bothwell, Max L.; Chipps, Steven R.; Carreiro, John

2015-01-01

Blooms of the benthic alga, Didymosphenia geminata [Lyngbye (Schmidt)], were first documented in Rapid Creek, South Dakota, in 2002 and have since been associated with changes to aquatic resources. Low concentration of P has been associated with D. geminata stalk development (i.e., blooms), so we considered elevating P as a possible method to reduce D. geminata blooms. We conducted 2 whole-stream P-enrichment experiments in Rapid Creek during 2007 and 2008. Enrichment with a slow-release fertilizer (Osmocote®: 14-14-14) in 2007 significantly reduced D. geminata blooms (indexed by D. geminata biomass) compared to upstream control sites. The reduction in biomass was less pronounced as distance from the enrichment source increased, a result indicating that P augmentation effectively decreased D. geminata biomass. In 2008, we implemented a before-after–control-impact (BACI) study to assess effects of a quick-release fertilizer (MAP: 11-52-0) on D. geminata biomass. The addition of 6 μg/L P to Rapid Creek resulted in a significant decrease in D. geminata biomass within 0.6 km downstream of the nutrient-addition point. Effects on D. geminata biomass were not evident further downstream. This study provides evidence to support the hypothesis that low P concentration regulates D. geminata blooms.

The effect of enamel proteins on erosion

NASA Astrophysics Data System (ADS)

Baumann, T.; Carvalho, T. S.; Lussi, A.

2015-10-01

Enamel proteins form a scaffold for growing hydroxyapatite crystals during enamel formation. They are then almost completely degraded during enamel maturation, resulting in a protein content of only 1% (w/v) in mature enamel. Nevertheless, this small amount of remaining proteins has important effects on the mechanical and structural properties of enamel and on the electrostatic properties of its surface. To analyze how enamel proteins affect tooth erosion, human enamel specimens were deproteinated. Surface microhardness (SMH), surface reflection intensity (SRI) and calcium release of both deproteinated and control specimens were monitored while continuously eroding them. The deproteination itself already reduced the initial SMH and SRI of the enamel significantly (p < 0.001 and p < 0.01). During the course of erosion, the progression of all three evaluated parameters differed significantly between the two groups (p < 0.001 for each). The deproteinated enamel lost its SMH and SRI faster, and released more calcium than the control group, but these differences were only significant at later stages of erosion, where not only surface softening but surface loss can be observed. We conclude that enamel proteins have a significant effect on erosion, protecting the enamel and slowing down the progression of erosion when irreversible surface loss starts to occur.

The effect of enamel proteins on erosion

PubMed Central

Baumann, T.; Carvalho, T. S.; Lussi, A.

2015-01-01

Enamel proteins form a scaffold for growing hydroxyapatite crystals during enamel formation. They are then almost completely degraded during enamel maturation, resulting in a protein content of only 1% (w/v) in mature enamel. Nevertheless, this small amount of remaining proteins has important effects on the mechanical and structural properties of enamel and on the electrostatic properties of its surface. To analyze how enamel proteins affect tooth erosion, human enamel specimens were deproteinated. Surface microhardness (SMH), surface reflection intensity (SRI) and calcium release of both deproteinated and control specimens were monitored while continuously eroding them. The deproteination itself already reduced the initial SMH and SRI of the enamel significantly (p < 0.001 and p < 0.01). During the course of erosion, the progression of all three evaluated parameters differed significantly between the two groups (p < 0.001 for each). The deproteinated enamel lost its SMH and SRI faster, and released more calcium than the control group, but these differences were only significant at later stages of erosion, where not only surface softening but surface loss can be observed. We conclude that enamel proteins have a significant effect on erosion, protecting the enamel and slowing down the progression of erosion when irreversible surface loss starts to occur. PMID:26468660

Regulation of Glucose Homeostasis by GLP-1

PubMed Central

Nadkarni, Prashant; Chepurny, Oleg G.; Holz, George G.

2014-01-01

Glucagon-like peptide-1(7–36)amide (GLP-1) is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion. GLP-1 is secreted from L cells of the gastrointestinal mucosa in response to a meal, and the blood glucose-lowering action of GLP-1 is terminated due to its enzymatic degradation by dipeptidyl-peptidase-IV (DPP-IV). Released GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function. The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM). These therapeutic agents include GLP-1R agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and langlenatide) and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin). Investigational agents for use in the treatment of T2DM include GPR119 and GPR40 receptor agonists that stimulate the release of GLP-1 from L cells. Summarized here is the role of GLP-1 to control blood glucose homeo-stasis, with special emphasis on the advantages and limitations of GLP-1-based therapeutics. PMID:24373234

Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications

PubMed Central

Chan, Ka Man Carmen; Li, Randolph H.; Chapman, Joseph W.; Trac, Eric M.; Kobler, James B.; Zeitels, Steven M.; Langer, Robert; Karajanagi, Sandeep S.

2014-01-01

Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515 μm and stiffness ranging from 190 to 1600 Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers. PMID:24561708

Extended release dosage form of glipizide: development and validation of a level A in vitro-in vivo correlation.

PubMed

Ghosh, Animesh; Bhaumik, Uttam Kumar; Bose, Anirbandeep; Mandal, Uttam; Gowda, Veeran; Chatterjee, Bappaditya; Chakrabarty, Uday Sankar; Pal, Tapan Kumar

2008-10-01

Defining a quantitative and reliable relationship between in vitro drug release and in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process. During the development of once daily extended-release (ER) tablet of glipizide, a predictive in vitro drug release method was designed and statistically evaluated using three formulations with varying release rates. In order to establish internally and externally validated level A in vitro-in vivo correlation (IVIVC), a total of three different ER formulations of glipizide were used to evaluate a linear IVIVC model based on the in vitro test method. For internal validation, a single-dose four-way cross over study (n=6) was performed using fast-, moderate-, and slow-releasing ER formulations and an immediate-release (IR) of glipizide as reference. In vitro release rate data were obtained for each formulation using the United States Pharmacopeia (USP) apparatus II, paddle stirrer at 50 and 100 rev. min(-1) in 0.1 M hydrochloric acid (HCl) and pH 6.8 phosphate buffer. The f(2) metric (similarity factor) was used to analyze the dissolution data. The formulations were compared using area under the plasma concentration-time curve, AUC(0-infinity), time to reach peak plasma concentration, T(max), and peak plasma concentration, C(max), while correlation was determined between in vitro release and in vivo absorption. A linear correlation model was developed using percent absorbed data versus percent dissolved from the three formulations. Predicted glipizide concentrations were obtained by convolution of the in vivo absorption rates. Prediction errors were estimated for C(max) and AUC(0-infinity) to determine the validity of the correlation. Apparatus II, pH 6.8 at 100 rev. min(-1) was found to be the most discriminating dissolution method. Linear regression analysis of the mean percentage of dose absorbed versus the mean percentage of in vitro release resulted in a significant correlation (r(2)>or=0.9) for the three formulations.

How Source Content Determines Intracellular Ca2+ Release Kinetics. Simultaneous Measurement of [Ca2+] Transients and [H+] Displacement in Skeletal Muscle

PubMed Central

Pizarro, Gonzalo; Ríos, Eduardo

2004-01-01

In skeletal muscle, the waveform of Ca2+ release under clamp depolarization exhibits an early peak. Its decay reflects an inactivation, which locally corresponds to the termination of Ca2+ sparks, and is crucial for rapid control. In cardiac muscle, both the frequency of spontaneous sparks (i.e., their activation) and their termination appear to be strongly dependent on the Ca2+ content in the sarcoplasmic reticulum (SR). In skeletal muscle, no such role is established. Seeking a robust measurement of Ca2+ release and a way to reliably modify the SR content, we combined in the same cells the “EGTA/phenol red” method (Pape et al., 1995) to evaluate Ca2+ release, with the “removal” method (Melzer et al., 1987) to evaluate release flux. The cytosol of voltage-clamped frog fibers was equilibrated with EGTA (36 mM), antipyrylazo III, and phenol red, and absorbance changes were monitored simultaneously at three wavelengths, affording largely independent evaluations of Δ[H+] and Δ[Ca2+] from which the amount of released Ca2+ and the release flux were independently derived. Both methods yielded mutually consistent evaluations of flux. While the removal method gave a better kinetic picture of the release waveform, EGTA/phenol red provided continuous reproducible measures of calcium in the SR (CaSR). Steady release permeability (P), reached at the end of a 120-ms pulse, increased as CaSR was progressively reduced by a prior conditioning pulse, reaching 2.34-fold at 25% of resting CaSR (four cells). Peak P, reached early during a pulse, increased proportionally much less with SR depletion, decreasing at very low CaSR. The increase in steady P upon depletion was associated with a slowing of the rate of decay of P after the peak (i.e., a slower inactivation of Ca2+ release). These results are consistent with a major inhibitory effect of cytosolic (rather than intra-SR) Ca2+ on the activity of Ca2+ release channels. PMID:15337820

Effects of introducing foxes and raccoons on herring gull colonies

USGS Publications Warehouse

Kadlec, J.A.

1971-01-01

Red foxes (Vulpes fulva) and raccoons (Procyon lotor) released at colonies of herring gulls (Larus argentatus) on islands off the Massachusetts coast effectively eliminated the production of young gulls. Annual predator introductions for 2-4 years caused major reductions in colony size and occasionally total abandonment of the island as a colony site. Observations of the experimental islands for 2 years after cessation of predator introductions showed slow repopulation of the islands and lower breeding success than on control islands. The size of the regional population was reduced largely because of the movements of gulls off the experimental islands. The introduced predators are, in most cases, difficult to maintain on the islands; this restricts their utility in population management.

Ocular Complications of Diabetes and Therapeutic Approaches

PubMed Central

Vieira-Potter, Victoria J.; Karamichos, Dimitrios; Lee, Darren J.

2016-01-01

Diabetes mellitus (DM) is a metabolic disease defined by elevated blood glucose (BG). DM is a global epidemic and the prevalence is anticipated to continue to increase. The ocular complications of DM negatively impact the quality of life and carry an extremely high economic burden. While systemic control of BG can slow the ocular complications they cannot stop them, especially if clinical symptoms are already present. With the advances in biodegradable polymers, implantable ocular devices can slowly release medication to stop, and in some cases reverse, diabetic complications in the eye. In this review we discuss the ocular complications associated with DM, the treatments available with a focus on localized treatments, and what promising treatments are on the horizon. PMID:27119078

Correlation of in vitro and in vivo paracetamol availability from layered excipient suppositories.

PubMed

Chicco, D; Grabnar, I; Skerjanec, A; Vojnovic, D; Maurich, V; Realdon, N; Ragazzi, E; Belic, A; Karba, R; Mrhar, A

1999-11-05

An in vivo investigation of paracetamol availability was carried out on eight healthy volunteers, comparing two paracetamol suppository formulations prepared using two different gliceride bases, a fast drug-releasing one and a slow drug-releasing one, i.e. Witepsol H15 and W35, respectively. The formulations were selected on the basis of a previous in vitro drug release study, which showed that, by superimposing the excipients in two layers within the same suppository, the drug release kinetics could be modulated using different ratios between the two layers. The comparison between the two different formulations in terms of plasma profiles and total amounts of drug excreted in urine revealed an increase in the extent of drug absorption from the layered excipient suppository. As the W35 has a higher monoglyceride content than the H15, this improved paracetamol availability could be ascribed to the absorption-enhancing effect of the monoglycerides. Moreover, the W35 has also a higher viscosity, which could possibly cause the suppository to be retained for a longer time in the lower part of the rectum, where the blood is drained directly to the systemic circulation. It was therefore hypothesized that the enhanced paracetamol availability could be also due to a liver bypass mechanism. For a further examination of the paracetamol absorption kinetics after rectal administration, a one-compartment model was fitted to the drug plasma concentration data. This approach allowed to draw absorption versus time profiles, which showed that a retardation actually occurred in paracetamol absorption when using suppositories containing the slow drug releasing excipient W35. These absorption data were then employed for an A level in vitro-in vivo correlation testing, and a linear relationship was found between in vitro release rate and in vivo absorption rate, both for fast releasing and for the layered excipient suppositories.

The effect of melatonin from slow-release implants on basic and TLR-4-mediated gene expression of inflammatory cytokines and their receptors in the choroid plexus in ewes.

PubMed

Kowalewska, M; Herman, A P; Szczepkowska, A; Skipor, J

2017-08-01

The present study concerns the effect of melatonin from slow-release implants on the expression of genes coding interleukin-1β (Il1B), inerleukin-6 (Il6), tumour necrosis factor α (Tnf) and their receptors: IL-1 receptor type I (Il1r1) and type II (Il1r2), IL-6 receptor (Il6r) and signal transducer (Il6st), TNFα receptor type I (Tnfrsf1a) and II (Tnfrsf1b) and retinoid-related orphan receptor α (RorA) and Rev.-erbα in the ovine choroid plexus (CP) under basal and lipopolysaccharide (LPS)-challenged conditions. Studies were performed on four groups: 1) sham-implanted and placebo-treated, 2) melatonin-implanted (Melovine, 18mg) and placebo-treated, 3) sham-implanted and LPS-treated (400ng/kg of body weight) and 4) melatonin-implanted and LPS-treated. Under basal conditions, we observed weak expression of Tnf, low expression of Il1B, Il6 and Il1r2 and intermediate expression of other cytokines receptors. LPS treatment induced (P≤0.05) expression in all cytokines and their receptors, except Il6r 3h after the administration. Melatonin attenuated (P≤0.05) LPS-induced up-regulation of Il6 but had no effect on other cytokines and their receptors and up-regulated (P≤0.05) Rev.-erbα expression under basal conditions. This indicates that melatonin from slow-release implants suppresses TLR4-mediated Il6 expression in the ovine CP via a mechanism likely involving clock genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using slow-release permanganate candles to remove TCE from a low permeable aquifer at a former landfill.

PubMed

Christenson, Mark D; Kambhu, Ann; Comfort, Steve D

2012-10-01

Past disposal of industrial solvents into unregulated landfills is a significant source of groundwater contamination. In 2009, we began investigating a former unregulated landfill with known trichloroethene (TCE) contamination. Our objective was to pinpoint the location of the plume and treat the TCE using in situ chemical oxidation (ISCO). We accomplished this by using electrical resistivity imaging (ERI) to survey the landfill and map the subsurface lithology. We then used the ERI survey maps to guide direct push groundwater sampling. A TCE plume (100-600 μg L(-1)) was identified in a low permeable silty-clay aquifer (K(h)=0.5 md(-1)) that was within 6m of ground surface. To treat the TCE, we manufactured slow-release potassium permanganate candles (SRPCs) that were 91.4 cm long and either 5. cm or 7.6 cm in dia. For comparison, we inserted equal masses of SRPCs (7.6-cm versus 5.1-cm dia) into the low permeable aquifer in staggered rows that intersected the TCE plume. The 5.1-cm dia candles were inserted using direct push rods while the 7.6-cm SRPCs were placed in 10 permanent wells. Pneumatic circulators that emitted small air bubbles were placed below the 7.6-cm SRPCs in the second year. Results 15 months after installation showed significant TCE reductions in the 7.6-cm candle treatment zone (67-85%) and between 10% and 66% decrease in wells impacted by the direct push candles. These results support using slow-release permanganate candles as a means of treating chlorinated solvents in low permeable aquifers. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis, characterization and application of ion exchange resin as a slow-release fertilizer for wheat cultivation in space

NASA Astrophysics Data System (ADS)

Li, Bowei; Dong, Chen; Chu, Zhengpei; Zhang, Weizhe; Wang, Minjuan; Liu, Hong; Xie, Beizhen

2016-10-01

In addition to the bio-regenerative air revitalization, water recycling and waste management systems and their associated challenges, enhancing the crop yield with less fertilizer input for sustainable food production in space is also a challenge that needs to be overcome. The purpose of this study is to investigate the feasibility of applying ion exchange resin as a slow-release fertilizer for wheat cultivation in space. Strong-acid cationic exchange resins and weak-base anion exchange resins soaked in 1X, 5X, 10X and 15X Hoagland nutrient solutions, respectively, were used as fertilizers in clinoptilolite to cultivate wheat plants, and the morphological and physiological characteristics of the wheat plants were studied and compared with that of the wheat planted in vermiculite and nutrient solutions. The results showed that more ions were attached on the surface of the ion exchange resins as the solution concentration increased. After 14 days, the fresh weight of wheat planted in the ion exchange resin-clinoptilolite (IER-clinoptilolite) treated with 10X and 15X solutions were 190% and 192% higher than that of wheat planted in nutrient solution with the same concentration. Chlorophyll content of wheat plants cultivated in the two kinds of solid medium is significantly higher than that of liquid cultivation. The lowest peroxidase (POD) activity and malondialdehyde (MDA) contents of wheat plants cultivated in the IER-clinoptilolite appeared on the 14th day. According to all the experimental data, it's promising to produce slow-release nutrient fertilizer by using strong-acid cationic exchange resins and weak-base anion exchange resins for wheat cultivation in space.

Implications of L1 Observations for Slow Solar Wind Formation by Solar Reconnection

NASA Technical Reports Server (NTRS)

Kepko, L.; Viall, N. M.; Antiochos, S. K.; Lepri, S. T.; Kasper, J. C.; Weberg, M.

2016-01-01

While the source of the fast solar wind is known to be coronal holes, the source of the slow solar wind has remained a mystery. Long time scale trends in the composition and charge states show strong correlations between solar wind velocity and plasma parameters, yet these correlations have proved ineffective in determining the slow wind source. We take advantage of new high time resolution (12 min) measurements of solar wind composition and charge state abundances at L1 and previously identified 90 min quasi periodic structures to probe the fundamental timescales of slow wind variability. The combination of new high temporal resolution composition measurements and the clearly identified boundaries of the periodic structures allows us to utilize these distinct solar wind parcels as tracers of slowwind origin and acceleration. We find that each 90 min (2000 Mm) parcel of slow wind has near-constant speed yet exhibits repeatable, systematic charge state and composition variations that span the entire range of statistically determined slow solar wind values. The classic composition-velocity correlations do not hold on short, approximately hour long, time scales. Furthermore, the data demonstrate that these structures were created by magnetic reconnection. Our results impose severe new constraints on slow solar wind origin and provide new, compelling evidence that the slow wind results from the sporadic release of closed field plasma via magnetic reconnection at the boundary between open and closed flux in the Sun's atmosphere.

Segmentation of Slow Slip Events in South Central Alaska Possibly Controlled by a Subducted Oceanic Plateau

NASA Astrophysics Data System (ADS)

Li, Haotian; Wei, Meng; Li, Duo; Liu, Yajing; Kim, YoungHee; Zhou, Shiyong

2018-01-01

Recent GPS observations show that slow slip events in south central Alaska are segmented along strike. Here we review several mechanisms that might contribute to this segmentation and focus on two: along-strike variation of slab geometry and effective normal stress. We then test them by running numerical simulations in the framework of rate-and-state friction with a nonplanar fault geometry. Results show that the segmentation is most likely related to the along-strike variation of the effective normal stress on the fault plane caused by the Yakutat Plateau. The Yakutat Plateau could affect the effective normal stress by either lowering the pore pressure in Upper Cook Inlet due to less fluids release or increasing the normal stress due to the extra buoyancy caused by the subducted Yakutat Plateau. We prefer the latter explanation because it is consistent with the relative amplitudes of the effective normal stress in Upper and Lower Cook Inlet and there is very little along-strike variation in Vp/Vs ratio in the fault zone from receiver function analysis. However, we cannot exclude the possibility that the difference in effective normal stress results from along-strike variation of pore pressure due to the uncertainties in the Vp/Vs estimates. Our work implies that a structural anomaly can have a long-lived effect on the subduction zone slip behavior and might be a driving factor on along-strike segmentation of slow slip events.

Observation of fast and slow interatomic Coulombic decay in argon dimers induced by electron-impact ionization

NASA Astrophysics Data System (ADS)

Ren, Xueguang; Miteva, Tsveta; Kolorenč, Přemysl; Gokhberg, Kirill; Kuleff, Alexander I.; Cederbaum, Lorenz S.; Dorn, Alexander

2017-09-01

We investigate the interatomic Coulombic decay (ICD) in argon dimers induced by electron-impact ionization (E0=90 eV ) using a multiparticle coincidence experiment in which the momentum vectors and, consequently, the kinetic energies for electrons and fragment ions are determined. The signature of the ICD process is obtained from a correlation map between ejected electron energy and kinetic energy release (KER) for Ar++Ar+ fragment ions where low-energy ICD electrons can be identified. Furthermore, two types of ICD processes, termed fast and slow interatomic decay, are separated by the ICD initial-state energies and projectile energy losses. The dependence of the energies of emitted low-energy ICD electrons on the initial-state energy is studied. ICD electron energy spectra and KER spectra are obtained separately for fast and slow decay processes where the KER spectra for the slow decay channel are strongly influenced by nuclear motion. The KER and ICD electron energy spectra are well reproduced by ab initio calculations.

SNARE proteins synaptobrevin, SNAP-25 and syntaxin are involved in rapid and slow endocytosis at synapses

PubMed Central

Xu, Jianhua; Luo, Fujun; Zhang, Zhen; Xue, Lei; Wu, Xinsheng; Chiang, Hsueh-Cheng; Shin, Wonchul; Wu, Ling-Gang

2013-01-01

Rapid endocytosis, which takes only a few seconds, is widely observed in secretory cells. Although it is more efficient in recycling vesicles than slow clathrin-mediated endocytosis, its underlying mechanism, thought to be clathrin-independent, is largely unclear. Here we reported that cleavage of three SNARE proteins essential for exocytosis, including synaptobrevin, SNAP-25 and syntaxin, inhibited rapid endocytosis at the calyx of Held nerve terminal, suggesting the involvement of three SNARE proteins in rapid endocytosis. These SNARE proteins were also involved in slow endocytosis. In addition, SNAP-25 and syntaxin facilitated vesicle mobilization to the readily releasable pool, likely via their roles in endocytosis and/or exocytosis. We concluded that both rapid and slow endocytosis share the involvement of SNARE proteins. The dual role of three SNARE proteins in exo- and endocytosis suggests that SNARE proteins may be molecular substrates contributing to the exo-endocytosis coupling, which maintains exocytosis in secretory cells. PMID:23643538

Myopia Control: A Review.

PubMed

Walline, Jeffrey J

2016-01-01

Slowing the progression of myopia has become a considerable concern for parents of myopic children. At the same time, clinical science is rapidly advancing the knowledge about methods to slow myopia progression. This article reviews the peer-reviewed literature regarding several modalities attempting to control myopia progression. Several strategies have been shown to be ineffective for myopia control, including undercorrection of myopic refractive error, alignment fit gas-permeable contact lenses, outdoor time, and bifocal of multifocal spectacles. However, a recent randomized clinical trial fitted progressing myopic children with executive bifocals for 3 years and found a 39% slowing of myopia progression for bifocal-only spectacles and 50% treatment effect for bifocal spectacles with base-in prism, although there was not a significant difference in progression between the bifocal-only and bifocal plus prism groups. Interestingly, outdoor time has shown to be effective for reducing the onset of myopia but not for slowing the progression of myopic refractive error. More effective methods of myopia control include orthokeratology, soft bifocal contact lenses, and antimuscarinic agents. Orthokeratology and soft bifocal contact lenses are both thought to provide myopic blur to the retina, which acts as a putative cue to slow myopic eye growth. Each of these myopia control methods provides, on average, slightly less than 50% slowing of myopia progression. All studies have shown clinically meaningful slowing of myopia progression, including several randomized clinical trials. The most investigated antimuscarinic agents include pirenzepine and atropine. Pirenzepine slows myopia progression by approximately 40%, but it is not commercially available in the United States. Atropine provides the best myopia control, but the cycloplegic and mydriatic side effects render it a rarely prescribed myopia control agent in the United States. However, low-concentration atropine has been shown to provide effective myopia control with far fewer side effects than 1.0% atropine. Finally, two agents, low-concentration atropine and outdoor time have been shown to reduce the likelihood of myopia onset. Over the past few years, much has been learned about how to slow the progression of nearsightedness in children, but we still have a lot to learn.

50 CFR 216.274 - Mitigation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... safe speed. Release of ordnance through cloud cover is prohibited: aircraft must be able to actually... would be used. These aircraft would be capable of flying at the slow safe speeds necessary to enable... patrol aircraft aircrews, and Anti-submarine Warfare (ASW)/Mine Warfare (MIW) helicopter crews shall...

50 CFR 216.274 - Mitigation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... safe speed. Release of ordnance through cloud cover is prohibited: aircraft must be able to actually... would be used. These aircraft would be capable of flying at the slow safe speeds necessary to enable... patrol aircraft aircrews, and Anti-submarine Warfare (ASW)/Mine Warfare (MIW) helicopter crews shall...

50 CFR 216.274 - Mitigation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... safe speed. Release of ordnance through cloud cover is prohibited: aircraft must be able to actually... would be used. These aircraft would be capable of flying at the slow safe speeds necessary to enable... patrol aircraft aircrews, and Anti-submarine Warfare (ASW)/Mine Warfare (MIW) helicopter crews shall...

Future treatments for Parkinson's disease: surfing the PD pipeline.

PubMed

Hauser, Robert A

2011-01-01

Our current wish list for the treatment of Parkinson's disease (PD) includes therapies that will provide robust and sustained antiparkinsonian benefit through the day, ameliorate or prevent dyskinesia, and slow or prevent the progression of the disease. In this article, I review selected new therapies in clinical development for motor features or treatment complications of PD, and some that may slow disease progression. These include adenosine 2a (A2a) antagonists (istradefylline, preladenant, and SYN115), levodopa/carbidopa intestinal gel (LCIG), IPX066--an extended-release formulation of carbidopa/levodopa, XP21279--a sustained-release levodopa prodrug, ND0611--a carbidopa subcutaneous patch, safinamide--a mixed mechanism of action medication that may provide both MAO-B and glutamate inhibition, PMY50028--an oral neurotrophic factor inducer, antidyskinesia medications (AFQ056 and fipamezole), and gene therapies (AAV2-neurturin and glutamic acid decarboxylase gene transfer). Some of these therapies will never be proven efficacious and will not come to market while others may play a key role in the future treatment of PD.

Curcumin-carrying nanoparticles prevent ischemia-reperfusion injury in human renal cells.

PubMed

Xu, Yong; Hu, Ning; Jiang, Wei; Yuan, Hong-Fang; Zheng, Dong-Hui

2016-12-27

Renal ischemia-reperfusion injury (IRI) is a major complication in clinical practice. However, despite its frequency, effective preventive/treatment strategies for this condition are scarce. Curcumin possesses antioxidant properties and is a promising potential protective agent against renal IRI, but its poor water solubility restricts its application. In this study, we constructed curcumin-carrying distearoylphosphatidylethanolamine-polyethylene glycol nanoparticles (Cur-NPs), and their effect on HK-2 cells exposed to IRI was examined in vitro. Curcumin encapsulated in NPs demonstrated improved water solubility and slowed release. Compared with the IRI and Curcumin groups, Cur-NP groups displayed significantly improved cell viability, downregulated protein expression levels of caspase-3 and Bax, upregulated expression of Bcl-2 protein, increased antioxidant superoxide dismutase level, and reduced apoptotic rate, reactive oxygen species level, and malondialdehyde content. Results clearly showed that Cur-NPs demonstrated good water solubility and slow release, as well as exerted protective effects against oxidative stress in cultured HK-2 cells exposed to IRI.

Assessing the impacts of sustainable agricultural practices for water quality improvements in the Vouga catchment (Portugal) using the SWAT model.

PubMed

Rocha, João; Roebeling, Peter; Rial-Rivas, María Ermitas

2015-12-01

The extensive use of fertilizers has become one of the most challenging environmental issues in agricultural catchment areas. In order to reduce the negative impacts from agricultural activities and to accomplish the objectives of the European Water Framework Directive we must consider the implementation of sustainable agricultural practices. In this study, we assess sustainable agricultural practices based on reductions in N-fertilizer application rates (from 100% to 0%) and N-application methods (single, split and slow-release) across key agricultural land use classes in the Vouga catchment, Portugal. The SWAT model was used to relate sustainable agricultural practices, agricultural yields and N-NO3 water pollution deliveries. Results show that crop yields as well as N-NO3 exportation rates decrease with reductions in N-application rates and single N-application methods lead to lower crop yields and higher N-NO3 exportation rates as compared to split and slow-release N-application methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients

NASA Technical Reports Server (NTRS)

Zerwekh, J. E.; Antich, P. P.; Sakhaee, K.; Prior, J.; Gonzales, J.; Gottschalk, F.; Pak, C. Y.

1992-01-01

We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

In situ synthesis of silver-nanoparticles/bacterial cellulose composites for slow-released antimicrobial wound dressing.

PubMed

Wu, Jian; Zheng, Yudong; Song, Wenhui; Luan, Jiabin; Wen, Xiaoxiao; Wu, Zhigu; Chen, Xiaohua; Wang, Qi; Guo, Shaolin

2014-02-15

Bacterial cellulose has attracted increasing attention as a novel wound dressing material, but it has no antimicrobial activity, which is one of critical skin-barrier functions in wound healing. To overcome such deficiency, we developed a novel method to synthesize and impregnate silver nanoparticles on to bacterial cellulose nanofibres (AgNP-BC). Uniform spherical silver nano-particles (10-30 nm) were generated and self-assembled on the surface of BC nano-fibers, forming a stable and evenly distributed Ag nanoparticles coated BC nanofiber. Such hybrid nanostructure prevented Ag nanoparticles from dropping off BC network and thus minimized the toxicity of nanoparticles. Regardless the slow Ag(+) release, AgNP-BC still exhibited significant antibacterial activities with more than 99% reductions in Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, AgNP-BC allowed attachment and growth of epidermal cells with no cytotoxicity emerged. The results demonstrated that AgNP-BC could reduce inflammation and promote wound healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rupture process of a multiple main shock sequence: analysis of teleseismic, local and field observations of the Tennant Creek, Australia, earthquakes of January 22, 1988

USGS Publications Warehouse

Choy, G.L.; Bowman, J.R.

1990-01-01

On January 22, 1988, three large intraplate earthquakes (with MS 6.3, 6.4 and 6.7) occurred within a 12-hour period near Tennant Creek, Australia. Broadband displacement and velocity records of body waves from teleseismically recorded data are analyzed to determine source mechanisms, depths, and complexity of rupture of each of the three main shocks. Hypocenters of an additional 150 foreshocks and aftershocks constrained by local arrival time data and field observations of surface rupture are used to complement the source characteristics of the main shocks. The interpretation of the combined data sets suggests that the overall rupture process involved unusually complicated stress release. Rupture characteristics suggest that substantial slow slip occurred on each of the three fault interfaces that was not accompanied by major energy release. Variation of focal depth and the strong increase of moment and radiated energy with each main shock imply that lateral variations of strength were more important than vertical gradients of shear stress in controlling the progression of rupture. -from Authors

Cadmium contamination of agricultural soils and crops resulting from sphalerite weathering.

PubMed

Robson, T C; Braungardt, C B; Rieuwerts, J; Worsfold, P

2014-01-01

The biogeochemistry and bioavailability of cadmium, released during sphalerite weathering in soils, were investigated under contrasting agricultural scenarios to assess health risks associated with sphalerite dust transport to productive soils from mining. Laboratory experiments (365 d) on temperate and sub-tropical soils amended with sphalerite (<63 μm, 0.92 wt.% Cd) showed continuous, slow dissolution (0.6-1.2% y(-1)). Wheat grown in spiked temperate soil accumulated ≈38% (29 μmol kg(-1)) of the liberated Cd, exceeding food safety limits. In contrast, rice grown in flooded sub-tropical soil accumulated far less Cd (0.60 μmol kg(-1)) due to neutral soil pH and Cd bioavailability was possibly also controlled by secondary sulfide formation. The results demonstrate long-term release of Cd to soil porewaters during sphalerite weathering. Under oxic conditions, Cd may be sufficiently bioavailable to contaminate crops destined for human consumption; however flooded rice production limits the impact of sphalerite contamination. Copyright © 2013 Elsevier Ltd. All rights reserved.

High Surface Area, Thermally Stable, Hydrophobic, Microporous, Rigid Gels Generated at Ambient from MeSi(OEt)3 /(EtO)3 SiCH2 CH2 Si(OEt)3 Mixtures by F- -Catalyzed Hydrolysis.

PubMed

Furgal, Joseph C; Yamane, Honami; Odykirk, Timothy R; Yi, Eongyu; Chujo, Yoshiki; Laine, Richard M

2018-01-02

High surface area materials are of considerable interest for gas storage/capture, molecular sieving, catalyst supports, as well as for slow-release drug-delivery systems. We report here a very simple and fast route to very high surface area, mechanically robust, hydrophobic polymer gels prepared by fluoride-catalyzed hydrolysis of mixtures of MeSi(OEt) 3 and bis-triethoxysilylethane (BTSE) at room temperature. These materials offer specific surface areas up to 1300 m 2  g -1 , peak pore sizes of 0.8 nm and thermal stabilities above 200 °C. The gelation times and surface areas can be controlled by adjusting the solvent volume (dichloromethane), percent fluoride (as nBu 4 NF or TBAF) and the BTSE contents. Polymers with other corners and linkers were also explored. These materials will further expand the materials databank for use in vacuum insulation panels and as thermally stable release and capture media. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photothermal-triggered control of sub-cellular drug accumulation using doxorubicin-loaded single-walled carbon nanotubes for the effective killing of human breast cancer cells

NASA Astrophysics Data System (ADS)

Oh, Yunok; Jin, Jun-O.; Oh, Junghwan

2017-03-01

Single-walled carbon nanotubes (SWNTs) are often the subject of investigation as effective photothermal therapy (PTT) agents owing to their unique strong optical absorption. Doxorubicin (DOX)-loaded SWNTs (SWNTs-DOX) can be used as an efficient therapeutic agent for combined near infrared (NIR) cancer photothermal and chemotherapy. However, SWNTs-DOX-mediated induction of cancer cell death has not been fully investigated, particularly the reaction of DOX inside cancer cells by PTT. In this study, we examined how the SWNTs-DOX promoted effective MDA-MB-231 cell death compared to DOX and PTT alone. We successfully synthesized the SWNTs-DOX. The SWNTs-DOX exhibited a slow DOX release, which was accelerated by NIR irradiation. Furthermore, DOX released from the SWNTs-DOX accumulated inside the cells at high concentration and effectively localized into the MDA-MB-231 cell nucleus. A combination of SWNTs-DOX and PTT promoted an effective MDA-MB-231 cell death by mitochondrial disruption and ROS generation. Thus, SWNTs-DOX can be utilized as an excellent anticancer agent for early breast cancer treatment.

Current Strategies in the Modification of PLGA-based Gene Delivery System.

PubMed

Ramezani, Mohammad; Ebrahimian, Mahboubeh; Hashemi, Maryam

2017-01-01

Successful gene therapy has been limited by safe and efficient delivery of nucleic acid to the target cells. Poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are able to deliver drugs and genes efficiently. This formulation has several advantages in comparison with other formulations including improvement in solubility, stability, controlling of degradation and release of the entrapped agents. For application of PLGA as a gene carrier, there exist many challenges. PLGA NPs could protect the encapsulated DNA from in vivo degradation but the DNA release is slow and the negative charge acts as a barrier to DNA incorporation and delivery. Also, during the preparation process, DNA could be exposed to high shear stress and organic solvents which could result in its inactivation. Moreover, PLGA NPs could be modified with different agents to reduce cytotoxicity, to enhance delivery efficiency and to target specific tissues/cells. This review summarizes different methods used for the preparation of PLGA NPs as gene carriers and recent strategies for the modification of PLGA particles applied in gene therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of sewage sludge addition to Norway spruce seedlings on nitrogen availability and soil fauna in clear-cut areas.

PubMed

Nieminen, Jouni K; Räisänen, Mikko

2013-07-01

Anaerobically digested and composted sewage sludge (CSS) has been suggested to be a slow-release fertilizer in forestry and an alternative to quick-release inorganic fertilizers. The effects of CSS with or without added carbohydrate on inorganic nitrogen availability and on soil animals were tested in two Norway spruce plantations. Half of the seedlings were individually fertilized with CSS, and the rest were left as controls. Solid sucrose was added to half of the fertilized and untreated seedlings. Soil samples were taken in the autumn in the first and the second year after the treatments. CSS increased soil NH4-N (2100%), the proportion of soil NO3-N, and the N concentration of spruce needles. CSS greatly reduced the abundances of enchytraeids, tardigrades and collembolans, but increased the proportion and abundance of bacterial-feeding nematodes irrespective of carbohydrate addition. A better stabilization method needs to be developed before CSS can be used as a forest fertilizer. Copyright © 2013 Elsevier Ltd. All rights reserved.