Slow-release Formulation Research Articles

FERTILIZANTE DE LIBERAÇÃO LENTA NO DESENVOLVIMENTO DE MUDAS DE <i> Anadenanthera peregrina </i> (L.) Speg. (ANGICO-VERMELHO) E <i> Schinus terebinthifolius </i> Raddi (AROEIRA-VERMELHA)

http://dx.doi.org/10.5902/1980509820582Com o objetivo de avaliar o desenvolvimento de duas espécies arbóreas nativas - Anadenanthera peregrina (angico-vermelho) e Schinus terebinthifolius (aroeira-vermelha) - submetidas a doses de fertilizante de liberação lenta na formulação 13-06-16, conduziu-se um experimento em viveiro utilizando uma mistura de matérias-primas com composto orgânico, vermiculita e Plantmax® para compor substrato base. O experimento foi conduzido no delineamento experimental inteiramente casualizado com seis tratamentos em quatro repetições. Os tratamentos foram: T1–0 kg (testemunha); T2–2 kg; T3–4 kg; T4–6 kg; T5–8 kg e T6–10 kg de fertilizante de liberação lenta por metro cúbico de substrato base. Avaliou-se aos 189 dias após a semeadura a altura total, diâmetro do colo, biomassa fresca da parte aérea, biomassa seca da parte aérea, biomassa seca da raiz, biomassa seca total, relação entre altura e diâmetro do colo e o índice de qualidade de Dickson. Os resultados evidenciam que a aplicação de fertilizante de liberação lenta leva a ganhos significativos de crescimento em ambas as espécies, sendo as melhores doses 6,68 a 5,54 kg m-3 para a espécie Anadenanthera peregrina, e 8,38 a 14,42 kg m-3 para Schinus terebinthifolius.

Constructing herbicide metribuzin sustained-release formulations based on the natural polymer poly-3-hydroxybutyrate as a degradable matrix

ABSTRACTPolymer poly(3-hydroxybutyrate) [P(3HB)] has been used as a matrix in slow-release formulations of the herbicide metribuzin (MET). Physical P(3HB)/MET mixtures in the form of solutions, powders, and emulsions were used to construct different metribuzin formulations (films, granules, pellets, and microparticles). SEM, X-Ray, and DSC proved the stability of these formulations incubated in sterile water in vitro for long periods of time (up to 49 days). Metribuzin release from the polymer matrix has been also studied. By varying the shape of formulations (microparticles, granules, films, and pellets), we were able to control the release time of metribuzin, increasing or decreasing it.

Characterization of biodegradable poly-3-hydroxybutyrate films and pellets loaded with the fungicide tebuconazole.

Biodegradable polymer poly(3-hydroxybutyrate) (P3HB) has been used as a matrix to construct slow-release formulations of the fungicide tebuconazole (TEB). P3HB/TEB systems constructed as films and pellets have been studied using differential scanning calorimetry, X-ray structure analysis, and Fourier transform infrared spectroscopy. TEB release from the experimental formulations has been studied in aqueous and soil laboratory systems. In the soil with known composition of microbial community, polymer was degraded, and TEB release after 35 days reached 60 and 36 % from films and pellets, respectively. That was 1.23 and 1.8 times more than the amount released to the water after 60 days in a sterile aqueous system. Incubation of P3HB/TEB films and pellets in the soil stimulated development of P3HB-degrading microorganisms of the genera Pseudomonas, Stenotrophomonas, Variovorax, and Streptomyces. Experiments with phytopathogenic fungi F. moniliforme and F. solani showed that the experimental P3HB/TEB formulations had antifungal activity comparable with that of free TEB.

Abstract 13158: Impact of Enhancing Fetal Lung Vascular and Alveolar Development by Slow-release Novel Synthetic Prostacyclin Agonist for Treatment of Fetal Lung Hypoplasia

Background: Lung hypoplasia and persistent pulmonary hypertension associated with critical pathologies, such as congenital diaphragmatic hernia (CDH), is the major cause of mortality in the neonates. Although prostaglandins pathway is known to play a pivotal role in the lung development, effectiveness of postnatal treatment by prostaglandin agonists was reported to be suboptimal. We hypothesized that prenatal treatment by ONO-1301SR, slow-release form of a novel synthetic prostacyclin agonist with thromboxane inhibitory activity, might promote development of lungs having hypoplasia in the fetal period. Methods: On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to produce a CDH-relating lung hypoplasia model, while normal rats (n=4) received vehicle only. At the same day, either ONO-1301SR or placebo was randomly given to the nitrofen-treated rats (placebo; n=7, ONO; n=5). On E21.5, the normal fetuses, and the fetuses having CDH were analyzed. Results: Prenatal ONO-1301SR administration had no influence on incidence of nitrofen-induced CDH. One-seventh of maternal blood concentration of ONO-1301 was transferred to fetal blood at E21.5, warranting efficient placental permeability of this molecule. Prostacyclin receptor was expressed in pulmonary arterial smooth muscle cells in the fetus. Lung-to-body weight ratio (%) in the ONO group (1.88±0.07) was greater than that in the placebo group (1.60±0.04, p<0.01). Histologically, medial wall thickness in the ONO group was two-third thinner than that in the placebo group (p<0.01). In addition, the number of Ttf-1-positive cells and capillary density were 1.5 times or more greater in the ONO group than that in the placebo group (p<0.05), associated with a greater expression of VEGF and SDF-1 in the ONO group, suggesting enhanced development of the alveolar and capillary network. Conclusions: Prenatal ONO-1301SR administration promoted efficient development of hypoplastic lungs associated with CDH in the nitrofen-induced rat model, indicating potential of this treatment for pathologies having lung hypoplasia.

Semi-solid state fermentation of food waste for production of Bacillus thuringiensis biopesticide

In this study, Bacillus thuringiensis (Bt) biopesticide was produced through different fermentation processes using food waste with different water contents. The semi-solid state sample with 75% water content presented the highest δ-endotoxin efficiency of 862 μg/mL. δ-endotoxin efficiency increased by 30.2% from that of the solid-state sample (50% water content) and 73.8% from that of the submerged sample (99% water content). Results confirmed that semi-solid state fermentation presents considerable advantages compared with other fermentation types (solid-state and submerged). The timing adjustment of pH and recycling fermentation effectively counteracted the inhibition of pH and product, thereby increasing δ- endotoxin efficiency to 1,648 and 2,478 μg/mL (accumulated value of all four fermentation loops), respectively. A δ- endotoxin slow-release formulation using polylactic acid as the carrier was also developed to effectively promote the stability of Bt biopesticide.

Administration of Exogenous Growth Hormone Is Associated with Changes in Plasma and Intracellular Mammary Amino Acid Profiles and Abundance of the Mammary Gland Amino Acid Transporter SLC3A2 in Mid-Lactation Dairy Cows

The objectives of this study were to (1) identify changes in plasma and mammary intracellular amino acid (AA) profiles in dairy cows treated with growth hormone (GH), and (2) evaluate the expression of mammary gland genes involved in the transport of AA identified in (1). Eight non-pregnant (n = 4 per group) lactating dairy cows were treated with a single subcutaneous injection of either a slow-release formulation of commercially available GH (Lactotropin 500 mg) or physiological saline solution. Six days after treatment, cows were milked and blood collected from the jugular vein for the analysis of free AA in the plasma. Cows were euthanized and mammary tissue harvested. Treatment with GH increased milk, protein, fat and lactose yields, with no effect on dry matter intake. Plasma concentrations of lysine and group I AA decreased significantly, and arginine, methionine, tyrosine and arginine-family AA tended to decrease in GH-treated cows. Concentrations of intracellular glycine, serine and glutamate increased significantly, with a trend for decreased arginine observed in the mammary gland of GH-treated cows. A trend for increased concentrations of intracellular total AA, NEAA and arginine-family AA were observed in the mammary gland of GH-treated cows. Variance in the concentration of plasma methionine, tyrosine, valine, alanine, ornithine, BCAA, EAA was significantly different between treatments. Variance in the concentration of intracellular lysine, valine, glutamine, EAA and group II was significantly different between treatments. AA changes were associated with increased mRNA abundance of the mammary gland AA transporter SLC3A2. We propose that these changes occur to support increased milk protein and fatty acid production in the mammary gland of GH-treated cows via potential mTOR pathway signaling.

Development of slow release formulations of β-carotene employing amphiphilic polymers and their release kinetics study in water and different pH conditions.

β-carotene, a potent antioxidant, has been encapsulated and slow release (SR) formulations were prepared using laboratory synthesized poly(ethylene glycols) (PEGs) based functionalized amphiphilic copolymers. Encapsulation efficiency and loading capacity of the developed formulations were determined which ranged from 22.60 to 28.08% and 2.2 to 2.8% respectively. The release kinetics of β-carotene from developed formulations in water revealed increased solubility and prolonged stability of β-carotene. The formulations were further subjected to different pH conditions (viz., 1.8, 6.8 and 7.8) corresponding to human gastrointestinal tract to study the effect of pH on the release of β-carotene. The diffusion exponent (n values) ranged from the 0.1540 to 0.2342 for developed formulation. The results showed that developed slow release formulations were unaffected by the highly acidic conditions referring to the gastric environment of human body. However, the release of β-carotene was high at pH7.8 and slightly higher at pH6.8.

Hydrogel/clinoptilolite nanocomposite-coated fertilizer: swelling, water-retention and slow-release fertilizer properties

Preparation of a new core–shell slow-release fertilizer formulation was conducted through the coating of commercial NPK fertilizer with hydrogel/clinoptilolite (Hyd/CL) nanocomposite. The Hyd/CL nanocomposite was prepared from free radical polymerization of sodium alginate, acrylic acid, acrylamide, and clinoptilolite zeolite. The uniform coating on the surface of the fertilizer granules was verified by scanning electron microscopy. The swelling kinetics as well as the water-retention property and water absorption rate of the prepared samples was studied. Furthermore, the release of fertilizer from Hyd/CL nanocomposite-coated fertilizer granules into soil showed that the Hyd/CL nanocomposite layer around the fertilizer granules caused the system to liberate the nutrient in a more controlled manner (lower than 57 % of loaded fertilizer on the 30 days) than that with the uncoated fertilizer. The overall results eventually suggested that the hydrogel nanocomposite designed in this work can be used as a coating on granular fertilizer compounds for application in agriculture due to its water-retention and slow-release properties.

Mitigation of experimental, chronic post-thoracotomy pain by preoperative infiltration of local slow-release bupivacaine microspheres.

Postoperative pain is treated incompletely and ineffectively in many circumstances, and chronic postoperative pain causes suffering and diminishes productivity. The objective of this project is to determine whether a recently developed slow-release formulation of bupivacaine was effective in reducing the experimental chronic postoperative pain. In male Sprague-Dawley rats (250-300 g body weight), bupivacaine-releasing microspheres (MS-Bupi), containing 60 mg of bupivacaine base, were locally injected (MS-Bupi-L) 2 hours preoperatively into the subcutaneous compartment at the locus for experimental thoracotomy. Hypersensitivity to tactile stimulation was assessed by reductions in the threshold force required to induce a response to von Frey filaments (VFH) applied to the hairy back near the incision/retraction site. Pain behavior was assessed using a Qualitative Hyperalgesia Profile. Control groups included rats receiving the same dose of MS-Bupi but at a distant site on the back (MS-Bupi-D, testing for systemic drug actions) and rats receiving the same mass of microspheres with no drug (MS-Placebo) at the wound site. Rats were tested for 3 days before and 28 days (postoperative days [PODs]) after the procedure. Withdrawal threshold differences, which were the primary outcome measure, among all treatment groups were assessed by the Kruskal-Wallis test, after which pairwise comparisons were made by determining Wilcoxon-Mann-Whitney odds (WMWodds), with Bonferroni correction of the confidence intervals. Microsphere bupivacaine released near the incision reduced the chronic tactile allodynia after thoracotomy. The threshold values during PODs 14 to 28 were different among the 3 treatment groups when examined on PODs 14, 16, 18, 23, 25, and 28 but not on POD21 (P = 0.0603). WMWodds showed that threshold of the MS-Bupi-L group differed from those of the MS-Bupi-D and the MS-Placebo groups for all the tested PODs, whereas the thresholds of the MS-Bupi-D group never differed from those of the MS-Placebo group. Area-under-curve analysis for threshold reductions below baseline, using WMWodds, also showed a reduction during the entire 28 PODs that was greater for the MS-Bupi-L group compared with the MS-Placebo or MS-Bupi-D group. The incidence of intense pain scores by the Qualitative Hyperalgesia Profile analysis was observed in 7 of 8 rats in the MS-Placebo group and in 5 of 8 rats in the MS-Bupi-L group. Local slow release of bupivacaine subcutaneously from the MS-Bupi formulation suppresses postoperative mechanical hypersensitivity for ≥4 weeks after experimental thoracotomy. Systemic bupivacaine from this treatment has no effect on this hypersensitivity.

Fate and efficiency of 15N-labelled slow- and controlled-release fertilizers

Slow- and controlled-release N fertilizers are designed to increase efficiency and reduce N losses by better synchronizing N availability with plant demand. This paper reviews the use of 15N with these fertilizers to collect quantitative data on the efficiency, residual value and N losses for which relatively few data are available compared with conventional labelled urea and ammonium-based fertilizers. In general, studies of slow-release forms (isobutylidene diurea, oxamide, ureaform) with rice and upland crops show one or more benefits, including improved N uptake efficiency, and reduced N losses via leaching or NH3 volatilization under conditions which favor such losses (coarse textured soils, alkaline pH, respectively). Benefits from residual 15N may accrue in the year following application. Studies with controlled-release 15N-labelled sulfur coated urea (SCU) show benefits in situations such as paddy soils where losses from broadcast urea are a substantial problem. In experiments with 15N polyolefin-coated urea (POCU), rice plant recovery of broadcast conventional urea or ammonium salts ranged from 24 % with losses of 50–45 % with losses of 33 %. Where 15N labelled SCU or POCU was used, the rice recovery ranged from 26 % with losses of 14–72 % with losses of 10 %. Experiments using POCU with corn, barley and potato show similar results. The paucity of published data obtained using 15N points to the need for further studies that will provide concrete evidence for the development of innovative fertilizers with enhanced efficiency and an evidence-based set of recommendations for their selection and use.

Encapsulation and characterization of slow-release microbial fertilizer from the composites of bentonite and alginate

Raoultella planticola Rs-2 was innovatively encapsulated with sodium bentonite and alginate (NaAlg) composites to develop efficient slow-release biofertilizer formulations and minimize production costs. These microcapsules were spherical in shape and their encapsulation efficiency was nearly 100%. Approximately 88.9% of Rs-2 in dried microcapsules of bentonite–NaAlg survived after 6months of storage. The NaAlg amount required to produce desirable bentonite-blended Rs-2 microcapsules was significantly lower than that of single NaAlg. Swelling, biodegradability, and release rate increased with increasing NaAlg content and decreased with increasing bentonite content. All release curves of bacteria from the bentonite–NaAlg microcapsules presented an initial burst followed by a gradual increase manner, which mainly implied the release behavior followed a first-order release model. Thus, bentonite–NaAlg composites could be ideal low-cost encapsulated wall materials for slow-release bacterial fertilizers in farmlands.

Screening for an ivermectin slow-release formulation suitable for malaria vector control.

BackgroundThe prospect of eliminating malaria is challenged by emerging insecticide resistance and vectors with outdoor and/or crepuscular activity. Ivermectin can simultaneously tackle these issues by killing mosquitoes feeding on treated animals and humans. A single oral dose, however, confers only short-lived mosquitocidal plasma levels.MethodsThree different slow-release formulations of ivermectin were screened for their capacity to sustain mosquito-killing levels of ivermectin for months. Thirty rabbits received a dose of one, two or three silicone implants containing different proportions of ivermectin, deoxycholate and sucrose. Animals were checked for toxicity and ivermectin was quantified periodically in blood. Potential impact of corresponding long-lasting formulation was mathematically modelled.ResultsAll combinations of formulation and dose released ivermectin for more than 12 weeks; four combinations sustained plasma levels capable of killing 50% of Anopheles gambiae feeding on a treated subject for up to 24 weeks. No major adverse effects attributable to the drug were found. Modelling predicts a 98% reduction in infectious vector density by using an ivermectin formulation with a 12-week duration.ConclusionsThese results indicate that relatively stable mosquitocidal plasma levels of ivermectin can be safely sustained in rabbits for up to six months using a silicone-based subcutaneous formulation. Modifying the formulation of ivermectin promises to be a suitable strategy for malaria vector control.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0618-2) contains supplementary material, which is available to authorized users.

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): a multicentre, parallel-group, randomised placebo-controlled trial

BackgroundDiarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2 g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.ObjectivesOur primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.Design/participants/interventionWe performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.SettingsParticipants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.ResultsA total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53);p = 0.66.ConclusionsMesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.Trial registrationCurrent Controlled Trials ISRCTN76612274.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

Development and employment of slow-release pendimethalin formulations for the reduction of root penetration into subsurface drippers.

Subsurface drip irrigation supplies water directly to the root zone and is an efficient irrigation technology. One of the main challenges is preventing plant roots from clogging the drippers. With the aim of inhibiting root penetration, slow-release pendimethalin formulations based on its solubilization in micelles adsorbed and unadsorbed to clay were developed. In the past unadsorbed micelles were considered inadequate for slow release, because release was too fast. In contrast, the advantage of a two-mode release formulation, composed of adsorbed and unadsorbed micelles, is demonstrated. A bioassay to study pendimethalin leaching at a refined scale of 1-2 cm was developed and reduced leaching from the micelle-clay formulations in comparison to the commercial formulation (Stomp) was exhibited. In a greenhouse study the application of the formulations by injection into an irrigation system was extremely efficient with 0-10% root penetration in comparison to 100% penetration upon Stomp injection.

Comparison of a new metamizole formulation and carprofen for extended post-operative analgesia in dogs undergoing ovariohysterectomy

A newly developed slow-release tablet formulation of metamizole was compared with carprofen for post-operative analgesia in dogs undergoing ovariohysterectomy. Twenty-three dogs were randomly assigned to one of two groups, and administered 50 mg/kg metamizole PO (Group M) or 4 mg/kg carprofen PO (Group C) 1 h before anaesthetic induction and 24 and 48 h later. Anaesthesia was induced with propofol and maintained with isoflurane and fentanyl, after premedication with 0.005 mg/kg medetomidine and 0.3 mg/kg methadone IM. A blinded observer assessed post-operative sedation, and analgesia using a visual analogue scale, a dynamic interactive visual analogue scale, the Glasgow composite pain scale (GCPS), and a mechanical nociceptive threshold device (T = 0.5, 1, 2, 4, 8, 12, 18, 21, 24, 36, 45, 60 and 70 h after surgery). Rescue methadone was administered if the GCPS was >6/24 in ambulatory dogs, or >5/20 in non-ambulatory dogs. Plasma concentrations of test drugs were quantified.The dose range for metamizole was 39–56 mg/kg. At T = 0.5 h sedation scores were significantly higher in Group C and GCPS scores were significantly higher in Group M. Three dogs required rescue methadone (Group M, n = 1; Group C, n = 2). Vomiting occurred post-operatively in 45% of dogs in Group M. Carprofen and metamizole were both well absorbed; peak concentrations occurred within 4–24 h, and 4–16 h for carprofen and metamizole, respectively. Both drugs provided adequate analgesia of similar duration. No side effects were observed with carprofen while vomiting was frequent following administration of metamizole.

Polysaccharides as safer release systems for agrochemicals

Agrochemicals are used to improve the production of crops. Conventional formulations of agrochemicals can contaminate the environment, in particular in the case of intensive cropping. Hence, there is a need for controlled-release formulations of agrochemicals such as polysaccharides to reduce pollution and health hazards. Natural polysaccharides are hydrophilic, biodegradable polymers. This article reviews the use of polysaccharides in the form of micro- and nanoparticles, beads and hydrogels. The main points are: (1) slow release formulations minimize environmental impact by reducing agrochemical leaching, volatilization and degradation. For example, 50 % of the encapsulated insecticide chlorpyrifos is released in 5 days, whereas free chlorpyrifos is released in 1 day. (2) Slow release formulations increase the water-holding capacity of soil. (3) Slow release formulations better control weeds in the long run. (4) Polymer-clay formulations store ionic plant nutrients. (5) Polymer hydrogel formulations reduce compaction, erosion, and water run-off. They increase soil permeability and aeration, infiltration rates, and microbial activity, and, in turn, plant performance. In conclusion, polysaccharide formulations can be used for safer use of agrochemicals.

Model-based determination of the influence of textile fabric on bioassay analysis and the effectiveness of a textile slow-release system of DEET in mosquito control.

Determining the effectiveness of a product in repelling mosquitoes or other flying insects is a difficult task. One approach is to use a bioassay with textile fabric. We investigated the role of the textile substrate in a bioassay with a numerical model, and compared the outcome with known results for DEET. The model was then used to determine the effectiveness of textile slow-release formulations based on coatings, and results were compared with those of a field study in the Cameroon. Slow-release formulations are difficult to evaluate with standard tests, as the compound needs a build-up time not present in these tests. We found excellent correspondence between the model and the known DEET results without matching parameters. Slow-release approaches are deemed possible but have several drawbacks. Modelling can help in identifying optimal use conditions. The field test with a slow-release system performed better than anticipated by the model, with initially more than 90% repellency. DEET-coated textile was considered not to be marketable, however. We advise that bioassays characterise in more detail the type of textile fabric used so as to allow conclusions to be drawn by textile modelling. As regards coated-textile slow-release systems, more research is needed. We nevertheless advise usage mainly at entry points, e.g. as scrims.

Abstract 541: Adenosine Inhibits C-Kit+ Progenitor Smooth Muscle Cell (P-SMC) Infiltration In Injury-Induced Neointima Formation And Human P-SMC Growth: Role of A2B Adenosine Receptor-Mediated Growth Regulation

Adenosine inhibits injury-induced neointimal formation; however, the mechanism is incompletely understood. Marrow-derived C-Kit+ progenitor cells (P-SMCs) express a smooth muscle phenotype and contribute to injury-induced neointimal thickening. The goal of our investigation was to determine whether adenosine attenuates neointimal hyperplasia in part by inhibiting the growth of P-SMCs and to clarify which adenosine receptor subtypes are involved. Digitized pixel analysis demonstrated that administration of adenosine (20 μM) peri-arterially for 7 days in a slow-release formulation inhibited injury-induced neointimal hyperplasia in the rat carotid artery by 71% (p<0.05: neointimal thickness: 37,424 ± 18,371 pixels in vehicle-treated [n=7] versus 10,352 ± 2,824 pixels in adenosine-treated [n=7]). Microscopic analysis following immunostaining for c-Kit+ cells showed a marked decrease (> 50%) in staining for c-Kit+ cells in the neointima of rats receiving adenosine. In cultured human P-SMCs, serum-induced growth (as determined by quantification of DNA synthesis and cell number), cell-migration, and collagen synthesis was inhibited by adenosine and 2-chloroadenosine, but not by N 6 -cyclopentyladenosine (selective A 1 -receptor agonist), CGS21680 (selective A 2A -receptor agonist) or N 6 -(3-iodobenzyl)adenosine-5'-N-methyluronamide (selective A 3 -receptor agonist). This agonist profile was consistent with an A 2B -receptor-mediated effect. Augmentation of endogenous adenosine levels with erythro -9-(2-hydroxy-3-nonyl)adenine (adenosine deaminase inhibitor) and 5-iodotubericidin (adenosine kinase inhibitor) attenuated P-SMC growth. Moreover the antimitogenic effects of both exogenous and endogenous adenosine were abrogated by blockade of A 2B receptors (MRS 1754), but not by antagonism of A 1 (8-cyclopentyl-1,3-dipropylxanthine), A 2A (SCH 58261) or A 3 (VUF 5574) receptors. We conclude that adenosine, via activation of A 2B receptors, inhibits neointimal formation in part by inhibiting infiltration and growth of C-Kit+ P-SMCs. These findings suggest that A 2B receptor stimulation may prevent vascular remodeling associated with coronary artery disease, hypertension, atherosclerosis and restenosis.

Removal and slow release studies of phosphate on surfactant loaded hydrothermally synthesized silicate nanoparticles

The reported work is mainly focused on the use of as-synthesized silicates (clinoptilolite and montmorillonite) nanoparticles and their surfactant modified forms for the removal and slow release formulation of phosphate. Batch experiments have been carried out to determine the influence of parameters like initial phosphate concentration, pH of the medium, contact time between the adsorbate and adsorbent, weight of adsorbent, and system temperature on phosphate removal. Furthermore, slow phosphate release studies have been performed by thin layer-funnel analytical test and soil column percolating system. The results of batch adsorption studies reveal that surfactant modified forms of clinoptilolite and montmorillonite show better adsorption potential for phosphate than their unmodified form and phosphate removal ability of surfactant modified silicates increases with increasing amount of loaded surfactant. The maximum adsorption of phosphate is observed around pH 7 and maximum Langmuir monolayer phosphate adsorption capacity 93.46mgg−1 is observed for hexadecyltrimethylammonium (CH3(CH2)15N+(CH3)3) loaded clinoptilolite (HC). The obtained results indicate that surfactant loaded silicates are very good adsorbent for phosphate removal and slow release of phosphate is also achievable as it releases phosphate still after 15 days of leaching.

Selection criteria for initiation and renewal of luteinizing hormone-releasing hormone agonist therapy in patients with prostate cancer: a French prospective observational study.

To define the profile of patients with prostate cancer (PCa) receiving a 3-month or 6-month formulation of luteinizing hormone-releasing hormone (LHRH) agonist in France and the reasons for choosing between formulations. This prospective 1-year observational study included patients with PCa starting LHRH agonist therapy in everyday practice. Reasons for prescription and patient preference were recorded at inclusion, 3 or 6 months, and 12 months. The percentage of patients with a renewed initial prescription was recorded during follow up. A total of 1438 patients with PCa were included. Hormonotherapy was initiated more frequently with a 6-month (n = 903; 62.8%) than with a 3-month formulation (n = 535; 37.2%). The initial prescription was renewed in most patients after 3 or 6 months (86.1%) and 12 months (71%); 170 patients switched from a 3-month to a 6-month formulation during follow up. Presence of metastases influenced initial prescription (odds ratio 0.439; 95% confidence interval 1.095-1.892), with a 3-month formulation more often prescribed than a 6-month formulation to men with metastatic PCa at diagnosis (21.3% versus 15.8%, respectively). The most frequent reasons given by physicians for choosing the 6-month formulation were 'simplification of therapeutic regimen' (86.9%) or 'fewer unnecessary visits' (46.8%). Similar reasons were given for switching from a 3-month to a 6-month formulation during follow up. The most frequent reasons given by physicians to initiate therapy with a 3-month formulation were 'usual practice/habit' (55.5%) or 'closer patient management' (46.2%). 'Closer patient management' and 'reassuring effect upon patient' were the main reasons for switching from a 6-month to a 3-month formulation during follow up. Approximately 80% of patients were satisfied with the formulation they were prescribed and patients' reasons for preferring one formulation over another were similar to the physicians' reasons for prescribing these formulations. Slow-release formulations of LHRH agonists are useful therapies for physicians treating patients with PCa and there may be a preference for the 6-month formulation.