Systemic exposure to tobramycin after local antibiotic treatment with calcium sulphate as carrier material.

INTRODUCTION: Osteoset(®) T is a calcium sulphate void filler containing 4% tobramycin sulphate, used to treat bone and soft tissue infections. Despite systemic exposure to the antibiotic, there are no pharmacokinetic studies in humans published so far. Based on the observations made in our patients, a model predicting tobramycin serum levels and evaluating their toxicity potential is presented. METHODS: Following implantation of Osteoset(®) T, tobramycin serum concentrations were monitored systematically. A pharmacokinetic analysis was performed using a non-linear mixed effects model based on a one compartment model with first-degree absorption. RESULTS: Data from 12 patients treated between October 2006 and March 2008 were analysed. Concentration profiles were consistent with the first-order slow release and single-compartment kinetics, whilst showing important variability. Predicted tobramycin serum concentrations depended clearly on both implanted drug amount and renal function. DISCUSSION AND CONCLUSION: Despite the popularity of aminoglycosides for local antibiotic therapy, pharmacokinetic data for this indication are scarce, and not available for calcium sulphate as carrier material. Systemic exposure to tobramycin after implantation of Osteoset(®) T appears reassuring regarding toxicity potential, except in case of markedly impaired renal function. We recommend in adapting the dosage to the estimated creatinine clearance rather than solely to the patient's weight.

Intraocular implants for extended drug delivery: therapeutic applications.

An overview of ocular implants with therapeutic application potentials is provided. Various types of implants can be used as slow release devices delivering locally the needed drug for an extended period of time. Thus, multiple periocular or intraocular injections of the drug can be circumvented and secondary complications minimized. The various compositions of polymers fulfilling specific delivery goals are described. Several of these implants are undergoing clinical trials while a few are already commercialized. Despite the paramount progress in design, safety and efficacy, the place of these implants in our clinical therapeutic arsenal remains limited. Miniaturization of the implants allowing for their direct injection without the need for a complicated surgery is a necessary development avenue. Particulate systems which can be engineered to target specifically certain cells or tissues are another promising alternative. For ocular diseases affecting the choroid and outer retina, transscleral or intrasscleral implants are gaining momentum.

Non-viral ocular gene therapy: potential ocular therapeutic avenues.

Non-viral vectors for potential gene replacement and therapy have been developed in order to overcome the drawbacks of viral vectors. The diversity of non-viral vectors allows for a wide range of various products, flexibility of application, ease of use, low-cost of production and enhanced "genomic" safety. Using non-viral strategies, oligonucleotides (ODNs) can be delivered naked (less efficient) or entrapped in cationic lipids, polymers or peptides forming slow release delivery systems, which can be adapted according to the organ targeted and the therapy purposes. Tissue and cell internalization can be further enhanced by changing by physical or chemical means. Moreover, a specific vector can be selected according to disease course and intensity of manifestations fulfilling specific requirements such as the duration of drug release and its level along with cells and tissues specific targeting. From accumulating knowledge and experience, it appears that combination of several non-viral techniques may increase the efficacy and ensure the safety of these evolving and interesting gene therapy strategies.

Trials using a crossover design and ambulatory blood pressure recordings to determine the efficacy of antihypertensive agents in individual patients.

The antihypertensive effects of the beta-blocking agent betaxolol and the calcium entry blocker verapamil were compared in a crossover single-blind trial. Seventeen patients with uncomplicated essential hypertension took either betaxolol or a slow-release formulation of verapamil for two consecutive 6-week periods. The sequence of treatment phases was randomly allocated and a 2-week washout period preceded each treatment. The antihypertensive effect of the test drugs was assessed both at the physician's office and during everyday activities using a portable blood pressure recorder. The crossover design of the trial made it possible to evaluate the antihypertensive efficacy of betaxolol and verapamil both in the group as a whole and in the individual patient. The individual patient response to one of these agents was not a reliable indicator of the same patient's response to the alternative agent. Betaxolol brought both office and ambulatory recorded blood pressures under control in a larger fraction of patients than verapamil, although the magnitude of the blood pressure fall in the responders was equal for each drug. These observations stress the need for an individualized approach to the evaluation of antihypertensive therapy. The present results also demonstrate that optimal antihypertensive therapy is still a matter of trial and error. The precise methodology that ought to characterize crossover trials may make it possible to improve the therapeutic approach to hypertensive patients.

Obtenció d'estruvita a partir de la fracció líquida digerida de purins de vaca

Actualment a Catalunya existeixen zones amb importants limitacions per l’aplicació de purins al sòl, pel que és imprescindible trobar alternatives de gestió i tractament que permetin l’aprofitament adequat dels recursos continguts a les dejeccions ramaderes sense afectar el medi. La digestió anaeròbia és una de les tècniques utilitzades en el tractament de les dejeccions ramaderes. L’efluent líquid que s’obté d’aquest tractament no modifica el contingut de nitrogen i fòsfor i per tant ha de ser gestionat correctament. L’objectiu general d’aquest projecte és avaluar la precipitació d’estruvita (sal de magnesi, amoni i fosfat) com una alternativa de gestió de l’efluent líquid d’una planta de digestió anaeròbia i compostatge que tracta dejeccions ramaderes conjuntament amb altres residus orgànics. S’han avaluat els efectes dels diferents paràmetres operacionals en la formació d’estruvita (pH, temperatura, velocitat d’agitació, alcalinitat), mitjançant assaigs en discontinu amb solució sintètica. A continuació s’ha procedit a obtenir estruvita a partir de la fracció líquida digerida de purí (FLD), en assaigs en discontinu per estudiar l’efecte del contingut de matèria orgànica i sòlids Totals (ST), així com el contingut en fosfats i el pH de reacció. Finalment, s’han optimitzat els paràmetres de procés en continu, mitjançant la posada en marxa d’un reactor a escala de laboratori i estudi de l’efecte de la velocitat d’agitació i de la introducció del stripping de CO2, tant amb solució sintètica com amb la fracció líquida digerida del purí. Dels resultats obtinguts es pot concloure que els factors que tenen una major influència en el procés d’obtenció d’estruvita són el pH (el pH òptim es situa al voltant de 9), i la presència de matèria orgànica i sòlids ens suspensió, que interfereix de forma quantitativa i qualitativa en la formació de l’estruvita. En el procés en continu s’ha aconseguit reduccions d’un 84% i 98% d’amoni i fòsfor respectivament, obtenintse estruvita que pot ser utilitzada com a fertilitzant d’alliberació lenta. Es pot concloure que la precipitació d’estruvita és una bona alternativa per millorar la gestió de les dejeccions ramaderes alhora que permet recuperar nutrients i tancar cicles. La combinació amb un tractament previ que elimini la matèria orgànica, com podria ser la digestió anaeròbia, i una separació de fases, per eliminar els sòlids en suspensió, es presenta com una configuració amb molts avantatges.

Formulações de atrazina em xerogéis: síntese e caracterização

In this study, controlled release formulations of Atrazine (ATZ) were synthesized by the sol-gel method and characterized by elemental, FTIR, SEM, BET and DSC analyses. The release kinetic of ATZ from the formulations in CaCl2 0.01 mol L-1 medium was monitored by UV/Vis spectroscopy. In all formulations, ATZ was physically dispersed on the Si-polymer, and the dispersion grade decreased with increasing amount of herbicide. The ATZ release kinetics was controlled mainly by dissolution, and the data could be fitted to the Korsmeyer - Pepper model. The ATZ as xerogel presents a lower affinity for soil than as granulated form.

GABA and 5-HT chitosan nanoparticles enhanced liver cell proliferation and neuronal survival in partially hepatectomised rats: GABAB and 5-HT2A receptors functional

Nanoparticulate drug delivery systems provide wide opportunities for solving problems associated with drug stability or disease states and create great expectations in the area of drug delivery (Bosselmann & Williams, 2012). Nanotechnology, in a simple way, explains the technology that deals with one billionth of a meter scale (Ochekpe, et al., 2009). Fewer side effects, poor bioavailability, absorption at intestine, solubility, specific delivery to site of action with good pharmacological efficiency, slow release, degradation of drug and effective therapeutic outcome, are the major challenges faced by most of the drug delivery systems. To a great extent, biopolymer coated drug delivery systems coupled with nanotechnology alleviate the major drawbacks of the common delivery methods. Chitosan, deacetylated chitin, is a copolymer of β-(1, 4) linked glucosamine (deacetylated unit) and N- acetyl glucosamine (acetylated unit) (Radhakumary et al., 2005). Chitosan is biodegradable, non-toxic and bio compatible. Owing to the removal of acetyl moieties that are present in the amine functional groups of chitin, chitosan is readily soluble in aqueous acidic solution. The solubilisation occurs through the protonation of amino groups on the C-2 position of D-glucosamine residues whereby polysaccharide is converted into polycation in acidic media. Chitosan interacts with many active compounds due to the presence of amine group in it. The presence of this active amine group in chitosan was exploited for the interaction with the active molecules in the present study. Nanoparticles of chitosan coupled drugs are utilized for drug delivery in eye, brain, liver, cancer tissues, treatment of spinal cord injury and infections (Sharma et al., 2007; Li, et a., 2009; Paolicelli et al., 2009; Cho et al., 2010). To deliver drugs directly to the intended site of action and to improve pharmacological efficiency by minimizing undesired side effects elsewhere in the body and decrease the long-term use of many drugs, polymeric drug delivery systems can be used (Thatte et al., 2005).

The effects of organic and conventional fertilizers on cereal aphids and their natural enemies

Aphids are important pests of spring cereals and their abundance and the impact of their natural enemies may be influenced by fertilizer regime.2We conducted a 2-year field study investigating the effects of organic slow-release and conventional fertilizers on cereal aphids, hymenopteran parasitoids and syrphid predators and considered how the effects of fertilizers on barley morphology and colour might influence these species.3Barley yield was greater in conventionally fertilized pots. Barley morphology was also affected by treatment: vegetative growth was greater under conventional treatments. Barley receiving organic fertilizers or no fertilizer was visually more attractive to aphids compared with plants receiving conventional fertilizers.4Aphids were more abundant in conventionally fertilized barley but the reason for this increased abundance was species specific. Metopolophium dirhodum was responding to fertilizer effects on plant morphology, whereas Rhopalosiphum padi was sensitive to the temporal availability of nutrients.5Syrphid eggs were more numerous in conventionally fertilized pots, whereas the response of parasitoids appeared to be dependent on the abundance of aphids, although the number of parasitoid mummies was low in both years.6This research shows that the fertilizer treatment used can affect numerous characteristics of plant growth and colour, which can then influence higher trophic levels. This knowledge might be used to make more informed fertilizer application choices.

Mineralização de carbono e de nitrogênio provenientes de composto de lixo urbano em argissolo

Estudos da mineralização do C e do N em solos que receberam aplicação de composto de lixo urbano são importantes para avaliar o comportamento desse resíduo no solo e dar subsídios para definir as doses adequadas às culturas, com vistas em atender à necessidade de N das plantas. Foram realizados dois experimentos em condições de laboratório com o objetivo de avaliar a mineralização de C e de N em um Argissolo textura média adubado com composto de lixo urbano. No primeiro experimento, utilizou-se delineamento inteiramente ao acaso, com cinco tratamentos e três repetições, com os tratamentos constituídos de cinco doses de composto de lixo urbano, equivalentes a 0, 30, 60, 90 e 120 t ha-1. No segundo experimento, empregou-se esquema fatorial, com delineamento inteiramente ao acaso e três repetições, combinando as mesmas cinco doses de composto de lixo urbano utilizadas no primeiro experimento e 11 tempos de incubação (0, 7, 14, 28, 42, 56, 70, 84, 98, 112 e 126 dias). Os maiores aumentos de N-NO3- no solo foram obtidos até os 42 dias de incubação, independentemente da dose de composto de lixo aplicada, percebendo-se, a partir dos 70 dias, tendência de estabilização. A fração de mineralização de C-orgânico em C-CO2 menor do que 2 % em 168 dias indica que o composto de lixo urbano é material que contribui para aumentar os estoques de matéria orgânica do solo. Na ausência de adubação nitrogenada complementar, a fração de mineralização de N-orgânico de 12 % em 126 dias evidencia que o composto de lixo urbano apresenta potencial fertilizante de liberação lenta de N para as plantas.

Uso fertilizante de resíduo da indústria processadora de goiabas

O resíduo da indústria processadora de goiabas vem sendo aplicado em algumas áreas, entretanto não é conhecido o seu efeito na fertilidade do solo. Foi realizado experimento em casa de vegetação, com o objetivo de avaliar o efeito da aplicação do resíduo da indústria processadora de goiabas na fertilidade do solo, tendo como planta-teste o milho. O delineamento experimental utilizado foi em blocos ao acaso, em esquema fatorial 5x2, com quatro repetições, combinando-se cinco doses do resíduo da indústria processadora de goiabas (0; 20; 40; 60 e 80 t ha-1) na presença e ausência de adubação mineral. A adição de resíduo da indústria processadora de goiabas propiciou aumento nos teores de P e K do solo. O resíduo da indústria processadora de goiabas é uma fonte de liberação lenta de N e P para as plantas.

The effect of elevated blood cortisol levels on the extinction of a conditioned stress response in rainbow trout

Following previously published observations that a conditioned response (CR) was lost more quickly by rainbow trout (Oncorhynchus mykiss) exhibiting a high responsiveness to stressors than by low responding individuals this study was designed to investigate the effects of exogenous cortisol on the retention of a CR in unselected rainbow trout. Fish held in isolation were conditioned over a 10-day period by pairing an innocuous signal (conditioned stimulus, CS: a water jet played on the surface of the tank water) with a mild stressor (unconditioned stimulus, US: 30 min of confinement). This resulted in a brief elevation of plasma cortisol levels (the CR) when the fish was exposed to the CS only. The effect of exogenous cortisol on the retention of the CR was evaluated by comparing the performance of fish that received cortisol-containing slow-release intraperitoneal implants, with fish receiving vehicle-only implants. Retention of the CR was assessed at intervals up to 35 days after conditioning ceased. The CR was considered to be evident when 30 min following presentation of the CS, mean plasma cortisol levels were significantly higher in conditioned than untrained fish. on day 1 both cortisol-implanted and vehicle-implanted conditioned fish exhibited a CR. However, from day 5 onwards the CR was observed only in the vehicle-implanted and conditioned group. This finding indicates that administration of cortisol accelerated the extinction of the CR in the cortisol-implanted fish, suggesting that elevated plasma cortisol levels can impair memory processes in rainbow trout. (c) 2006 Elsevier B.V. All rights reserved.

Efeitos da uréia coberta com enxofre sobre a perda de nitrogênio por lixiviação em um latossol roxo

Foi conduzido um experimento a fim de estudar, comparativamente, o efeito da uréia coberta com enxofre (SCU) e uréia não coberta sobre a perda de nitrogênio (N-NH+4 + N-NO-3) por lixiviaçao em um Latossol Roxo que ocorre sob vegetação de cerrado no Município de Botucatu, SP-Brasil, bem como a influência de doses destes fertilizantes e do pH do solo. Verificou-se que SCU reduziu as perdas de nitrogênio, através do processo de lixiação, apresentando lenta liberação do elemento. O efeito das doses refletiu-se nas perdas por lixiviaçao com uma maior perda para a dose mais elevada (120 kg n/ ha). Houve influência do pH ocorrendo maiores perdas de N para o valor mais elenado, ou seja, no pH 6,5, para ambos os tipos de uréia, verificando-se também que o pH não influiu na liberação do N retido no grânulo de SCU.

Volume do recipiente, adubação e sua forma de mistura ao substrato no crescimento inicial de Peltophorum dubium (sprengel) taubert em viveiro

O ensaio comparou três volumes de recipientes, três tipos de adubação e duas formas de mistura do fertilizante ao substrato, no crescimento inicial de plântulas de Peltophorum dubium (Sprengel) Taubert (canafístula) em viveiro, num esquema fatorial 3 x 3 x 2. Foram utilizados tubetes de 100 e 180 cm³ preenchidos com substrato comercial e sacos plásticos de 10 x 15 cm cheios com mistura de solo e vermiculita em partes iguais, fertilizados com fertilizante de liberação lenta (FLL) nas dosagens de 1,75 e 3,5 kg m-3 e com formulação NPK a 1,0 kg m-3 de substrato. As formas de misturas adotadas foram aquelas com base por metro cúbico de substrato ou individualmente para cada recipiente. Na análise destrutiva realizada 12 semanas após a emergência, avaliaram-se o número de folhas, a altura da planta, o diâmetro do coleto e as massas secas da parte aérea, o sistema radicular e o total. Os resultados indicaram que a redução no volume do recipiente causou diminuição na massa seca, diâmetro e altura. O número de folhas, a massa seca da parte aérea e a massa seca total foram semelhantes nas plântulas sob fertilização com NPK, independentemente do volume do recipiente, o que não ocorreu naquelas sob FLL, onde esse parâmetro diminuiu com o volume do recipiente. O cálculo do índice de Dickson após 12 semanas indicou valores superiores em mudas com a forma de mistura convencional em relação à individual e maior naquelas sob fertilização com NPK, em comparação com as sob FLL.

Influência do substrato e do tipo de fertilizante na aclimatação de mudas de bananeira 'Prata-Anã'

Objetivando-se avaliar a influência do substrato e tipo de fertilizante na aclimatação de mudas de bananeira 'Prata-Anã', provenientes de micropropagação, foi instalado um experimento em blocos casualizados, no esquema fatorial 5 x 3, com quatro repetições. Os substratos utilizados foram: S1 - Terra de subsolo + casca de arroz carbonizada + substrato comercial Rendimax Floreira®; S2 - Terra de subsolo + casca de arroz carbonizada + composto orgânico Organifol®; S3 - Terra de subsolo + casca de arroz carbonizada + composto orgânico Organifol® 9% SiO; S4 - substrato comercial Technes Vivatto®; S5 - Areia grossa + casca de arroz carbonizada + Rendimax Floreira®, todos na proporção 1:1:1 (v/v/v). Os fertilizantes utilizados foram: SF - sem fertilizante; FLL - fertilizante de liberação lenta, 14-14-14 (5,0 kg m-3) misturado ao substrato; e FLN - fertilizante de liberação normal, 14-14-14 (5,0 kg m-3) aplicado em cobertura, 30 dias após o plantio. As mudas foram plantadas em sacos de polietileno quando apresentavam quatro a cinco folhas, sendo mantidas em viveiro com 50% de sombreamento. Foram feitas medidas de altura, diâmetro do colo e número de folhas, e determinada a massa seca das mudas. As diferenças químicas das misturas utilizadas como substrato, juntamente com o tipo de fertilizante utilizado, proporcionaram crescimento diferenciado das mudas. O substrato S4 pode ser utilizado sem fertilização. Os substratos S2 e S3 devem ser utilizados com fertilizante de liberação normal ou lenta de nutrientes, e S1 e S5, sendo pobres em nutrientes, com fertilizante de liberação lenta.

Crescimento de mudas micropropagadas da bananeira cv. Nanicão, em diferentes substratos e fontes de fertilizante

With the objective of evaluating the effect of different substrates combined with fertilizers in the growth of micropropagated seedlings of Cavendish banana (Musa spp. AAA), ail experiment was conducted in a randomized block design, in a 5 x 3 factorial scheme, with four repetitions. The substrates used were: S1 - subsoil land + carbonized rice hull + Rendmax Floreira (R); S2 - subsoil land + carbonized rice hull + Organifol (R); S3 - subsoil land + carbonized rice hull + Organifol (R) 9% SiO; S4 - Technes Vivatto (R); S5 - thick sand + carbonized rice hull + Rendmax Floreira (R). The fertilizer sources were: SA - without fertilizer; LL - slow-release fertilizer - Osmocote (R) 3M 14-14-14 (5.0 kg m(-3)) inixed in the substrate; and LN - normal-release fertilizer, 14-14-14 (7.5 g seedling(-1)) applied in covering. The height, collar diameter, leaf number, leaf area and dry matter were determined. Based on the differences of growth, substrates S 1, S2, S3 and S4 can be used with fertilizer 14-14-14, with slow (5.0 kg m(-3)) or normal (7.5 g seedling(-1)) release of nutrients.