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Biomedical subjects

P Frutos

Publications and source records attributed to P Frutos.

18 recordsLinked to original sources

Anthelmintic and nutritional effects of heather supplementation on Cashmere goats grazing perennial ryegrass-white clover pastures.

To investigate anthelmintic and nutritional effects of heather supplementation in goats grazing perennial ryegrass-white clover pastures, 40 dry Cashmere goats were randomly assigned to 4 treatments in a 2 x 2 factorial arrangement: 2 grazing management treatments (supplementation with heather vs. nonsupplementation) and 2 anthelmintic treatments (treatment vs. nontreatment). Goats grazed continuously from May to September 2004. At the end of the grazing period, the number of dead goats due to gastrointestinal parasitism was 1 in the group supplemented with heather and dosed with anthelmintic, 4 in the group that received neither supplementation nor anthelmintic, and 0 in the other 2 groups. For goats that did not receive anthelmintic treatment, the percentage of heather in the diet was negatively correlated with fecal egg count in August (r = -0.59, P < 0.05) and September (r = -0.49, P < 0.1) and positively correlated (r = 0.54, P < 0.05) with BW changes during the grazing season. Therefore, the correlation coefficient between BW change and fecal egg count was negative (r = -0.62, P < 0.05). Rumen ammonia concentrations were always lower in supplemented goats (P < 0.05). However, VFA concentrations were greater in goats consuming heather (58.9 vs. 50.9 mmol/L), which suggests that ruminal fermentation was not adversely affected by consumption of tannins. Heather availability in the vegetation might represent a valuable opportunity and sustainable method to control gastrointestinal nematode infections in a goat production system based on grazing perennial ryegrass-white clover pastures.

Ammonia↗

Effect of undegradable protein supply on testicular size, spermiogram parameters and sexual behavior of mature Assaf rams.

Eighteen mature Assaf rams were used to study the effect of undegradable protein (UDP) supply on testicular size, sperm production and quality, testosterone secretion and reproductive behavior. Animals were allocated to three groups of six animals each and fed during 10 weeks with different diets which were designed to supply approximately 0.5MJ of metabolisable energy (ME)/kg LBW(0.75) and 9g of effective rumen degradable protein (ERDP)/MJ of fermentable ME to all animals and to induce differences in rumen UDP intake (0.97, 1.72 and 3.08g of UDP/kg LBW(0.75) for LP, MP and HP diets, respectively). Neither plasma testosterone concentration nor reproductive behavior parameters (number of services, number of mounts without ejaculation and reaction time to first mount) were affected (P > 0.05) by protein intake. Nevertheless, there were significant (P < 0.05) differences between diets in both testicular size and sperm production. Scrotal circumference was lower in LP compared to MP and HP groups, no significant differences being observed between these latter two groups at any time. In relation to sperm production, the lowest and the highest values were always observed in LP and HP groups, respectively. MP group showed intermediate values, significantly different from those of LP and HP groups on Week 5 and only from those of LP group on Week 9. The present results provide a better understanding of the effect of protein nutrition and suggest that UDP should be supplied to Assaf rams during the mating season to improve their reproductive performance.

Animal Nutritional Physiological Phenomena↗

Intoxication of sheep with quebracho tannin extract.

This experiment was carried out to study the toxicity of quebracho tannin extract (containing 760 g of condensed tannins [CTs] per kg), with the aim of validating its use as a feed additive for improving the digestive utilization of protein-rich feeds. Four groups (Q(0), Q(1), Q(2) and Q(3)) of four sheep were dosed intra-ruminally once daily, for up to 21 days with, respectively, 0, 0.5, 1.5 or 3.0 g quebracho tannin extract/kg live-weight (LW). Feed intake, live-weight changes, plasma biochemistry, indicators of hepatic detoxification function, gross lesions and histopathology were examined. Animals in groups Q(0), Q(1) and Q(2) consumed all the offered feed. In contrast, feed intake was practically nil after 6 days of quebracho dosing in group Q(3), this being associated with a loss of 4.7+/-1.30 kg LW in 10 days (P<0.05). Sheep from groups Q(0), Q(1) and Q(2) remained healthy throughout the experiment. Ewes from group Q(3) became weak and depressed on day 5 and after 8 days of dosing remained recumbent. They were humanely killed after 10 days to avoid suffering. In general, neither gross lesions nor microscopical changes were observed in animals from groups Q(0), Q(1) and Q(2). However, Q(3) sheep showed striking lesions in the digestive tract (well-demarcated ulcers filled with necrotic material in the mucosa of the rumen and reticulum, distension of abomasum and small intestine, and dense mucous material in the caecum), and changes in plasma biochemistry. Cytochrome P-450 and glutathione concentrations were significantly reduced in Q(3) sheep (P<0.05). It is concluded that quebracho tannin extract is not toxic for ruminants, except in concentrations too high to be encountered under practical conditions.

Abomasum↗

Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose.

Modified polymethylmethacrylate (PMMA) bone cements formulations were prepared by including different proportions of gentamicin and release modulators such as lactose or hydroxypropylmethylcellulose (HPMC). Surface aspect, gentamicin release and porosity of these modified formulations were studied by means of scanning electron microscopy (SEM), a specially designed system for the dissolution studies of the bone cements, and mercury intrusion porosimetry. Lactose modified cements presented an irregular surface with numerous hollows and voids due to the lactose dissolution. HPMC cements presented a characteristic laminated and flaky surface. The drug release of lactose formulations was up to four-fold greater (13%) than the commercial bone cement CMW1 Gentamicin one (3%). The amount of gentamicin eluted at the first withdrawn sample ranged from 30% to 60% of total gentamicin released over the assay. Gentamicin release from lactose formulations increased as lactose percentage was increased which agree with the porosity results. Nevertheless, the use of release modulator HPMC increased porosity, but did not produce an increase in the gentamicin release. HPMC dissolution creates a surrounding sticky and viscous medium similar to a gel that makes the gentamicin release from the cement matrix difficult.

Anti-Bacterial Agents↗

Release of gentamicin sulphate from a modified commercial bone cement. Effect of (2-hydroxyethyl methacrylate) comonomer and poly(N-vinyl-2-pyrrolidone) additive on release mechanism and kinetics.

The influence of the (2-hydroxyethyl methacrylate) (HEMA) monomer addition as a comonomer to the cement liquid component and of a polymer, poly(N-vinyl-2-pyrrolidone) (PVP) to the solid component of a standard CMW-1 bone cement on gentamicin sulphate (GS) on its drug release properties have been studied. The addition of HEMA modifies the habit of the delivery curves. The incorporation of PVP into the cement matrix, apparently, did not very much modify the shape of the HEMA modified cement release curves, but led to a remarkable increase of the maximum amount of GS released. This effect was proportional to the PVP concentration incorporated. From the matrix composition and SEM data, a model based on the morphology of the matrix has been proposed. The cumulative amount of GS released by each slab Mt is most adequately fitted and represented by the equation Mt = c + at 1/2 + b[1 - exp(-nt)], which corroborates that the release occurs according to the model proposed. by means of three discrete mechanisms, namely: (i) a short-term initial elution due to the imperfections in the poly(methyl methacrylate) covering of the most external GS beads, burst effect by the buffer solution; (ii) followed by a fracture by stress cracking in an active media of the coated GS beads located on the external surface of the matrix where water molecules enter to dissolve GS molecules releasing them into the buffer solution by a diffusion-controlled process; and (iii) a third process in which the buffer solution penetrates into the internal voids and cracks creating a series of channels in a labyrinthic structure, which may facilitate the access of water molecules to the plastic-coated GS beads within the bulk matrix. This third process is enhanced by the incorporation of PVP beads as dissolved molecules within the matrix. This water-soluble additive is leachable, generating a highly porous structure in the cement. This HEMA and PVP modified cement may be used as a drug delivery system to modulate the GS release rate.

Anti-Bacterial Agents↗

Gentamicin bone cements: characterisation and release (in vitro and in vivo assays).

Due to the extended use of acrylic bone cements, its necessary to develop improved formulations in order to resolve their many drawbacks. The present work was conducted to make a physical-chemical characterisation of this kind of acrylic cement in order to introduce future changes in the formulations to: (1) improve or at least maintain their mechanical properties; (2) diminish their toxicity, and (3) control the drug release (rate and amount). From the dissolution method we can conclude that the preparation method (with or without pressure) of specimens is not responsible for the erratic release. The cumulative amount of gentamicin released was fitted to a semi-empirical equation to explain the possible release mechanism. The powder size, shape and distribution that could affect several properties of bone cement were studied with the aid of different techniques such as SEM, laser diffraction spectroscopy, and powder X-ray diffraction. From SEM micrographs, it was possible to observe that the surfaces of the specimens were very irregular with numerous small craters that may serve as conduits for eluting the antibiotic. An 'in vitro' drug diffusion model is proposed to elucidate the drug release mechanism. Finally an 'in vivo' study was performed to evaluate the antibiotic release to the neighbouring bone sites.

Acrylic Resins↗

Lyophilized lecithin based oil-water microemulsions as a new and low toxic delivery system for amphotericin B.

PURPOSE: To develop and investigate lecithin based oil-water microemulsions as potential amphotericin B (AmB) delivery systems and to evaluate their in vivo acute toxicity. METHODS: AmB was added to the microemulsion and its location was evaluated by partitioning studies and UV-visible spectrophotometric analysis of the drug. Both, non-lyophilized and reconstituted microemulsions were characterised and assessed for their stability. Single-dose acute toxicity of the AmB microemulsion was studied on male albino Webster-derived CD-1 mice and compared with Fungizone. RESULTS: The studies performed showed that AmB was intercalated on the oil-water interface of the microemulsion as a complex formed with lecithin molecules. AmB addition did not seem to modify the rheological properties of the original system, but had an effect on its particle size distribution. Lyophilization of the microemulsion led to an oily cake, easily reconstituted and stable at the conditions studied. Single-dose acute toxicity studies proved that the LD50 of AmB microemulsions was of 4 mg kg(-1) of animal weight, compared with 1 mg kg(-1) found for Fungizone. CONCLUSIONS: Lyophilized lecithin based oil-water microemulsions appear to be valuable systems for the delivery of AmB in terms of easy and low-cost manufacturing, stability and safety compared with the formulations already in market.

Amphotericin B↗

In vitro release of metoclopramide from hydrophobic matrix tablets. influence of hydrodynamic conditions on kinetic release parameters.

There has been growing interest in the subject of drug delivery and the design and evaluation of controlled-release systems. The simplest way to control the release of an active agent is to disperse it in an inert polymeric matrix. Controlled-release systems are of interest because they are technologically simple, relatively cheap, and practically unaffected by physiological changes. In this study, a new matrix system was formed by an active principle, metoclopramide hydrochloride, scattered into a biocompatible hydrophobic polymerical mesh, polyamide 12, to achieve sustained and controlled delivery of metoclopramide hydrochloride. This research was conducted to investigate the in vitro drug release behavior from these new inert polymeric matrix tablets. The drug release process was investigated both experimentally and by means of mathematical models. Different models were applied for the evaluation of drug release data. On the basis of our results, a biexponential equation was proposed, Q=Qfast(1)(1 - e(-Kfast t)) + Qslow(2)(1 - e(-Kslow t)), in an attempt to explain the mechanism responsible for the release process. Additionally, the influence of the experimental conditions of the dissolution devices, such as rate of flow and pH of dissolution medium, on the parameters that characterize the release mechanism was studied, and it was found that the main factor was the hydrodynamic condition of rate of flow.

Algorithms↗

A validated quantitative colorimetric assay for gentamicin.

A colorimetric procedure was developed for the quantification of gentamicin. The method was based on the ninhydrin reaction with primary and secondary amines present in the gentamicin. This reaction produces a purple colour. The effects of several factors including pH, ninhydrin concentration and reaction time were investigated to optimize the assay method. Using the assay protocol, the absorption of the gentamicin-ninhydrin mixtures at 400 nm had a linear relationship with the gentamicin concentration ranging from 30 to 120 microg/ml. The colorimetric gentamicin assay reported herein is of great practical value because it is reproducible, sensitive, simple and extremely inexpensive.

Colorimetry↗

Comparison of UV spectrophotometric and LC methods for the determination of nortriptyline hydrochloride in polysorbate 80 based oil/water (o/w) microemulsions.

A new rapid, reliable and specific UV spectrophotometric method was developed for the determination of nortriptyline hydrochloride formulated into o/w microemulsions. The UV spectra of nortriptyline standard solution in methanol and placebo (microemulsion without nortriptyline) were recorded over the wavelength range 200-600 nm and the spectra for placebo and nortriptyline loaded microemulsion were recorded over the range 260-400 nm in order to determine the overlapping that might appears, and hence to set the wavelength that could be used for the quantitative analysis. This method was validated and compared with a liquid chromatography (LC) procedure used for the quantitative analysis of the drug. Both methods showed excellent precision and accuracy with RSD values of 2.37 and 1.41%, respectively, for the LC method, and values of 1.24 and 2.88%, respectively, for the UV spectrophotometric method. The established linearity range was 10-50 microg ml(-1) (r2 = 0.9985) and 20-60 microg ml(-1) (r2 = 0.9979) for the HPLC and UV spectrophotometric methods respectively. The recoveries of nortriptyline from spiked placebos were > 95% for both methods over the linear range. The methods have been successfully used for determining the nortriptyline content of microemulsions and for evaluating the chemical stability of the drug in nortriptyline-loaded microemulsions.

Antidepressive Agents, Tricyclic↗

Release of nortriptyline hydrochloride from oil-water microemulsions.

The release of nortritptyline hydrochloride from oil-in-water (o/w) microemulsions (isopropyl myristate as oil, propylene glycol as cosurfactant, polysorbate 80 as surfactant and phosphate buffer, pH 7.4, as the continuous phase) containing increasing concentrations of polyethylene glycol 400, used to facilitate the diffusion of a drug from the inner oily phase of the microemulsion to the outer aqueous phase of such a dispersion system, was studied by determining the permeability constants of the drug through hydrophilic and lipophilic membranes separating the o/w microemulsions from the receiving aqueous phase (phosphate buffer pH 7.4). The permeability of nortriptyline hydrochloride from microemulsions through the lipophilic membrane increased as the concentration of polyethylene glycol 400 in the disperse system increased. The apparent permeability constant for nortriptyline hydrochloride, from the microemulsion without polyethylene glycol, was 1.36 x 10(-3) cm x h(-1), it increased up to 7.80 x 10(-3) cm x h(-1) in the presence of polyethylene glycol at a concentration of 50% (v/v) of the initial volume of the aqueous phase.

Adrenergic Uptake Inhibitors↗

The effect of rumen adaptation to oxalic acid on selection of oxalic-acid-rich plants by goats.

Rumen microbial degradation is an important route for detoxification of secondary plant compounds encountered in the diets of free-grazing ruminants. Exposure to diets containing particular secondary plant compounds can lead to increased rates of secondary compound degradation in the rumen. An experiment was conducted to determine whether rumen adaptation to oxalic acid would influence the diet selection of goats offered choices between plant species differing in their oxalic acid content. Twelve adult female goats were divided into two groups of six animals each. One group received a daily oral dose, in gelatin capsules, of 0.6 mmol oxalic acid/kg live weight per d throughout the experiment while the other group received placebos consisting of empty gelatin capsules. After an adaptation period of 8 d, the animals were allowed to graze a mixture of spinach (rich in oxalic acid) and cabbage (low in oxalic acid) for 7 h/d on two consecutive days per week during four consecutive 1-week periods. Intervening days were spent on grass pasture. Diet composition and intake were measured using cuticular wax n-alkanes as internal markers. Results showed that adapted goats included a higher proportion of spinach in their diet (P < 0.05) although absolute intakes of spinach were the same for the two groups. Goats in the oxalic-acid-adapted group consumed less cabbage than control animals (P < 0.05) suggesting that adaptation to oxalic acid at the rumen level may have interfered with detoxification of cabbage-derived secondary plant compounds. Voluntary intake increased progressively through the four experimental periods (P < 0.001) with a tendency for higher intakes among control than among adapted animals (P < 0.1). The experiment demonstrates how differences in the rate of degradation of secondary plant compounds may influence diet selection in ruminants.

Adaptation, Physiological↗

Analysis of diclofenac sodium and derivatives.

There are two reasons explaining why several researchers have carried out the in vitro release studies of diclofenac sodium (DFNa) using pH media of above 6.5. Firstly the pH dependence of solubility, and secondly the intramolecular cyclization suffered under acidic conditions which causes the salt to become inactivated. Nevertheless, many commercially available pharmaceutical dosage forms have no protective coat to avoid the inactivation in the gastric juices. A possible explanation may be found if reconstitution of the cyclated form takes place. It is therefore necessary to study the behaviour of diclofenac sodium when it is submitted to the action of different solutions in a wide pH range. To perform this study five analytical methods have been employed: UV-vis spectrophotometry, differential scanning calorimetry (DSC), infrared analysis (IR), X-ray diffractometry (DRX) and energy dispersive X-ray analysis (EDS).

Anti-Inflammatory Agents, Non-Steroidal↗

A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis.

Analysis of a TnblaM mutant of Brucella suis 1330, identified as being unable to multiply in Hela cells, allowed us to identify a 11 860 bp region of the B. suis genome encoding a type IV secretion system, homologous to the VirB system of Agrobacterium tumefaciens and the Ptl system of Bordetella pertussis. DNA sequence revealed 12 open reading frames (ORFs) encoding homologues of the 11 VirB proteins present in the pTi plasmid of Agrobacterium with a similar genetic organization, and a twelfth ORF encoding a putative lipoprotein, homologous to a protein involved in mating pair formation during bacterial conjugation and to adhesins used by Pseudomonas species to bind to plant roots. Phylogenetic trees based on the sequences of VirB4 and VirB9 protein homologues suggest that evolution of the systems from DNA transfer towards protein secretion did not stem from a single event but that the protein secretion systems have evolved independently. Four independent mutants in virB5, virB9 or virB10 were highly attenuated in an in vitro infection model with human macrophages. The virulence was restored by complementation with a plasmid containing the full virB region. The virB region appears to be essential for the intracellular survival and multiplication of B. suis.

Agrobacterium tumefaciens↗

Preparation and in vitro characterization of gelatin microspheres containing Levodopa for nasal administration.

Transnasal absorption of pharmaceutical drugs has been recognized as an interesting alternative to the more conventional routes of administration. The aim of this paper was to develop a method of administrating L-dopa following the transnasal route. Gelatin microspheres were prepared by the w/o emulsification solvent extraction technique: the microspheres had a median particle size of 16.2 +/- 4.2 microm and were prepared using a stirring speed of 600 rpm for 5 min at 80 degrees C. The microspheres obtained were spherical and smooth-surfaced, and the microsphere size was inversely proportional to stirring speed (300-700 rpm) and to the percentage of the emulsifier (Tween 85, 1.4-2.7% v/v). L-dopa was incorporated into the microspheres with an efficiency of 65 +/- 6.7%. L-dopa was released from the microspheres, showing an initial fast release rate, followed by a second slower release rate.

Absorption↗

Solvent and plasticizer influences on ethylcellulose-microcapsules.

Variations in microencapsulation processes give rise to different products and it seems there are no firm rules. It is thus difficult to know what kind of product will be obtained before the research is carried out. Changes in temperature, rate, time and type of stirring can cause great modifications in the system, most of which are responsible for variations in standard techniques. In our study, we investigate the solvent influence on ethylcellulose (EC) microcapsule formation. We have selected four different solvents: ethanol as an aqueous solvent and acetone, chloroform and toluene as organic solvents. Diclofenac sodium (DFNa), a non-steroidal anti-inflammatory agent, has been used as an encapsulated substance as it is inactivated in the gastric juices. This polymer and microencapsulation process was selected after an exhaustive study with different polymers and processes. Once the solvent influence was determined, ethylphthalate was incorporated in one type of microcapsule in order to study the influence of this plasticizer on drug release by the modification of film-permeability.

Anti-Inflammatory Agents, Non-Steroidal↗