Total milk fat extraction and quantification of polar and neutral lipids of cow, goat, and ewe milk by using a pressurized liquid system and chromatographic techniques.

Although milk polar lipids such as phospholipids and sphingolipids located in the milk fat globule membrane constitute 0.1 to 1% of the total milk fat, those lipid fractions are gaining increasing interest because of their potential beneficial effects on human health and technological properties. In this context, the accurate quantification of the milk polar lipids is crucial for comparison of different milk species, products, or dairy treatments. Although the official International Organization for Standardization-International Dairy Federation method for milk lipid extraction gives satisfactory results for neutral lipids, it has important disadvantages in terms of polar lipid losses. Other methods using mixtures of solvents such as chloroform:methanol are highly efficient for extracting polar lipids but are also associated with low sample throughput, long time, and large solvent consumption. As an alternative, we have optimized the milk fat extraction yield by using a pressurized liquid extraction (PLE) method at different temperatures and times in comparison with those traditional lipid extraction procedures using 2:1 chloroform:methanol as a mixture of solvents. Comparison of classical extraction methods with the developed PLE procedure were carried out using raw whole milk from different species (cows, ewes, and goats) and considering fat yield, fatty acid methyl ester composition, triacylglyceride species, cholesterol content, and lipid class compositions, with special attention to polar lipids such as phospholipids and sphingolipids. The developed PLE procedure was validated for milk fat extraction and the results show that this method performs a complete or close to complete extraction of all lipid classes and in less time than the official and Folch methods. In conclusion, the PLE method optimized in this study could be an alternative to carry out milk fat extraction as a routine method.

Release-Recapture Test of Dispersal and Survival of Sterile Males of Ceratitis capitata (Diptera: Tephritidae).

The sterile insect technique is used around the world to suppress or eradicate populations of Ceratitis capitata (Wiedemann) with successful results. It consists of inundative releases of sterile insects into a wide area to reduce reproduction in a field population of the same species. It is necessary to know the dispersion of the sterile males in the field in order to define the maximum distance between the release points that ensures the distribution of the sterile flies in the entire target area. The release methods may vary depending on the area to be covered and the resources available. Manual ground release requires less technology. The aim of this research was to estimate the ability of sterile males to survive and disperse in the field, in the two main areas of citrus production in Uruguay. A release of 20,000 sterile males of C. capitata TslV8 (-inv D53) was performed at the central point of each area defined for the trials. Around these points, a network of 54 Jackson traps baited with trimedlure was installed forming five concentric rings, which were placed on days 1, 3, 5, and 7 after the release and were removed at 24 h in all cases. The emergence rate, flight ability, dispersion, and longevity were estimated. The standard distances obtained by the regression models were 127 m and 131 m for Salto and San José respectively. In Salto, the traps had catches until the eighth day, and in San José, there were no catches after the sixth day.

Therapeutic drug monitoring of tumour necrosis factor inhibitors in the management of chronic inflammatory diseases.

Tumour necrosis factor inhibitor therapy has drastically changed the management of chronic inflammatory diseases. Some important drawbacks that can cause loss of response during treatment with these drugs are related to their large individual variability, the disease burden and the formation of antidrug antibodies that increase its clearance. Therapeutic drug monitoring of these drugs is not yet recommended by all scientific societies, and if so, only in patients with inflammatory symptoms. Proactive therapeutic drug monitoring represents a new strategy with many potential clinical benefits, including the prevention of immunogenicity, a reduction in the need for rescue therapy and greater durability of tumour necrosis factor inhibitor treatment. The review is based on a systematic search of the literature for controlled trials, systematic reviews, experimental studies, guideline papers and cohort studies addressing the best practice in tumour necrosis factor inhibitor therapeutic drug monitoring. Although there is ample evidence supporting the use of therapeutic drug monitoring in clinical practice to achieve better outcomes, some challenges have been detected. Many studies are focused on finding solutions for the lack of standardization of analytical methods to measure tumour necrosis factor inhibitor and antidrug antibodies concentrations. Other challenges are development of effective cost-saving proactive algorithms to identify optimal drug concentrations and the research on the role of antidrug antibodies, especially in the management and prevention of loss of response. Therapeutic drug monitoring of tumour necrosis factor inhibitor offers a rational approach to the optimization of the treatment of chronic inflammatory disease. Although prospective controlled trials yield little conclusive evidence of its benefits, there is growing acceptance of its value in clinical practice.

[V debate forum of the SENPE. Current issues on home-based and ambulatory artificial nutrition]. / V Foro de Debate SENPE: Problemática actual de la nutrición artificial domiciliaria y ambulatoria.

A multidisciplinary and multiprofessional debate is established trying to detect and find plausible solutions regarding Home-based and Ambulatory Enteral Nutrition (HBAEN) in Spain, due to the little attention paid by the Administration to the global problem of hyponutrition, the little interest showed by the collectivity of health care professionals, and the lack of a regulation differentiating the patient at his/her home and the patient at a nursing home. It was concluded that the current legislation on Home Based Enteral Nutrition (HBEN) has been variedly applied and does not contemplate the real clinical health care, with some pathologies subsidiary of this kind of therapy being excluded. Proposals to improve both financing and pathologies irrespective of the kind of nutritional therapy are made.

Attraction of Male Nymphs to Adult Male Volatiles in the Bronze Bug Thaumastocoris peregrinus Carpintero & Dellape (Heteroptera: Thaumastocoridae).

The bronze bug, Thaumastocoris peregrinus Carpintero & Dellape (Heteroptera: Thaumastocoridae), is an exotic emerging pest in Eucalyptus commercial forests in South America, Africa and southern Europe. Information on the chemical communication system and reproductive ecology of this insect is scant, and it may be relevant for designing management strategies for eucalypt plantations. Adults and nymphs usually aggregate in the field, possibly by means of chemical signals. Males emit large amounts of 3-methyl-2-butenyl butyrate, which attracts conspecific adult males but not females. The ecological role of this putative male aggregation pheromone remains unknown. Here, we report olfactometer bioassays showing that late-instar male nymphs are also attracted to synthetic 3-methyl-2-butenyl butyrate and to adult male volatile extracts, which contain this compound as the major component. As previously shown for adult females, nymphs that moulted into females were not attracted to either volatile stimulus. The intra-gender attraction of nymphs and adults may be related to the exploitation of food resources, or as a reproductive strategy for newly emerged males. Further studies on the reproductive behaviour and mating system of T. peregrinus will contribute to understanding the ecological significance of male-male, adult-nymph attraction, as well as the practical applications that may result from these findings.

Comparative kinetic study of lipases A and B from Candida rugosa in the hydrolysis of lipid p-nitrophenyl esters in mixed micelles with Triton X-100.

(1) Lipases A and B from Candida rugosa catalyzing the hydrolysis of esters in micellar media have been characterized kinetically by studies on substrate specificity, rate equation forms and modeling of enzyme mechanisms. (2) The study on specificity revealed that both lipases are non-specific esterases with similar activity against lipid p-nitrophenyl esters micellized with Triton X-100. The slight difference was that lipase A has its maximum activity centered in the caprylate while that of lipase B is in the laurate. (3) Kinetic studies for both lipases were carried out with p-nitrophenyl laurate under three experimental conditions: (I) the molar fraction of substrate is fixed and the bulk concentration of substrate and Triton X-100 are varied; (II) the bulk concentration of substrate is held constant and the molar fraction of substrate and bulk concentration of Triton X-100 are varied; and (III) the bulk concentration of Triton X-100 is held constant but the bulk concentration of substrate and molar fraction of substrate are varied. (4) In case I, a similar Michaelis-Menten behaviour was observed with both lipases; the curve fitting gave kappcat/Kappm values of 3.0.10(5) and 5.6.10(5) s-1 M-1 for lipases A and B respectively. In case II, for both lipases the relationship between rate and the molar fraction of substrate required a fitting equation of 2:2 degree polynomial quotient. In case III, both lipases showed non-Michaelian behaviour with concave-up curves in the Eadie-Hofstee plot, a minimum degree of 2:2 in substrate concentration being detected for the rate equation. (5) The above results are interpreted in terms of the hypothesis that the mechanism of both lipases must include at least two different inputs for the molecule of substrate which would explain the quadratic terms observed in the rate equation.

[Cochlear implants in Aragón]. / Diez años de implantación coclear en Aragón.

Cochlear implants are, actually, one of the major advances in the treatment for profound deafness. His use is, already, a routine in the daily practice of our specialty. Due to its special aspects, cochlear implants have to be done following a protocol that organizes and coordinates the different aspects of the diagnoses and treatment of profound deafness, in the different administrative and geographical fields. The health system in our country and the smale dimension of our area, has taken us to create and follow a special program in which all the available resources are used. Following this protocol, we have performed 63 cochlear implants, in the last 10 years. We show here the results and complications.

Geostatistics and Geographic Information Systems to Study the Spatial Distribution of Grapholita molesta (Busck) (Lepidoptera: Tortricidae) in Peach Fields.

The oriental fruit moth, Grapholita molesta (Busck), is the most serious pest in peach, and several insecticide applications are required to reduce crop damage to acceptable levels. Geostatistics and Geographic Information Systems (GIS) are employed to measure the range of spatial correlation of G. molesta in order to define the optimum sampling distance for performing spatial analysis and to determine the current distribution of the pest in peach orchards of southern Uruguay. From 2007 to 2010, 135 pheromone traps per season were installed and georeferenced in peach orchards distributed over 50,000 ha. Male adult captures were recorded weekly from September to April. Structural analysis of the captures was performed, yielding 14 semivariograms for the accumulated captures analyzed by generation and growing season. Two sets of maps were constructed to describe the pest distribution. Nine significant models were obtained in the 14 evaluated periods. The range estimated for the correlation was from 908 to 6884 m. Three hot spots of high population level and some areas with comparatively low populations were constant over the 3-year period, while there is a greater variation in the size of the population in different generations and years in other areas.

Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies.

OBJECTIVE: This study evaluates the cost-effectiveness of vancomycin serum concentration monitoring in patients with hematologic malignancies. METHODS: The study was designed as a prospective randomized study. Seventy immunocompromised febrile patients with hematologic malignancies were randomly assigned to either a vancomycin therapeutic drug monitoring group (TDM group; n = 37) or to a control group (n = 33). Intervention in the TDM group involved patient follow-up by a clinical pharmacist to obtain and pharmacokinetically interpret serum vancomycin concentrations for dosage individualization. RESULTS: Evaluation of all patients included global clinical response and nephrotoxicity, as well as the economic costs and effectiveness derived from the vancomycin monitoring program. There were no significant differences between the TDM and control groups in the outcome measures, except for the incidence of nephrotoxicity: the rates of minor nephrotoxicity were 33.3% and 13.5% in the control and TDM groups, respectively. The corresponding figures for moderate nephrotoxicity were 9.1% and 0%. Logistic regression analysis confirmed that TDM independently reduced the incidence of nephrotoxicity in this patient population. On the basis of this reduced nephrotoxicity, a incremental cost of $435 per case of nephrotoxicity prevented was found for vancomycin serum concentration monitoring. CONCLUSIONS: A decreased incidence of nephrotoxicity provides evidence of a real clinical benefit to patient management in patients with hematologic malignancies. The TDM for vancomycin therapy in this high-risk population has been shown to be a cost-effective procedure.

Results of treatment with sodium sulbenicillin in thirty elderly patients with acute bronchopulmonary infection.

Thirty elderly patients with acute bronchopulmonary infections were treated with intravenous sodium sulbenicillin for up to 20 days at a dose of 4-6 g/day. Clinical results were excellent in 19 cases and good in 10 cases. In one case treatment had to be discontinued due to a dermal side-effect. It is concluded that sulbenicillin is a useful therapy for acute bronchopulmonary infections in the elderly.

Multicriteria decision analysis for determining drug therapy for intermittent claudication.

Drugs of various classes are prescribed for intermittent claudication. However, there is some discrepancy between medical practice and the scientific basis for drug selection. We have developed a quantitative criteria-based decision analysis to evaluate all implications of drug treatment choices for intermittent claudication. Pentoxifylline, buflomedil, naftidrofuryl and ticlopidine were the drugs selected for analysis. The evaluation criteria were 1) therapeutic efficacy, 2) safety, 3) patient acceptance and 4) cost. A review panel of experts determined the relative importance of each criterion by assigning points (or utility values) to each one. The points were 48, 20, 14 and 18, respectively, for criteria 1, 2, 3 and 4. A probability value, or numerical estimate of how well a drug meets a criterion, was assigned to each drug for each of the 4 criteria. The probability value was multiplied by the utility value to determine the score for each drug and criterion. The criteria points for each drug were added for a total score for the drug. The drug with the highest overall score was pentoxifylline, with 69 points out of an ideal score of 100. The rank order for the other drugs was buflomedil, ticlopidine and naftidrofuryl. A sensitive analysis showed that the relative ranking of the drugs remained unchanged over a series of data modifications.

[Cost-effectiveness of individualized enteral nutrition by a nutrition support team in laryngectomized cancer patients]. / Coste-efectividad de la nutrición enteral individualizada por un equipo de soporte nutricional en pacientes laringectomizados por neoplasia.

The purpose of this study was to evaluate the effectiveness of a Nutritional Support Team (NST) in the control and follow-up of enteral nutrition (EN) in patients subjected to laryngectomy as a result of neoplasia. The study was performed on two groups of patients (A and B) who had been admitted into the Otorhinolaryngological Department, and who required EN by nasogastric tube during the postoperative period. Group A consisted of 20 patients in whom EN was based on standard guidelines, with a daily intake of 11.1 g of Nitrogen and 2.000 kcals. Group B included 23 patients who received EN individually, using NST with a daily intake of Nitrogen of between 8 and 21 g, and energy intake of between 2.000 and 3.000 kcals. The total cost of nutrition was calculated using the following partial costs: diet, administration, laboratory analysis and NST head responsible for follow-up of Group B. Individualized EN was more effective in nutritional terms than a standard diet in all patients. Using this form of treatment, positive Nitrogen balance were achieved, levels of seric albumin were maintained as well as weight, and complications were reduced. The average cost of nutrition per patient in Group B was 46.258 pesetas and in Group A, 43.963 pesetas. However, in the latter Group, there was an average additional weight loss of 4 kg per patient, and an increase in cost effectiveness ratio of 573 pesetas in weight gained in Group B compared to Group A.

[Best practices for the safe use of parenteral nutrition multi-chamber bags. Spanish Society of Hospital Pharmacist's Clinical Nutrition Group]. / Buenas prácticas para el uso seguro de las bolsas tricamerales de nutrición parenteral.

Patient security is one of the key aspects of the Health-System. Parenteral Nutrition is included in the ISMP's list of high-alert medication, being its appropiate use an essential element in maximizing effectiviness while minimizing the potential risk of errors associated with its use. Multi-chamber bags offer several advantages versus pharmacy bespoke bags. However, their apparent simplicity may induce to misuse, asuming their use requires limited consideration, thus increasing the risk of potential errors. For this reason, the Spanish Society of Hospital Pharmacist's Clinical Nutrition Group considered it essential to develop a list of safety practices regarding the use of parenteral nutrition multi-chamber bags. These recommendations are based on practices globally accepted to diminish errors in PN therapy.

La seguridad del paciente es un aspecto clave de la asistencia sanitaria. La Nutrición Parenteral está incluida en la lista de medicamentos de alto riesgo del ISMP, siendo su uso apropiado un elemento esencial para maximizar su efectividad y minimizar el riesgo potencial de errores asociados con su empleo. Las bolsas tricamerales presentan numerosas ventajas frente a las elaboradas en los Servicios de Farmacia. Sin embargo, su aparente simplicidad puede inducir a un uso inadecuado de las mismas, al asumir que su utilización requiere considerar menos aspectos, incrementando con ello el riesgo potencial de errores. Por este motivo, el Grupo de Nutrición Clínica de la SEFH consideró necesario elaborar una relación de buenas prácticas para el uso seguro de las bolsas tricamerales de NP. Estas recomendaciones están basadas en prácticas globalmente aceptadas para disminuir los errores con el empleo de NP.

Pharmacokinetic monitoring of antiepileptic drugs.

Monitoring plasma levels of antiepileptic drugs for the treatment and prophylaxis of epilepsy is one of the strategies enabling clinical results to improve by reducing adverse affects and increasing effectiveness. The objective of this article is to review the basic aspects in the monitoring of antiepileptic drugs using a consensus document prepared and endorsed by the pharmacokinetics and pharmacogenetics working group (PK.gen) of the Sociedad Española de Farmacia Hospitalaria (Spanish Society of Hospital Pharmacists).

Time-dependent pharmacokinetics of cyclosporine (Neoral) in de novo renal transplant patients.

PURPOSE: A model for the large scale temporal trend in the oral bioavailability of microemulsion cyclosporine (Neoral) (CsA) is established, with dependence on post-(renal) transplantation day (PTD). METHODS: Twenty de novo adult renal transplant recipients were monitored for CsA administered orally q12 h. A model development group (11 patients, 315 blood concentration samples) was screened at 2 h (C(2); n = 92), 3 h (C(3); n = 56) and at predose troughs (C(min); n = 167) over periods of up to 75 days. The final model was tested in nine patients with C(min) (n = 580) monitored across 4-5 years. The doses varied between 100 and 538 mg with an apparent hyperbolic trend in C(2)/dose vs. PTD. A nonlinear mixed effects modelling (NONMEM) approach was used to obtain population and individual patient one-compartment pharmacokinetic (PK) parameters for oral CsA, which carry implicit the bioavailability (F). RESULTS: In the final PK model (PK-f) the F was modelled via a simple function for the temporal (days) trend of the bioavailability after transplantation as, F(f) = 1-alpha * exp(-lambda * PTD) resulting in a 28% reduction in the unexplained intra-individual variability. The population PK-f parameters were, for apparent clearance [mean, 95% confidence interval (interindividual CV%)] Cl/F(f) = 17.0 (13.8-20.2) L/h (27%), apparent central compartment volume of distribution, V/F(f) = 134 L (108-160) (28%), and lambda = 0.037/day (0.005-0.069) (120%). The absorption rate k(a) and the parameter alpha were approximated iteratively as 4/h and 0.62 respectively. The PK-f was structurally superior to the base model in explaining part of the within subject (occasion) variability and predicting the exposure surrogates C(2) and C(3). Also, the PK-f was better than the base model with Bayesian fitting of individual profiles in that group. CONCLUSION: The PTD-dependent relative bioavailability model provides a rational means of steering dose titration of CsA in de novo renal transplantation patients by removing the large scale PK adjustment signal, either through nomograms or as a Bayesian prior.

Interaction of naproxen with cholestyramine.

'In vitro' and 'in vivo' studies were used to determine the interaction of naproxen, an anti-inflammatory agent, and cholestyramine, a hypocholesterolemic substance. Cholestyramine shows a marked affinity for naproxen and the intensity of this is governed by the pH values. The maximum amount of naproxen adsorbed by the resin is close to 2.2 mM g-1. The pharmacokinetics of naproxen was studied in eight healthy volunteers after concurrent oral administration in a single dose of 250 mg of naproxen and 4 g of cholestyramine. The resin causes an important delay in the incorporation of naproxen into the systemic circulation, though no significant modifications are seen to take place in any other pharmacokinetic parameters of the drug.