Critical mass for a Patlak-Keller-Segel model with degenerate diffusion in higher dimensions

"Vegeu el resum a l'inici del document del fitxer adjunt."

Evolution of holometabola insect digestive systems: physiological and biochemical aspects

This review takes into account primarily the work done in our laboratory with insects from the major Holometabola orders. Only the most significant data for each insect will be presented and a proposal on the evolution of Holometabola insect digstive systems will be advanced.

Immunological aspects of host-schistosome relationships

The complex immunological relationships between schistosomes and their vertebrate hosts are considered to be conveniently divisible into four distinct, though interrelated categories: the parasite's vulnerability to, its evasion of, and its exploitation of the host's immune response, and its stimulation of the host's immune response to produce immunopathology. Some significant recent advances in the first three categories are discussed, as well as their relationships to the fourth category of immunopathology.

Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia.

Objectives Nosocomial Pseudomonas aeruginosa pneumonia remains a major concern in critically ill patients. We explored the potential impact of microorganism-targeted adjunctive immunotherapy in such patients. Patients and methods This multicentre, open pilot Phase 2a clinical trial (NCT00851435) prospectively evaluated the safety, pharmacokinetics and potential efficacy of three doses of 1.2 mg/kg panobacumab, a fully human monoclonal anti-lipopolysaccharide IgM, given every 72 h in 18 patients developing nosocomial P. aeruginosa (serotype O11) pneumonia. Results Seventeen out of 18 patients were included in the pharmacokinetic analysis. In 13 patients receiving three doses, the maximal concentration after the third infusion was 33.9 ± 8.0 μg/mL, total area under the serum concentration-time curve was 5397 ± 1993 μg h/mL and elimination half-life was 102.3 ± 47.8 h. Panobacumab was well tolerated, induced no immunogenicity and was detected in respiratory samples. In contrast to Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction, all 13 patients receiving three doses survived, with a mean clinical resolution in 9.0 ± 2.7 days. Two patients suffered a recurrence at days 17 and 20. Conclusions These data suggest that panobacumab is safe, with a pharmacokinetic profile similar to that in healthy volunteers. It was associated with high clinical cure and survival rates in patients developing nosocomial P. aeruginosa O11 pneumonia. We concluded that these promising results warrant further trials.

Schistosomiasis mansoni: immunodiagnosis aspects and search for an immunological marker related to therapeutic efficacy

The recent findings on immunodiagnosis of schistosomiasis mansoni have shown that purified Schistosoma mansoni antigens do not provide maximum positivity. Therefore, the authors suggest the use of semi-purified antigens for diagnostic purposes. So far, no serological marker for cured patients as shown by negative stool examination was found. However, a tendency of IgG antibody titre decrease was observed, when egg antigen was used.

Biological aspects of the DM28C clone of Trypanosoma cruzi after metacylogenesis in chemically defined media

The biological characterization of the Trypanosoma cruzi clone Dm 28c in terms of its growth in LIT medium, cell-cycle, infectivity to mice and interaction with professional and non-professional phagocytic cells shows that it behaves as a bona fide T. cruzi representant. The biological properties of this myotropic clone do not change according to the origin of the trypomastigote forms (i. e., from triatomines, infected mice, cell-culture or from the chemically defined TAUP and TAU3AAG media). In addition Dm 28c metacyclic trypomastigotes from TAU3AAG medium display a high infectivity level to fibroblasts and muscle cells. Experiments on binding of cationized ferritin to trypomastigotes surface show the existence of cap-like structures of ferritin in regions near the kinetoplast. However the nature and role of these anionic sites remain to be determined. The results indicate that metacyclic trypomastigotes from Dm 28c clone obtained under chemically defined conditions reproduce the biological behaviour of T. cruzi, rendering this system very suitable for the study of cell-parasite interactions and for the isolation of trypanosome relevant macromolecules.

Development and current use of parenteral nutrition in critical care - an opinion paper.

Critically ill patients depend on artificial nutrition for the maintenance of their metabolic functions and lean body mass, as well as for limiting underfeeding-related complications. Current guidelines recommend enteral nutrition (EN), possibly within the first 48 hours, as the best way to provide the nutrients and prevent infections. EN may be difficult to realize or may be contraindicated in some patients, such as those presenting anatomic intestinal continuity problems or splanchnic ischemia. A series of contradictory trials regarding the best route and timing for feeding have left the medical community with great uncertainty regarding the place of parenteral nutrition (PN) in critically ill patients. Many of the deleterious effects attributed to PN result from inadequate indications, or from overfeeding. The latter is due firstly to the easier delivery of nutrients by PN compared with EN increasing the risk of overfeeding, and secondly to the use of approximate energy targets, generally based on predictive equations: these equations are static and inaccurate in about 70% of patients. Such high uncertainty about requirements compromises attempts at conducting nutrition trials without indirect calorimetry support because the results cannot be trusted; indeed, both underfeeding and overfeeding are equally deleterious. An individualized therapy is required. A pragmatic approach to feeding is proposed: at first to attempt EN whenever and as early as possible, then to use indirect calorimetry if available, and to monitor delivery and response to feeding, and finally to consider the option of combining EN with PN in case of insufficient EN from day 4 onwards.

Pharmacokinetic aspects of Tert-Butylaminoethyl disulfide, an experimental drug against schistosomiasis in mice

A preliminary study of the pharmacokinetic parameters of t-Butylaminoethyl disulfide was performed after administration of two different single doses (35 and 300 mg/kg) of either the cold or labelled drug. Plasma or blood samples were treated with dithiothreitol, perchloric acid, and, after filtration, submitted to further purification with anionic resein. In the final step, the drug was retained on a cationic resin column, eluted with NaCl 1M and detected according to the method of Ellman (1958). Alternatively, radioactive drug was detected by liquid scintillation counting. The results corresponding to the smaller dose of total drug suggested a pharmacokinetic behavior related to a one open compartment model with the following parameters: area under the intravenous curve (AUC i.v.):671 ± 14; AUC oral: 150 ± 40 µg.min. ml [raised to the power of -1]; elimination rate constant: 0.071 min [raised to the power of -1]; biological half life: 9.8 min; distribution volume: 0.74 ml/g. For the higher dose, the results seemed to obey a more complex undertermined model. Combining the results, the occurence of a dose-dependent pharmacokinetic behavior is suggested, the drug being rapidly absorbed and rapidly eliminated; the elimination process being related mainly to metabolization. The drug seems to be more toxic when administered I.V. because by this route it escapes first pass metabolism, while being quickly distributed to tissues. The maximum tolerated blood level seems to be around 16 µg/ml.

Evaluation of a summary score of cognitive performance for use in trials in perioperative and critical care.

Background/Aims: Cognitive dysfunction after medical treatment is increasingly being recognized. Studies on this topic require repeated cognitive testing within a short time. However, with repeated testing, practice effects must be expected. We quantified practice effects in a demographically corrected summary score of a neuropsychological test battery repeatedly administered to healthy elderly volunteers. Methods: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Assessment Battery (for which a demographically corrected summary score was developed), phonemic fluency tests, and trail-making tests were administered in healthy volunteers aged 65 years or older on days 0, 7, and 90. This battery allows calculation of a demographically adjusted continuous summary score. Results: Significant practice effects were observed in the CERAD total score and in the word list (learning and recall) subtest. Based on these volunteer data, we developed a threshold for diagnosis of postoperative cognitive dysfunction (POCD) with the CERAD total score. Conclusion: Practice effects with repeated administration of neuropsychological tests must be accounted for in the interpretation of such tests. Ignoring practice effects may lead to an underestimation of POCD. The usefulness of the proposed demographically adjusted continuous score for cognitive function will have to be tested prospectively in patients.