Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I: Interspecies allometric scaling

A sample of 22 subjects was studied from a population of adults who had suffered from bacterial meningitis in childhood. Audiovestibular, oculomotor and neuropsychological investigations were performed and quality of life was assessed. An age-matched control group of 20 subjects was recruited. In the meningitis group, nine subjects had abnormal pure tone audiograms. One was previously undiagnosed and a progression was found in four. There was an overrepresentation of subclinical vestibular pathology (6 out of 9 (67%)) in this group. Audiovestibular test results showed a peripheral pattern and oculomotor tests were normal. The quality of life scores of those with hearing loss were significantly higher than those in the control group. Neuropsychological tests of brain dysfunction were abnormal in six out of 22 (27%) who had recovered from meningitis. The prevalence of such dysfunctions was not related to audiovestibular disorder. The quality of life scores of those with brain dysfunctions were similar to those of the control group. The findings of reduced auditory memory and tone level perception in four out of 22 (18%), suggest that lesions of central auditory pathways may follow from bacterial meningitis. The results support the idea that inner ear damage is the major cause of hearing loss after bacterial meningitis. Despite the absence of brainstem involvement, central nervous system lesions with disturbed auditory processing and language functions can be of significance. The high frequency of discrete brain dysfunctions indicate that a thorough neuropsychological investigation is required after bacterial meningitis.     

Overall efficiency evaluation of commercial distillation columns with valve and dualflow trays

The main objective of this work is to establish appropriated ways for estimating the overall efficiencies of industrial distillation columns with valve trays with downcomer and dualflow trays. The knowledge of efficiencies has fundamental importance in the design and performance evaluation of distillation columns. Searching in the literature, a tree of alternatives was identified to compose the tray efficiency model, depending on the mass transfer models, the liquid distribution and vapor flow models on the tray, the liquid entrainment model, the multicomponent mixture equilibrium model, the physical properties models, the height of froth on the tray model and the efficiency definition. In this work, different methods to predict the overall efficiency of distillation columns with valve and dualflow trays were composed and compared with data from three commercial distillation columns under different operating conditions. The models were inserted in the Aspen Plus 12.1 simulator, in Fortran language, together with tray geometrical data, fluid properties and operating data of the distillation columns. For each column, the best thermodynamic package was chosen by checking the temperature profile and overhead and bottom compositions obtained via simulation against the corresponding actual data of industrial columns. A modification in the fraction of holes evaluation that is jetting parameter of the Garcia's hydraulic model of dispersion above the tray was proposed. This modification produced better results than the original model to predict the fraction of holes that are jetting and in the efficiency of dualflow trays and similar results to Garcia model in the efficiency evaluation of valve trays. © 2010 American Institute of Chemical Engineers AIChE J, 2010     

Tensile behaviour of three-dimensional carbon-epoxy adhesively bonded single- and double-strap repairs

An experimental and numerical study of the tensile behaviour of three-dimensional carbon-epoxy adhesively bonded strap repairs is presented. Experimentally, the failure mode, elastic stiffness and strength were evaluated for different overlap lengths and patch thicknesses. The numerical simulations, performed in ABAQUS^®, allowed obtaining the elastic stiffness and the patch debonding load, used to understand the repairs behaviour. The adhesive layer was simulated with cohesive elements including a mixed-mode cohesive damage model with trapezoidal traction-separation laws in pure modes I and II, to account for the ductile behaviour of the adhesive used. These laws were determined by an inverse method, which consists on the estimation of the cohesive parameters with a fitting procedure of the experimental and numerical load–displacement curves of the respective fracture characterization test. The pure mode III cohesive law was equalled to the pure mode II one. This numerical methodology was found adequate to reproduce the experimentally observed behaviour of these repairs.     

Nanocomposite piezoelectric films of P(VDF‐TrFE)/LiNbO3

Piezoelectric films were prepared by incorporation of lithium niobate (LiNbO₃) nanoparticles into copolymer of vinylidene difluoride and trifluoroethylene. Nanoparticles of LiNbO₃ with ferroelectric phase were successfully synthesized and dispersed homogenously by ultrasonication in the copolymer matrix without any surfactant or surface functionalization. The nanocomposites were fully characterized by electronic microscopy, X‐ray diffraction, differential scanning calorimetry, dynamical mechanical analysis, and piezometer. Surprisingly, the copolymer matrix crystallinity and morphology were not affected by the incorporation of nanoparticles. Therefore the nanocomposites remained good mechanicals properties and high ferroelectricity coupled to nonlinear optical activity thanks to the noncentro symmetric space group of lithium niobate. This could be a novel approach to develop new multifunctional materials. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Evaluation of an educational program for asthma control in adults

We have developed a 6-month educational plan associated with outpatient follow-up and special clinical care for asthmatic patients in a deprived population, with serious socioeconomic problems and a very low level of education. The objective was to determine the effects of the program on clinical asthma outcomes, lung function, and quality of life. Forty patients were enrolled in the program with a regular schedule of outpatient visits, and 31 finished the 6-month intervention, which included information about asthma, instruction in appropriate use of medication, training in metered-dose inhaler technique, how to identify and control asthma triggers, how to use symptom diary cards, and how to recognize early signs of deterioration. Patients included 8 males and 23 females, 47.8 +/- 16.5 years old, with 77.4% elementary school education and 22.6% illiterate, and an average monthly income of around $450. After the 6-month program there was a significant change in asthma control with a reduction in asthma emergency visits and hospitalization, reduction of score symptoms, and improvement in quality of life. Based on the results, educational programs are recommended and should be adapted to the socioeconomic and cultural characteristics of the target population.     

Photodegradation of psychiatric pharmaceuticals in aquatic environments--kinetics and photodegradation products

Benzodiazepines are widely consumed psychiatric pharmaceuticals which are frequently detected in the environment. The environmental persistence and fate of these pharmaceuticals as well as their degradation products is of high relevance and it is, yet, scarcely elucidated. In this study, the relevance of photodegradation processes on the environmental persistence of four benzodiazepines (oxazepam, diazepam, lorazepam and alprazolam) was investigated. Benzodiazepines were irradiated under simulated solar irradiation and direct and indirect (together with three different fractions of humic substances) photodegradation kinetics were determined. Lorazepam was shown to be quickly photodegradated by direct solar radiation, with a half-life time lower than one summer sunny day. On the contrary, oxazepam, diazepam and alprazolam showed to be highly resistant to photodegradation with half-life times of 4, 7 and 228 summer sunny days, respectively. Apparent indirect and direct photodegradation rates are of the same order of magnitude. However, humic acids were consistently responsible for a decrease in the photodegradation rates while fulvic acids and XAD4 fraction caused an enhancement of the photodegradation. Overall, the results highlight that photodegradation might not be an efficient pathway to prevent the aquatic environmental accumulation of oxazepam, diazepam and alprazolam. Also, nineteen direct photodegradation products were identified by electrospray mass spectrometry, the majority of which are newly identified photoproducts. This identification is crucial to a more complete understanding of the environmental impact of benzodiazepines in aquatic systems.     

Leucine transport in Xenopus laevis oocytes: functional and morphological analysis of different defolliculation procedures

L-leucine uptake in stage V Xenopus laevis oocytes was affected by the specific methods used to remove the follicle cells. In the presence of 100 mM NaCl, L-leucine uptake was reduced by 67.5% +/- 5.7 when defolliculation was performed enzymatically by collagenase treatment, whereas the reduction was 30.5% +/- 6.4 after mechanical defolliculation. The Na(+)-dependent uptake of 0.1 mM L-leucine was 18.6 +/- 4.6 pmol oocyte-1 40 min-1 in folliculated oocytes and 5.6 +/- 1.9 in collagenase defolliculated oocytes (means +/- SE). L-leucine uptake was not affected by the removal of the follicular layer if defolliculation occurred after the transport period; radiolabeled L-leucine is therefore not taken up into a compartment that is removed by the defolliculation process. The different L-leucine uptake rates observed in folliculated and defolliculated oocytes were not due to non-specific L-leucine binding to membranes. L-leucine kinetics showed that the L-leucine Vmax and Km values were lower in oocytes deprived of the follicular layer than in control oocytes enveloped in intact follicular layers. The Vmax and Km values of Na(+)-dependent L-leucine transport, calculated from data obtained the day after defolliculation by collagenase treatment, were: 16 +/- 1.5 pmol oocyte-1 40 min-1 and 57 +/- 21 mumol (mean +/- SD). The Na(+)-activation curve of 0.1 mM L-leucine was hyperbolic in folliculated oocytes and sigmoidal in defolliculated oocytes. The morphological analysis performed in parallel with the transport experiments showed that after defolliculation, the fibers forming the vitelline membrane tended to be arranged in a more regular orthogonal array, and the number of oocyte microvilli was reduced after collagenase treatment. Mechanical defolliculation did not appreciably affect the oocyte microvilli, however this procedure did not completely remove all follicle cells. The damage to collagenase treated oocytes was reversible, and the functional and structural features of most oocytes improved upon subsequent in vitro incubation. The recovery process seemed to involve protein synthesis in view of the increased value of L-leucine Vmax, and microscopic observation showing recovery of the microvillar apparatus.     

Monitoring eosinophil activation and liver function after liver transplantation

BACKGROUND: Portal tract eosinophil infiltration and an increase in the blood eosinophil count (EOS) have been shown to be specific markers of liver allograft rejection. The graft eosinophil infiltration is associated with the local release of eosinophil cationic protein. Therefore, serum eosinophil cationic protein concentration (ECP) is a potential marker for acute allograft rejection. We investigated the chronological relationship among and diagnostic value of serial changes in EOS, ECP, and liver function tests (LFTs) following liver transplantation. METHODS: EOS, ECP, serum alpha-glutathione S-transferase concentration, and conventional LFTs were measured in serial samples collected over the first 3 postoperative months following 58 liver transplants. The diagnostic potential of each test, alone or in combination, was reviewed over the entire follow-up period. RESULTS: EOS and ECP increased at a median period of 3.5 and 4 days, respectively, before the diagnosis of acute rejection, and this increase was significantly earlier than the corresponding changes in LFTs (P<0.05). There was a significant correlation between the day of the first increase in EOS and alpha-glutathione S-transferase (rs=0.535; P=0.009) and EOS and alanine transaminase (rs=0.629; P=0.004). The optimum combination of tests for the diagnosis of acute rejection was an increase in both EOS and GST with a predictive efficiency of 84%. CONCLUSIONS: Increases in EOS and ECP are early indicators of acute liver allograft rejection and precede evidence of hepatocellular damage. However, an increase in ECP was also frequently associated with infection. Therefore, we recommend the regular monitoring of EOS in conjunction with routine LFTs after liver transplantation as an aid to the early diagnosis of acute rejection.