Membrane-coated fiber array approach for predicting skin permeability of chemical mixtures from different vehicles.

A membrane-coated fiber (MCF) array approach was developed for quantitative assessment of skin absorption from chemical mixtures, which was based on the similarity in the absorption mechanisms of the MCF membrane and the stratum corneum of the skin. A set of probe compounds were used to detect the relative molecular interaction strengths of chemicals with the vehicle and the membranes, which provided a linkage between the skin permeability (log k) and MCF partition coefficients (log KF). A predictive model was established via multiple linear regression analysis of the data matrix of experimentally measured log k value and log KFm values; log k=a0+a1 log KF1+a2 log KF2+...+an log KFm, where m is the number of diverse MCFs. Twenty-five probe compounds and three MCFs (polydimethylsiloxane for lipophilic, polyacrylate for polarizable, and CarboWax for polar interactions) were used to demonstrate the model development processes in the MCF array approach. The skin permeability of the probe compounds was measured with conventional diffusion cell experiments using dermatomed porcine skin. Three predictive models were established for skin permeability prediction from chemical mixtures in water, 50% ethanol, and 1% sodium lauryl sulfate (SLS) with R2 values of 93, 91, and 83, respectively. The log k and log KF values were considerably altered by the addition of ethanol or SLS into the dose vehicle; however, their correlations to skin permeability remained strong under various conditions. These results suggested that the experimentally based MCF array approach can be used to predict skin absorption from chemical mixtures in different vehicles or formulations.     

Linitis plástica primaria rectal

Primary linitis plastica of the rectum is an infrequent and unusual rectal carcinoma. We report a new case that presented clinically as a haemorrhoidal syndrome. We comment on the characteristics--clinical picture and histopathology--of this uncommon presentation of rectal tumour, as well as its clinical history and prognosis taking into account that the literature consulted indicated the unusualness of primary linitis plastica of the rectum.     

Categorization and deductive reasoning: predictors of instrumental activities of daily living performance in adults with brain injury.

OBJECTIVE: The purpose of this study was to examine the predictive relationship of categorization and deductive reasoning abilities to performance of instrumental activities of daily living (IADL) among adults with brain injury. METHOD: A correlational research design was used to examine the performance of 19 patients from a neurosurgery acute care unit on Toglia's Category Assessment (TCA), the Deductive Reasoning test (DR), and the Observed Tasks of Daily Living-Revised. RESULTS: Multiple regression analysis indicated that categorization and deductive reasoning accounted for a significant proportion of the variance in IADL performance scores, with deductive reasoning making the greater contribution. Demographic characteristics such as age and education reduced the power of the previous variables, especially of the categorization. CONCLUSION: The results of this study indicate that assessments of categorization and deductive reasoning abilities of persons with brain injury may be good predictors of IADL functional performance. Results support the use of the TCA and DR as quick measures of a person's cognitive and functional abilities. Furthermore, this study provides preliminary results to support that categorization and deductive reasoning abilities are fundamental for the performance of IADL skills.     

Nocturnal melatonin plasma levels in patients with OSAS: the effect of CPAP.

Melatonin is a pineal hormone that regulates the human cycle of sleep and wakefulness. Plasma melatonin levels were investigated in patients with obstructive sleep apnoea syndrome (OSAS). In total, 20 patients with OSAS and 11 healthy controls were studied. OSAS patients were tested twice: on the night of diagnostic polysomnography and the night of continuous positive airway pressure (CPAP) titration. Controls were tested on one occasion. Plasma melatonin levels were determined at 23:00 h (light period), at 02:00 h (dark period) and at 06:00 h (light period) in patients and control subjects using the radioimmunoassay method. The control subjects showed a nocturnal melatonin peak value at 02:00 h (70.6+/-14 pg.mL(-1)). However, this nocturnal melatonin peak was absent in the OSAS patients. The highest melatonin value was found in OSAS patients on the night of diagnosis, at 06:00 h (49.3+/-36.8 pg.mL(-1)). It was found that the melatonin level in OSAS patients at 06:00 h was significantly lower in the night of titration (35.6+/-37.9 pg.mL(-1)) than in the diagnosis night. However, the melatonin levels at either 23:00 h or 02:00 h in OSAS patients did not differ significantly when comparing levels in the night of diagnostic polysomnography (23:00 h: 31.6+/-29.8 pg.mL(-1); 02:00 h: 47.4+/-33.8 pg.mL(-1)) with levels in the night of CPAP titration (23:00 h: 20.2+/-10.3 pg.mL(-1); 02:00 h: 37.7+/-27.5 pg.mL(-1)). Patients with obstructive sleep apnoea syndrome have an abnormal melatonin secretion pattern. The absence of a nocturnal serum melatonin peak could be partially related to the difficulty that these patients have in achieving a normal sleep-wakefulness pattern.     

3He MRI in mouse models of asthma.

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) (3)He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such (3)He imaging of MCh response in mice, where voxels must be approximately 3000 times smaller than in humans and (3)He diffusion becomes an impediment to resolving the airways. We show three-dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 microm(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 microm(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of (3)He MRI to mouse models should make it a valuable translational tool in asthma research.