Localisation of drug permeability along the rat small intestine, using markers of the paracellular, transcellular and some transporter routes

The small intestine is the major site of drug absorption. Some reports in the literature have evoked the concept of “absorption windows” in the small intestine: are there specific regions where drug absorption is significantly higher than others? To investigate this question, we used an everted gut sac method to study the permeability of drugs and markers every 3–4 cm down the entire small intestine in rat. These markers were chosen to be representative of the mechanisms by which drugs cross the small intestinal mucosa: paracellular and transcellular passive diffusion, via influx transporters, and a drug (digoxin) that is effluxed from cells by P-glycoprotein (P-gp). The passive diffusion and influx transporter markers gave similar profiles with a plateau of permeability along the jejunum, and with the exception of L-Dopa, lower permeability in the ileum. Digoxin showed a linear decrease in the profile from the proximal jejunum to the ileum. Permeability in the duodenum was two to three times lower than the jejunum for all compounds. There were no narrow specific regions of high permeability and so the concept of discrete “absorption windows” along the small intestine as suggested from some pharmacokinetic studies may be related to other effects such as pH and/or solubility.     

Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood.

Recent reports have described neurobehavioral impairments in human subjects carrying a V66M polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF). Inasmuch as ventral nervous system (CNS) deficits associated with this BDNF polymorphism are similar to those observed among subjects with chronic exposure to elemental mercury (Hg degrees ), we examined the potential effect of this BDNF polymorphism on symptoms and mood in an established cohort of dental practitioners with chronic low-level Hg degrees exposure. Self-reported symptoms and mood were obtained by computerized questionnaire from 193 male dentists (DTs) and 230 female dental assistants (DAs). Spot urine samples were analyzed for mercury concentrations to evaluate recent exposure. Detailed work histories were obtained to calculate chronic indices of Hg degrees exposure. Buccal cell samples were obtained to identify the V66M polymorphism of BDNF. Scores for 11 current and 12 recent and chronic symptom groups, along with six mood factors, were evaluated with respect to recent and chronic Hg degrees exposure and BDNF polymorphism. Multiple regression analysis controlled for age, race, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for DTs and DAs. Twenty-three associations between recent or chronic Hg degrees exposure and BDNF status and self-reported symptoms were observed with p < 0.10. All but three were in the expected direction (symptom scores increasing with Hg degrees exposure or BDNF polymorphism), and all but six were among DAs. All eight correlations between chronic exposure indices and recent and chronic symptoms among DAs were in the expected direction. All seven associations between BDNF and symptoms were in the expected direction and split between DTs and DAs. All three associations with mood factors were among DAs and in the expected direction. These results indicate that among DAs very low levels of occupational Hg degrees exposure are associated with increased symptoms. The BDNF polymorphism is also associated with increased symptom and mood scores. Notably, Hg degrees and BDNF polymorphism were additive with respect to their associations with the same symptom group.     

A home-based intervention for attentional slips during reading following head injury: A single case study

Abstract

In the absence of evidence of generalisation of computer-based attention training effects to everyday life, a single-case, goal setting methodology employing simple materials was used to train a head-injured subject to reduce the frequency of attention slips during reading. The intervention was carried out at home from 9–13 months post-injury, before the subject attempted to return to work. Training initially led to his being able to read a novel for 5 minutes without a slip when there was no distraction. Further training against background noise led to a statistically significant reduction in frequency of attention slips while reading a technical text, a measure used throughout the study.     

Infusion Phlebitis Assessment Scales: A Systematic Review of Their Use and Psychometric Adequacy

The American Society for Microbiology recommends a standard of 3% or less for blood culture contamination rates. The purpose of this study was to evaluate blood culture bundles on the blood culture contamination rates when blood culture was obtained through a central venous access device (CVAD). The study utilizes a non-experimental pre/post audit intervention design. The pre audit rates were compared to post audit rates of contamination after introduction of blood culture bundle. Mean results     

Adaptation in human somatosensory cortex as a model of sensory memory construction: a study using high-density EEG

Adaptation in sensory cortices has been seen as a mechanism allowing the creation of transient memory representations. Here we tested the adapting properties of early responses in human somatosensory areas SI and SII by analysing somatosensory-evoked potentials over the very first repetitions of a stimulus. SI and SII generators were identified by well-defined scalp potentials and source localisation from high-density 128-channel EEG. Earliest responses (~20 ms) from area 3b in the depth of the post-central gyrus did not show significant adaptation to stimuli repeated at 300 ms intervals. In contrast, responses around 45 ms from the crown of the gyrus (areas 1 and 2) rapidly lessened to a plateau and abated at the 20th stimulation, and activities from SII in the parietal operculum at ~100 ms displayed strong adaptation with a steady amplitude decrease from the first repetition. Although responses in both SI (1–2) and SII areas showed adapting properties and hence sensory memory capacities, evidence of sensory mismatch detection has been demonstrated only for responses reflecting SII activation. This may index the passage from an early form of sensory storage in SI to more operational memory codes in SII, allowing the prediction of forthcoming input and the triggering of a specific signal when such input differs from the previous sequence. This is consistent with a model whereby the length of temporal receptive windows increases with progression in the cortical hierarchy, in parallel with the complexity and abstraction of neural representations.     

The relationship between knowledge of pain neurophysiology and fear avoidance in people with chronic pain: A point in time,observational study

Chronic pain is prevalent in the western world; however fear of pain often has a greater impact than the degree of initial injury. The aim of this study was to explore the relationship between knowledge of the neurophysiology of pain and fear avoidance in individuals diagnosed with chronic pain. Twenty-nine people with chronic musculoskeletal pain were recruited and completed questionnaires to determine their understanding of pain neurophysiology and the degree of their fear avoidance beliefs. There was an inverse relationship between knowledge of pain neurophysiology and the level of fear avoidance. Patients with higher pain knowledge reported less fear avoidance and lower perceived disability due to pain. There was no relationship with the educational level or compensable status for either variable. The findings suggest that fear avoidance is positively influenced by neurophysiology of pain education, so that a higher level of pain knowledge is associated with less activity-related fear. The clinical implication is that reducing fear avoidance/kinesiophobia using neurophysiology of pain education in people with chronic pain may provide an effective strategy to help manage fear avoidance and related disability in the chronic pain population in order to improve treatment outcomes.