Maintenance of corneal endothelial cell shape by prostaglandin E2: effects of EGF and indomethacin

Confluent, cultured, rabbit corneal endothelial cells maintain a polygonal shape which is characteristic of these cells in vivo. When cultured in the presence of EGF (10 ng/ml) and/or indomethacin (1.0 microM), the endothelial cells have markedly different shapes at confluency. By morphometry, untreated cells are polygonal and have a maximum axis of 33 mu; EGF treatment causes a spindle-shaped elongation to 48 mu and indomethacin treatment causes a stellate-shaped elongation to 48 mu. There is a slight increase in cell density. When cells are cultured in the presence of both drugs, elongation is more pronounced to a fibroblastic appearing cell population, with maximum axes of 60 mu and more, but no additive increase in cell density. Continuity of cell borders is often lost. Corneal endothelial cells cultured in the presence of EGF, indomethacin, and PGE2 (0.5 microgram/ml) maintain their polygonal shape; PGF2 alpha is not effective at reversing the drugs' effects. Untreated and EGF-treated cells synthesize and release substantial quantities of PGE2 (2-4 ng/10(4) cells). Indomethacin completely inhibits PGE2 synthesis. It is concluded that PGE2 maintains the polygonal cell shape of the corneal endothelium in vitro and, perhaps, in vivo. The elongated forms of the cell may be related to migration and important in wound closure.     

Comparison of the effects of vigabatrin, lamotrigine, and topiramate on quantitative EEGs in patients with epilepsy

Information on the effects of newer antiepileptic drug (AEDs) on the electroencephalogram (EEG) is sparse and contradictory. Quantitative EEG (qEEG) provides a method of estimating the effects of drugs on the central nervous system. Twenty-three adult patients with difficult-to-control complex partial seizures, with or without secondary generalization, participated in an add-on study with one of three newer AEDs: vigabatrin (n = 10), lamotrigine (n = 6), and topiramate (n = 7). Frequency analysis and topographic mapping of awake EEGs before and during treatment with the drug were compared. Statistical analysis was performed using 2-way analysis of variance (ANOVA) with repeated measures. Vigabatrin administration was followed by a diffuse decrease in the absolute alpha (p < 0.05) and beta (p < 0.02) activities and a decrease in the absolute theta in the frontal and parieto-occipital regions (p < 0.03). Lamotrigine caused a significant diffuse increase in the faster frequencies (relative alpha p < 0.04 and relative beta p < 0.02), and decrease in the slower activities (relative theta in the posterior head regions p < 0.03 and relative delta diffusely p < 0.05). Topiramate increased the absolute beta (p < 0.05) and theta (p < 0.02) activities diffusely and decreased the relative alpha activity over the left hemisphere (p < 0.03). The different effect profiles of the newer AEDs on the electrical brain activity may reflect their different mechanisms of action.     

Drinking patterns and harm of unrecorded alcohol in Russia: a qualitative interview study

Background: Consumption of unrecorded alcohol (alcohol, consumed as a beverage, but not reflected in official statistics) has been linked to heavy drinking and alcohol-related mortality in Russia, with different studies looking for possible toxic components or other explanations. This study explores self-reported drinking behaviors of people diagnosed with alcohol dependence to elicit the perspectives of consumers of unrecorded alcohol.

Methods: Semi-structured in-depth expert interviews were conducted with patients (n?=?25) of state-run addiction treatment centers of two Russian cities. Interviews were analyzed using thematic content analysis.

Results: A strict hierarchy between different types of unrecorded alcohol products, their ascribed quality, and the subjective harm caused by their consumption was found, with home-made spirits for own consumption at the top and technical fluids at the bottom. The ranking order correlated with product price, social status of associated consumers, and severity of their alcohol dependence. Binge drinking was the prevailing drinking pattern and shifts from recorded to unrecorded consumption within a single binge or a zapoi (continuous drinking for at least two days) were typical. Consumption of low-quality unrecorded alcohol was associated with stronger hang-overs, zapois, alcohol psychoses and poisonings, and other indicators of alcohol attributable harm, while no such connection was found for spirits for own consumption.

Conclusions: In the dominant explanation patterns of the consumers, the experienced alcohol-induced harm is attributed to alcohol quality, while a thorough analysis of their reported drinking behaviors cannot exclude specific drinking patterns linked to the severity of alcohol dependence as the main determinants of the described health detriments.     

Polyelectrolyte biomaterial interactions provide nanoparticulate carrier for oral insulin delivery

Nanospheres are being developed for the oral delivery of peptide-based drugs such as insulin. Mucoadhesive, biodegradable, biocompatible, and acid-protective biomaterials are described using a combination of natural polyelectrolytes, with particles formulated through nanoemulsion dispersion followed by triggered in situ gel complexation. Biomaterials meeting these criteria include alginate, dextran, chitosan, and albumin in which alginate/dextran forms the core matrix complexed with chitosan and albumin coat. Smaller size and higher albumin-based acid-protective formulation was orally administered to diabetic rats and glucose reduction and physiological response analyzed. Insulin encapsulation efficiency was 90, 82, and 66% for uncoated, chitosan-coated, and albumin-chitosan-coated alginate nanospheres, respectively. The choice of coating polymer seems to influence insulin release profile and to be crucial to prevent peptic digestion. Physiological response following oral delivery showed that insulin albumin-chitosan-coated alginate nanospheres reduced glycemia ∼ 72% of basal values. Albumin serves as an important enteric coating providing acid- and protease protection enabling uptake of active drug following oral dosage.     

The Diagnosis of Delirium Superimposed on Dementia: An Emerging Challenge

Delirium occurring in patients with dementia is referred to as delirium superimposed on dementia (DSD). People who are older with dementia and who are institutionalized are at increased risk of developing delirium when hospitalized. In addition, their prior cognitive impairment makes detecting their delirium a challenge. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision are considered the standard reference for the diagnosis of delirium and include criteria of impairments in cognitive processes such as attention, additional cognitive disturbances, or altered level of arousal. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision does not provide guidance regarding specific tests for assessment of the cognitive process impaired in delirium. Importantly, the assessment or inclusion of preexisting cognitive impairment is also not addressed by these standards. The challenge of DSD gets more complex as types of dementia, particularly dementia with Lewy bodies, which has features of both delirium and dementia, are considered. The objective of this article is to critically review key elements for the diagnosis of DSD, including the challenge of neuropsychological assessment in patients with dementia and the influence of particular tests used to diagnose DSD. To address the challenges of DSD diagnosis, we present a framework for guiding the focus of future research efforts to develop a reliable reference standard to diagnose DSD. A key feature of a reliable reference standard will improve the ability to clinically diagnose DSD in facility-based patients and research studies.     

Language and stigmatization of individuals with mental health problems or substance addiction in the Netherlands: An experimental vignette study

Persons with mental health problems and/or substance addictions (MHPSA) are stigmatised more than persons with physical conditions. This includes stigmatisation by care professionals. Stigma is considered one of the most important barriers for recovery from these conditions. There is an ongoing debate that use of language can exacerbate or diminish stigmatisation. Therefore, we conducted an experiment examining how four different ways of referring to a person with (a) alcohol addiction, (b) drug addiction, (c) depression and (d) schizophrenia are related to stigmatising attitudes by care professionals in the Netherlands. We partially replicated two studies performed in the United States and used surveys with vignettes containing either ‘disorder‐first’, ‘person‐first’, ‘victim’ and ‘recovery’ language, which were randomly assigned to participants (n = 361). No significant differences between language conditions were found for any of the vignettes. Our findings suggest that subtle differences in language to refer to persons with mental health problems or substance addictions have no effect on stigmatising attitudes by care professionals in the Netherlands. However, more research is needed to determine the effect of language use on other groups, such as individuals with MHPSA.     

Highly Pathogenic Avian Influenza Virus A (H7N3) in Domestic Poultry, Saskatchewan, Canada, 2007

Epidemiologic, serologic, and molecular phylogenetic methods were used to investigate an outbreak of highly pathogenic avian influenza on a broiler breeding farm in Saskatchewan, Canada. Results, coupled with data from influenza A virus surveillance of migratory waterfowl in Canada, implicated wild birds as the most probable source of the low pathogenicity precursor virus.     

Synthesis and biological evaluation of analogues of the peptaibol ampullosporin A

A series of analogues of the fungal peptaibol type metabolite ampullosporin A containing modifications in the C and N terminus as well as alpha-aminoisobutyric acid (Aib) substitutions in different positions of the peptide were synthesized by solid phase synthesis using the 9-fluorenylmethyloxycarbonyl strategy. Depending on the sequence position, couplings were performed with 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/1-hydroxybenzotriazole and tetramethylfluoroformamidinium hexafluorophosphate, respectively. The structures of the target peptides were analyzed by electrospray ionization mass spectrometry and chromatographic methods (high-performance liquid chromatography, thin-layer chromatography). The biological activities of these compounds have been evaluated by assaying their potencies for the induction of pigment formation on the fungus Phoma destructiva as well as for the induction of hypothermia and inhibition of locomotoric activity in mice and were compared to the naturally occurring ampullosporins. Native ampullosporin A and analogues with C-terminal Leu or Leu-NH(2) showed comparable activity in the pigmentation assay. Similarly, the ampullosporin A analogues with N-terminal aromatic amino acid residues, such as D-Trp and Tic, also have high potency for pigment formation. The peptides containing structural modifications of ampullosporin A by systematic replacement of Aib by Ala (Ala scan) displayed moderate or high activity in the pigmentation assay, whereas simultaneous substitution of all Aib residues by Ala and Ile, respectively, or by insertion of nonaromatic residues into position 1 resulted in a loss of the effect on P. destructiva. Most of the compounds with no or weak activity in the microbial assay were not active in the hypothermic test, too, except the compound with 1-amino-1-cyclohexane carboxylic acid in position 4 instead of Aib. However, only a few compounds with high potency for pigmentation induction were found to produce strong hypothermia in mice. Thus, in contrast to the native ampullosporins, we succeeded to a certain degree in differentiation of the bioactivities with our synthetic analogues.