Functional gap junctions in corneal fibroblasts and myofibroblasts

PURPOSE: Within the corneal stroma, keratocytes communicate through gap junctions. These plasma membrane channels, which connect the cytoplasm of adjacent cells, are composed of connexins. In a cell culture model, an investigation was conducted to determine whether connexin-based gap junction intercellular communication is present in fibroblasts and myofibroblasts, both of which replace keratocytes after wounding. METHODS: Fibroblasts and myofibroblasts were grown according to preestablished methods. Phenotype was determined by immunocytochemistry. A gap junction-permeant dye, Lucifer yellow or Cascade blue, and nonpermeant 10-kDa Texas red-dextran were used. Tracer fluorescent dyes were introduced by scrape-loading or by microinjection, and their diffusion into adjacent cells was recorded photographically. Inhibition of gap junction dye transfer was elicited by treatment with 18-alpha-glycyrrhetinic acid (AGA). RESULTS: In confluent fibroblast or myofibroblast cultures, the scrape-loaded dextran probe remained within wounded cells, whereas the Lucifer yellow or Cascade blue dye diffused into adjacent intact cells. Similarly, in nonconfluent fibroblast and myofibroblast cultures, microinjected Lucifer yellow rapidly diffused from the microinjected cell to adjacent cells. Treatment with 2 microM AGA, an uncoupling agent, blocked the spread of Lucifer yellow in fibroblast and myofibroblast cultures. CONCLUSIONS: Cultured fibroblasts and myofibroblasts have functional gap junctions as has previously been demonstrated for keratocytes in vivo. Thus, fibroblasts and myofibroblasts have the ability to establish and maintain intercellular communication with themselves and with nonactivated keratocytes. This property may be critical in the wound-healing process, especially in the avascular corneal environment.     

Determinants of stillbirth mortality in Greece

A population-based case-control study of the determinants of stillbirths was conducted in Greece from 1989 to 1991. All reported stillbirths after 28 weeks of pregnancy (N = 2,006) during the three year study period comprised the case group. The control group derived from random sampling of 10% of all livebirths in Greece, during the same period (N = 30,705). The data were analysed by modelling through multiple logistic regression. The adjusted relative risk of stillbirth was significantly higher for males compared to females. A statistically significant monotonic increase in relative risk was observed with shorter gestational age, low maternal education, and older maternal age. Birthweight and parity showed a statistically significant U-shaped association with stillbirth risk, with a higher risk being observed among both low and high birthweight deliveries, as well as among primiparous or multiparous (4+) mothers. Positive associations of stillbirth with multiple births, out-of-wedlock marriage and non-Greek-orthodox maternal religion were noted in crude analyses, but these associations almost disappeared in logistic regression model. Maternal urban or rural residence showed no relation to risk. Overall, the prospective risk of stillbirth after the 24th week of gestation in Greece has been estimated to be higher than that in Japan (a more developed country) with more than 40% of stillbirths occurring after the 36th week of pregnancy.     

Supplementation with CLA: Isomer incorporation into serum lipids and effect on body fat of women

Animal studies have suggested that CLA, a natural component of meat and dairy products, may confer beneficial effects on health. However, human studies using supplementation with CLA have produced contradictory results. The aim of the present study was to further investigate the effect of CLA supplementation on human body fat, serum leptin, and serum lipids, as well as the incorporation of CLA isomers into serum lipids classes. Sixteen young healthy nonobese sedentary women received 2.1 g of CLA (divided equally between the cis,trans-9,11 and trans,cis-10,12 isomers) daily for 45 d and placebo for 45 d in a randomized double-blind crossover design. Body fat was estimated (by measurement of skinfold thickness at 10 sites), and blood was sampled at the beginning, middle, and end of the entire intervention period; an additional blood sample was obtained 2 wk thereafer. No significant differences in energy, carbohydrate, lipid, or protein intake existed between the CLA and placebo intake periods. No significant differences were found in body fat or serum leptin, TAG, total cholesterol, HDL-cholesterol, and alanine aminotransferase between CLA and placebo. The CLA isomer content of serum TAG, phospholipids, and total lipids increased 2–5 times with CLA supplementation (P<0.05). In contrast, the CLA content of cholesteryl esters did not change significantly. The period of 2 wk after the end of CLA supplementation was sufficient for its washout from serum lipids. These data indicate that supplementation with 2.1 g of CLA daily for 45 d increased its levels in blood but had no effect on body composition or the lipidemic profile of nonobese women.     

Cancer consequences of the Chernobyl accident in Europe outside the former USSR: a review

Therapeutic research is being stepped up to light Alzheimer's disease (AD), although its heterogeneity, the insufficiency of physiopathological knowledge, and the lack of a reference treatment impede the development of a drug to combat it. However, progress has opened up many avenues. Some recent approaches that have led to therapeutic research are identification of biochemical abnormalities, identification of dysfunction in several neurotransmitter systems (cholinergic, catecholaminergic, serotonergic, and peptidergic systems), and the study of senile plaques and neurofibrillary degeneration tangles. Although some types of therapy have been used for a long time (e.g., metabolic products such as nootropes), recently developed drugs target different systems: for example, neurotransmitter systems are important for symptomatic improvements in cognitive functions. The principal improvements expected with some new anticholinesterases whose role is to increase the available amount of central acetylcholine are in memory and attention. Second, retarding neuronal degeneration by acting on amyloid plaques is another possible future therapy. Here, protease inhibitors appear to be interesting tools. Third, the endototoxin etiology of neurodegenerative illnesses remains uncertain. After the first attempts with N-methyl-D-aspartate (NMDA) antagonists that had inescapable side effects, hopes rose with some new pharmacological tools such as the AMPA/kainate antagonists. Fourth, a possible stimulation of neuronal plasticity by neurotrophic factors such as nerve growth factor (NGF) constitutes another prospected research area. Fifth, the inflammatory aspects of degenerative diseases attract the attention of many laboratories and preliminary reports are hopeful. Finally, out of the established pharmacological tools, gene therapy, though still hypothetical, may become the expected treatment in the future. Pharmacotherapy used in the most common types of dementia has until now been largely palliative and dealt with symptoms. It is nonetheless not unreasonable to look forward to the development of drugs that will be able to combat the evolution of the dementia itself, rather than its symptoms. A list of different products developed to treat AD is concluded by an evaluation of the expected results and, in particular, the orientations likely to be necessary.     

International variation in clinical injury incidence: exploring the performance of indicators based on health care, anatomical and outcome criteria

OBJECTIVE: To analyse international variation in clinical injury incidence, and explore the performance of different injury indicators in cross-country comparisons. METHODS: Hospital discharge data of seven European countries (Austria, Denmark, Ireland, Netherlands, Norway, England and Wales) were analysed. We tested existing and newly developed indicators based on (a) health care use, (b) anatomical criteria, or (c) expected health outcome: admissions excluding day-cases (a), hospital stay 4+ (a) and 7+ days (a), (serious) long-bone fractures (b), selected radiological verifiable fractures 'SRVFs' (b), and indicators based on international (Global Burden of Disease) and Dutch disability weights). Assessment criteria were reduction in incidence variation and length of stay in hospital, and the association between incidence and mortality rates. RESULTS: Indicators based on health care use led to increased variation in incidence rates. Long bone fractures and SRVFs, and both indicators based on injuries with moderate to high disability showed similar variation in clinical incidence compared to the crude rates, smaller variation in median length of stay in hospital and a good association with mortality rates. CONCLUSION: No perfect or near perfect indicators of clinical injury incidence exist. For international comparisons, indicators based on disability weights, SRVFs and long bone fractures may be sensible indicators to use, in the absence of a direct measure of anatomical severity.     

Modelling risk factors for injuries from dog bites in Greece: a case-only design and analysis

We conducted a study using a newly developed dataset based on Emergency Departments records of a network of hospitals from Greece on injuries from dog bites. Our goal is three-fold: (a) to investigate if surrogate factors of leisure time are associated with increased risk of injury from bites; (b) to address recently reported contradictory results on putative association of lunar periods and injuries from dog bites; and (c) to offer a general methodology for addressing similar case-only designs with combined factors of which some can exhibit cyclical patterns. To address these goals, we used a case-only design of our dataset, and conducted an analysis where we controlled simultaneously for weekday/weekend effects, season of year (winter, spring/fall, summer), and lunar periods, because any one of these factors can contribute to the degree of exposure to injuries from dog bites. We found that increased risk of injury from bites was associated with weekends versus weekdays (RR=1.19, 95% CI: 1.10-1.29), summer versus winter (RR=1.24, 95% CI: 1.11-1.39), and fall or spring versus winter (RR=1.31, 95% CI: 1.19-1.45). The results support the hypothesis that longer leisure time at these levels of factors does increase the risk of having a bite injury. Moreover, after controlling for these factors, risk of bite injury was not associated with moon periods, thereby also helping settle a longstanding argument.     

A vision of 14 T MR for fundamental and clinical science

Objective

We outline our vision for a 14 Tesla MR system. This comprises a novel whole-body magnet design utilizing high temperature superconductor; a console and associated electronic equipment; an optimized radiofrequency coil setup for proton measurement in the brain, which also has a local shim capability; and a high-performance gradient set.

Research fields

The 14 Tesla system can be considered a ‘mesocope’: a device capable of measuring on biologically relevant scales. In neuroscience the increased spatial resolution will anatomically resolve all layers of the cortex, cerebellum, subcortical structures, and inner nuclei. Spectroscopic imaging will simultaneously measure excitatory and inhibitory activity, characterizing the excitation/inhibition balance of neural circuits. In medical research (including brain disorders) we will visualize fine-grained patterns of structural abnormalities and relate these changes to functional and molecular changes. The significantly increased spectral resolution will make it possible to detect (dynamic changes in) individual metabolites associated with pathological pathways including molecular interactions and dynamic disease processes.

Conclusions

The 14 Tesla system will offer new perspectives in neuroscience and fundamental research. We anticipate that this initiative will usher in a new era of ultra-high-field MR.