A microcapsule technique for long-term conduction block of the sciatic nerve by tetrodotoxin.

Tetrodotoxin (TTX) is a selective blocker of voltage-gated Na+ channels that is used to block action potentials in vitro and in vivo. Maintaining a sufficiently high local concentration of TTX in vivo to block conduction in a peripheral nerve is technically demanding and carries a risk of systemic toxicity. We report that slow diffusion of TTX out of a microcapsule (glass capillary) inserted beneath the epineurium of the sciatic nerve, with a loose cuff around the nerve, combines high blocking efficacy with low systemic toxicity in rats and mice.

Dietary antioxidants and cardiovascular disease.

Purpose Of Review: Oxidative damage is involved in cardiovascular diseases. Intervention with alpha-tocopherol, ascorbic acid and beta-carotene does not appear to reduce pathogenesis. The purpose of this review is to describe alternative antioxidant mechanisms that may be involved.

From superior adaptation and function to brain dysfunction--the neglect of epigenetic factors.

With optimal pregnancy conditions (natural, enriched diet which includes fish) African (Digo) infants are 3-4 weeks ahead of European/American infants in sensorimotor terms at birth, and during the first year. Infants of semi-aquatic sea-gypsies swim before they walk, and have superior visual acuity compared with us. With adverse pregnancy behaviour (fear of fat, a trend to dieting), neglecting the need for brain fat to secure normal brain development and function, we run a risk of dysfunction--death.

Work, food and physical activity. A qualitative study of coping strategies among men in three occupations.

Life style diseases contribute heavily to inequalities in health. Thus, there is a need for a better understanding of factors affecting health-related habits, such as diet and exercise, among different groups of people. In this study, the work situation is chosen as a point of departure for analyses on health-related perceptions and habits among men from three different occupations: 20 carpenters, 15 engineers and 11 drivers in Oslo, Norway.

Activity-dependent excitability changes in hippocampal CA3 cell Schaffer axons.

The membrane potential changes following action potentials in thin unmyelinated cortical axons with en passant boutons may be important for synaptic release and conduction abilities of such axons. In the lack of intra-axonal recording techniques we have used extracellular excitability testing as an indirect measure of the after-potentials. We recorded from individual CA3 soma in hippocampal slices and activated the axon with a range of stimulus intensities.

Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles.

Electrophile responsive element (EpRE)-mediated gene induction is a pivotal mechanism of cellular defense against the toxicity of electrophiles and reactive oxygen species (ROS). Nrf2, which belongs to the cap'-n'-collar family of basic region-leucine zipper transcription factors, has emerged as an essential component of an EpRE-binding transcriptional complex. Detailed analysis of the regulatory mechanism governing Nrf2 activity led to the identification of Keap1, which represses Nrf2 activity by directly binding to the N-terminal Neh2 domain.

The vascular response to the K+ channel inhibitor 4-aminopyridine in hypertensive rats.

The K+ channel inhibitor 4-aminopyridine induced an immediate increase in blood pressure and tension in spontaneously hypertensive rats (SHR). Further analysis strongly suggested this to be due to closure of vascular smooth muscle K+ channels, as previously concluded for normotensive rats (WKY). The tension response was greater in SHR than WKY, suggesting an increased channel activity in order to compensate for the high total peripheral vascular resistance in SHR.

A kinase anchoring protein (AKAP) interaction and dimerization of the RIalpha and RIbeta regulatory subunits of protein kinase a in vivo by the yeast two hybrid system.

Protein kinase A (PKA) regulatory (R) subunits dimerize through an N-terminal motif. Such dimerization is necessary for binding to PKA anchoring proteins (AKAPs) and targeting of PKA to its site of action. In the present study, we used the yeast two-hybrid system as an in vivo bio-reporter assay and analyzed the formation of homo- and heterodimeric complexes of RIalpha and RIbeta as well as AKAP binding of RI dimers.

Manic depressive psychosis and schizophrenia are neurological disorders at the extremes of CNS maturation and nutritional disorders associated with a deficit in marine fat.

The maturational theory of brain development comprises manic depressive psychosis and schizophrenia. It holds that the disorders are part of human diversity in growth and maturation, which explains their ubiquity, shared susceptibility genes and multifactorial inheritance. Rate of maturation and age at puberty are the genotype; the disorders are localized at the extremes with normality in between.

Quantitative axial profiles of retinoic acid in the embryonic mouse spinal cord: 9-cis retinoic acid only detected after all-trans-retinoic acid levels are super-elevated experimentally.

Studies using bioassays in normal mice and gene activation in transgenic reporter mice have demonstrated peaks of retinoic acid receptor (RAR) signaling in the brachial and lumbar regions of the spinal cord. Recently, Solomin et al. (Solomin et al.

Quantitative assessment of retinoid signaling pathways in the developing eye and retina of the chicken embryo.

Retinoid signaling has been implicated as an important regulator of retinal development and differentiation. We have used state of the art high-pressure liquid chromatography to identify and quantitate biologically active retinoids, immunohistochemistry to localize the retinoic acid synthetic enzyme retinaldehyde dehydrogenase 2 (RALDH2), and nucleic acid assays to quantitate and localize retinoid receptor gene transcripts in the developing eye and retina of the chicken. Our results demonstrate spatial distinctions in retinoid synthesis and signaling that may be related to laminar differentiation in the developing retina.

The hippocampal lamella hypothesis revisited.

We have re-examined the hippocampal lamellar organization of the CA3-to-CA1 connection. Based on a new technique with electrophysiological quantification of Schaffer collateral density, and a review of recent literature, we conclude that the lamellar organization remains a useful concept for understanding hippocampal connectivity. Using a sheet-like hippocampal preparation, containing the whole CA1 region, we mapped the distribution of Schaffer collaterals by two procedures.

Comparing methods for estimating the variation of risks of cancer between small areas.

Background: Analysing the geographical variation of cancer incidence is an important issue in epidemiological research. It might suggest new aetiologic hypotheses, provide guidelines for the design of new surveys and give ideas for preventive campaigns.

Methods: Four different methods for estimating the variation of cancer risks between small areas and three homogeneity tests were evaluated by simulation.

Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study.

In a randomized double-blind study, 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses: 100-mg enteric-coated diclofenac tablets; 1 g acetaminophen (INN, paracetamol); 1 g acetaminophen plus 60 mg codeine; 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen; or 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine. Patients recorded pain intensity and pain relief for 8 hours. Upside assay sensitivity was confirmed because acetaminophen plus codeine was superior to acetaminophen.

Regulatory mechanisms of cellular response to oxidative stress.

An antioxidant responsive element (ARE) or electrophile responsive element (EpRE) mediates the transcriptional activation of genes encoding phase II drug metabolizing enzymes. The ARE consensus sequence shows high similarity to an erythroid gene regulatory element, and based on the observation, we have recently found that transcription factor Nrf2 is essential for the coordinate induction of phase II detoxifying enzymes. The expression of anti-oxidative stress enzyme genes is also regulated by Nrf2.

Spatial smoothing of cancer survival: a Bayesian approach.

A major aim of this paper is to propose and evaluate a method for describing the geographical variation in cancer survival. A fully hierarchical Bayesian approach (FB) which incorporates spatial autocorrelation of the hazard ratios is presented. The method was tried out on data sets of breast cancer and malignant melanoma patients from a population-based cancer registry.

Iterative random aggregation of small units using regional measures of spatial autocorrelation for cluster localization.

A method for localization of spatial disease clusters which uses a regional measure of spatial autocorrelation (RSAC) was recently developed by Munasinghe and Morris. They found this method to be an effective tool for the identification of regional disease clusters. In order to reduce the spurious variability of the estimated relative risks, the smallest geographic units were aggregated into analytic areas, consisting of a predefined minimum number of persons at risk (PAR).

Regional pattern of retinoid X receptor-alpha gene expression in the central nervous system of the chicken embryo and its up-regulation by exposure to 9-cis retinoic acid.

We have investigated the expression of the retinoid X receptor-alpha (RXRalpha) gene in the developing chicken embryo by using nonradioactive wholemount in situ hybridization. At the earliest stage of development examined (stage 9; Hamburger and Hamilton [1951] J. Morphol.