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The geomagnetic deep sounding (GDS) method is one of electromagnetic (EM) methods in geophysics that allows the estimation of the subsurface electrical conductivity distribution. This paper presents the inversion modeling of GDS data employing Markov Chain Monte Carlo (MCMC) algorithm to evaluate the marginal posterior probability of the model parameters. We used thin-sheet model to represent quasi-3D conductivity variations in the heterogeneous subsurface. The algorithm was applied to invert field GDS data from the zone covering an area that spans from eastern margin of the Bohemian Massif to the West Carpathians in Europe. Conductivity anomalies obtained from this study confirm the well-known large-scale tectonic setting of the area.

The domination is a central concept of the sociological analysis. To such a point that a sociology of the domination made the key word of its explanations. This article redraws the meanings that was able to receive this notion in the history of the thought and in the contemporary sociology. It brings out the theoretical difficulties which meets a sociology of the domination which registers this concept as tools and as the end of the approach and commits the sociologist to clarify a little better the explanatory status which he recognizes by this word.

From a fieldwork experience which occurred in Havana, Cuba, during the summer of 2011, this article suggests overcoming « scientific » precautions usually expressed towards countries whose political systems differ significantly from ours. This is the occasion to discuss current issues in the community of sociologists regarding the imperativeness of methodological and ethical rules that they have implement. To formalize excessively these last ones, fieldwork research blocks itself from its asset and interest: a form of heuristic.

Family sociology, more especially in France, tends to admit two types of paradigm to explain the family fact. One grants social institutions, and particularly the State, a diriment role. The other considers that the establishment of the family fact is a matter for the autonomous individual. We suggest regarding the family fact as the product of multifactorial dynamics. This leads us to favour a sociological approach that attributes the key role to the operations of deconstruction/reconstruction of the family fact, taking into account the model of the social world in which it takes place.

Modern agriculture favours the selection and spread of novel plant diseases. Furthermore, crop genetic resistance against pathogens is often rendered ineffective within a few years of its commercial deployment. Leptosphaeria maculans, the cause of phoma stem canker of oilseed rape, develops gene-for-gene interactions with its host plant, and has a high evolutionary potential to render ineffective novel sources of resistance in crops. Here, we established a four-year field experiment to monitor the evolution of populations confronted with the newly released Rlm7 resistance and to investigate the nature of the mutations responsible for virulence against Rlm7. A total of 2551 fungal isolates were collected from experimental crops of a Rlm7 cultivar or a cultivar without Rlm7. All isolates were phenotyped for virulence and a subset was genotyped with neutral genetic markers. Virulent isolates were investigated for molecular events at the AvrLm4-7 locus. Whilst virulent isolates were not found in neighbouring crops, their frequency had reached 36% in the experimental field after four years. An extreme diversity of independent molecular events leading to virulence was identified in populations, with large-scale Repeat Induced Point mutations or complete deletion of AvrLm4-7 being the most frequent. Our data suggest that increased mutability of fungal genes involved in the interactions with plants is directly related to their genomic environment and reproductive system. Thus, rapid allelic diversification of avirulence genes can be generated in L. maculans populations in a single field provided that large population sizes and sexual reproduction are favoured by agricultural practices.

The author takes as starting point what is said about affiliations and ties in the discourses collected in his investigations. He assumes that from “ordinary” discourses held on “membership” and “social ties” a sociological point of view can be extricated, and that these discourses participate to the elaboration of a theoretical perspective on what it means to have a “membership” in our individualistic societies. At first, he will look at how affiliations and social ties are perceived, received and conceived by people who talk about them. Then, he will aim at specifying the type of relationship that people establish between what they say is their affiliations and how they experience their social integration. At last, he will test the hypothesis according to which membership would be on what social ties would form, stabilize, or strengthen themselves, understood as the major form of integration to the social body or as an affirmation mode of its valued existence as a social individual.

The author, who has himself analysed the transformation of French social policy systems and organisations and who has presented a social-historical interpretation in terms of an “insurance for state aids”, discusses Didier Vrancken’s approach in his book Nouvel ordre protectionnel. He concentrates first on identifying to what extent this approach leads us to renew the conceptions that dominated sociological analyses of social protection systems during the 20th century. He then critically examines the approach’s real pertinence as well as its limits. Finally, having identified some inconsistencies of Didier Vrancken’s argument, he proposes a number of ideas in order to understand, adjust or develop the central argument of his book.

No dia 7 de dezembro de 2009, em um fim de tarde de calor intenso, o saguão do Teatro Noel Rosa recebeu um público surpreendentemente numeroso para assistir às conversas entre Angela Melim, Chacal, Laura Erber e Michel Melamed. Escutar seus poemas e fazer-lhes perguntas. Nossa ideia era que em uma revista sobre Poesia, cuja ementa estava fortemente voltada para questões contemporâneas, as vozes dos poetas deveriam também estar inscritas nas páginas da revista. A seguir, apresentamos uma versão editada desse encontro, durante o qual os poetas discutiram temas como seus processos de composição, sua relação com as mídias, suas influências.

According to Aristotle, rhetoric is the counterpart of argumentation. How can we understand the relationship between literary, rhetoric and legal reasoning, if we do not have a general theory of rhetoric? Problematology purports to be precisely that. Questions can be addressed either directly, as in law and legal conflict, where the questions, the pros and the contras are, so to speak, on the table, or indirectly,through their answers, as if they were solved thereby. Rhetoric is the negotiation of the differences between the orator and the audience on a given question, which can be more or less problematic, rhetorical or argumentative. Problematology is the founding theory behind this “new” rhetoric. From the figures of speech to plausible inference, the theory of questioning offers an integrated view of reason, language and persuasion.

This paper compares results used by two methodological research inquiries. The first one is the questionnaire used by the INSEE « life stories » survey. The second consists of face-to-face interviews with the participants to the INSEE’s survey. The comparison between the two methods shows some interesting outcomes in terms of knowledge gains. However, this is not always the case. More importantly, truth and the coherence of the speech are less at stake here than the nature of the response or the knowledge’ status.

Background and Objectives Diffuse large B-cell lymphomas (DLBCL) have a variable outcome, and powerful methods of prognostication are needed in order to choose the best treatment for each patient. Immunophenotypic classification of the tumor as germinal center (GC) or non-germinal center-like (nGC) and early response evaluation with 18fluorodeoxyglucose positron emission tomography (18FDG-PET) scanning have been correlated with survival in DLBCL but the two methods have never been evaluated simultaneously in the same patient population. Our aim was to investigate their respective prognostic values in the same series of patients.Design and Methods We investigated the expression of CD10, Bcl-6, and MUM1 in 81 patients with DLBCL evaluated early with 18FDG-PET. The tumors were classified as GC or nGC using the algorithm of Hans et al. The results of both methods were correlated with the patients’ characteristics and survival.Results CD10 was positive in 27/76 (36%), Bcl-6 in 43/74 (58%), and MUM1 in 33/73 (45%) interpretable cases. Thirty-eight (51%) were in the GC group, and 36 (49%) in the nGC group. With a median follow-up of 33 months, estimated 3-year event-free survival (EFS) of the whole population was 67%. There was no influence of GC/nGC phenotype on survival. Three-year EFS was 46% in the early PET-positive group versus 80% in the PET-negative group (p=0.0003).Interpretation and Conclusions The prognostic value of GC/nGC phenotype is not confirmed in this heterogeneous series, whereas early PET findings are confirmed to be a powerful predictor of outcome. The impact of treatment decisions based on early PET results should be evaluated.

A porous hydroxyapatite (p-HAp) was prepared and employed for the removal of lead(II) ions at different concentrations from aqueous solution to determine the adsorption properties of p-HAp and compare them with those of a commercial hydroxyapatite (CAp) sample. The kinetic data obtained indicated that the adsorption performances of the adsorbents depended both on their specific surface area and crystallinity. Complexation of the Pb(II) ion on the adsorbent surface favoured the dissolution of hydroxyapatites characterized by a Ca/Pb molar ratio in the 0.85–1.5 range. The maximum adsorption capacity of p-Hap for Pb(II) ions at 30 ± 2°C was 2.30 mmol/g relative to 1.38 mmol/g for the commercial compound Cap at the same temperature. The higher capacity of p-HAp was explained in terms of its porosity and crystallinity. The Pb(II) ions sorption results could be modelled by the Langmuir and Freundlich isotherms.

The institutionalization of mountaineering clubs belongs to each nation’s cultural history. These processes were carried out throughout ideological conflicts such as nationalisms. The Austrian-German Club being one of the most prominent examples. Right at the beginning, the club’s original members had to choose between two different types of structure, embodying either an idea of « Little Germany » or of « Large Germany ». The type of club eventually chosen, i.e. an Austrian-German Club, (in other words « Large Germany »), was not asserted by its founders as a political keystone, but much more as a fundamental act symbolizing a cultural specificity. After the first world war, the club stood for the abrogation of the Treaty of Versailles, advocating the return of the Southern Tyrol Territories into a German-speaking community. It also let its most extremist members carry out an « Aryan » policy within the club. Last but not least, the club widely supported a colonialistic policy turning mountaineers into explorers of unknown territories as well as symbols of the German Nationalism.

La philosophie tente généralement de définir la responsabilité morale dans des termes absolutisants, en prenant soin de se tenir à distance de la réalité empirique du monde social. Cet article présente une approche d'orientation pragmatiste qui plaide en faveur d'un rapprochement entre philosophie et sciences humaines dans l'étude de la responsabilité et qui opère ce rapprochement en se donnant pour objet les « pratiques de responsabilité », plutôt que les critères ou les fondements de la responsabilité. Elle vise à analyser les structures d'interaction à travers lesquelles les agents sociaux s'engagent dans des pratiques concrètes de responsabilisation. Cette approche se veut en prise sur la réalité de l'ordre moral caractéristique des sociétés de la modernité avancée, qu'il faut concevoir comme un système ouvert, mouvant, en perpétuelle reconstruction. C'est un système où les responsabilités ne sont plus attribuées sur un mode autoritaire, dans des cadres rigides et suivant des critères prédéfinis et stables, mais sont largement abandonnées à l'initiative des acteurs sociaux.

Contrairement à la « pourriture vulgaire » qui correspond au développement simultané de Botrytis cinerea et de divers champignons (Penicillium, Aspergillus, etc...) sur la baie de raisin éclatée, « la pourriture noble » correspond à un développement presque exclusif de Botrytis sur des baies mûres et apparemment intactes. Dans ce travail, on montre que la pénétration des tubes germinatifs ou du mycélium de Botrytis ne peut se faire qu'à travers des microlésions de la pellicule, autres que les cassures péristomatiques, les hyphes se développent entre les cellules de la pellicule mais ressortent à l'extérieur, soit sous forme de mycélium, soit sous forme de conidiophores et assurent ainsi la propagation de la pourriture. +++ Contrary to « common rot » which corresponds to the simultaneous development of Botrytis cinerea and various fungi (Penicillium, Aspergillus, etc...) on the burst grape berry, « noble rot » corresponds to an almost exclusive development of Botrytis on ripe and apparently intact berries. In this work, it is shown that the penetration of the germinative tubes or mycelium of Botrytis can only take place through the micro-lesions of the pellicle, the hyphae develop between the cells of other than the peristomatic breaks the pellicle but come out on the outside, either in the form of mycelium, or in the form of conidiophores and thus propagate the rot.

Abstract Mining projects are often budgeted in millions of dollars, making it of interest to the investor to measure a project’s uncertainties and risks, which include the changes in the commodity price. The simulation of asset prices is valid because it enables displaying, with a degree of certainty, the future behavior of a financial asset. One of the most commonly used mathematical forecast models is the Geometric Brownian Motion (GBM) model. This article aims at simulating the forecast price of an iron ore commodity with the GBM method based on the historical price series and comparing it to other forecast approaches used in the financial market. The results of this study indicate that the model has limitations, which should be considered. However, it is an overall good tool to support the economic evaluation of a project, if performed along with other approaches.

Public authorities in charge of preparing and implementing the 1964 French water law and the 2000 European Water framework Directive similarly relied on inventories. In order to justify public action, they needed to objectify a situation which was either poorly known or informed by heterogeneous criteria. We show that political considerations are embedded in the indicators and the monitoring network of both inventories. They pertain to the type of realism which allows comparisons, shapes the frontiers of public policy, legitimates uses of water, and defines the sharing of restoration’s financial burden. We compare the controversies that rose during both inventories’ construction to conclude on their political meaning.

Environmental health science seeks to predict how environmental toxins, chemical toxicants, and prescription drugs accumulate and interact within the body. Xenobiotic transporters of the ATP-binding cassette (ABC) and solute carrier (SLC) superfamilies are major determinants of the uptake and disposition of xenobiotics across the kingdoms of life. The goal of this study was to integrate drug and environmental chemical interactions of mammalian ABC and SLC proteins in a centralized, integrative database. We built upon an existing publicly accessible platform-the "TransPortal"-which was updated with novel data and searchable features on transporter-interfering chemicals from manually curated literature data. The integrated resource TransPortal-TICBase (https://transportal.compbio.ucsf.edu) now contains information on 46 different mammalian xenobiotic transporters of the ABC- and SLC-type superfamilies, including 13 newly added rodent and 2 additional human drug transporters, 126 clinical drug-drug interactions, and a more than quadrupled expansion of the initial in vitro chemical interaction data from 1,402 to 6,296 total interactions. Based on our updated database, environmental interference with major human and rodent drug transporters occurs across the ABC- and SLC-type superfamilies, with kinetics indicating that some chemicals, such as the ionic liquid 1-hexylpyridinium chloride and the antiseptic chlorhexidine, can act as strong inhibitors with potencies similar or even higher than pharmacological model inhibitors. The new integrated web portal serves as a central repository of current and emerging data for interactions of prescription drugs and environmental chemicals with human drug transporters. This archive has important implications for predicting adverse drug-drug and drug-environmental chemical interactions and can serve as a reference website for the broader scientific community of clinicians and researchers., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Electrical synapses are neuronal gap junction (GJ) channels associated with a macromolecular complex called the electrical synapse density (ESD), which regulates development and dynamically modifies electrical transmission. However, the proteomic makeup and molecular mechanisms utilized by the ESD that direct electrical synapse formation are not well understood. Using the Mauthner cell of zebrafish as a model, we previously found that the intracellular scaffolding protein ZO1b is a member of the ESD, localizing postsynaptically, where it is required for GJ channel localization, electrical communication, neural network function, and behavior. Here, we show that the complexity of the ESD is further diversified by the genomic structure of the ZO1b gene locus. The ZO1b gene is alternatively initiated at three transcriptional start sites resulting in isoforms with unique N-termini that we call ZO1b-Alpha, -Beta, and -Gamma. We demonstrate that ZO1b-Beta and ZO1b-Gamma are broadly expressed throughout the nervous system and localize to electrical synapses. By contrast, ZO1b-Alpha is expressed mainly non-neuronally and is not found at synapses. We generate mutants in all individual isoforms, as well as double mutant combinations in cis on individual chromosomes, and find that ZO1b-Beta is necessary and sufficient for robust GJ channel localization. ZO1b-Gamma, despite its localization to the synapse, plays an auxiliary role in channel localization. This study expands the notion of molecular complexity at the ESD, revealing that an individual genomic locus can contribute distinct isoforms to the macromolecular complex at electrical synapses. Further, independent scaffold isoforms have differential contributions to developmental assembly of the interneuronal GJ channels. We propose that ESD molecular complexity arises both from the diversity of unique genes and from distinct isoforms encoded by single genes. Overall, ESD proteomic diversity is expected to have critical impacts on the development, structure, function, and plasticity of electrical transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Michel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The purpose of this Special Communication is to summarize guidelines and recommendations stemming from an expert panel convened by the National Institutes of Health, National Center for Medical Rehabilitation Research (NCMRR) for a workshop entitled The Future of Medical Rehabilitation Clinical Trials, held September 29-30, 2016, at the NCMRR offices in Bethesda, Maryland. The ultimate goal of both the workshop and this summary is to offer guidance on clinical trials design and operations to the medical rehabilitation research community, with the intent of maximizing the effect of future trials., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Congenital lipomatous overgrowth with vascular, epidermal, and skeletal (CLOVES) anomalies and Klippel-Trenaunay (KTS) syndromes are caused by somatic gain-of-function mutations in PIK3CA, encoding a catalytic subunit of phosphoinositide 3-kinase. Affected tissue is needed to find mutations, as mutant alleles are not detectable in blood. Because some patients with CLOVES develop Wilms tumor, we tested urine as a source of DNA for mutation detection. We extracted DNA from the urine of 17 and 24 individuals with CLOVES and KTS, respectively, and screened 5 common PIK3CA mutation hotspots using droplet digital polymerase chain reaction. Six of 17 CLOVES participants (35%) had mutant PIK3CA alleles in urine. Among 8 individuals in whom a mutation had been previously identified in affected tissue, 4 had the same mutant allele in the urine. One study participant with CLOVES had been treated for Wilms tumor. We detected the same PIK3CA mutation in her affected tissue, urine, and tumor, indicating Wilms tumors probably arise from PIK3CA mutant cells in patients with CLOVES. No urine sample from a participant with KTS had detectable PIK3CA mutations. We suggest that urine, which has the advantage of being collected non-invasively, is useful when searching for mutations in individuals with CLOVES syndrome., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public. This article provides an overview of the need for this research plan, an outline of its development, and a listing of six priority areas for research. The NIH is committed to working with all stakeholder communities engaged in rehabilitation research to track progress made on these priorities and to work to advance the science of medical rehabilitation.This article is being published almost simultaneously in the following six journals: American Journal of Occupational Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and Rehabilitation Psychology. Citation information is as follows: NIH Medical Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407., (Copyright © Wolters Kluwer Health, Inc. 2017.)

Substance abuse is a leading cause of death and disability throughout the world. The mission of the National Institute on Drug Abuse (NIDA) is to lead the United States in bringing the power of science to bear on drug abuse and addiction. This charge has two critical components: (a) strategic support of research across a broad range of disciplines and (b) rapid, effective dissemination of research results that can improve prevention and treatment efforts, with potential to inform policy. The NIDA Clinical Trials Network and the Blending Initiative are critical elements of this strategy, and the social work field is poised to use these resources to expand its role in the dissemination and implementation of NIDA's mission.

Background: Recruitment and retention in randomized clinical trials are difficult in general and particularly so in trials of substance abuse treatments. Understanding trial design characteristics that could affect recruitment and retention rates would help in the design of future trials., Objective: To test whether any of the following factors are associated with recruitment or retention: type of intervention, type of therapy, duration of treatment, total duration of trial, number of treatment sessions, number of follow-up visits, number of primary assessments, timing of primary assessments, number of case report form (CRF) pages at baseline, and number of CRF pages for the entire trial., Methods: Recruitment and retention data from 24 Clinical Trials Network (CTN) trials conducted and completed between 2001 and 2010 were analyzed using single-factor analysis of variance and single-predictor regression methods to test their association with trial design characteristics., Results: Almost all of the analyses performed did not show statistically significant patterns between recruitment and retention rates and the trial design characteristics considered., Conclusion: In CTN trials, the relationship between assessment burden on participants and length of trial, on the one hand, and recruitment and retention, on the other, is not as strong and direct as expected. Other factors must impinge on the conduct of the trial to influence trial participation., Scientific Significance: Researchers may deem slightly more justifiable to permit inclusion of some of the design features that previously were assumed to have a strong, negative influence on recruitment and retention, and should consider other strategies that may have a stronger, more direct effect on trial participation.

The evolution of pregnancies following uterine-artery embolisation (UAE) for symptomatic fibroids remains uncertain. We report a case of pregnancy after UAE, complicated of adherent placenta with uterine rupture, in a context of uterine leiomyomata with a prior cesarean delivery. Through a recent review of the literature, we discuss the main obstetrical complications following UAE. Appropriate management of these high-risk pregnancies, notably in case of risk of adherent placenta, seems to be necessary.

Near-completion of the Human Genome Project has stimulated scientists to begin looking for the next step in unraveling normal and abnormal functions within biological systems. Consequently, there is new focus on the role of proteins in these processes. Proteomics is a burgeoning field that may provide a valuable approach to evaluate the post-traumatic central nervous system (CNS). Although we cannot provide a comprehensive assessment of all methods for protein analysis, this report summarizes some of the newer proteomic technologies that have propelled this field into the limelight and that are available to most researchers in neurotrauma. Three technical approaches (two-dimensional gel electrophoresis, direct analysis by mass spectrometry, including two-dimensional chromatography coupled to mass spectrometry and isotope coded affinity tags, and antibody technologies) are reviewed, and their advantages and disadvantages presented. A discussion of proteomic technology in the context of brain and spinal cord trauma follows, addressing current and future challenges. Proteomics will likely be very useful for developing diagnostic predictors after CNS injury and for mapping changes in proteins after injury in order to identify new therapeutic targets. Neurotrauma results in complex alterations to the biological systems within the nervous system, and these changes evolve over time. Exploration of the "new nervous system" that follows injury will require methods that can both fully assess and simplify this complexity.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

Surfaces of precooked, roast beef slices were inoculated with Clostridium perfringens , Staphylococcus aureus , Escherichia coli , Salmonella typhimurium , or Listeria monocytogenes , vacuum packaged and then stored at 3°C for 70 d to determine survival of pathogens under extended refrigerated storage in the presence of a natural competing microflora. S. typhimurium and L. monocytogenes remained present on the slices for the duration of the experiment. Numbers of S. aureus did not decrease significantly (P>0.05), and counts of C. perfringens decreased steadily over the 70-d storage period. Numbers of E. coli also declined, but more rapidly than the other pathogens during initial storage of the product. Total bacterial numbers for both uninoculated (control) and inoculated slices were similar. Samples obtained at selected locations in the processing sequence of a commercial restructured beef product contained L. monocytogenes at most sampling locations prior to heat processing, but not after heating. Salmonella was occasionally isolated from the product prior to heating. Total bacterial numbers decreased as processing day progressed, as did counts for S. aureus , E. coli , and coliforms. Counts of S. aureus and total bacterial numbers increased after the cooked product was removed from the package and coated with a seasoning mix. Data collected in this study support the designation of the following locations as critical control points: initial bacterial levels on raw products, cooking temperature and time, proper cooling after cooking, sanitation after opening the package (rubbing with seasonings and rebagging), and temperature control of the final product.

The sciatic nerve of the frog was perfused in vivo with isotonic Ringer solution followed by Ringer made hypertonic by addition of sucrose or of NaCl. Nerve diameter and endoneurial hydrostatic pressure fell during hypertonic Ringer perfusion. Using a model that describes the elastic and osmotic properties of the nerve, sigma sLp, the product of the osmotic reflection coefficient at endoneurial capillaries for s equals sucrose or NaCl (which approximates 1), and of capillary hydraulic conductivity, was found to equal 73 X 10(-13) cm3 X s-1 X dyn-1. The nerve is elastic. It has a compliance K of 3.7 X 10(-5) cm2 X mmHg-1, corresponding to a modulus of elasticity E of the perineurium equal to 1.2 X 10(6) dyn X cm-2. The results indicate that the nerve behaves as an osmometer during vascular perfusion, due to the low permeability of endoneurial capillaries to small solutes such as NaCl and sucrose. A low capillary hydraulic conductivity limits bulk water flow between blood and nerve, and a low compliance limits nerve swelling and edema.

Lanthanum, applied to the outside of the fixed sciatic nerve of Rana pipiens, did not enter the endoneurium, but was halted by functionally tight junctions at the inner layers of the perineurium. This component of the blood-nerve barrier consists of several concentric layers of cells interspersed with an extracellular matrix of amorphous ground substance, collagen fibrils, and fine filaments. Numerous vesicular profiles are closely associated with the surface membranes of all the cells. The application of lanthanum to fixed tissue revealed that these profiles are attached to the cell surface by narrow necks, and open to the extracellular space. The attenuated cells are filled by the vesicular structures, which often appear to overlap. Stereoscopic electron microscopy showed that these vesicles did not fuse with each other or with the apposing cell surface to form transcellular channels. Channel formation does not appear to contribute significantly to the permeability of any of the perineurial layers.

The effect of 120 mL (4 oz) of scotch whiskey (40% alcohol) on nocturnal gastroesophageal reflux was studied by ambulatory esophageal pH monitoring. Seventeen healthy volunteers were studied on two occasions, using a computerized radiotelemetric esophageal pH monitoring system. The subjects were given the alcohol during the second session, three hours after the evening meal, and went to bed at their usual time. Seven of the 17 subjects had prolonged supine reflux episodes on the night of alcohol ingestion. These lasted an average of 47.1 minutes (23.2 to 91.8 minutes) and occurred on an average of 3 1/2 hours after ingestion of whiskey and 1.4 hours after lying down. None of the subjects had these episodes on the control night. There was also a significant acidic shift in the cumulative percentage of data points below a pH of 3 and a pH of 4 in the supine position on the night of alcohol ingestion compared with the control night. This study has shown that there was a significant exposure of the distal esophagus to acid and that the normal acid clearance of the esophagus in the supine position was impaired after only moderate amounts of alcohol.

Blood flow was examined in sciatic nerves of pentobarbital-anesthetized rats by means of laser Doppler flowmetry (LDF) and intravenous [14C]iodoantipyrine infusion. Continuous LDF signals demonstrated slow oscillations and acute, pressure-related changes in flow. The steady-state LDF signal was related linearly to nerve blood flow, as measured with [14C]iodoantipyrine, in intact nerves and nerves stripped of the epineurium. In 14 intact nerves, nerve blood flow averaged 0.27 +/- 0.03 (SE) ml X min-1 X g-1, whereas it averaged 0.13 +/- 0.01 in 5 stripped nerves. Autoradiographs of [3H]-nicotine-infused nerves and intra-arterial injection of 57Co-labeled microspheres demonstrated that flow was not uniform throughout the nerve cross section. The results indicate that LDF can be used to examine nerve blood flow in vivo, demonstrate a linear relation between the LDF signal and flow, and establish absolute values for blood flow in intact and stripped nerves of the anesthetized rat.

A novel opiate antagonist, Nalmefene (0.5 or 5.0 mg/kg/day) was tested for its ability to modulate regional brain glucose uptake rates in genetically diabetic C57BL/KsJ mice, which normally exhibit a depressed CNS carbohydrate metabolism relative to age-matched controls. Daily Nalmefene treatment had no effect on circulating blood glucose levels in either normal or diabetic mice over a 7-week test period. However, all brain regions, except the olfactory bulbs, exhibited normalized glucose uptake rates in diabetic mice relative to controls. These data suggest a role for opiate antagonists in the modulation of CNS glucose metabolism during hyperglycemic states.

Nalmefene (6-methylene-naltrexone) is a potent, orally active, opiate antagonist. IC50's were obtained for nalmefene, naloxone and naltrexone using radiolabelled prototype ligands for mu, kappa and delta receptors in homogenates of rat brain minus cerebellum. Nalmefene antagonized the bindings of [3H]-dihydromorphine, [3H]-ethylketocyclazocine and [3H]-D-ala-D-leu enkephalin with IC50's in the low nanomolar range. At the central mu receptor, nalmefene bound with an IC50 of 1.0 nM, equal to that of naltrexone and approximately four times lower than that of naloxone. At central kappa and delta sites the IC50's for nalmefene were somewhat lower than those of naltrexone and considerably lower than those of naloxone. All three antagonists had sodium indices less than 1.0. These results indicate that nalmefene is a universal opiate antagonist, has no agonist character at the central mu site and binds more effectively to central opiate receptors than either naloxone or naltrexone.

Condensation products of beta-cyclodextrin with propylene oxide or epichlorohydrin, which are amorphous and thus very soluble in water, were used to form complexes with testosterone, progesterone, and estradiol. Sublingual/buccal administration of tablets of these complexes led to effective absorption and entry of the hormones into the systemic circulation, followed by gradual elimination; rapid first-pass loss was avoided. beta-Cyclodextrin itself, its 2,6-dimethyl derivative, and a nonionic detergent did not enable effective buccal absorption. Absorption from the GI tract of hormones complexed with hydrophilic cyclodextrins was also less effective. Effective absorption of drugs from the oral cavity requires (a) that the drug and solubilizer form a complex of the inclusion type which dissolves completely and rapidly and (b) that the solubilizer neither enters nor damages oral tissue.