Molecular and macromolecular diffusion in human meniscus: relationships with tissue structure and composition.

OBJECTIVE: To date, the pathophysiology of the meniscus has not been fully elucidated. Due to the tissue's limited vascularization, nutrients and other molecular signals spread through the extracellular matrix via diffusion or convection (interstitial fluid flow). Understanding transport mechanisms is crucial to elucidating meniscal pathophysiology, and to designing treatments for repair and restoration of the tissue. Similar to other fibrocartilaginous structures, meniscal morphology and composition may affect its diffusive properties. The objective of this study was to investigate the role of solute size, and tissue structure and composition on molecular diffusion in meniscus tissue. DESIGN: Using a custom FRAP technique developed in our lab, we measured the direction-dependent diffusivity in human meniscus of six different molecular probes of size ranging from ∼300Da to 150,000Da. Diffusivity measurements were related to sample water content. SEM images were used to investigate collagen structure in relation to transport mechanisms. RESULTS: Diffusivity was anisotropic, being significantly faster in the direction parallel to collagen fibers when compared the orthogonal direction. This was likely due to the unique structural organization of the tissue presenting pores aligned with the fibers, as observed in SEM images. Diffusion coefficients decreased as the molecular size increased, following the Ogston model. No significant correlations were found among diffusion coefficients and water content of the tissue. CONCLUSIONS: This study provides new knowledge on the mechanisms of molecular transport in meniscal tissue. The reported results can be leveraged to further investigate tissue pathophysiology and to design treatments for tissue restoration or replacement.

[Torsade de pointe resulting from a drug interaction between sotalol and ciprofloxacin]. / Torsade de pointe sur interaction médicamenteuse entre sotalol et ciprofloxacine.

Sotalol is a bêta-blocker and class 3 anti-arrhythmic. Ciprofloxacin is a fluoroquinolone antibiotic used against Gram - germs. Both drugs have a common adverse effect : they increase QT interval with a risk of torsade de pointe. The risk increases even more if other risk factors are present such as old age, female gender, renal failure, high blood pressure and ionic disturbances. Because a long QT interval is not associated with symptoms, only an electrocardiogram can establish the diagnosis. However, it's not rare that a torsade de pointe will reveal it. We report a clinical case of a long QT interval due to the association of sotalol and ciprofloxacin, which led to a torsade de pointe. Intravenous magnesium sulphate is the recommended treatment if haemodynamic parameters are good. If not, an external electric shock may be needed.

Le sotalol est un bêta-bloquant utilisé principalement comme anti-arythmique de classe 3. La ciprofloxacine est un antibiotique de la classe des fluoroquinolones, actif sur les germes Gram négatif. Ces deux médicaments présentent, comme effet secondaire commun, le fait d'augmenter l'espace QT avec un risque de torsade de pointe. Si on y ajoute les autres facteurs de risque d'un allongement de QT que sont notamment l'âge, le sexe féminin, l'insuffisance rénale, l'hypertension artérielle et les troubles ioniques, le risque de torsade de pointe est encore majoré. Comme un QT long ne s'accompagne pas de symptômes, seul l'électrocardiogramme permet d'établir le diagnostic. Il n'est néanmoins pas rare qu'une torsade de pointe le révèle. Nous rapportons ici un cas dont le QT long engendré par une association sotalol-ciprofloxacine s'est manifesté par une torsade de pointe chez une patiente âgée avec insuffisance rénale. Le traitement est le sulfate de magnésium par voie intraveineuse si les paramètres hémodynamiques restent bons. S'ils viennent à se dégrader, un choc électrique externe peut s'avérer nécessaire.

Early expression of yeast genes affected by chemical stress.

The variety of environmental stresses is probably the major challenge imposed on transcription activators and the transcriptional machinery. To precisely describe the very early genomic response developed by yeast to accommodate a chemical stress, we performed time course analyses of the modifications of the yeast gene expression program which immediately follows the addition of the antimitotic drug benomyl. Similar analyses were conducted with different isogenic yeast strains in which genes coding for relevant transcription factors were deleted and coupled with efficient bioinformatics tools. Yap1 and Pdr1, two well-known key mediators of stress tolerance, appeared to be responsible for the very rapid establishment of a transient transcriptional response encompassing 119 genes. Yap1, which plays a predominant role in this response, binds, in vivo, promoters of genes which are not automatically up-regulated. We proposed that Yap1 nuclear localization and DNA binding are necessary but not sufficient to elicit the specificity of the chemical stress response.

yMGV: a database for visualization and data mining of published genome-wide yeast expression data.

The yeast Microarray Global Viewer (yMGV) is an on-line database providing a synthetic view of the transcriptional expression profiles of Saccharomyces cerevisiae genes in most of the published expression datasets. yMGV displays a one-screen graphical representation of gene expression variations for each published genome-wide experiment, allowing quick retrieval of experimental conditions affecting expression of this gene. yMGV also provides tools to isolate groups of genes sharing similar transcription profiles in a defined subset of experiments. Additionally, yMGV furnishes a set of statistical tools for critical assessment of published data. We therefore believe that yMGV is an efficient tool that affords a quick and comprehensive overview of microarray data and generates new gene classifications. As of 20 March 2001 the yMGV database contains 6 000 000 measurements, representing genome-wide expression comparisons of 932 experiments from 39 microarray publications. The yMGV interface is available at http://transcriptome.ens.fr/ymgv/.

An artificial transcription activator mimics the genome-wide properties of the yeast Pdr1 transcription factor.

We analysed the genome-wide regulatory properties of an artificial transcription activator in which the DNA-binding domain of the yeast transcription factor, Pdr1, was fused to the activation domain of Gal4 (Pdr1*GAD). This Pdr1*GAD chimera was put under the control of the inducible GAL1 promoter. DNA microarray analyses showed that all the target genes upregulated by the well-studied native gain-of-function Pdr1-3 mutant were similarly activated by the chimerical factor Pdr1*GAD upon galactose induction. Additionally, this kinetic approach led us not only to confirm previously published targets, but also to define a hierarchy among members of the Pdr1 regulon. Our observations prove, for the first time at the complete genome level, that the DNA-binding domain of Pdr1 is sufficient to guide its specificity. We propose that this approach could be useful for the study of new transcription factors identified in silico from sequenced organisms. Complete data are available at www.biologie.ens.fr/yeast-publi.html.

Transcriptomes, transcription activators and microarrays.

Gene-specific transcription activators are among the main factors which specifically shape the transcriptome profiles. It is tempting to take advantage of their properties to decipher the genome expression circuitry. The advent of microarray technology has offered fantastic opportunities to quickly analyze the expression profiles dictated by specific transcription factors. This review will first focus on the strategies which have been devised to control the activity of transcription factors and in the second part on the microarray experiments which addressed the role of these transcription factors in the genome-wide expression profile. This last part will mainly consider the case of the yeast Saccharomyces cerevisiae genome. All the collected data are available through the on-line database yTAFNET (http://transcriptome.ens.fr/ytafnet/). yTAFNET is designed to help the characterization of connections between the different yeast regulatory networks.

Image Upconversion from the Visible to the UV Domain: Application to Dynamic UV Microstereolithography.

We present what to our knowledge is a new application of optical frequency upconversion of images in quadratic materials to dynamic UV microstereolithography. A 150 x 150 point visible image transmitted by a liquid-crystal display was upconverted in a lithium triborate crystal, and the UV image was successfully used to polymerize a commercial stereolithographic resin.

Gain in phase sensitive parametric image amplification

We report an experiment of type 2 parametric image amplification in a phase sensitive configuration. In the spatial frequency domain, the parametric gain corresponds to amplification or deamplification, depending on the relative phase of the input image with respect to the pump wave and on the spatial frequencies of the input image.

Two-dimensional time-resolved direct imaging through thick biological tissues: a new step toward noninvasive medical imaging.

We report an original two-dimensional time-resolved direct imaging method for transillumination optical tomography that combines the time-gating and forward phase-conjugation properties of type II degenerate parametric amplification. An object with subcentimeter resolution embedded in 4-cm-thick chicken breast tissue was imaged with a signal-to-noise ratio of 2.

Image restoration through aberrant media by optical phase conjugation in a type II three-wave mixing interaction.

Restoration of an image through an aberrant plate has been achieved by use of optical phase conjugation in a type II parametric interaction in which the amplified signal and idler waves are reflected back through the aberrant medium. The resolution of the restored phase-conjugate images is equal to 0.18 mm, and the amplification gain is ~4dB.

Imaging through scattering media by parametric amplification of images: study of the resolution and the signal-to-noise ratio.

An imaging scheme through scattering media in which parametric image amplification is used is presented. An image of a resolution chart through a solution of latex microspheres with an attenuation of 22 mean free paths is obtained with a resolution of 20 mum. The evolution of the signal-to-noise ratio with respect to the medium attenuation is studied and compared with a rough modeling of the imaging process.

Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise.

In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of beta-adrenoceptor blockade on renin-aldosterone and alpha-ANF during exercise at altitude.

The renin-aldosterone system may be depressed in subjects exercising at high altitude, thereby preventing excessive angiotensin I (ANG I) and aldosterone levels, which could favor the onset of acute mountain sickness. The role of beta-adrenoceptors in hormonal responses to hypoxia was investigated in 12 subjects treated with a nonselective beta-blocker, pindolol. The subjects performed a standardized maximal bicycle ergometer exercise with (P) and without (C) acute pindolol treatment (15 mg/day) at sea level, as well as during a 5-day period at high altitude (4,350 m, barometric pressure 450 mmHg). During sea-level exercise, pindolol caused a reduction in plasma renin activity (PRA, 2.83 +/- 0.35 vs. 5.13 +/- 0.7 ng ANG I.ml-1.h-1, P less than 0.01), an increase in plasma alpha-atrial natriuretic factor (alpha-ANF) level (23.1 +/- 2.9 (P) vs. 10.4 +/- 1.5 (C) pmol/1, P less than 0.01), and no change in plasma aldosterone concentration [0.50 +/- 0.04 (P) vs. 0.53 +/- 0.03 (C) nmol/1]. Compared with sea-level values, PRA (3.45 +/- 0.7 ng ANG I.ml-1.h-1) and PA (0.39 +/- 0.03 nmol/1) were significantly lower (P less than 0.05) during exercise at high altitude. alpha-ANF was not affected by hypoxia. When beta-blockade was achieved at high altitude, exercise-induced elevation in PRA was completely abolished, but no additional decline in PA occurred. Plasma norepinephrine and epinephrine concentrations tended to be lower during maximal exercise at altitude; however, these differences were not statistically significant. Our results provide further evidence that hypoxia has a suppressive effect on the renin-aldosterone system. However, beta-adrenergic mechanisms do not appear to be responsible for inhibition of renin secretion at high altitude.

A fully automated system using a microcomputer for the hypertensive activity assays of drugs in the anesthetized rat.

A complete system is described for the computerized automation of the determination of activity of hypertensive drugs in the anesthetized rat. The microcomputer used was the Apple IIe, and the automation was performed by a purpose-designed command module. The series of injections of hypertensive drugs was controlled by the microcomputer through the intermediary of the command module. All processing of the signal (hypertension peak), calculation of the data obtained, statistical processing, and archive storage of the results was carried out entirely by the microcomputer. The computer was able unaided to control three work stations simultaneously without requiring synchronization.

[Reference values of chemical constituents and plasma enzymes in minipigs]. / Valeurs de référence des constituants chimiques et des enzymes plasmatiques chez le miniporc.

Nine male minipigs Pitman Moore have been studied from weaning (To) and during 6 months and the following constituents have been measured: albumin, amylase, bilirubin, calcium, CK, cholesterol, creatinine, copper, iron, GGT, glucose, LDH, magnesium, PAL, phospholipids, potassium, proteins, sodium, ALT, ASP, triglycerides, urea, zinc. These animals were fed a standardized diet. At 6 months of age their weight increased progressively to 12 kg. Several factors of variation have been studied; time of blood sampling age of animals. We obtained the following results: values of bilirubin, CK and TGO were always lower at 8 a.m. than 12 a.m. and 6 p.m. The effects of age were variable. They are no variation in the values of only 4 parameters (calcium, sodium, potassium and triglycerides), while the others constituents were increased or decreased. Reference values for 21 blood parameters in Pitman Moore minipigs are described.