Evaluation of arterial compliance-pressure curves. Effect of antihypertensive drugs.

A new high-precision ultrasonic device was developed to determine noninvasively arterial compliance as a function of blood pressure. Because of the nonlinear elastic properties of arterial walls, measurements of compliance can be appropriately compared only if obtained over a range of pressures. This apparatus was used to evaluate in a double-blind, parallel fashion the effect of three different antihypertensive drugs and of a placebo on radial artery compliance. Thirty-two normotensive volunteers were randomly allocated to an 8-day, once-a-day oral treatment with either a placebo, 100 mg atenolol, 20 mg nitrendipine, or 20 mg lisinopril. Blood pressure, heart rate, radial artery diameter, and arterial compliance were measured immediately before as well as 6 hours after dosing on the first and last days of the study. On the eighth day of administration, within 6 hours after dosing, lisinopril induced an acute increase in radial artery diameter, from 2.99 +/- 0.06 to 3.28 +/- 0.09 mm (mean +/- SEM, p less than 0.01). The compliance-pressure curve was shifted upward on day 1 (p less than 0.01) as well as on day 8 (p less than 0.05). None of the other drugs induced any significant modification of these parameters. Arterial compliance has a strong nonlinear dependency on intra-arterial pressure and therefore has to be defined as a function of pressure. Antihypertensive drugs acting by different mechanisms may have different effects on the mechanical properties of large arteries.

Etude de l'activation et de l'inactivation pH-dépendantes des canaux ASICs (Acide-Sensing Ion Channels)

RESUME: Etude de l'activation et de l'inactivation pH-dépendantes des canaux ASICs (Acid-Sensing Ion Channels) Benoîte BARGETON, Département de Pharmacologie et de Toxicologie, Université de Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Suisse Les canaux sodiques ASICs (Acid-Sensing Ion Channels) participent à la signalisation neuronale dans les systèmes nerveux périphérique et central. Ces canaux non voltage dépendants sont impliqués dans l'apprentissage, l'expression de la peur, la neurodégénération consécutive à une attaque cérébrale et la douleur. Les bases moléculaires sous-tendant leur activité ne sont pas encore totalement comprises. Ces canaux sont activés par une acidification du milieu extracellulaire et régulés, entre autres, par des ions tels que le Ca2+, le Zn2+ et le CI". La cristallisation de ASIC inactivé a été publiée. Le canal est un trimére de sous-unités identiques ou homologues. Chaque sous-unité a été décrite en analogie à un avant bras, un poignet et une main constituée d'un pouce, d'un doigt, d'une articulation, une boule β et une paume. Nous avons appliqué une approche bioinformatique systématique pour identifier les pH senseurs putatifs de ASICIa. Le rôle des pH senseurs putatifs a été testé par mutagénèse dirigée et des modifications chimiques combinées à une analyse fonctionnelle afin de comprendre comment les variations de ρ H ouvrent ces canaux. Les pH senseurs sont des acides aspartiques et glutamiques éparpillés sur la boucle extracellulaire suggérant que les changements de pH contrôlent l'activation et l'inactivation de ASIC en (dé)protonant ces résidus en divers endroits de la protéine. Par exemple lors de l'activation, la protonation des résidus à l'interface entre le pouce, la boule β et le doigt d'une même sous-unité induit un mouvement du pouce vers la bouie β et le doigt. De même lors de l'inactivation du canal les paumes des trois sous-unités formant une cavité se rapprochent. D'après notre approche bioinformatique, aucune histidine n'est impliquée dans la détection des variations de pH extracellulaire c'est-à-dire qu'aucune histidine ne serait un pH-senseur. Deux histidines de ASIC2a lient le Zn2+ et modifient l'affinité apparente du canal pour les protons. Une seule des deux est conservée parmi tous les ASICs, hASICIa H163. Elle forme un réseau de liaison hydrogène avec ses voisins conservés. L'étude détaillée de ce domaine, Pinterzone, montre son importance dans l'expression fonctionnelle des canaux. La perturbation de ce réseau par l'introduction d'un résidu hydrophobe (cystéine) par mutagénèse dirigée diminue l'expression du canal à la membrane plasmique. La modification des cystéines introduites par des réactifs spécifiques aux groupements sulfhydryle inhibe les canaux mutés en diminuant leur probabilité d'ouverture. Ces travaux décrivent les effets de l'acidification du milieu extracellulaire sur les canaux ASICs. ABSTRACT: Study of pH-dependent activation and inactivation of ASIC channels Benoîte BARGETON, Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, CH-1G05 Lausanne, Switzerland The ASIC (Acid-Sensing Ion Channels) sodium channels are involved in neuronal signaling in the central and peripheral nervous system. These non-voltage-gated channels are involved in learning, the expression of fear, neurodegeneration after ischemia and pain sensation. The molecular bases underlying their activity are not yet fully understood. ASICs are activated by extracellular acidification and regulated, eg by ions such as Ca2+, the Zn2+ and CI". The crystallization of inactivated ASIC has been published. The channel is a trimer of identical or homologous subunits. Each subunit has been described in analogy to a forearm, wrist and hand consisting of a thumb, a finger, a knuckle, a β-ball and a palm. We applied a systematic computational approach to identify putative pH sensor(s) of ASICIa. The role of putative pH sensors has been tested by site-directed mutagenesis and chemical modification combined with functional analysis in order to understand how changes in pH open these channels. The pH sensors are aspartic and glutamic acids distributed throughout the extracellular loop, suggesting that changes in pH control activation and inactivation of ASIC by protonation / deprotonation of many residues in different parts of the protein. During activation the protonation of various residues at the interface between the finger, the thumb and the β-ball induces the movement of the thumb toward the finger and the β-ball. During inactivation of the channel the palms of the three subunits forming a cavity approach each other. No histidine has been shown to be involved in extracellular pH changes detection, i.e. no histidine is a pH- sensor. Two histidines of ASIC2 bind Zn2+ and alter the apparent affinity of channel for protons. Only one of the two His is conserved among all ASICs, hASICIa H163. This residue is part of a network of hydrogen bonding with its conserved neighbors. The detailed study of this area, the interzone, shows its importance in the functional expression of ASICs. Disturbance of this network by the introduction of hydrophobic residues decreases the cell surface channel expression. Chemical modification of the introduced cysteines by thiol reactive compounds inhibits the mutated channels by a reduction of their open probability. These studies describe the effects of extracellular acidification on ASICs. RESUME GRAND PUBLIC: Etude de l'activation et de l'inactivation pH-dépendantes des canaux ASICs (Acid-Sensing Ion Channels) Benoîte BARGETON, Département de Pharmacologie et de Toxicologie, Université de Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Suisse La transmission synaptique est un processus chimique entre deux neurones impliquant des neurotransmetteurs et leurs récepteurs. Un dysfonctionnement de certains types de synapses est à l'origine de beaucoup de troubles nerveux, tels que certaine forme d'épilepsie et de l'attention. Les récepteurs des neurotransmetteurs sont de très bonnes cibles thérapeutiques dans de nombreuses neuropathologies. Les canaux ASICs sont impliqués dans la neurodégénération consécutive à une attaque cérébrale et les bloquer pourraient permettre aux patients d'avoir moins de séquelles. Les canaux ASICs sont des détecteurs de l'acidité qui apparaît lors de situations pathologiques comme l'ischémie et l'inflammation. Ces canaux sont également impliqués dans des douleurs. Cibler spécifiquement ces canaux permettrait d'avoir de nouveaux outils thérapeutiques car à l'heure actuelle l'inhibiteur de choix, l'amiloride, bloque beaucoup d'autres canaux empêchant son utilisation pour bloquer les ASICs. C'est pourquoi il faut connaître et comprendre les bases moléculaires du fonctionnement de ces récepteurs. Les ASICs formés de trois sous-unités détectent les variations de l'acidité puis s'ouvrent transitoirement pour laisser entrer des ions chargés positivement dans la cellule ce qui active la signalisation neuronale. Afin de comprendre les bases moléculaires de l'activité des ASICs nous avons déterminé les sites de liaison des protons (pH-senseurs), ligands naturels des ASICs et décrit une zone importante pour l'expression fonctionnelle de ces canaux. Grâce à une validation systématique de résultats obtenus en collaboration avec l'Institut Suisse de Bioinformatique, nous avons décrit les pH-senseurs de ASICIa. Ces résultats, combinés à ceux d'autres groupes de recherche, nous ont permis de mieux comprendre comment les ASICs sont ouverts par une acidification du milieu extracellulaire. Une seconde étude souligne le rôle structural crucial d'une région conservée parmi tous les canaux ASICs : y toucher c'est diminuer l'activité de la protéine. Ce domaine permet l'harmonisation des changements dus à l'acidification du milieu extracellulaire au sein d'une même sous-unité c'est-à-dire qu'elle participe à l'induction de l'inactivation due à l'activation du canal Cette étude décrit donc quelle région de la protéine atteindre pour la bloquer efficacement en faisant une cible thérapeutique de choix.

Hydrogen-induced changes in the breakdown voltage of InP HEMTs

In this work, electrical measurements show that the breakdown voltage,BVDG, of InP HEMTs increases following exposure to H2. This BVDG shift is nonrecoverable. The increase in BVDG is found to be due to a decrease in the carrier concentration in the extrinsic portion of the device.We provide evidence that H2 reacts with the exposed InAlAs surface in the extrinsic region next to the gate, changing the underlying carrier concentration. Hall measurements of capped and uncapped HEMT samples show that the decrease in sheet carrier concentration can be attributed to a modification of the exposed InAlAs surface. Consistent with this, XPS experiments on uncapped heterostructures give evidence of As loss from the InAlAs surface upon exposure to hydrogen.

In vitro evaluation of staphylococcus aureus biofilm formation on bone grafts and bone substitues

Background: Bacteria form a biofilm on the surface of orthopaedic devices, causing persistent and infection. Little is known about biofilms formation on bone grafts and bone substitutes. We analyzed various representative materials regarding their propensity for biofilm formation caused by Staphylococcus aureus.Methods: As bone graft beta-tricalciumphosphate (b-TCP, CyclOsTM) and as bone substitute a tantalum metal mesh (trabecular metalTM) and PMMA (Pala-cosTM) were investigated. As test organism S. aureus (strain ATCC 29213) was used. Test materials were incubated with bacterial solution of 105 colony-forming units (cfu)/ml at 37°C for 24 h without shaking. After 24 h, the test materials were removed and washed 3 times in normal saline, followed by sonication in 50 ml Ringer solution at 40 kHz for 5 minutes. The resulting sonication fluid was plated in aliquots of 0.1 ml onto aerobe blood agar with 5% sheep blood and incubated at 37°C with 5% CO2 for 24 h. Then, bacterial counts were enumerated and expressed as cfu/ml. All experiments were performed in triplicate to calculate the mean ± standard deviation. The Wilcoxon test was used for statistical calculations.Results: The three investigated materials show a differing specific surface with b-TCB>trabecular metal>PMMA per mm2. S. aureus formed biofilm on all test materials as confirmed by quantitative culture after washing and sonication. The bacterial counts in sonication fluid (in cfu/ml) were higher in b-TCP (5.1 x 106 ± 0.6 x 106) and trabecular metal (3.7 x 106 ± 0.6 x 106) than in PMMA (3.9 x 104 ± 1.8 x 104), p<0.05.Conclusion: Our results demonstrate that about 100-times more bacteria adhere on b-TCP and trabecular metal than on PMMA, reflecting the larger surface of b-TCP and trabecuar metal compared to the one of PMMA. This in-vitro data indicates that bone grafts are susceptible to infection. Further studies are needed to evaluate efficient approaches to prevent and treat infections associated with bone grafts and substitutes, including modification of the surface or antibacterial coating.

Numerical algorithm for Ginzburg-Landau equations with multiplicative noise: Application to domain growth

We consider stochastic partial differential equations with multiplicative noise. We derive an algorithm for the computer simulation of these equations. The algorithm is applied to study domain growth of a model with a conserved order parameter. The numerical results corroborate previous analytical predictions obtained by linear analysis.

Evaluation of Bridge Replacement Alternatives for the County Bridge System, HR-365 August 1994

Recent reports have indicated that 23.5 percent of the nation's highway bridges are structurally deficient and 17.7 percent are functionally obsolete. A significant number of these bridges are on the Iowa county road system. The objective of the investigation described in this report was to identify, review and evaluate replacement bridges currently being used by various counties in Iowa and surrounding states. Iowa county engineers, county engineers in neighboring states as well as private manufacturers of bridge components, and regional precad prestressed concrete manufacturers were contacted to determine the most common replacement bridge types being used. Depending upon the findings of the review, possible improvements and/or new replacement bridge systems were to be proposed. A questionnaire was developed and sent to county engineers in Iowa and several counties in surrounding states. The results of the questionnaire showed that the most common replacement bridges in Iowa are the continuous concrete slab and prestressed concrete bridges. The primary reason these types are used is because of the availability of standard designs and because of their ease of maintenance. Counties seldom construct these types of bridges using their own labor forces, but instead contract the work. However, county forces are used to construct steel stringer, precast reinforced concrete and timber bridges. In general, 69 percent of the counties indicate an ability and willingness to use their own forces to design and construct relatively short span bridges (i.e., 40 A or less) provided the construction procedures are relatively simple. Several unique replacement bridge types used in Iowa that are constructed by county forces are documented and presented in this report. Sufficient details are provided to allow county engineers to determine if some of these bridges could be used to resolve some of their own replacement bridge problems. Where possible, cost information has also been provided. Each of these bridge types were evaluated for various criteria (e.g., cost effectiveness, conformance to AASI-ITO standards, range of sizes, etc.) by a panel of four Iowa county engineers; a summary of this critique is included. After evaluating the questionnaire responses from the counties and evaluating the various bridge replacement concepts currently in use, one new bridge replacement concept and one modification of a current Iowa county bridge replacement concept were developed. Both of these concepts would utilize county labor forces.

Inhibition of cell migration and invasion mediated by the TAT-RasGAP317-326 peptide requires the DLC1 tumor suppressor.

TAT-RasGAP317-326, a peptide corresponding to the 317-326 sequence of p120 RasGAP coupled with a cell-permeable TAT-derived peptide, sensitizes the death response of various tumor cells to several anticancer treatments. We now report that this peptide is also able to increase cell adherence, prevent cell migration and inhibit matrix invasion. This is accompanied by a marked modification of the actin cytoskeleton and focal adhesion redistribution. Interestingly, integrins and the small Rho GTP-binding protein, which are well-characterized proteins modulating actin fibers, adhesion and migration, do not appear to be required for the pro-adhesive properties of TAT-RasGAP317-326. In contrast, deleted in liver cancer-1, a tumor suppressor protein, the expression of which is often deregulated in cancer cells, was found to be required for TAT-RasGAP317-326 to promote cell adherence and inhibit migration. These results show that TAT-RasGAP317-326, besides its ability to favor tumor cell death, hampers cell migration and invasion.

Emplacement of ultramafic rocks into the continental crust monitored by light and other trace elements: An example from the Geisspfad body (Swiss-Italian Alps)

In order to evaluate the influence of continental crustal rocks on trace element budgets of serpentinized peridotites incorporated into the continental crust, we have analyzed the chemical composition of whole rock samples and minerals of the Geisspfad ultramafic complex (Swiss-Italian Alps). This complex represents a relict oceanic succession composed of serpentinites, ophicarbonates and metabasic rocks, emplaced into crustal gneisses during Alpine collision. Following peak metamorphic amphibolite facies conditions, fluid flow modified some of the trace element contents of ophicarbonates and deformed serpentinites close to the contact with country rocks. The fluid originated from the surrounding continental crustal rocks as documented by the increase of Pb in the serpentinites, and by the strongly negative all) values (-112 parts per thousand) of some ultramafic rocks close to the contact with surrounding gneisses. Little or no modification of the fluid mobile elements Li, B or U was observed in the serpentinite. In-situ analysis of light elements of serpentinite minerals indicate redistribution of light elements coupled to changes of mineral modes towards the outer 100-150 m of the massif. In the centre of the massif, Li is preferentially concentrated in olivine, while Be and B are hosted by tremolite. In contrast, at the outer rim of the massif, Li and Be are preferentially incorporated into diopside, and B into antigorite. This redistribution of light elements among the different minerals is visible in the serpentinite, at a maximum distance of -100-150 m from the ophicarbonate-metabasite contact. Our results show that interaction of ultramafic rocks and crust-derived fluids can be easily detected by studies of Pb and partial derivative D in whole rocks. We argue that small ultramafic bodies potentially record an emplacement-related trace element signature, and that crustal light element values in ultramafic rocks are not necessarily derived from a subducting slab. (C) 2008 Elsevier B.V. All rights reserved.

Mismatch of arterial and central venous blood gas analysis during haemorrhage.

BACKGROUND AND OBJECTIVE: Arterial base excess and lactate levels are key parameters in the assessment of critically ill patients. The use of venous blood gas analysis may be of clinical interest when no arterial blood is available initially. METHODS: Twenty-four pigs underwent progressive normovolaemic haemodilution and subsequent progressive haemorrhage until the death of the animal. Base excess and lactate levels were determined from arterial and central venous blood after each step. In addition, base excess was calculated by the Van Slyke equation modified by Zander (BE(z)). Continuous variables were summarized as mean +/- SD and represent all measurements (n = 195). RESULTS: Base excess according to National Committee for Clinical Laboratory Standards for arterial blood was 2.27 +/- 4.12 versus 2.48 +/- 4.33 mmol(-l) for central venous blood (P = 0.099) with a strong correlation (r(2) = 0.960, P < 0.001). Standard deviation of the differences between these parameters (SD-DIFBE) did not increase (P = 0.355) during haemorrhage as compared with haemodilution. Arterial lactate was 2.66 +/- 3.23 versus 2.71 +/- 2.80 mmol(-l) in central venous blood (P = 0.330) with a strong correlation (r(2) = 0.983, P < 0.001). SD-DIFLAC increased (P < 0.001) during haemorrhage. BE(z) for central venous blood was 2.22 +/- 4.62 mmol(-l) (P = 0.006 versus arterial base excess according to National Committee for Clinical Laboratory Standards) with strong correlation (r(2) = 0.942, P < 0.001). SD-DIFBE(z)/base excess increased (P < 0.024) during haemorrhage. CONCLUSION: Central venous blood gas analysis is a good predictor for base excess and lactate in arterial blood in steady-state conditions. However, the variation between arterial and central venous lactate increases during haemorrhage. The modification of the Van Slyke equation by Zander did not improve the agreement between central venous and arterial base excess.

Involvement of gap junctional intercellular communication in the pathophysiology of inflammation

SUMMARY Inflammation has evolved as a mechanism to defend the body against invading microorganisms and to respond to injury. It requires the coordinated response of a large number of cell types from the whole organism in a time- and space-dependent fashion. This coordination involves several cell-cell communication mechanisms. Exchange of humoral mediators such as cytokines is a major one. Moreover, direct contact between cells happens and plays a primordial role, for example when macrophages present antigens to lymphocytes. Contact between endothelial cells and leucocytes occurs when the latter cross the blood vessel barrier and transmigrate to the inflammatory site. A particular way by which cells communicate with each other in the course of inflammation, which at this time starts to gain attention, is the intercellular communication mediated by gap junctions. Gap junctions are channels providing a direct pathway (i.e. without transit through the extracellular space) for the diffusion of small molecules between adjacent cells. This process is known as gap junctional intercellular communication (GJIC). The general aim of this thesis was to study a possible involvement of GJIC in the pathophysiology of inflammation. A first part of the work was dedicated to study the implication of GJIC in the modification of vascular endothelial function by inflammation. In a second part, we were interested in the possible role of GJIC in the transmigration of neutrophil polymorphonuclear leucocytes through the endothelium. The main positive finding of this work is that acute inflammation preferentially modulates the expression of connexin 40 (Cx40), a gap junction protein specifically expressed in vascular endothelium. The modulation could be towards overexpression (aortic endothelium of septic rats) or towards downregulation (acutely inflamed mouse lung). We put a lot of efforts in search of possible functions of these modulations, in two directions: a potential protective role of Cx40 increased expression against sepsis-induced endothelial dysfunction, and a facilitating role of Cx40 decreased expression in neutrophil transmigration. To pursue both directions, it seemed logical to study the impact of Cx40 deletion using knock-out mice. Concerning the potential protective role of Cx40 overexpression we encountered a roadblock as we observed, in the aorta, a Cx40 downregulation in wild type mouse whereas Cx40 was upregulated in the rat. Regarding the second direction and using an in vivo approach, we observed that pulmonary neutrophil transmigration was not affected by the genetic deletion of Cx40. In spite of their negative nature, these results are the very first ones regarding the potential implication of GJIC concerning leucocyte transmigration in vivo. Because this process involves such tight cell-cell physical contacts, the hypothesis for a role of GJIC remains attractive.

Effect of substrate temperature on deposition rate of rf plasma-deposited hydrogenated amorphous silicon thin films

We present a study about the influence of substrate temperature on deposition rate of hydrogenated amorphous silicon thin films prepared by rf glow discharge decomposition of pure silane gas in a capacitively coupled plasma reactor. Two different behaviors are observed depending on deposition pressure conditions. At high pressure (30 Pa) the influence of substrate temperature on deposition rate is mainly through a modification of gas density, in such a way that the substrate temperature of deposition rate is similar to pressure dependence at constant temperature. On the contrary, at low pressure (3 Pa), a gas density effect cannot account for the observed increase of deposition rate as substrate temperature rises above 450 K with an activation energy of 1.1 kcal/mole. In accordance with laser‐induced fluorescence measurements reported in the literature, this rise has been ascribed to an increase of secondary electron emission from the growing film surface as a result of molecular hydrogen desorption.

Hydroxyapatite coatings grown by pulsed laser deposition with a beam of 355 nm wavelength

Calcium phosphate coatings, obtained at different deposition rates by pulsed laser deposition with a Nd:YAG laser beam of 355-nm wavelength, were studied. The deposition rate was changed from 0.043 to 1.16 /shot by modification of only the ablated area, maintaining the local fluence constant to perform the ablation process in similar local conditions. Characterization of the coatings was performed by scanning electron microscopy, x-ray diffractometry, and infrared, micro-Raman, and x-ray photoelectron spectroscopy. The coatings showed a compact surface morphology formed by glassy gains with some droplets on them. Only hydroxyapatite (HA) and alpha-tricalcium phosphate (alpha-TCP) peaks were found in the x-ray diffractograms. The relative content of alpha TCP diminished with decreasing deposition rates, and only HA peaks were found for the lowest rate. The origin of alpha TCP is discussed.

Optical correlation by use of partial phase-only modulation with VGA liquid-crystal displays

The development of liquid-crystal panels for use in commercial equipment has been aimed at improving the pixel resolution and the display efficiency. These improvements have led to a reduction in the thickness of such devices, among other outcomes, that involves a loss in phase modulation. We propose a modification of the classical phase-only filter to permit displays in VGA liquid-crystal panels with a constant amplitude modulation and less than a 2¿(PI) phase modulation. The method was tested experimentally in an optical setup.

Influence of the dipolar interactions in the magnetization reversal asymmetry of hard-soft magnetic ribbons

Partial crystallization of the metallic glass Co66Si16B12Fe4Mo2 was performed by annealing at temperatures between 500 and 540°C for 10-20 min, resulting in crystallite volume fractions of (0.7-5)×10¿3 and sizes of 50-100 nm. This two-phase alloy presents a remarkable feature: a hysteresis loop shift that can be tailored by simply premagnetizing the sample in the adequate magnetic field. Shifts as large as five times the coercive field have been obtained which make them interesting for application as magnetic cores in dc pulse transformers. The asymetrical magnetic reversal is explained in terms of the magnetic dipolar field interaction and the observed hysteresis loops have been satisfactorily simulated by a modification of Stoner-Wohlfarth¿s model of coherent rotations.

Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma.

5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases. It is known to inhibit the production of cytokines and inflammatory mediators, but the mechanism underlying the intestinal effects of 5-ASA remains unknown. Based on the common activities of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands and 5-ASA, we hypothesized that this nuclear receptor mediates 5-ASA therapeutic action. To test this possibility, colitis was induced in heterozygous PPAR-gamma(+/-) mice and their wild-type littermates, which were then treated with 5-ASA. 5-ASA treatment had a beneficial effect on colitis only in wild-type and not in heterozygous mice. In epithelial cells, 5-ASA increased PPAR-gamma expression, promoted its translocation from the cytoplasm to the nucleus, and induced a modification of its conformation permitting the recruitment of coactivators and the activation of a peroxisome-proliferator response element-driven gene. Validation of these results was obtained with organ cultures of human colonic biopsies. These data identify PPAR-gamma as a target of 5-ASA underlying antiinflammatory effects in the colon.