Strengthening of Existing Single Span Steel Beam and Concrete Deck Bridges, HR-238, Part 1, 1983

The Phase I research, Iowa Department of Transportation (IDOT) Project HR-214, "Feasibility Study of Strengthening Existing Single Span Steel Beam Concrete Deck Bridges," verified that post-tensioning can be used to provide strengthening of the composite bridges under investigation. Phase II research, reported here, involved the strengthening of two full-scale prototype bridges - one a prototype of the model bridge tested during Phase I and the other larger and skewed. In addition to the field work, Phase II also involved a considerable amount of laboratory work. A literature search revealed that only minimal data existed on the angle-plus-bar shear connectors. Thus, several specimens utilizing angle-plus-bar, as well as channels, studs and high strength bolts as shear connectors were fabricated and tested. To obtain additional shear connector information, the bridge model of Phase I was sawed into four composite concrete slab and steel beam specimens. Two of the resulting specimens were tested with the original shear connection, while the other two specimens had additional shear connectors added before testing. Although orthotropic plate theory was shown in Phase I to predict vertical load distribution in bridge decks and to predict approximate distribution of post-tensioning for right-angle bridges, it was questioned whether the theory could also be used on skewed bridges. Thus, a small plexiglas model was constructed and used in vertical load distribution tests and post-tensioning force distribution tests for verification of the theory. Conclusions of this research are as follows: (1) The capacity of existing shear connectors must be checked as part of a bridge strengthening program. Determination of the concrete deck strength in advance of bridge strengthening is also recommended. (2) The ultimate capacity of angle-plus-bar shear connectors can be computed on the basis of a modified AASHTO channel connector formula and an angle-to-beam weld capacity check. (3) Existing shear connector capacity can be augmented by means of double-nut high strength bolt connectors. (4) Post-tensioning did not significantly affect truck load distribution for right angle or skewed bridges. (5) Approximate post-tensioning and truck load distribution for actual bridges can be predicted by orthotropic plate theory for vertical load; however, the agreement between actual distribution and theoretical distribution is not as close as that measured for the laboratory model in Phase I. (6) The right angle bridge exhibited considerable end restraint at what would be assumed to be simple support. The construction details at bridge abutments seem to be the reason for the restraint. (7) The skewed bridge exhibited more end restraint than the right angle bridge. Both skew effects and construction details at the abutments accounted for the restraint. (8) End restraint in the right angle and skewed bridges reduced tension strains in the steel bridge beams due to truck loading, but also reduced the compression strains caused by post-tensioning.

Design Manual for Strengthening Single-Span Composite Bridges by Post-Tensioning Part 3, HR-238, 1985

The authors have post-tensioned and monitored two Iowa bridges and have field tested the post-tensioning of a composite bridge in Florida. In order to provide the practical post-tensioning distribution factors given in this manual, the authors developed a finite element model of a composite bridge and checked the model against a one-half scale laboratory bridge and two actual composite bridges, one of which had a 45 deg skew. Following a brief discussion of this background research, this manual explains the use of elastic, composite beam and bridge section properties, the distribution fractions for symmetrically post-tensioned exterior beams, and a method for computing the strength of a post-tensioned beam. Also included is a design example for a typical, 51.25-ft (15.62-m) span, four-beam composite bridge. Moments for Iowa Department of Transportation rating trucks, H 20 and HS 20 trucks, have been tabulated for design convenience and are included in the appendix.

Composite Precast Prestressed Concrete Bridge Slabs, HR-310, 1991

Precast prestressed concrete panels have been used as subdecks in bridge construction in Iowa and other states. To investigate the performance of these types of composite slabs at locations adjacent to abutment and pier diaphragms in skewed bridges, a research prcject which involved surveys of design agencies and precast producers, field inspections of existing bridges, analytical studies, and experimental testing was conducted. The survey results from the design agencies and panel producers showed that standardization of precast panel construction would be desirable, that additional inspections at the precast plant and at the bridge site would be beneficial, and that some form of economical study should be undertaken to determine actual cost savings associated with composite slab construction. Three bridges in Hardin County, Iowa were inspected to observe general geometric relationships, construction details, and to note the visual condition of the bridges. Hairline cracks beneath several of the prestressing strands in many of the precast panels were observed, and a slight discoloration of the concrete was seen beneath most of the strands. Also, some rust staining was visible at isolated locations on several panels. Based on the findings of these inspections, future inspections are recommended to monitor the condition of these and other bridges constructed with precast panel subdecks. Five full-scale composite slab specimens were constructed in the Structural Engineering Laboratory at Iowa State University. One specimen modeled bridge deck conditions which are not adjacent to abutment or pier diaphragms, and the other four specimens represented the geometric conditions which occur for skewed diaphragms of 0, 15, 30, and 40 degrees. The specimens were subjected to wheel loads of service and factored level magnitudes at many locations on the slab surface and to concentrated loads which produced failure of the composite slab. The measured slab deflections and bending strains at both service and factored load levels compared reasonably well with the results predicted by simplified Finite element analyses of the specimens. To analytically evaluate the nominal strength for a composite slab specimen, yield-line and punching shear theories were applied. Yield-line limit loads were computed using the crack patterns generated during an ultimate strength test. In most cases, these analyses indicated that the failure mode was not flexural. Since the punching shear limit loads in most instances were close to the failure loads, and since the failure surfaces immediately adjacent to the wheel load footprint appeared to be a truncated prism shape, the probable failure mode for all of the specimens was punching shear. The development lengths for the prestressing strands in the rectangular and trapezoidal shaped panels was qualitatively investigated by monitoring strand slippage at the ends of selected prestressing strands. The initial strand transfer length was established experimentally by monitoring concrete strains during strand detensioning, and this length was verified analytically by a finite element analysis. Even though the computed strand embedment lengths in the panels were not sufficient to fully develop the ultimate strand stress, sufficient stab strength existed. Composite behavior for the slab specimens was evaluated by monitoring slippage between a panel and the topping slab and by computation of the difference in the flexural strains between the top of the precast panel and the underside of the topping slab at various locations. Prior to the failure of a composite slab specimen, a localized loss of composite behavior was detected. The static load strength performance of the composite slab specimens significantly exceeded the design load requirements. Even with skew angles of up to 40 degrees, the nominal strength of the slabs did not appear to be affected when the ultimate strength test load was positioned on the portion of each slab containing the trapezoidal-shaped panel. At service and factored level loads, the joint between precast panels did not appear to influence the load distribution along the length of the specimens. Based on the static load strength of the composite slab specimens, the continued use of precast panels as subdecks in bridge deck construction is recommended.

Thermoset Composite Concrete Reinforcement, HR-325, Part 1, 1992

The feasibility of substituting fibercomposite (FC) (thermoset) pavement dowels for steel pavement dowels was investigated in this research project. Load transfer capacity, flexural capacity, and material properties were examined. The objectives of Part 1 of this final report included the shear behavior and strength deformations of FC dowel bars without aging. Part 2 will contain the aging effects. This model included the effects of modulus of elasticity for the pavement dowel and concrete, dowel diameter, subgrade stiffness, and concrete compressive strength. An experimental investigation was carried out to establish the modulus of dowel support which is an important parameter for the analysis of dowels. The experimental investigation included measured deflections, observed behavioral characteristics, and failure mode observations. An extensive study was performed on various shear testing procedures. A modified Iosipescu shear method was selected for the test procedure. Also, a special test frame was designed and fabricated for this procedure. The experimental values of modulus of support for shear and FC dowels were used for arriving at the critical stresses and deflections for the theoretical model developed. Different theoretical methods based on analyses suggested by Timoshenko, Friberg, Bradbury, and Westergaard were studied and a comprehensive theoretical model was developed. The fibercomposite dowels were found to provide strengths and behavioral characteristics that appear promising as a potential substitute for steel dowels.

Flood-Plain and Channel Aggradation at Selected Bridge Sites in the Iowa and Skunk River Basins, Iowa, HR-350, 1996

Flood-plain and channel-aggradation rates were estimated at selected bridge sites in central and eastern Iowa using four aggradation-measurement methods. Aggradation rates were quantified at 10 bridge sites on the Iowa River upstream of Coralville Lake and at two bridge sites in the central part of Skunk River Basin. Measurement periods used to estimate average aggradation rates ranged in length from 1 to 98 years and varied among methods and sites. A direct comparison cannot be made between aggradation rates calculated using each of the four measurement methods because of differences in time periods and aggradational processes that were measured by each method.

The contact region between three domains of the extracellular loop of ASIC1a is critical for channel function.

Acid-sensing ion channels are members of the epithelial Na(+) channel/degenerin family. They are neuronal nonvoltage-gated Na(+) channels that are activated by extracellular acidification. In this study, we investigated the role of a highly conserved region of the extracellular part of ASIC1a that forms the contact between the finger domain, the adjacent beta-ball, and the upper palm domain in ASIC1a. The finger domain contributes to the pH-dependent gating and is linked via this contact zone to the rest of the protein. We found that mutation to Cys of residues in this region led to decreased channel expression and current amplitudes. Exposure of the engineered Cys residues to Cd(2+) or to charged methane thiosulfonate sulfhydryl reagents further reduced current amplitudes. This current inhibition was not due to changes in acid-sensing ion channel pH dependence or unitary conductance and was likely due to a decrease of the probability of channel opening. For some mutants, the effect of sulfhydryl reagents depended on the pH of exposure in the range 7.4 to 6.8, suggesting that this zone undergoes conformational changes during inactivation. Our study identifies a region in ASIC1a whose integrity is required for normal channel function.

Trypsin cleaves acid-sensing ion channel 1a in a domain that is critical for channel gating.

Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that are members of the epithelial Na(+) channel/degenerin family and are transiently activated by extracellular acidification. ASICs in the central nervous system have a modulatory role in synaptic transmission and are involved in cell injury induced by acidosis. We have recently demonstrated that ASIC function is regulated by serine proteases. We provide here evidence that this regulation of ASIC function is tightly linked to channel cleavage. Trypsin cleaves ASIC1a with a similar time course as it changes ASIC1a function, whereas ASIC1b, whose function is not modified by trypsin, is not cleaved. Trypsin cleaves ASIC1a at Arg-145, in the N-terminal part of the extracellular loop, between a highly conserved sequence and a sequence that is critical for ASIC1a inhibition by the venom of the tarantula Psalmopoeus cambridgei. This channel domain controls the inactivation kinetics and co-determines the pH dependence of ASIC gating. It undergoes a conformational change during inactivation, which renders the cleavage site inaccessible to trypsin in inactivated channels.

Neuronal calcium channel mutation in a patient with congenital ataxia and attacks of hemiplegic migraine with cerebral edema

Background: Familial Hemiplegic Migraine (FHM), characterized by a prolonged unilateral hemiparesis, mainly results from mutations in the alpha-1a subunit of the calcium channel gene CACNA1A that can also cause two other dominantly inherited neurological disorders, Episodic Ataxia type 2 (EA2, with sometimes migrainous headaches) and Spinocerebellar Ataxia type 6 (SCA6, late-onset and progressive). A same mutation can have different clinical expression in a family (hemiplegic migraine, migraine-coma, cerebellar ataxia). CACNA1A mutations in FHM are usually missense, leading to gain-of-function, while truncating mutations leading to loss-of-function are usually associated with EA2. Case report: This 9-year-old girl was seen as a baby for hypotonia and transient vertical nystagmus. Her first brain MRI was normal. She evolved as a congenital ataxia, but since the age of two, she had attacks of coma, hemiparesis (either side), partial seizures, dystonic movements and fever. Attacks were initially triggered by minor head bumps, subsequently spontaneous. Brain MRIs in the acute stage always showed transient unilateral hemisphere swelling. Follow-up images revealed atrophic lesions in the temporo-occipital regions and cerebellar atrophy. A prophylactic trial with flunarizine was ineffective. Acetazolamide was recently introduced. Methods: Since our patient shared features of both FHM and EA2, we studied the CACNA1A gene by direct sequencing in the patient's and parents' DNA. Results: We identified an unreported de novo heterozygous deletion of three base pairs (c.4503_4505delCTT) predicting the deletion of one amino acid (p.Phe1502del). The CACNA1A protein contains 4 domains, each formed by six transmembrane segments. The deletion is located in a highly conserved region in segment 6 (S6) of the third domain. Mutations in S6 segments of calcium channels change single-channel conductance and channel selectivity, most resulting in loss-of-function. Outlook: In vitro expression studies of the identified mutation are underway, aiming at understanding its functional consequences and finding an efficient treatment.

Role of the epithelial sodium channel (ENaC) and its regulator CAP1/Prss8 in colon

Dans les cellules épithéliales sensibles à l'aldostérone, le canal sodique épithélial (ENaC) joue un rôle critique dans le contrôle de l'équilibre sodique, le volume sanguin, et la pression sanguine. Le rôle d'ENaC est bien caractérisé dans le rein et les poumons, cependant le rôle d'ENaC et son régulateur positif la protéase activatrice de canal 1 (CAP1 /Prss8) sur le transport sodique dans le côlon reste en grande partie inconnu. Nous avons étudié l'importance d'ENaC et de CAPMPrss8 dans le côlon. Les souris déficientes pour la sous- unité aENaC (souris ScnnlaKO) dans les cellules superficielles intestinales étaient viables et ne montraient pas de létalité embryonnaire ou postnatale. Sous diète normale (RS) ou pauvre en sodium (LS), la différence de potentiel rectale sensible à l'amiloride (APDamii) était drastiquement diminuée et son rythme circadien atténué. Sous diète normale (RS) ou diète riche en sodium (HS) ou fort chargement de potassium, le sodium et le potassium plasmatique et urinaire n'étaient pas significativement changé. Cependant, sous LS, les souris Senni aK0 perdaient des quantités significativement augmentées de sodium dans leurs fèces, accompagnées par de très hauts taux d'aldostérone plasmatique et une rétention urinaire en sodium augmentée. Les souris déficientes en CAPl/PmS (Prss8K0) dans les cellules superficielles intestinales étaient viables et ne montraient pas de létalité embryonnaire ou postnatale. Sous diètes RS et HS cependant, les souris Prss8KO montraient une diminution significative du APDamil dans l'après-midi, mais le rythme circadien était maintenu. Sous diète LS, la perte de sodium par les fèces était accompagnée par des niveaux d'aldostérone plasmatiques plus élevés. Par conséquent, nous avons identifié la protéase activatrice de canal CAP 1 IPrss8 comme un régulateur important d'ENaC dans le côlon in vivo. De plus, nous étudions l'importance d'ENaC et de CAPIIPrss8 dans les conditions pathologiques comme les maladies inflammatoires chroniques de l'intestin (MICI). Le résultat préliminaire out montre qu'une déficience d'Prss8 mènait à la détérioration de la colite induite par le DSS comparé aux modèles contrôles respectifs. En résumé, l'étude a montré que sous restriction de sel, l'absence d'ENaC dans Pépithélium de surface du côlon était compensée par 1'activation du système rénine-angiotensine- aldostérone (RAAS) dans le rein. Ceci a mené à un pseudohypoaldostéronisme de type I spécifique au côlon avec résistance aux minéralocorticoïdes sans signe d'altération de rétention de potassium. - In aldosterone-responsive epithelial cells of kidney and colon, the epithelial sodium channel (ENaC) plays a critical role in the control of sodium balance, blood volume, and blood pressure. The role of ENaC is well characterized in kidney and lung, whereas role of ENaC and its positive regulator channel-activating protease 1 (CAPl/PrasS) on sodium transport in colon is largely unknown. We have investigated the importance of ENaC and CAPI/Prss8 in colon for sodium and potassium balance. Mice lacking the aENaC subunit (Scnnla mice) in intestinal superficial cells were viable and did not show any fetal or perinatal lethality. Under regular (RS) or low salt (LS) diet, the amiloride sensitive rectal potential difference (APDamii) was drastically decreased and its circadian rhythm blunted. Under regular salt (RS) or high salt (HS) diets or under potassium loading, plasma and urinary sodium and potassium were not significantly changed. However, upon LS, the ScnnlaK0 mice lost significant amounts of sodium in their feces, accompanied by very high plasma aldosterone and increased urinary sodium retention. Mice lacking the CAPl/PrasS (Prss8K0) in intestinal superficial cells were viable and did not show any fetal or perinatal lethality. Upon RS and HS diets, however, Prss8K0 exhibited a significantly reduced APDamii in the afternoon, but its circadian rhythm was maintained. Upon LS diet, sodium loss through feces was accompanied by higher plasma aldosterone levels. Thus, we have identified the channel-activating protease CAPl/Prss8 as an important in vivo regulator of ENaC in colon. Furthermore, we are investigating the importance of ENaC and CAPI/Prss8 in pathological conditions like inflammatory bowel disease (IBD). Preliminary data showed that PmS-deficiency led to worsening of DSS-induced colitis as compared to their respective controls. Overall, the present study has shown that under salt restriction, the absence of ENaC in colonic surface epithelium was compensated by the activation of renin-angiotensin- aldosterone (RAAS) system in the kidney. This led to a colon specific pseudohypoaldosteroni sm type 1 with mineralocorticoid resistance without evidence of impaired potassium retention.

Design Manual for Strengthening of Continuous-Span Composite Bridges, HR-333, 1993

The need for upgrading a large number of understrength bridges in the United States has been well documented in the literature. This manual presents two methods for strengthening continuous-span composite bridges: post-tensioning of the positive moment regions of the bridge stringers and the addition of superimposed trusses at the piers. The use of these two systems is an efficient method of reducing flexural overstresses in undercapacity bridges. Before strengthening a given bridge however, other deficiencies (inadequate shear connection, fatigue problems, extensive corrosion) should be addressed. Since continuous-span composite bridges are indeterminant structures, there is longitudinal and transverse distribution of the strengthening axial forces and moments. This manual basically provides the engineer with a procedure for determining the distribution of strengthening forces and moments throughout the bridge. As a result of the longitudinal and transverse force distribution, the design methodology presented in this manual for continuous-span composite bridges is extremely complex. To simplify the procedure, a spreadsheet has been developed for use by practicing engineers. This design aid greatly simplifies the design of a strengthening system for a given bridge in that it eliminates numerous tedious hand calculations, computes the required force and moment fractions, and performs the necessary iterations for determining the required strengthening forces. The force and moment distribution fraction formulas developed in this manual are primarily for the Iowa DOT V12 and V14 three-span four-stringer bridges. These formulas may be used on other bridges if they are within the limits stated in this manual. Use of the distribution fraction formulas for bridges not within the stated limits is not recommended.

Fatigue and Residual Stress Investigation of Composite Prestressed Steel Beams, HR-74, 1963

Two composite, prestressed, steel beams, fabricated by slightly different methods, were fatigue tested to destruction. Stresses and deflections were measured at regular intervals, and the behavior of each beam as failure progressed was recorded. Residual stresses were then evaluated by testing segments of each beam. An attempt was made to assess the effects of the residual stresses on fatigue strength.

Role of the epithelial sodium channel (ENaC) in the epidermal barrier function of the skin

Abstract In humans, the skin is the largest organ of the body, covering up to 2m2 and weighing up to 4kg in an average adult. Its function is to preserve the body from external insults and also to retain water inside. This barrier function termed epidermal permeability barrier (EPB) is localized in the functional part of the skin: the epidermis. For this, evolution has built a complex structure of cells and lipids sealing the surface, the stratum corneum. The formation of this structure is finely tuned since it is not only formed once at birth, but renewed all life long. This active process gives a high plasticity and reactivity to skin, but also leads to various pathologies. ENaC is a sodium channel extensively studied in organs like kidney and lung due to its importance in regulating sodium homeostasis and fluid volume. It is composed of three subunits α, ß and r which are forming sodium selective channel through the cell membrane. Its presence in the skin has been demonstrated, but little is known about its physiological role. Previous work has shown that αENaC knockout mice displayed an abnormal epidermis, suggesting a role in differentiation processes that might be implicated in the EPB. The principal aim of this thesis has been to study the consequences for EPB function in mice deficient for αENaC by molecular and physiological means and to investigate the underlying molecular mechanisms. Here, the barrier function of αENaC knockout pups is impaired. Apparently not immediately after birth (permeability test) but 24h later, when evident water loss differences appeared compared to wildtypes. Neither the structural proteins of the epithelium nor the tights junctions showed any obvious alterations. In contrary, stratum corneum lipid disorders are most likely responsible for the barrier defect, accompanied by an impairment of skin surface acidification. To analyze in details this EPB defect, several hypotheses have been proposed: reduced sensibility to calcium which is the key activator far epidermal formation, or modification of ENaC-mediated ion fluxes/currents inside the epidermis. The cellular localization of ENaC and the action in the skin of CAPl, a positive regulator of ENaC, have been also studied in details. In summary, this study clearly demonstrates that ENaC is a key player in the EPB maintenance, because αENaC knockout pups are not able to adapt to the new environment (ex utero) as efficiently as the wildtypes, most likely due to impaired of sodium handling inside the epidermis. Résumé Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses pathologies. ENaC est un canal sodique très étudié dans le rein et le poumon pour son importance dans la régulation de l'homéostasie sodique et la régulation du volume du milieu intérieur. Il est composé de 3 sous unités, α, ß et y qui forment un pore sélectif pour le sodium dans les membranes. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris dont le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la différentiation et pourrait même être impliqué dans la barrière épithéliale. Le but de cette thèse fut l'étude de la barrière dans ces souris knockouts avec des méthodes moléculaires et physiologiques et la caractérisation des mécanismes moléculaire impliqués. Dans ce travail, il a été montré que les souris mutantes présentaient un défaut de la barrière. Ce défaut n'est pas visible immédiatement à la naissance (test de perméabilité), mais 24h plus tard, lorsque les tests de perte d'eau transépithéliale montrent une différence évidente avec les animaux contrôles. Ni les protéines de structures ni les jonctions serrées de l'épiderme ne présentaient d'imperfections majeures. A l'inverse, les lipides de la couche cornée présentaient un problème de maturation (expliquant le phénotype de la barrière), certainement consécutif au défaut d'acidification à la surface de la peau que nous avons observé. D'autres mécanismes ont été explorées afin d'investiguer cette anomalie de la barrière, comme la réduction de sensibilité au calcium qui est le principal activateur de la formation de l'épiderme, ou la modification des flux d'ions entre les couches de l'épiderme. La localisation cellulaire d'ENaC, et l'action de son activateur CAPl ont également été étudiés en détails. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des knockouts ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme. Résumé tout public Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses maladies. ENaC est une protéine formant un canal qui permet le passage sélectif de l'ion sodium à travers la paroi des cellules. Il est très étudié dans le rein pour son importance dans la récupération du sel lors de la concentration de l'urine. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris où le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la peau et plus particulièrement la fonction de barrière de l'épiderme. Le but de cette thèse fut l'étude de la fonction de barrière dans ces souris mutantes, au niveau tissulaire et cellulaire. Dans ce travail, il a été montré que les souris mutantes présentaient une peau plus perméable que celle des animaux contrôles, grâce à une machine mesurant la perte d'eau à travers la peau. Ce défaut n'est visible que 24h après la naissance, mais nous avons pu montrer que les animaux mutants perdaient quasiment 2 fois plus d'eau que les contrôles. Au niveau moléculaire, nous avons pu montrer que ce défaut provenait d'un problème de maturation des lipides qui composent la barrière de la peau. Cette maturation est incomplète vraisemblablement à cause d'un défaut de mouvement des ions dans les couches les plus superficielles de l'épiderme, et cela à cause de l'absence du canal ENaC. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des mutants ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme.

Microfiltración en restauraciones clase II de composite fotopolimerizadas a través de un cono transparente

Estudios clínicos han demostrado la existencia de importantes problemas cuando el composite es utilizado en restauraciones posteriores. Dentro de ellos cabe destacar la contracción del material y la microfiltración. Una adecuada fotopolimerización de la resina influye positivamente en el resultado final de la restauración. La utilización de un cono transparente de plástico ha sido sugerido por algunos autores como un procedimiento para mejorar la fotopolimerización de la resina a nivel del área gingival en las restauraciones clase II de composite, lográndose un aumento en la dureza y nivel de conversión del material, así como una disminución de la brecha entre la restauración y las paredes cavitarias a ese nivel. En el presente trabajo se investigaron los efectos de la utilización del cono transparente propuesto por Ericson en 1987, en la fotopolimerización de la resina y sus consecuencias en la microfiltración. Los resultados mostraron una leve tendencia a la disminución de la microfiltración en el área cervical de las restauraciones clase II cuando el cono fue utilizado, aunque sin diferencias significativas respecto a la técnica convencional.

Scnn1 sodium channel gene family in genetically engineered mice.

The amiloride-sensitive epithelial sodium channel is the limiting step in salt absorption. In mice, this channel is composed of three subunits (alpha, beta, and gamma), which are encoded by different genes (Scnn1a, Scnn1b, and Scnn1c, respectively). The functions of these genes were recently investigated in transgenic (knockout) experiments, and the absence of any subunit led to perinatal lethality. More defined phenotypes have been obtained by introducing specific mutations or using transgenic rescue experiments. In this report, these approaches are summarized and a current gene-targeting strategy to obtain conditional inactivation of the channel is illustrated. This latter approach will be indispensable for the investigation of channel function in a wide variety of organ systems.

Treatment of extended skin defects with autologous composite cultured skin grafts in a patient with epidermolysis bullosa

Rationale: The purpose of this article is to demonstrate the use of homologous culture cells in treating an advanced coccon formation of the hand and three extended squamous cell carcinomas of the lower and upper limb in a patient with recessive dystrophic epidermolysis bullosa. The preparation and application of these cells in the operation room are being described. Methods: A number of surgical approaches have been described to correct these deformities in order to improve function.We propose a new therapeutic approach of treating loss of motion and independent digital function as well as coverage of large skin defects in a patient with recessive dystrophic epidermolysis bullosa by using autologous culture cells. Surgical treatment of these patients is really difficult because of the existing skin fragility. Furthermore, surgical wounds do not easily heal because of recurrent blisters and erosions as well as due to the patients' poor nutricial status. Results: We report our experience of mutiple extended cutaneous squamous cell carcinomas arising in our patient which were successfully managed using autologous composite cultured skin grafts. The cocoon hand deformity was also treated with the limb becoming functional. Conclusion: The use of autologous keratinocytes and fibroblasts in epidermolysis bullosa is hereby outlined for the fist time.