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Sample records for larval-to-adult intestinal remodeling

  1. Endocrine remodelling of the adult intestine sustains reproduction in Drosophila

    PubMed Central

    Reiff, Tobias; Jacobson, Jake; Cognigni, Paola; Antonello, Zeus; Ballesta, Esther; Tan, Kah Junn; Yew, Joanne Y; Dominguez, Maria; Miguel-Aliaga, Irene

    2015-01-01

    The production of offspring is energetically costly and relies on incompletely understood mechanisms that generate a positive energy balance. In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically. In this study, we show that, in adult Drosophila females, the midgut is dramatically remodelled to enhance reproductive output. In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them. With spatially and temporally directed manipulations, we identify juvenile hormone (JH) as an anticipatory endocrine signal released after mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal progenitors to yield a larger organ, and adjusts gene expression and sterol regulatory element-binding protein (SREBP) activity in enterocytes to support increased lipid metabolism. Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output. DOI: http://dx.doi.org/10.7554/eLife.06930.001 PMID:26216039

  2. Remodeling Intestinal Flora with Sleeve Gastrectomy in Diabetic Rats

    PubMed Central

    Huang, Xiaofei; Weng, Pan; Zhang, Huixin; Lu, Yingli

    2014-01-01

    Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals' weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism. PMID:25165722

  3. Stem cell-based growth, regeneration, and remodeling of the planarian intestine

    PubMed Central

    Forsthoefel, David J.; Park, Amanda E.; Newmark, Phillip A.

    2011-01-01

    Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. In planarians, pluripotent somatic stem cells called neoblasts supply new cells for growth, replenish tissues in response to cellular turnover, and regenerate tissues after injury. For most tissues and organs, however, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Utilizing in vivo imaging and bromodeoxyuridine pulse-chase experiments, we have analyzed growth and regeneration of the planarian intestine, the organ responsible for digestion and nutrient distribution. During growth, we observe that new gut branches are added along the entire anteroposterior axis. We find that new enterocytes differentiate throughout the intestine rather than in specific growth zones, suggesting that branching morphogenesis is achieved primarily by remodeling of differentiated intestinal tissues. During regeneration, we also demonstrate a previously unappreciated degree of intestinal remodeling, in which pre-existing posterior gut tissue contributes extensively to the newly formed anterior gut, and vice versa. By contrast to growing animals, differentiation of new intestinal cells occurs at preferential locations, including within newly generated tissue (the blastema), and along pre-existing intestinal branches undergoing remodeling. Our results indicate that growth and regeneration of the planarian intestine are achieved by coordinated differentiation of stem cells and the remodeling of pre-existing tissues. Elucidation of the mechanisms by which these processes are integrated will be critical for understanding organogenesis in a post-embryonic context. PMID:21664348

  4. Stem cell-based growth, regeneration, and remodeling of the planarian intestine.

    PubMed

    Forsthoefel, David J; Park, Amanda E; Newmark, Phillip A

    2011-08-15

    Although some animals are capable of regenerating organs, the mechanisms by which this is achieved are poorly understood. In planarians, pluripotent somatic stem cells called neoblasts supply new cells for growth, replenish tissues in response to cellular turnover, and regenerate tissues after injury. For most tissues and organs, however, the spatiotemporal dynamics of stem cell differentiation and the fate of tissue that existed prior to injury have not been characterized systematically. Utilizing in vivo imaging and bromodeoxyuridine pulse-chase experiments, we have analyzed growth and regeneration of the planarian intestine, the organ responsible for digestion and nutrient distribution. During growth, we observe that new gut branches are added along the entire anteroposterior axis. We find that new enterocytes differentiate throughout the intestine rather than in specific growth zones, suggesting that branching morphogenesis is achieved primarily by remodeling of differentiated intestinal tissues. During regeneration, we also demonstrate a previously unappreciated degree of intestinal remodeling, in which pre-existing posterior gut tissue contributes extensively to the newly formed anterior gut, and vice versa. By contrast to growing animals, differentiation of new intestinal cells occurs at preferential locations, including within newly generated tissue (the blastema), and along pre-existing intestinal branches undergoing remodeling. Our results indicate that growth and regeneration of the planarian intestine are achieved by co-ordinated differentiation of stem cells and the remodeling of pre-existing tissues. Elucidation of the mechanisms by which these processes are integrated will be critical for understanding organogenesis in a post-embryonic context.

  5. Extensive Intestinal Resection Triggers Behavioral Adaptation, Intestinal Remodeling and Microbiota Transition in Short Bowel Syndrome

    PubMed Central

    Mayeur, Camille; Gillard, Laura; Le Beyec, Johanne; Bado, André; Joly, Francisca; Thomas, Muriel

    2016-01-01

    Extensive resection of small bowel often leads to short bowel syndrome (SBS). SBS patients develop clinical mal-absorption and dehydration relative to the reduction of absorptive area, acceleration of gastrointestinal transit time and modifications of the gastrointestinal intra-luminal environment. As a consequence of severe mal-absorption, patients require parenteral nutrition (PN). In adults, the overall adaptation following intestinal resection includes spontaneous and complex compensatory processes such as hyperphagia, mucosal remodeling of the remaining part of the intestine and major modifications of the microbiota. SBS patients, with colon in continuity, harbor a specific fecal microbiota that we called “lactobiota” because it is enriched in the Lactobacillus/Leuconostoc group and depleted in anaerobic micro-organisms (especially Clostridium and Bacteroides). In some patients, the lactobiota-driven fermentative activities lead to an accumulation of fecal d/l-lactates and an increased risk of d-encephalopathy. Better knowledge of clinical parameters and lactobiota characteristics has made it possible to stratify patients and define group at risk for d-encephalopathy crises. PMID:27681910

  6. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    PubMed

    Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

    2014-01-01

    Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  7. Morphometric and biomechanical remodeling of the small intestine during aging in rats.

    PubMed

    Zhao, Jingbo; Gregersen, Hans

    2015-12-16

    The present study aimed to study the morphometric and biomechanical remodeling of the small intestine during aging in rats. Twenty-four male Wistar rats, aged from 6 to 22 months, were used in the study. The body weight and the wet weight per length of duodenal and ileal segments were measured at the termination of the experiments. Morphometry data was obtained by measuring the wall thickness and cross-sectional area. The mechanical test was done as a step-wise distension experiment. The intestinal diameter and length were obtained from digitized images of the segments at pre-selected pressure levels and at the no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state geometry. The duodenal and ileal dimensions increased slightly from 6 to 22 months, e.g. the wall thickness and the wall cross-sectional area increased about 4% and 25% for duodenum and 5% and 8% for ileum. The opening angle gradually decreased from 154 to 117 degrees for duodenum and from 144 to 87 degrees for ileum during aging. The circumferential stress-strain curves significantly shifted to the left after 22 months (p<0.05) whereas the longitudinal stress-strain curves significantly shifted to the left after 18 months (p<0.01) both for duodenum and ileum. The intestinal wall became stiffer circumferentially and longitudinally during the aging. Furthermore, the intestinal wall was stiffer longitudinally than circumferentially. In conclusion, pronounced morphometric and biomechanical remodeling occurred in the rat intestine during aging.

  8. Direct activation of Xenopus iodotyrosine deiodinase by thyroid hormone receptor in the remodeling intestine during amphibian metamorphosis.

    PubMed

    Fujimoto, Kenta; Matsuura, Kazuo; Das, Biswajit; Fu, Liezhen; Shi, Yun-Bo

    2012-10-01

    Thyroid hormone (TH) plays critical roles during vertebrate postembryonic development. TH production in the thyroid involves incorporating inorganic iodide into thyroglobulin. The expression of iodotyrosine deiodinase (IYD; also known as iodotyrosine dehalogenase 1) in the thyroid gland ensures efficient recycling of iodine from the byproducts of TH biosynthesis: 3'-monoiodotyrosine and 3', 5'-diiodotyrosine. Interestingly, IYD is known to be expressed in other organs in adult mammals, suggesting iodine recycling outside the thyroid. On the other hand, the developmental role of iodine recycling has yet to be investigated. Here, using intestinal metamorphosis as a model, we discovered that the Xenopus tropicalis IYD gene is strongly up-regulated by TH during metamorphosis in the intestine but not the tail. We further demonstrated that this induction was one of the earliest events during intestinal metamorphosis, with IYD being activated directly through the binding of liganded TH receptors to a TH response element in the IYD promoter region. Because iodide is mainly taken up from the diet in the intestine and the tadpole stops feeding during metamorphosis when the intestine is being remodeled, our findings suggest that IYD transcription is activated by liganded TH receptors early during intestinal remodeling to ensure efficient iodine recycling at the climax of metamorphosis when highest levels of TH are needed for the proper transformations of different organs.

  9. Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet.

    PubMed

    Wang, Bo; Rong, Xin; Duerr, Mark A; Hermanson, Daniel J; Hedde, Per Niklas; Wong, Jinny S; Vallim, Thomas Q de Aguiar; Cravatt, Benjamin F; Gratton, Enrico; Ford, David A; Tontonoz, Peter

    2016-03-08

    Phospholipids are important determinants of membrane biophysical properties, but the impact of membrane acyl chain composition on dietary-lipid absorption is unknown. Here we demonstrate that the LXR-responsive phospholipid-remodeling enzyme Lpcat3 modulates intestinal fatty acid and cholesterol absorption and is required for survival on a high-fat diet. Mice lacking Lpcat3 in the intestine thrive on carbohydrate-based chow but lose body weight rapidly and become moribund on a triglyceride-rich diet. Lpcat3-dependent incorporation of polyunsaturated fatty acids into phospholipids is required for the efficient transport of dietary lipids into enterocytes. Furthermore, loss of Lpcat3 amplifies the production of gut hormones, including GLP-1 and oleoylethanolamide, in response to high-fat feeding, contributing to the paradoxical cessation of food intake in the setting of starvation. These results reveal that membrane phospholipid composition is a gating factor in passive lipid absorption and implicate LXR-Lpcat3 signaling in a gut-brain feedback loop that couples absorption to food intake.

  10. Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape

    PubMed Central

    Camp, J. Gray; Frank, Christopher L.; Lickwar, Colin R.; Guturu, Harendra; Rube, Tomas; Wenger, Aaron M.; Chen, Jenny; Bejerano, Gill; Crawford, Gregory E.

    2014-01-01

    Microbiota regulate intestinal physiology by modifying host gene expression along the length of the intestine, but the underlying regulatory mechanisms remain unresolved. Transcriptional specificity occurs through interactions between transcription factors (TFs) and cis-regulatory regions (CRRs) characterized by nucleosome-depleted accessible chromatin. We profiled transcriptome and accessible chromatin landscapes in intestinal epithelial cells (IECs) from mice reared in the presence or absence of microbiota. We show that regional differences in gene transcription along the intestinal tract were accompanied by major alterations in chromatin accessibility. Surprisingly, we discovered that microbiota modify host gene transcription in IECs without significantly impacting the accessible chromatin landscape. Instead, microbiota regulation of host gene transcription might be achieved by differential expression of specific TFs and enrichment of their binding sites in nucleosome-depleted CRRs near target genes. Our results suggest that the chromatin landscape in IECs is preprogrammed by the host in a region-specific manner to permit responses to microbiota through binding of open CRRs by specific TFs. PMID:24963153

  11. Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

    PubMed Central

    Luissint, Anny-Claude; Parkos, Charles A.; Nusrat, Asma

    2017-01-01

    The intestinal tract is lined by a single layer of columnar epithelial cells that forms a dynamic, permeable barrier allowing for selective absorption of nutrients, while restricting access to pathogens and food-borne antigens. Precise regulation of epithelial barrier function is therefore required for maintaining mucosal homeostasis and depends, in part, on barrier-forming elements within the epithelium and a balance between pro- and anti-inflammatory factors in the mucosa. Pathologic states, such as inflammatory bowel disease, are associated with a leaky epithelial barrier, resulting in excessive exposure to microbial antigens, recruitment of leukocytes, release of soluble mediators, and ultimately mucosal damage. An inflammatory microenvironment affects epithelial barrier properties and mucosal homeostasis by altering the structure and function of epithelial intercellular junctions through direct and indirect mechanisms. We review our current understanding of complex interactions between the intestinal epithelium and immune cells, with a focus on pathologic mucosal inflammation and mechanisms of epithelial repair. We discuss leukocyte–epithelial interactions, as well as inflammatory mediators that affect the epithelial barrier and mucosal repair. Increased knowledge of communication networks between the epithelium and immune system will lead to tissue-specific strategies for treating pathologic intestinal inflammation. PMID:27436072

  12. Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

  13. Remodeling of Tight Junctions and Enhancement of Barrier Integrity of the CACO-2 Intestinal Epithelial Cell Layer by Micronutrients.

    PubMed

    Valenzano, Mary Carmen; DiGuilio, Katherine; Mercado, Joanna; Teter, Mimi; To, Julie; Ferraro, Brendan; Mixson, Brittany; Manley, Isabel; Baker, Valerissa; Moore, Beverley A; Wertheimer, Joshua; Mullin, James M

    2015-01-01

    The micronutrients zinc, quercetin, butyrate, indole and berberine were evaluated for their ability to induce remodeling of epithelial tight junctions (TJs) and enhance barrier integrity in the CACO-2 gastrointestinal epithelial cell culture model. All five of these chemically very diverse micronutrients increased transepithelial electrical resistance (Rt) significantly, but only berberine also improved barrier integrity to the non-electrolyte D-mannitol. Increases of Rt as much as 200% of untreated controls were observed. Each of the five micronutrients also induced unique, signature-like changes in TJ protein composition, suggesting multiple pathways (and TJ arrangements) by which TJ barrier function can be enhanced. Decreases in abundance by as much as 90% were observed for claudin-2, and increases of over 300% could be seen for claudins -5 and -7. The exact effects of the micronutrients on barrier integrity and TJ protein composition were found to be highly dependent on the degree of differentiation of the cell layer at the time it was exposed to the micronutrient. The substratum to which the epithelial layer adheres was also found to regulate the response of the cell layer to the micronutrient. The implications of these findings for therapeutically decreasing morbidity in Inflammatory Bowel Disease are discussed.

  14. Retinal remodeling.

    PubMed

    Jones, B W; Kondo, M; Terasaki, H; Lin, Y; McCall, M; Marc, R E

    2012-07-01

    Retinal photoreceptor degeneration takes many forms. Mutations in rhodopsin genes or disorders of the retinal pigment epithelium, defects in the adenosine triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine kinase defects, ciliopathies and transport defects, defects in both transducin and arrestin, defects in rod cyclic guanosine 3',5'-monophosphate phosphodiesterase, peripherin defects, defects in metabotropic glutamate receptors, synthetic enzymatic defects, defects in genes associated with signaling, and many more can all result in retinal degenerative disease like retinitis pigmentosa (RP) or RP-like disorders. Age-related macular degeneration (AMD) and AMD-like disorders are possibly due to a constellation of potential gene targets and gene/gene interactions, while other defects result in diabetic retinopathy or glaucoma. However, all of these insults as well as traumatic insults to the retina result in retinal remodeling. Retinal remodeling is a universal finding subsequent to retinal degenerative disease that results in deafferentation of the neural retina from photoreceptor input as downstream neuronal elements respond to loss of input with negative plasticity. This negative plasticity is not passive in the face of photoreceptor degeneration, with a phased revision of retinal structure and function found at the molecular, synaptic, cell, and tissue levels involving all cell classes in the retina, including neurons and glia. Retinal remodeling has direct implications for the rescue of vision loss through bionic or biological approaches, as circuit revision in the retina corrupts any potential surrogate photoreceptor input to a remnant neural retina. However, there are a number of potential opportunities for intervention that are revealed through the study of retinal remodeling, including therapies that are designed to slow down photoreceptor loss, interventions that are designed to limit or arrest remodeling events, and

  15. Teaching resources. Chromatin remodeling.

    PubMed

    Lue, Neal F

    2005-07-26

    This Teaching Resource provides lecture notes and slides for a class covering chromatin remodeling mechanisms and is part of the course "Cell Signaling Systems: a Course for Graduate Students." The lecture begins with a discussion of chromatin organization and then proceeds to describe the process of chromatin remodeling through a review of chromatin remodeling complexes and methods used to study their function.

  16. CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling.

    PubMed

    Masterson, Joanne C; McNamee, Eóin N; Jedlicka, Paul; Fillon, Sophie; Ruybal, Joseph; Hosford, Lindsay; Rivera-Nieves, Jesús; Lee, James J; Furuta, Glenn T

    2011-11-01

    Intestinal remodeling and stricture formation is a complication of inflammatory bowel disease (IBD) that often requires surgical intervention. Although eosinophils are associated with mucosal remodeling in other organs and are increased in IBD tissues, their role in IBD-associated remodeling is unclear. Histological and molecular features of ileitis and remodeling were assessed using immunohistochemical, histomorphometric, flow cytometric, and molecular analysis (real-time RT-PCR) techniques in a murine model of chronic eosinophilic ileitis. Collagen protein was assessed by Sircol assay. Using a spontaneous eosinophilic Crohn's-like mouse model SAMP1/SkuSlc, we demonstrate an association between ileitis progression and remodeling over the course of 40 weeks. Mucosal and submucosal eosinophilia increased over the time course and correlated with increased histological inflammatory indices. Ileitis and remodeling increased over the 40 weeks, as did expression of fibronectin. CCR3-specific antibody-mediated reduction of eosinophils resulted in significant decrease in goblet cell hyperplasia, muscularis propria hypertrophy, villus blunting, and expression of inflammatory and remodeling genes, including fibronectin. Cellularity of local mesenteric lymph nodes, including T- and B-lymphocytes, was also significantly reduced. Thus, eosinophils participate in intestinal remodeling, supporting eosinophils as a novel therapeutic target.

  17. Intestinal Cancer

    MedlinePlus

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  18. Intestinal leiomyoma

    MedlinePlus

    Leiomyoma - intestine ... McLaughlin P, Maher MM. The duodenum and small intestine. In: Adam A, Dixon AK, Gillard JH, Schaefer- ... Roline CE, Reardon RF. Disorders of the small intestine. In: Marx JA, Hockberger RS, Walls RM, et ...

  19. Intestinal obstruction

    MedlinePlus

    Paralytic ileus; Intestinal volvulus; Bowel obstruction; Ileus; Pseudo-obstruction - intestinal; Colonic ileus ... objects that are swallowed and block the intestines) Gallstones (rare) Hernias Impacted stool Intussusception (telescoping of 1 ...

  20. Intestinal Obstruction

    MedlinePlus

    An intestinal obstruction occurs when food or stool cannot move through the intestines. The obstruction can be complete or partial. ... abdomen Inability to pass gas Constipation A complete intestinal obstruction is a medical emergency. It often requires surgery. ...

  1. Remodeling A School Shop?

    ERIC Educational Resources Information Center

    Baker, G. E.

    1970-01-01

    Presents guidelines for remodeling a school shop combining major considerations of funds, program changes, class management, and flexibility, with the needs of wiring, painting, and placement of equipment. (Author)

  2. Remodeling the Media Center.

    ERIC Educational Resources Information Center

    Baule, Steven M.

    1998-01-01

    Discusses items that need to be considered when remodeling a school media center. Highlights include space and location for various functions, including projections of print versus electronic media; electrical and data wiring needs; lighting; security and supervision; and reuse of existing furniture and equipment. (LRW)

  3. Intestinal Obstruction

    MedlinePlus

    ... Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive ... Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of the Digestive ...

  4. Nucleosome Remodeling and Epigenetics

    PubMed Central

    Becker, Peter B.; Workman, Jerry L.

    2013-01-01

    Eukaryotic chromatin is kept flexible and dynamic to respond to environmental, metabolic, and developmental cues through the action of a family of so-called “nucleosome remodeling” ATPases. Consistent with their helicase ancestry, these enzymes experience conformation changes as they bind and hydrolyze ATP. At the same time they interact with DNA and histones, which alters histone–DNA interactions in target nucleosomes. Their action may lead to complete or partial disassembly of nucleosomes, the exchange of histones for variants, the assembly of nucleosomes, or the movement of histone octamers on DNA. “Remodeling” may render DNA sequences accessible to interacting proteins or, conversely, promote packing into tightly folded structures. Remodeling processes participate in every aspect of genome function. Remodeling activities are commonly integrated with other mechanisms such as histone modifications or RNA metabolism to assemble stable, epigenetic states. PMID:24003213

  5. Rhodopsin expression in the zebrafish pineal gland from larval to adult stage.

    PubMed

    Magnoli, Domenico; Zichichi, Rosalia; Laurà, Rosaria; Guerrera, Maria Cristina; Campo, Salvatore; de Carlos, Felix; Suárez, Alberto Álvarez; Abbate, Francesco; Ciriaco, Emilia; Vega, Jose Antonio; Germanà, Antonino

    2012-03-09

    The zebrafish pineal gland plays an important role in different physiological functions including the regulation of the circadian clock. In the fish pineal gland the pinealocytes are made up of different segments: outer segment, inner segment and basal pole. Particularly, in the outer segment the rhodopsin participates in the external environment light reception that represents the first biochemical step in the melatonin production. It is well known that the rhodopsin in the adult zebrafish is well expressed in the pineal gland but both the expression and the cellular localization of this protein during development remain still unclear. In this study using qRT-PCR, sequencing and immunohistochemistry the expression as well as the protein localization of the rhodopsin in the zebrafish from larval (10 dpf) to adult stage (90 dpf) were demonstrated. The rhodopsin mRNA expression presents a peak of expression at 10 dpf, a further reduction to 50 dpf before increasing again in the adult stage. Moreover, the cellular localization of the rhodopsin-like protein was always localized in the pinealocyte at all ages examined. Our results demonstrated the involvement of the rhodopsin in the zebrafish pineal gland physiology particularly in the light capture during the zebrafish lifespan.

  6. Composition of Anopheles coluzzii and Anopheles gambiae microbiota from larval to adult stages.

    PubMed

    Gimonneau, Geoffrey; Tchioffo, Majoline T; Abate, Luc; Boissière, Anne; Awono-Ambéné, Parfait H; Nsango, Sandrine E; Christen, Richard; Morlais, Isabelle

    2014-12-01

    During their immature life stages, malaria mosquitoes are exposed to a wide array of microbes and contaminants from the aquatic habitats. Although prior studies have suggested that environmental exposure shapes the microbial community structure in the adult mosquito, most reports have focused on laboratory-based experiments and on a single mosquito epithelium, the gut. In this study, we investigated the influence of the breeding site on the development of the Anopheles coluzzii and Anopheles gambiae microbiota in natural conditions. We characterized bacterial communities from aquatic habitats, at surface microlayer and subsurface water levels, to freshly emerge adult mosquitoes using multiplexed 16S rRNA gene pyrosequencing and we separately analyzed the microbiota associated with the different epithelia of adult individual, midguts, ovaries and salivary glands. We found that the distribution of bacterial communities in the aquatic habitats differed according to the depth of water collections. Inter-individual variation of bacterial composition was large in larvae guts but adult mosquitoes from a same breeding site shared quite similar microbiota. Although some differences in bacterial abundances were highlighted between the different epithelia of freshly emerged An. coluzzii and An. gambiae, an intriguing feature from our study is the particular similarity of the overall bacterial communities. Our results call for further investigations on the bacterial population dynamics in the different tissues to determine the distinctive characteristics of each microbiota during the mosquito lifespan and to identify specific interactions between certain key phyla or species and the insect life history traits.

  7. Chromatin Remodeling and Plant Immunity.

    PubMed

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    2017-01-01

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance?

  8. Remodeling with the sun

    SciTech Connect

    Bodzin, S.

    1997-05-01

    Remodeling is the perfect time to improve daylighting, direct gain heating and shading with passive solar techniques. It can also provide the best opportunity to add solar water heating or even photoboltaics to a home. This article describes addition of such energy efficient plans to a home in terms of what is needed and what the benefits are: adding windows, North glass, east and west glass, south glass, daylighting, the roof, shingles and roofing tiles, walls and floors, solar hot water, photovoltaics. Two side bars discuss the sunplace: a passive solar room and angles and overhangs.

  9. Intestinal Parasitoses.

    ERIC Educational Resources Information Center

    Lagardere, Bernard; Dumburgier, Elisabeth

    1994-01-01

    Intestinal parasites have become a serious public health problem in tropical countries because of the climate and the difficulty of achieving efficient hygiene. The objectives of this journal issue are to increase awareness of the individual and collective repercussions of intestinal parasites, describe the current conditions of contamination and…

  10. To Remodel or To Build?

    ERIC Educational Resources Information Center

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  11. No-Regrets Remodeling, 2nd Edition

    SciTech Connect

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  12. Intestinal Capillariasis

    DTIC Science & Technology

    1987-12-01

    bhIll inenais, the tiny nematode causing Intestinal capillariasis In humans, Is a Iunique parasite. It is one of the newest parasites that has been...Capillariaphilippinensis, the tiny nematode causing intestinal capillariasis in humans, is a unique parasite. It is one of the newest parasites that has been shown to...stichocytes surrounding the oesophagus. The posterior half of the nematode is wider than the anterior half and contains the digestive tract and the

  13. Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis

    PubMed Central

    Grosse, Ann S.; Pressprich, Mark F.; Curley, Lauren B.; Hamilton, Kara L.; Margolis, Ben; Hildebrand, Jeffrey D.; Gumucio, Deborah L.

    2011-01-01

    The cellular mechanisms that drive growth and remodeling of the early intestinal epithelium are poorly understood. Current dogma suggests that the murine fetal intestinal epithelium is stratified, that villi are formed by an epithelial remodeling process involving the de novo formation of apical surface at secondary lumina, and that radial intercalation of the stratified cells constitutes a major intestinal lengthening mechanism. Here, we investigate cell polarity, cell cycle dynamics and cell shape in the fetal murine intestine between E12.5 and E14.5. We show that, contrary to previous assumptions, this epithelium is pseudostratified. Furthermore, epithelial nuclei exhibit interkinetic nuclear migration, a process wherein nuclei move in concert with the cell cycle, from the basal side (where DNA is synthesized) to the apical surface (where mitosis takes place); such nuclear movements were previously misinterpreted as the radial intercalation of cells. We further demonstrate that growth of epithelial girth between E12.5 and E14.5 is driven by microtubule- and actinomyosin-dependent apicobasal elongation, rather than by progressive epithelial stratification as was previously thought. Finally, we show that the actin-binding protein Shroom3 is crucial for the maintenance of the single-layered pseudostratified epithelium. In mice lacking Shroom3, the epithelium is disorganized and temporarily stratified during villus emergence. These results favor an alternative model of intestinal morphogenesis in which the epithelium remains single layered and apicobasally polarized throughout early intestinal development. PMID:21880782

  14. Building and Remodeling Synapses

    PubMed Central

    Benson, Deanna L.; Huntley, George W.

    2011-01-01

    Synaptic junctions are generated by adhesion proteins that bridge the synaptic cleft to firmly anchor pre- and postsynaptic membranes. Several cell adhesion molecule (CAM) families localize to synapses, but it is not yet completely understood how each synaptic CAM family contributes to synapse formation and/or structure, and whether or how smaller groups of CAMs serve as minimal, functionally cooperative adhesive units upon which structure is based. Synapse structure and function evolve over the course of development, and in mature animals, synapses are composed of a greater number of proteins, surrounded by a stabilizing extracellular matrix, and often contacted by astrocytic processes. Thus, in mature networks undergoing plasticity, persistent changes in synapse strength, morphology or number must be accompanied by selective and regulated remodeling of the neuropil. Recent work indicates that regulated, extracellular proteolysis may be essential for this, and rather than simply acting permissively to enable synapse plasticity, is more likely playing a proactive role in driving coordinated synaptic structural and functional modifications that underlie persistent changes in network activity. PMID:20882551

  15. [Intestinal microbiota].

    PubMed

    Debré, Patrice; Le Gall, Jean-Yves

    2014-12-01

    The human body normally lives in symbiosis with a considerable microscopic environment present on all interfaces with the external environment; it hosts ten times more microbes (microbiota) that it has somatic or germ cells, representing a gene diversity (microbiome) 100-150 times higher than the human genome. These germs are located mainly in the gut, where they represent a mass of about one kilogram. The primary colonization of the gastrointestinal tract depends on the delivery route, the bacterial flora rewarding then depending on the environment, food hygiene, medical treatments. The intestinal microbiota plays an important role in the maturation of the immune system and in different physiological functions: digestion of polysaccharides, glycosaminoglycans and glycoproteins, vitamins biosynthesis, bile salt metabolism of some amino acids and xenobiotics. Quantitative and qualitative changes in the microbiota are observed in a wide range of diseases: obesity, colorectal cancer, liver cancer, inflammatory bowel disease, autoimmune diseases, allergies... pharmacobiotics aim to modify the intestinal microbiota in a therapeutic goal and this by various means: prebiotics, probiotics, antibiotics or fecal transplants. Intestinal flora also plays a direct role in the metabolism of certain drugs and the microbiota should be considered as a predictive parameter of response to some chemotherapies.

  16. Mechanisms of ATP Dependent Chromatin Remodeling

    PubMed Central

    Gangaraju, Vamsi K.; Bartholomew, Blaine

    2007-01-01

    The inter-relationship between DNA repair and ATP dependent chromatin remodeling has begun to become very apparent with recent discoveries. ATP dependent remodeling complexes mobilize nucleosomes along DNA, promote the exchange of histones, or completely displace nucleosomes from DNA. These remodeling complexes are often categorized based on the domain organization of their catalytic subunit. The biochemical properties and structural information of several of these remodeling complexes are reviewed. The different models for how these complexes are able to mobilize nucleosomes and alter nucleosome structure are presented incorporating several recent findings. Finally the role of histone tails and their respective modifications in ATP-dependent remodeling are discussed. PMID:17306844

  17. Intestinal capillariasis.

    PubMed Central

    Cross, J H

    1992-01-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan, but most infections occur in the Philippines and Thailand. As established experimentally, the life cycle involves freshwater fish as intermediate hosts and fish-eating birds as definitive hosts. Embryonated eggs from feces fed to fish hatch and grow as larvae in the fish intestines. Infective larvae fed to monkeys, Mongolian gerbils, and fish-eating birds develop into adults. Larvae become adults in 10 to 11 days, and the first-generation females produce larvae. These larvae develop into males and egg-producing female worms. Eggs pass with the feces, reach water, embryonate, and infect fish. Autoinfection is part of the life cycle and leads to hyperinfection. Humans acquire the infection by eating small freshwater fish raw. The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema develop. Chronic infections lead to malabsorption and hence to protein and electrolyte loss, and death results from irreversible effects of the infection. Treatment consists of electrolyte replacement and administration of an antidiarrheal agent and mebendazole or albendazole. Capillariasis philippinensis is considered a zoonotic disease of migratory fish-eating birds. The eggs are disseminated along flyways and infect the fish, and when fish are eaten raw, the disease develops. Images PMID:1576584

  18. Intestinal capillariasis.

    PubMed

    Cross, J H

    1992-04-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan, but most infections occur in the Philippines and Thailand. As established experimentally, the life cycle involves freshwater fish as intermediate hosts and fish-eating birds as definitive hosts. Embryonated eggs from feces fed to fish hatch and grow as larvae in the fish intestines. Infective larvae fed to monkeys, Mongolian gerbils, and fish-eating birds develop into adults. Larvae become adults in 10 to 11 days, and the first-generation females produce larvae. These larvae develop into males and egg-producing female worms. Eggs pass with the feces, reach water, embryonate, and infect fish. Autoinfection is part of the life cycle and leads to hyperinfection. Humans acquire the infection by eating small freshwater fish raw. The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema develop. Chronic infections lead to malabsorption and hence to protein and electrolyte loss, and death results from irreversible effects of the infection. Treatment consists of electrolyte replacement and administration of an antidiarrheal agent and mebendazole or albendazole. Capillariasis philippinensis is considered a zoonotic disease of migratory fish-eating birds. The eggs are disseminated along flyways and infect the fish, and when fish are eaten raw, the disease develops.

  19. Neural remodeling in retinal degeneration.

    PubMed

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  20. Frontiers in growth and remodeling

    PubMed Central

    Menzel, Andreas; Kuhl, Ellen

    2012-01-01

    Unlike common engineering materials, living matter can autonomously respond to environmental changes. Living structures can grow stronger, weaker, larger, or smaller within months, weeks, or days as a result of a continuous microstructural turnover and renewal. Hard tissues can adapt by increasing their density and grow strong. Soft tissues can adapt by increasing their volume and grow large. For more than three decades, the mechanics community has actively contributed to understand the phenomena of growth and remodeling from a mechanistic point of view. However, to date, there is no single, unified characterization of growth, which is equally accepted by all scientists in the field. Here we shed light on the continuum modeling of growth and remodeling of living matter, and give a comprehensive overview of historical developments and trends. We provide a state-of-the-art review of current research highlights, and discuss challenges and potential future directions. Using the example of volumetric growth, we illustrate how we can establish and utilize growth theories to characterize the functional adaptation of soft living matter. We anticipate this review to be the starting point for critical discussions and future research in growth and remodeling, with a potential impact on life science and medicine. PMID:22919118

  1. Vascular Remodeling in Pulmonary Hypertension

    PubMed Central

    Shimoda, Larissa A; Laurie, Steven S.

    2013-01-01

    Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting. PMID:23334338

  2. Epigenetics in Intestinal Epithelial Cell Renewal

    PubMed Central

    Roostaee, Alireza; Benoit, Yannick D.; Boudjadi, Salah

    2016-01-01

    A controlled balance between cell proliferation and differentiation is essential to maintain normal intestinal tissue renewal and physiology. Such regulation is powered by several intracellular pathways that are translated into the establishment of specific transcription programs, which influence intestinal cell fate along the crypt‐villus axis. One important check‐point in this process occurs in the transit amplifying zone of the intestinal crypts where different signaling pathways and transcription factors cooperate to manage cellular proliferation and differentiation, before secretory or absorptive cell lineage terminal differentiation. However, the importance of epigenetic modifications such as histone methylation and acetylation in the regulation of these processes is still incompletely understood. There have been recent advances in identifying the impact of histone modifications and chromatin remodelers on the proliferation and differentiation of normal intestinal crypt cells. In this review we discuss recent discoveries on the role of the cellular epigenome in intestinal cell fate, development, and tissue renewal. J. Cell. Physiol. 231: 2361–2367, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27061836

  3. Intestinal protozoa.

    PubMed

    Juckett, G

    1996-06-01

    Giardia is the best known cause of protozoal gastrointestinal disease in North America, producing significant but not life-threatening gastrointestinal distress and diarrhea. Although diagnosis of giardiasis may be challenging, treatment is usually successful. Entamoeba histolytica poses a rarer but far more difficult clinical challenge. Dysentery caused by E. histolytica may be the most feared intestinal protozoal infection, although Cryptosporidium parvum, Balantidium coli, Isospora belli, Sarcocystis species and other newly described protozoa also may cause diarrhea in healthy individuals and may result in intractable, life-threatening illness in patients with acquired immunodeficiency syndrome or other immunosuppressive diseases. Certain protozoa once considered relatively unimportant, such as Cryptosporidium, are now recognized as significant causes of morbidity even in the United States, since transmission readily occurs through contaminated water.

  4. Pulsatile Fluid Shear in Bone Remodeling

    NASA Technical Reports Server (NTRS)

    Frangos, John A.

    1997-01-01

    The objective of this investigation was to elucidate the sensitivity to transients in fluid shear stress in bone remodeling. Bone remodeling is clearly a function of the local mechanical environment which includes interstitial fluid flow. Traditionally, load-induced remodeling has been associated with low frequency (1-2 Hz) signals attributed to normal locomotion. McLeod and Rubin, however, demonstrated in vivo remodeling events associated with high frequency (15-30 Hz) loading. Likewise, other in vivo studies demonstrated that slowly applied strains did not trigger remodeling events. We therefore hypothesized that the mechanosensitive pathways which control bone maintenance and remodeling are differentially sensitive to varying rates of applied fluid shear stress.

  5. Intestinal dysbiosis: an emerging cause of pregnancy complications?

    PubMed

    Zhang, Dongxin; Huang, Yinping; Ye, Duyun

    2015-03-01

    The gut microbiota is intimately involved in numerous aspects of normal human physiology, including nutrition and metabolism, immunomodulation and behavior and stress response. Intestinal dysbiosis can be a contributing cause of many diseases, altering the function of both near and far organ systems. During pregnancy, the maternal body undergoes dramatic physiological changes to support the growth of fetus-placenta, while intestinal dysbiosis may directly or indirectly disturb the remodeling of physiological balance, leading to maternal maladaptation. Thus, intestinal dysbiosis, i.e., altered composition or metabolism of microbiota may adversely affect pregnancy outcome and lead to pregnancy complications via disrupting maternal adaptation. Indeed, pregnant women with potential maladaptations are at high risk of developing pregnancy disorders, which is increasingly observed in clinical cases. Here we discuss the hypothesis that intestinal dysbiosis may induce pregnancy complications via affecting maternal adaptation and the possible mechanistic pathways.

  6. [Intestinal microbiota].

    PubMed

    Perez, Horacio Joaquín; Menezes, Maria Elisabeth; d'Acâmpora, Armando José

    2014-01-01

    There is accumulative evidence on the multiple functions of the intestinal microflora in relation to the homeostasis of the host. At first considered as a simple mutualism, today this relationship proves to be essential to the health and to pathologic processes, particularly metabolic (eg, obesity) and gastrointestinal (eg, inflammatory bowel disease and functional disorders). The first studies were conducted on the microbiota from fecal material cultured anaerobically. With the advent of molecular biology, it has become possible to determine qualitative and quantitatively the dominant, subdominant and transients species. In recent years, there were advances in the understanding of the relationship betwen the microbiota and the host, as well as among the microorganisms in their respective niches. These advances result from translational integration of microbiology with specialities such as molecular biology, cell phisiology, immunology and ecology. There are few studies on the spatial distribution of the microflora in the gut. Unravelling the topography of the microflora in mammals is a way to validate new animal models for the study of microflora.

  7. Small artery remodelling in diabetes

    PubMed Central

    Rosei, Enrico Agabiti; Rizzoni, Damiano

    2010-01-01

    Abstract The aim of this article is to briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries of smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, although in some secondary forms of hypertension, a hypertrophic remodelling may be detected. Moreover, in non-insulin-dependent diabetes mellitus a hypertrophic remodelling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations of small resistance arteries with drugs blocking the renin–angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) was demonstrated. Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin–angiotensin system blockade seems to be effective in preventing/regressing alterations in microvascular structure. PMID:20646125

  8. Bone remodeling after renal transplantation.

    PubMed

    Bellorin-Font, Ezequiel; Rojas, Eudocia; Carlini, Raul G; Suniaga, Orlando; Weisinger, José R

    2003-06-01

    Several studies have indicated that bone alterations after transplantation are heterogeneous. Short-term studies after transplantation have shown that many patients exhibit a pattern consistent with adynamic bone disease. In contrast, patients with long-term renal transplantation show a more heterogeneous picture. Thus, while adynamic bone disease has also been described in these patients, most studies show decreased bone formation and prolonged mineralization lag-time faced with persisting bone resorption, and even clear evidence of generalized or focal osteomalacia in many patients. Thus, the main alterations in bone remodeling are a decrease in bone formation and mineralization up against persistent bone resorption, suggesting defective osteoblast function, decreased osteoblastogenesis, or increased osteoblast death rates. Indeed, recent studies from our laboratory have demonstrated that there is an early decrease in osteoblast number and surfaces, as well as in reduced bone formation rate and delayed mineralization after transplantation. These alterations are associated with an early increase in osteoblast apoptosis that correlates with low levels of serum phosphorus. These changes were more frequently observed in patients with low turnover bone disease. In contrast, PTH seemed to preserve osteoblast survival. The mechanisms of hypophosphatemia in these patients appear to be independent of PTH, suggesting that other phosphaturic factors may play a role. However, further studies are needed to determine the nature of a phosphaturic factor and its relationship to the alterations of bone remodeling after transplantation.

  9. In vitro cultivation of anisakis simplex: pepsin increases survival and moulting from fourth larval to adult stage.

    PubMed

    Iglesias, L; Valero, A; Benítez, R; Adroher, F J

    2001-09-01

    This paper describes the in vitro cultivation of the 3rd-larval stage (L3) of Anisakis simplex to adulthood in a much simpler and easier to prepare medium than those described to date. The adult males obtained are between 3.8 and 6.5 cm long and the females between 4.5 and 8.0 cm. Some individually cultivated females laid eggs which had an average size of 44.4 x 50.5 microm. The culture conditions were as follows: medium RPMI-1640 supplemented with 20% heat-inactivated fetal bovine serum and 1% commercial pepsin, at pH 4.0 and a temperature of 37 degrees C, and in air atmosphere with 5% CO2. The pepsin was found to be the key to the success of the culture. The average survival of the worms in the culture increased from 50 to 88 days, due to the fact that the survival of the adults practically doubled (increasing by 1.9 times). Furthermore, the number of worms that completed the 4th moulting (M4) increased by 4.2 times, from 22.9 to 95.6%. This culture medium may facilitate, due to its simplicity, the study of anisakids, or at least of A. simplex, constituting another step towards achieving a complete in vitro life-cycle for these parasites.

  10. Anisotropic growth shapes intestinal tissues during embryogenesis.

    PubMed

    Ben Amar, Martine; Jia, Fei

    2013-06-25

    Embryogenesis offers a real laboratory for pattern formation, buckling, and postbuckling induced by growth of soft tissues. Each part of our body is structured in multiple adjacent layers: the skin, the brain, and the interior of organs. Each layer has a complex biological composition presenting different elasticity. Generated during fetal life, these layers will experience growth and remodeling in the early postfertilization stages. Here, we focus on a herringbone pattern occurring in fetal intestinal tissues. Common to many mammalians, this instability is a precursor of the villi, finger-like projections into the lumen. For avians (chicks' and turkeys' embryos), it has been shown that, a few days after fertilization, the mucosal epithelium of the duodenum is smooth, and then folds emerge, which present 2 d later a pronounced zigzag instability. Many debates and biological studies are devoted to this specific morphology, which regulates the cell renewal in the intestine. After reviewing experimental results about duodenum morphogenesis, we show that a model based on simplified hypothesis for the growth of the mesenchyme can explain buckling and postbuckling instabilities. Being completely analytical, it is based on biaxial compressive stresses due to differential growth between layers and it predicts quantitatively the morphological changes. The growth anisotropy increasing with time, the competition between folds and zigzags, is proved to occur as a secondary instability. The model is compared with available experimental data on chick's duodenum and can be applied to other intestinal tissues, the zigzag being a common and spectacular microstructural pattern of intestine embryogenesis.

  11. Remodeling, Renovation, & Conversion of Educational Facilities.

    ERIC Educational Resources Information Center

    Association of Physical Plant Administrators of Universities and Colleges, Washington, DC.

    Based on a series of workshops, this collection of papers provides a framework for thought--emphasizing planning within time, flexibility, and maintenance constraints--as well as a practical guide for actual engineering of remodeling/renovation/conversion projects. Is remodeling always less expensive than new construction? Should high initial…

  12. Chromatin remodeling: nucleosomes bulging at the seams.

    PubMed

    Peterson, Craig L

    2002-04-02

    ATP-dependent chromatin remodeling enzymes, such as SWI/SNF, hydrolyze thousands of ATPs to regulate gene expression on chromatin fibers. Recent mechanistic studies suggest that these enzymes generate localized changes in DNA topology that drive formation of multiple, remodeled nucleosomal states.

  13. Nucleosome dynamics during chromatin remodeling in vivo.

    PubMed

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation.

  14. Role of thyroid hormones in ventricular remodeling.

    PubMed

    Rajagopalan, Viswanathan; Gerdes, A Martin

    2015-04-01

    Cardiac remodeling includes alterations in molecular, cellular, and interstitial systems contributing to changes in size, shape, and function of the heart. This may be the result of injury, alterations in hemodynamic load, neurohormonal effects, electrical abnormalities, metabolic changes, etc. Thyroid hormones (THs) serve as master regulators for diverse remodeling processes of the cardiovascular system-from the prenatal period to death. THs promote a beneficial cardiomyocyte shape and improve contractility, relaxation, and survival via reversal of molecular remodeling. THs reduce fibrosis by decreasing interstitial collagen and reduce the incidence and duration of arrhythmias via remodeling ion channel expression and function. THs restore metabolic function and also improve blood flow both by direct effects on the vessel architecture and decreasing atherosclerosis. Optimal levels of THs both in the circulation and in cardiac tissues are critical for normal homeostasis. This review highlights TH-based remodeling and clinically translatable strategies for diverse cardiovascular disorders.

  15. Bone remodeling in the context of cellular and systemic regulation: the role of osteocytes and the nervous system.

    PubMed

    Niedźwiedzki, Tadeusz; Filipowska, Joanna

    2015-10-01

    Bone is a dynamic tissue that undergoes constant remodeling. The appropriate course of this process determines development and regeneration of the skeleton. Tight molecular control of bone remodeling is vital for the maintenance of appropriate physiology and microarchitecture of the bone, providing homeostasis, also at the systemic level. The process of remodeling is regulated by a rich innervation of the skeleton, being the source of various growth factors, neurotransmitters, and hormones regulating function of the bone. Although the course of bone remodeling at the cellular level is mainly associated with the activity of osteoclasts and osteoblasts, recently also osteocytes have gained a growing interest as the principal regulators of bone turnover. Osteocytes play a significant role in the regulation of osteogenesis, releasing sclerostin (SOST), an inhibitor of bone formation. The process of bone turnover, especially osteogenesis, is also modulated by extra-skeletal molecules. Proliferation and differentiation of osteoblasts are promoted by the brain-derived serotonin and hypothetically inhibited by its intestinal equivalent. The activity of SOST and serotonin is either directly or indirectly associated with the canonical Wnt/β-catenin signaling pathway, the main regulatory pathway of osteoblasts function. The impairment of bone remodeling may lead to many skeletal diseases, such as high bone mass syndrome or osteoporosis. In this paper, we review the most recent data on the cellular and molecular mechanisms of bone remodeling control, with particular emphasis on the role of osteocytes and the nervous system in this process.

  16. [Ventricular "remodeling" after myocardial infarction].

    PubMed

    Cohen-Solal, A; Himbert, D; Guéret, P; Gourgon, R

    1991-06-01

    Cardiac failure is the principal medium-term complication of myocardial infarction. Changes in left ventricular geometry are observed after infarction, called ventricular remodeling, which, though compensatory initially, cause ventricular failure in the long-term. Experimental and clinical studies suggest that early treatment by coronary recanalisation, trinitrin and angiotensin converting enzyme inhibitors may prevent or limit the expansion and left ventricular dilatation after infarction, so improving ventricular function, and, at least in the animal, reduce mortality. Large scale trials with converting enzyme inhibitors are currently under way to determine the effects of this new therapeutic option. It would seem possible at present, independently of any reduction in the size of the infarction, to reduce or delay left ventricular dysfunction by interfering with the natural process of dilatation and ventricular modeling after infarction.

  17. Exercise-induced cardiac remodeling.

    PubMed

    Weiner, Rory B; Baggish, Aaron L

    2012-01-01

    Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

  18. Calcium signalling remodelling and disease.

    PubMed

    Berridge, Michael J

    2012-04-01

    A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease.

  19. Zika Virus Induced Cellular Remodeling.

    PubMed

    Rossignol, Evan D; Peters, Kristen N; Connor, John H; Bullitt, Esther

    2017-03-20

    Zika virus (ZIKV) has been associated with morbidities such as Guillain-Barré, infant microcephaly, and ocular disease. The spread of this positive-sense, single-stranded RNA virus and its growing public health threat underscore gaps in our understanding of basic ZIKV virology. To advance knowledge of the virus replication cycle within mammalian cells, we use serial section three-dimensional electron tomography to demonstrate the widespread remodeling of intracellular membranes upon infection with ZIKV. We report extensive structural rearrangements of the endoplasmic reticulum and reveal stages of the ZIKV viral replication cycle. Structures associated with RNA genome replication and virus assembly are observed integrated within the endoplasmic reticulum, and we show viruses in transit through the Golgi apparatus for viral maturation, and subsequent cellular egress. This study characterizes in detail the three-dimensional ultrastructural organization of the ZIKV replication cycle stages. Our results show close adherence of the ZIKV replication cycle to the existing flavivirus replication paradigm.

  20. Tissue remodelling in pulmonary fibrosis.

    PubMed

    Knudsen, Lars; Ruppert, Clemens; Ochs, Matthias

    2017-03-01

    Many lung diseases result in fibrotic remodelling. Fibrotic lung disorders can be divided into diseases with known and unknown aetiology. Among those with unknown aetiology, idiopathic pulmonary fibrosis (IPF) is a common diagnosis. Because of its progressive character leading to a rapid decline in lung function, it is a fatal disease with poor prognosis and limited therapeutic options. Thus, IPF has motivated many studies in the last few decades in order to increase our mechanistic understanding of the pathogenesis of the disease. The current concept suggests an ongoing injury of the alveolar epithelium, an impaired regeneration capacity, alveolar collapse and, finally, a fibroproliferative response. The origin of lung injury remains elusive but a diversity of factors, which will be discussed in this article, has been shown to be associated with IPF. Alveolar epithelial type II (AE2) cells play a key role in lung fibrosis and their crucial role for epithelial regeneration, stabilisation of alveoli and interaction with fibroblasts, all known to be responsible for collagen deposition, will be illustrated. Whereas mechanisms of collagen deposition and fibroproliferation are the focus of many studies in the field, the awareness of other mechanisms in this disease is currently limited to biochemical and imaging studies including quantitative assessments of lung structure in IPF and animal models assigning alveolar collapse and collapse induration crucial roles for the degradation of the lung resulting in de-aeration and loss of surface area. Dysfunctional AE2 cells, instable alveoli and mechanical stress trigger remodelling that consists of collapsed alveoli absorbed by fibrotic tissue (i.e., collapse induration).

  1. Small Intestine Disorders

    MedlinePlus

    Your small intestine is the longest part of your digestive system - about twenty feet long! It connects your stomach to ... many times to fit inside your abdomen. Your small intestine does most of the digesting of the foods ...

  2. Small intestine (image)

    MedlinePlus

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the ... the duodenum. This short first portion of the small intestine is followed by the jejunum and the ileum. ...

  3. Airway remodeling in asthma: what really matters.

    PubMed

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  4. Maternal Uterine Vascular Remodeling During Pregnancy

    PubMed Central

    Osol, George; Mandala, Maurizio

    2009-01-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms. PMID:19196652

  5. Simulations of trabecular remodeling and fatigue: is remodeling helpful or harmful?

    PubMed

    van Oers, René F M; van Rietbergen, Bert; Ito, Keita; Huiskes, Rik; Hilbers, Peter A J

    2011-05-01

    Microdamage-targeted resorption is paradoxal, because it entails the removal of bone from a region that was already overloaded. Under continued intense loading, resorption spaces could potentially cause more damage than they remove. To investigate this problem, we incorporated damage algorithms in a computer-simulation model for trabecular remodeling. We simulated damage accumulation and bone remodeling in a trabecular architecture, for two fatigue regimens, a 'moderate' regimen, and an 'intense' regimen with a higher number of loading cycles per day. Both simulations were also performed without bone remodeling to investigate if remodeling removed or exacerbated the damage. We found that remodeling tends to remove damage under the 'moderate' fatigue regimen, but it exacerbates damage under the 'intense' regimen. This harmful effect of remodeling may play a role in the development of stress fractures.

  6. Transdifferentiation and remodeling of post-embryonic C. elegans cells by a single transcription factor.

    PubMed

    Riddle, Misty R; Weintraub, Abraham; Nguyen, Ken C Q; Hall, David H; Rothman, Joel H

    2013-12-01

    Terminally differentiated post-mitotic cells are generally considered irreversibly developmentally locked, i.e. incapable of being reprogrammed in vivo into entirely different cell types. We found that brief expression of a single transcription factor, the ELT-7 GATA factor, can convert the identity of fully differentiated, highly specialized non-endodermal cells of the pharynx into fully differentiated intestinal cells in intact larvae and adult Caenorhabditis elegans. Stable expression of intestine-specific molecular markers parallels loss of markers for the original differentiated pharynx state; hence, there is no apparent requirement for a dedifferentiated intermediate during the transdifferentiation process. Based on high-resolution morphological characteristics, the transdifferentiated cells become remodeled to resemble typical intestinal cells at the level of both the cell surface and internal organelles. Thus, post-mitotic cells, though terminally differentiated, remain plastic to transdifferentiation across germ layer lineage boundaries and can be remodeled to adopt the characteristics of a new cell identity without removal of inhibitory factors. Our findings establish a simple model to investigate how cell context influences forced transdifferentiation of mature cells.

  7. Establishment of Intestinal Bacteriology

    PubMed Central

    MITSUOKA, Tomotari

    2014-01-01

    Research on intestinal bacteria began around the end of the 19th century. During the last 5 decades of the 20th century, research on the intestinal microbiota made rapid progress. At first, in my work, I first developed a method of comprehensive analysis of the intestinal microbiota, and then I established classification and identification methods for intestinal anaerobes. Using these methods I discovered a number of ecological rules governing the intestinal microbiota and the role of the intestinl microbiota in health and disease. Moreover, using germfree animals, it was proven that the intestinal microbiota has a role in carcinogenesis and aging in the host. Thus, a new interdisciplinary field, “intestinal bacteriology” was established. PMID:25032084

  8. Raise the Floor When Remodeling Science Labs

    ERIC Educational Resources Information Center

    Nation's Schools, 1972

    1972-01-01

    A new remodeling idea adopts the concept of raised floor covering gas, water, electrical, and drain lines. The accessible floor has removable panels set into an adjustable support frame 24 inches above a concrete subfloor. (Author)

  9. Lead Poisoning in Remodeling of Old Homes

    ERIC Educational Resources Information Center

    Barnes, Bart

    1973-01-01

    An article based on Dr. Muriel D. Wolf's study of elevated blood lead levels in children and adults present during the remodeling of old homes. Lead poisoning examples, symptoms, and precautions are given. (ST)

  10. B.B. Contracting & Remodeling Information Sheet

    EPA Pesticide Factsheets

    B.B. Contracting & Remodeling (the Company) is located in St. Louis, Missouri. The settlement involves renovation activities conducted at property constructed prior to 1978, located in St. Louis, Missouri.

  11. Ventricular remodeling in global ischemia.

    PubMed

    Anversa, P; Zhang, X; Li, P; Olivetti, G; Cheng, W; Reiss, K; Sonnenblick, E H; Kajstura, J

    1995-06-01

    To determine the effects of chronic constriction of the left coronary artery on the function and structure of the heart, coronary artery narrowing was surgically induced in rats and ventricular pump performance, extent and distribution of myocardial damage, and the hypertrophic and hyperplastic response of myocytes were examined. Alterations in cardiac hemodynamics were found in all rats, but the characteristics of the physiological properties of the heart allowed a separation of the animals into two groups which exhibited left ventricular dysfunction and failure, respectively. Left ventricular hypertrophy occurred in both groups and was characterized by ventricular dilatation and wall thinning which were more severe in the failing animals. Multiple foci of myocardial damage across the wall were seen in all animals but tissue injury was more prominent in the endomyocardium and in failing rats. The anatomical and hemodynamic changes resulted in a significant increase in diastolic wall stress which paralleled the depression in ventricular performance. Myocyte cell loss and myocyte cellular hypertrophy were more severe with ventricular failure than with dysfunction. Finally, diastolic overload appeared to be coupled with activation of the DNA synthetic machinery of myocytes and nuclear mitotic division. In conclusion, a fixed lesion of the left coronary artery leads to abnormalities in cardiac dynamics with marked increases in diastolic wall stress and extensive ventricular remodeling in spite of compensatory myocyte cellular hypertrophy and hyperplasia in the remaining viable tissue.

  12. Bone remodeling as a spatial evolutionary game.

    PubMed

    Ryser, Marc D; Murgas, Kevin A

    2017-04-07

    Bone remodeling is a complex process involving cell-cell interactions, biochemical signaling and mechanical stimuli. Early models of the biological aspects of remodeling were non-spatial and focused on the local dynamics at a fixed location in the bone. Several spatial extensions of these models have been proposed, but they generally suffer from two limitations: first, they are not amenable to analysis and are computationally expensive, and second, they neglect the role played by bone-embedded osteocytes. To address these issues, we developed a novel model of spatial remodeling based on the principles of evolutionary game theory. The analytically tractable framework describes the spatial interactions between zones of bone resorption, bone formation and quiescent bone, and explicitly accounts for regulation of remodeling by bone-embedded, mechanotransducing osteocytes. Using tools from the theory of interacting particle systems we systematically classified the different dynamic regimes of the spatial model and identified regions of parameter space that allow for global coexistence of resorption, formation and quiescence, as observed in physiological remodeling. In coexistence scenarios, three-dimensional simulations revealed the emergence of sponge-like bone clusters. Comparison between spatial and non-spatial dynamics revealed substantial differences and suggested a stabilizing role of space. Our findings emphasize the importance of accounting for spatial structure and bone-embedded osteocytes when modeling the process of bone remodeling. Thanks to the lattice-based framework, the proposed model can easily be coupled to a mechanical model of bone loading.

  13. Cardiac remodelling and RAS inhibition

    PubMed Central

    Ferrario, Carlos M.

    2016-01-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin–angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  14. Intestinal M cells

    PubMed Central

    Ohno, Hiroshi

    2016-01-01

    We have an enormous number of commensal bacteria in our intestine, moreover, the foods that we ingest and the water we drink is sometimes contaminated with pathogenic microorganisms. The intestinal epithelium is always exposed to such microbes, friend or foe, so to contain them our gut is equipped with specialized gut-associated lymphoid tissue (GALT), literally the largest peripheral lymphoid tissue in the body. GALT is the intestinal immune inductive site composed of lymphoid follicles such as Peyer’s patches. M cells are a subset of intestinal epithelial cells (IECs) residing in the region of the epithelium covering GALT lymphoid follicles. Although the vast majority of IEC function to absorb nutrients from the intestine, M cells are highly specialized to take up intestinal microbial antigens and deliver them to GALT for efficient mucosal as well as systemic immune responses. I will discuss recent advances in our understanding of the molecular mechanisms of M-cell differentiation and functions. PMID:26634447

  15. Periprosthetic Bone Remodelling in Total Knee Arthroplasty

    PubMed Central

    GEORGEANU, Vlad; ATASIEI, Tudor; GRUIONU, Lucian

    2014-01-01

    Introduction: The clinical studies have shown that the displacement of the prosthesis components, especially of the tibial one is higher during the first year, after which it reaches an equilibrum position compatible with a good long term functioning. This displacement takes place due to bone remodelling close to the implant secondary to different loading concentrations over different areas of bone. Material and Method: Our study implies a simulation on a computational model using the finite element analysis. The simulation started taking into account arbitrary points because of non-linear conditions of bone-prosthesis interface and it was iterative.. A hundred consecutive situations corresponding to intermediate bone remodelling phases have been calculated according to given loadings. Bone remodelling was appreciated as a function of time and bone density for each constitutive element of the computational model created by finite element method. For each constitutive element a medium value of stress during the walking cycle was applied. Results: Analyse of proximal epiphysis-prosthesis complex slices showed that bone density increase is maintained all over the stem in the immediately post-operative period. At 10 months, the moment considered to be the end of bone remodelling, areas with increased bone density are fewer and smaller. Meanwhile, their distribution with a concentration toward the internal compartment in the distal metaphysis is preserved. Conclusions: After the total knee arthroplasty the tibial bone suffered a process of remodelling adapted to the new stress conditions. This bone remodelling can influence, sometimes negatively, especially in the cases with tibial component varus malposition, the fixation, respectively the survival of the prosthesis. This process has been demonstrated both by clinical trials and by simulation, using the finite elements method of periprosthetic bone remodelling. PMID:25553127

  16. Intestinal lymphangiectasia in children

    PubMed Central

    Isa, Hasan M.; Al-Arayedh, Ghadeer G.; Mohamed, Afaf M.

    2016-01-01

    Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification. PMID:26837404

  17. Intestinal transplantation: a review.

    PubMed

    Desai, Chirag Sureshchandra; Khan, Khalid Mahmood; Girlanda, Raffaele; Fishbein, Thomas M

    2012-09-01

    Parenteral nutrition is a life-saving therapy for patients with intestinal failure. Intestinal transplantation is now recognized as a treatment for patients who develop complications of parenteral nutrition and in whom attempts at intestinal rehabilitation have failed. Patients with parenteral nutrition related liver disease will require a liver graft typically part of a multivisceral transplant. Isolated intestinal transplants are more commonly performed in adults while multivisceral transplants are most commonly performed in infants. Isolated intestinal transplants have the best short-term outcome, with over 80 % survival at 1 year. Patients requiring multivisceral transplants have a high rate of attrition with a 1 year survival less than 70 %. Prognostic factors for a poor outcome include patient hospitalization at the time of transplant and donor age greater than 40 years while systemic sepsis and acute rejection are the major determinant of early postoperative outcome. For patients surviving the first year the outcome of transplantation of the liver in addition to intestine affords some survival advantage though long-term outcome does not yet match other abdominal organs. Outcomes for intestinal retransplantation are poor as a result of immunology and patient debility. Overall intestinal transplantation continues to develop and is a clear indication with cost and quality of life advantages in patients with intestinal failure that do not remain stable on parenteral nutrition.

  18. Retinal remodeling in inherited photoreceptor degenerations.

    PubMed

    Marc, Robert E; Jones, Bryan W

    2003-10-01

    Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium usually evoke secondary cone death and sensory deafferentation of the surviving neural retina. In the mature central nervous system, deafferentation evokes atrophy and connective re-patterning. It has been assumed that the neural retina does not remodel, and that it is a passive survivor. Screening of advanced stages of human and rodent retinal degenerations with computational molecular phenotyping has exposed a prolonged period of aggressive negative remodeling in which neurons migrate along aberrant glial columns and seals, restructuring the adult neural retina (1). Many neurons die, but survivors rewire the remnant inner plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new circuits that are most likely corruptive. Remodeling in human and rodent retinas emerges regardless of the molecular defects that initially trigger retinal degenerations. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, the exposure of intrinsic retinal remodeling by the removal of sensory control in retinal degenerations suggests that neuronal organization in the normal retina may be more plastic than previously believed.

  19. Temperature-induced cardiac remodelling in fish

    PubMed Central

    Keen, Adam N.; Klaiman, Jordan M.; Shiels, Holly A.

    2017-01-01

    ABSTRACT Thermal acclimation causes the heart of some fish species to undergo significant remodelling. This includes changes in electrical activity, energy utilization and structural properties at the gross and molecular level of organization. The purpose of this Review is to summarize the current state of knowledge of temperature-induced structural remodelling in the fish ventricle across different levels of biological organization, and to examine how such changes result in the modification of the functional properties of the heart. The structural remodelling response is thought to be responsible for changes in cardiac stiffness, the Ca2+ sensitivity of force generation and the rate of force generation by the heart. Such changes to both active and passive properties help to compensate for the loss of cardiac function caused by a decrease in physiological temperature. Hence, temperature-induced cardiac remodelling is common in fish that remain active following seasonal decreases in temperature. This Review is organized around the ventricular phases of the cardiac cycle – specifically diastolic filling, isovolumic pressure generation and ejection – so that the consequences of remodelling can be fully described. We also compare the thermal acclimation-associated modifications of the fish ventricle with those seen in the mammalian ventricle in response to cardiac pathologies and exercise. Finally, we consider how the plasticity of the fish heart may be relevant to survival in a climate change context, where seasonal temperature changes could become more extreme and variable. PMID:27852752

  20. Obesity and carotid artery remodeling

    PubMed Central

    Kozakova, M; Palombo, C; Morizzo, C; Højlund, K; Hatunic, M; Balkau, B; Nilsson, P M; Ferrannini, E

    2015-01-01

    Background/Objective: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP). Subjects/Methods: Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24–159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age). Results: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 μm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 μm, P=0.001, P<0.05 and P=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, P<0.0001). As compared with gender- and age-matched lean individuals, obese subjects had highly increased CCA LD and BP (P<0.0001 for both), but only slightly higher CWS (P=0.05) due to a significant increase in IMT (P=0.005 after adjustment for confounders). Conclusions: Our findings suggest that in obese subjects, the CCA wall thickens to compensate the luminal enlargement caused by body size-induced increase in SV, and therefore, to normalize the wall stress. CCA diameter in obesity could

  1. Intestinal or bowel obstruction - discharge

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000150.htm Intestinal or bowel obstruction - discharge To use the sharing features on this ... your bowel (intestine). This condition is called an intestinal obstruction . The blockage may be partial or total (complete). ...

  2. Molecular Aspects of Exercise-induced Cardiac Remodeling.

    PubMed

    Bernardo, Bianca C; McMullen, Julie R

    2016-11-01

    Exercise-induced cardiac remodeling is typically an adaptive response associated with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers of cardiac remodeling include increased hemodynamic load, increased sympathetic activity, and the release of hormones and growth factors. Prolonged and strenuous exercise may lead to maladaptive exercise-induced cardiac remodeling including cardiac dysfunction and arrhythmia. In addition, this article describes novel therapeutic approaches for the treatment of heart failure that target mechanisms responsible for adaptive exercise-induced cardiac remodeling, which are being developed and tested in preclinical models.

  3. Intestinal obstruction repair - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100116.htm Intestinal obstruction repair - series—Normal anatomy To use the sharing ... M. Editorial team. Related MedlinePlus Health Topics Adhesions Intestinal Obstruction A.D.A.M., Inc. is accredited by ...

  4. Intestinal obstruction (pediatric) - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100165.htm Intestinal obstruction (pediatric) - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Intestinal Obstruction A.D.A.M., Inc. is accredited by ...

  5. The Chd Family of Chromatin Remodelers

    PubMed Central

    Marfella, Concetta G.A.; Imbalzano, Anthony N.

    2007-01-01

    Chromatin remodeling enzymes contribute to the dynamic changes that occur in chromatin structure during cellular processes such as transcription, recombination, repair, and replication. Members of the chromodomain helicase DNA-binding (Chd) family of enzymes belong to the SNF2 superfamily of ATP-dependent chromatin remodelers. The Chd proteins are distinguished by the presence of two N-terminal chromodomains that function as interaction surfaces for a variety of chromatin components. Genetic, biochemical, and structural studies demonstrate that Chd proteins are important regulators of transcription and play critical roles during developmental processes. Numerous Chd proteins are also implicated in human disease. PMID:17350655

  6. Intestinal Barrier and Behavior.

    PubMed

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses.

  7. Scar remodeling after strabismus surgery.

    PubMed Central

    Ludwig, I H

    1999-01-01

    limitation of versions, less separation of the tendons from sclera, and thicker appearance of the scar segments. The use of nonabsorbable sutures in the repair procedure reduced the recurrence rate. Histologic examination of the clinical stretched scar specimens showed dense connective tissue that was less well organized compared with normal tendon. In the tissue culture studies, cells cultured from the stretched scar specimens grew rapidly and were irregularly shaped. A high-molecular-weight protein was identified in the culture medium. By contrast, cells cultured from normal tendon (controls) grew more slowly and regularly, stopped growing at 4 days, and produced less total protein than cultured stretched scar specimens. In the animal model studies, the collagenase-treated sites showed elongated scars with increased collagen between the muscle and the sclera, as well as increased collagen creep rates, compared with the saline-treated controls. The use of nonabsorbable sutures in collagenase-treated animal model surgery sites was associated with shorter, thicker scars compared with similar sites sutured with absorbable sutures. CONCLUSIONS: A lengthened or stretched, remodeled scar between an operated muscle tendon and sclera is a common occurrence and is a factor contributing to the variability of outcome after strabismus repair, even years later. This abnormality may be revealed by careful exploration of previously operated muscles. Definitive repair requires firm reattachment of tendon to sclera with nonabsorbable suture support. Images FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 FIGURE 20 FIGURE 21 FIGURE 22 FIGURE 23 FIGURE 24 FIGURE 25 FIGURE 26 FIGURE 27 FIGURE 28 FIGURE 29 FIGURE 30 FIGURE 31 FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 35 FIGURE 36 FIGURE 37 FIGURE 38 FIGURE 39 FIGURE 40 FIGURE 41 FIGURE 42 FIGURE 43 FIGURE 44 FIGURE 45 FIGURE 46 FIGURE 52

  8. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster

    PubMed Central

    Krogsdam, Anne; Orth-Höller, Dorothea; Trajanoski, Zlatko; Lusser, Alexandra

    2016-01-01

    The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster. PMID:27093431

  9. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster.

    PubMed

    Sebald, Johanna; Willi, Michaela; Schoberleitner, Ines; Krogsdam, Anne; Orth-Höller, Dorothea; Trajanoski, Zlatko; Lusser, Alexandra

    2016-01-01

    The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster.

  10. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    SciTech Connect

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  11. Intestinal permeability, leaky gut, and intestinal disorders.

    PubMed

    Hollander, D

    1999-10-01

    A major task of the intestine is to form a defensive barrier to prevent absorption of damaging substances from the external environment. This protective function of the intestinal mucosa is called permeability. Clinicians can use inert, nonmetabolized sugars such as mannitol, rhamnose, or lactulose to measure the permeability barrier or the degree of leakiness of the intestinal mucosa. Ample evidence indicates that permeability is increased in most patients with Crohn's disease and in 10% to 20% of their clinically healthy relatives. The abnormal leakiness of the mucosa in Crohn's patients and their relatives can be greatly amplified by aspirin preadministration. Permeability measurements in Crohn's patients reflect the activity, extent, and distribution of the disease and may allow us to predict the likelihood of recurrence after surgery or medically induced remission. Permeability is also increased in celiac disease and by trauma, burns, and nonsteroidal anti-inflammatory drugs. The major determinant of the rate of intestinal permeability is the opening or closure of the tight junctions between enterocytes in the paracellular space. As we broaden our understanding of the mechanisms and agents that control the degree of leakiness of the tight junctions, we will be increasingly able to use permeability measurements to study the etiology and pathogenesis of various disorders and to design or monitor therapies for their management.

  12. Re-Modelling as De-Professionalisation

    ERIC Educational Resources Information Center

    Thompson, Meryl

    2006-01-01

    The article sets out the consequences of the British Government's remodelling agenda and its emphasis on less demarcation, for the professional status of teachers in England. It describes how the National Agreement on Raising Standards and Tackling Workload, reached between five of the six trade unions for teachers and headteachers paves the way…

  13. Challenging Modernization: Remodelling the Education Workforce

    ERIC Educational Resources Information Center

    Butt, Graham; Gunter, Helen

    2005-01-01

    This special edition enables an in-depth look at the process of modernization of education in England, in relation to other international developments. In particular we focus on the reform of teachers? work by examining the antecedence of the current policy of remodelling through three articles based on the Evaluation of the Department for…

  14. Revealing remodeler function: Varied and unique

    NASA Astrophysics Data System (ADS)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  15. Retinal remodeling in human retinitis pigmentosa.

    PubMed

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

  16. Immune modulation of resistance artery remodelling.

    PubMed

    Schiffrin, Ernesto L

    2012-01-01

    Low-grade inflammation plays a role in cardiovascular disease. The innate and the adaptive immune responses participate in mechanisms that contribute to inflammatory responses. It has been increasingly appreciated that different subsets of lymphocytes and the cytokines they produce modulate the vascular remodelling that occurs in cardiovascular disease. Effector T cells such as T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (that produce interleukin-4), as well as Th17 (that produce interleukin-17), and T suppressor lymphocytes including regulatory T cells (Treg), which express the transcription factor forkhead box P3 (Foxp3), are involved in the remodelling of small arteries that occurs under the action of angiotensin II, deoxycorticosterone-salt and aldosterone-salt, as well as in models of hypertension such as the Dahl-salt-sensitive rat. The mechanism whereby the immune system is activated is unclear, but it has been suggested that neo-antigens may be generated by the elevation of blood pressure or other stimuli, leading to the activation of the immune response. Activated Th1 may contribute to vascular remodelling directly on blood vessels via effects of the cytokines produced or indirectly by actions on the kidney. The protective effect of Treg may be mediated similarly directly or via renal effects. These data offer promise for the discovery of new therapeutic targets to ameliorate vascular remodelling, which could lead to improved outcome in cardiovascular disease in humans.

  17. Endothelial cell dynamics in vascular remodelling.

    PubMed

    Barbacena, Pedro; Carvalho, Joana R; Franco, Claudio A

    2016-01-01

    In this ESCHM 2016 conference talk report, we summarise two recently published original articles Franco et al. PLoS Biology 2015 and Franco et al. eLIFE 2016. The vascular network undergoes extensive vessel remodelling to become fully functional. Is it well established that blood flow is a main driver for vascular remodelling. It has also been proposed that vessel pruning is a central process within physiological vessel remodelling. However, despite its central function, the cellular and molecular mechanisms regulating vessel regression, and their interaction with blood flow patterns, remain largely unexplained. We investigated the cellular process governing developmental vascular remodelling in mouse and zebrafish. We established that polarised reorganization of endothelial cells is at the core of vessel regression, representing vessel anastomosis in reverse. Moreover, we established for the first time an axial polarity map for all endothelial cells together with an in silico method for the computation of the haemodynamic forces in the murine retinal vasculature. Using network-level analysis and microfluidics, we showed that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/11 renders endothelial cells more sensitive to shear, resulting in axial polarisation at lower shear stress levels. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.

  18. Biochemistry of intestinal development.

    PubMed Central

    Henning, S J

    1979-01-01

    In biochemical terms, the rat small intestine is relatively immature at birth and for the first two postnatal weeks. Then during the third week a dramatic array of enzymic changes begins, and by the end of the fourth week the intestine has the digestive and absorptive properties of the adult. Selective examples of these changes are discussed with emphasis on their implications for toxicological studies. The review also includes a detailed consideration of the roles of the dietary change of weaning and of glucocorticoid and thyroid hormones in the regulation of intestinal development. PMID:575507

  19. Intestinal Complications of IBD

    MedlinePlus

    ... that only affects the colon). LOCAL COMPLICATIONS OF CROHN’S DISEASE INTESTINAL OBSTRUCTION The most common complication of Crohn’s disease, obstruction may arise from swelling and the formation ...

  20. Intestinal pseudo-obstruction

    MedlinePlus

    ... Taking drugs that slow intestinal movements. These include narcotic (pain) medicines and drugs used when you are ... that may have caused the problem (such as narcotic drugs) may help. In severe cases, surgery may ...

  1. Association Between Myocardial Mechanics and Ischemic LV Remodeling.

    PubMed

    D'Elia, Nicholas; D'hooge, Jan; Marwick, Thomas H

    2015-12-01

    The outcomes associated with heart failure after myocardial infarction are still poor. Both global and regional left ventricular (LV) remodeling are associated with the progression of the post-infarct patient to heart failure, but although global remodeling can be accurately measured, regional LV remodeling has been more difficult to investigate. Preliminary evidence suggests that post-MI assessment of LV mechanics using stress and strain may predict global (and possibly regional) LV remodeling. A method of predicting both global and regional LV remodeling might facilitate earlier, targeted, and more extensive clinical intervention in those most likely to benefit from novel interventions such as cell therapy.

  2. Role of reactive oxygen species in myocardial remodeling.

    PubMed

    Zhang, Min; Shah, Ajay M

    2007-03-01

    Adverse cardiac remodeling is a fundamental process in the progression to chronic heart failure. Although the mechanisms underlying cardiac remodeling are multi-factorial, a significant body of evidence points to the crucial roles of increased reactive oxygen species. This article reviews recent advances in delineating the different sources of production for reactive oxygen species (namely mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases) that may be involved in cardiac remodeling and the aspects of the remodeling process that they affect. These data could suggest new ways of targeting redox pathways for the prevention and treatment of adverse cardiac remodeling.

  3. Intestinal parasitic infection.

    PubMed

    Park, Mi-Suk; Kim, Ki Whang; Ha, Hyun Kwon; Lee, Dong Ho

    2008-01-01

    In general, gastrointestinal tract is the primary involvement site of parasites during their life cycle. In this article, we will describe amebiasis, ascariasis, and anisakiasis among the many common intestinal parasitic diseases. We will review the epidemiology, life cycles, clinical manifestations and complications, and illustrate detailed imaging findings of intestinal parasites. Recognizing features of parasitic infection is important to establish an early diagnosis that leads to prompt treatment and helps avoid unnecessary surgery.

  4. Intestinal adaptation following resection.

    PubMed

    Tappenden, Kelly A

    2014-05-01

    Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

  5. Claudins in intestines

    PubMed Central

    Lu, Zhe; Ding, Lei; Lu, Qun; Chen, Yan-Hua

    2013-01-01

    Intestines are organs that not only digest food and absorb nutrients, but also provide a defense barrier against pathogens and noxious agents ingested. Tight junctions (TJs) are the most apical component of the junctional complex, providing one form of cell-cell adhesion in enterocytes and playing a critical role in regulating paracellular barrier permeability. Alteration of TJs leads to a number of pathophysiological diseases causing malabsorption of nutrition and intestinal structure disruption, which may even contribute to systemic organ failure. Claudins are the major structural and functional components of TJs with at least 24 members in mammals. Claudins have distinct charge-selectivity, either by tightening the paracellular pathway or functioning as paracellular channels, regulating ions and small molecules passing through the paracellular pathway. In this review, we have discussed the functions of claudin family members, their distribution and localization in the intestinal tract of mammals, their alterations in intestine-related diseases and chemicals/agents that regulate the expression and localization of claudins as well as the intestinal permeability, which provide a therapeutic view for treating intestinal diseases. PMID:24478939

  6. Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions

    PubMed Central

    Baranwal, Somesh

    2015-01-01

    Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. PMID:25792565

  7. Total sialic acid profile in regressing and remodelling organs during the metamorphosis of marsh frog (Pelophylax ridibundus Pallas 1771).

    PubMed

    Kaptan, Engin; Bas, Serap Sancar; Inceli, Meliha Sengezer

    2013-03-01

    This study aimed to investigate the functional relationship of sialic acid in regressing and remodelling organs such as the tail, small intestine and liver during the metamorphosis of Pelophylax ridibundus. For this purpose, four groups were composed according to developmental periods by considering Gosner's criteria (1964). Our findings showed that the sialic acid content of the larval tail has an opposite profile to cell death process. Although the sialic acid content of the small intestine and liver did not change evidently during metamorphosis, it increased after the completion of metamorphosis. Frog tail extensively exhibited cell death process and decreased proliferative activity and underwent complete degeneration during metamorphic climax. In spite of increased apoptotic index, a decreased sialic acid level in the tail tissues during climax can be the indication of a death cell removal process. However, the intestine and the liver included both cell death and proliferative process and remodelling in their adult forms. Thus, their sialic acid profiles during metamorphosis were different from the tail's profile. These data show that sialic acid may be an indicator of the presence of some cellular events during metamorphosis and that it can have different roles in the developmental process depending on the organ's fate throughout metamorphosis.

  8. Intestinal lymphangiectasia in adults.

    PubMed

    Freeman, Hugh James; Nimmo, Michael

    2011-02-15

    Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial

  9. Ventricular remodeling: from bedside to molecule.

    PubMed

    Jaffe, R; Flugelman, M Y; Halon, D A; Lewis, B S

    1997-01-01

    The multiple mechanisms that bring about the decompensation of the hypertrophic remodeled myocardium are synergistic and not fully understood. Our current hypothesis is that the increased stress on the ventricle is initially offset by compensatory myocardial hypertrophy. In many instances, however, progressive ventricular dilatation and heart failure occur as a result of maladaptive hypertrophy (abnormal myosin-actin production), programmed cell death (apoptosis) and/or changes in the interstitial vasculature and collagen composition. The molecular and genetic background to these processes includes changes in myocardial gene expression, activation of the local tissue renin-angiotensin and other neurohormonal systems, increased matrix metalloproteinase activity (including collagenase), and expression of certain components of the immune system, such as TNF-alpha. Future research will hopefully provide better methods for limiting the remodeling-ventricular dilatation process by novel pharmacotherapies, gene therapy and, possibly, surgical therapy, and determine the impact of such interventions on survival.

  10. Chromatin Remodeling, DNA Damage Repair and Aging

    PubMed Central

    Liu, Baohua; Yip, Raymond KH; Zhou, Zhongjun

    2012-01-01

    Cells are constantly exposed to a variety of environmental and endogenous conditions causing DNA damage, which is detected and repaired by conserved DNA repair pathways to maintain genomic integrity. Chromatin remodeling is critical in this process, as the organization of eukaryotic DNA into compact chromatin presents a natural barrier to all DNA-related events. Studies on human premature aging syndromes together with normal aging have suggested that accumulated damages might lead to exhaustion of resources that are required for physiological functions and thus accelerate aging. In this manuscript, combining the present understandings and latest findings, we focus mainly on discussing the role of chromatin remodeling in the repair of DNA double-strand breaks (DSBs) and regulation of aging. PMID:23633913

  11. [Remodeling of Cardiovascular System: Causes and Consequences].

    PubMed

    Lopatina, E V; Kipenko, A V; Penniyaynen, V A; Pasatetckaia, N A; Tsyrline, V A

    2016-01-01

    Literature and our data suggest the regulatory action of a number of biologically active substances (catecholamines, cardiac glycosides, β-blockers, angiotensin-converting-enzyme inhibitor) on the growth and proliferation of heart cells. By using of organotypic tissue culture has proved that the basis of this regulation is the ability of test substances, receptor- or transducer-mediated signaling to modulate the function of Na⁺, K⁺-ATPase. There is a delay in the development of vascular smooth muscle in the late postnatal period in rats with the blockade of the sympathetic nervous system in the prenatal period. The relationship between vascular remodeling and contractile activity is described. It seems that one of the causes of high blood pressure is a remodeling of the cardiovascular system, which precedes the development of hypertension.

  12. Remodeling of Calcium Entry Pathways in Cancer.

    PubMed

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2016-01-01

    Ca(2+) entry pathways play important roles in control of many cellular functions, including long-term proliferation, migration and cell death. In recent years, it is becoming increasingly clear that, in some types of tumors, remodeling of Ca(2+) entry pathways could contribute to cancer hallmarks such as excessive proliferation, cell migration and invasion as well as resistance to cell death or survival. In this chapter we briefly review findings related to remodeling of Ca(2+) entry pathways in cancer with emphasis on the mechanisms that contribute to increased store-operated Ca(2+) entry (SOCE) and store-operated currents (SOCs) in colorectal cancer cells. Finally, since SOCE appears critically involved in colon tumorogenesis, the inhibition of SOCE by aspirin and other NSAIDs and its possible contribution to colon cancer chemoprevention is reviewed.

  13. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Kravets, Victoria; Hu, David

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines Contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  14. The intestine is a blender

    NASA Astrophysics Data System (ADS)

    Yang, Patricia; Lamarca, Morgan; Hu, David

    2015-11-01

    According to the U.S. Department of Health and Human Services, digestive disease affects 60 to 70 million people and costs over 140 billion annually. Despite the significance of the gastrointestinal tract to human health, the physics of digestion remains poorly understood. In this study, we ask a simple question: what sets the frequency of intestinal contractions? We measure the frequency of intestinal contractions in rats, as a function of distance down the intestine. We find that intestines contract radially ten times faster than longitudinally. This motion promotes mixing and, in turn, absorption of food products by the intestinal wall. We calculate viscous dissipation in the intestinal fluid to rationalize the relationship between frequency of intestinal contraction and the viscosity of the intestinal contents. Our findings may help to understand the evolution of the intestine as an ideal mixer.

  15. Mechanisms of epigenetic remodelling during preimplantation development.

    PubMed

    Ross, Pablo Juan; Canovas, Sebastian

    2016-01-01

    Epigenetics involves mechanisms independent of modifications in the DNA sequence that result in changes in gene expression and are maintained through cell divisions. Because all cells in the organism contain the same genetic blueprint, epigenetics allows for cells to assume different phenotypes and maintain them upon cell replication. As such, during the life cycle, there are moments in which the epigenetic information needs to be reset for the initiation of a new organism. In mammals, the resetting of epigenetic marks occurs at two different moments, which both happen to be during gestation, and include primordial germ cells (PGCs) and early preimplantation embryos. Because epigenetic information is reversible and sensitive to environmental changes, it is probably no coincidence that both these extensive periods of epigenetic remodelling happen in the female reproductive tract, under a finely controlled maternal environment. It is becoming evident that perturbations during the extensive epigenetic remodelling in PGCs and embryos can lead to permanent and inheritable changes to the epigenome that can result in long-term changes to the offspring derived from them, as indicated by the Developmental Origins of Health and Disease (DOHaD) hypothesis and recent demonstration of inter- and trans-generational epigenetic alterations. In this context, an understanding of the mechanisms of epigenetic remodelling during early embryo development is important to assess the potential for gametic epigenetic mutations to contribute to the offspring and for new epimutations to be established during embryo manipulations that could affect a large number of cells in the offspring. It is of particular interest to understand whether and how epigenetic information can be passed on from the gametes to the embryo or offspring, and whether abnormalities in this process could lead to transgenerationally inheritable phenotypes. The aim of this review is to highlight recent progress made in

  16. REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING

    PubMed Central

    Aggarwal, Saurabh; Gross, Christine M.; Sharma, Shruti; Fineman, Jeffrey R.; Black, Stephen M.

    2014-01-01

    The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell (SMC) hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the anti-oxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting co-factor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension. PMID:23897679

  17. [Remodeling in asthma: review of the literature].

    PubMed

    Montero Mora, Patricia; González Espinosa, Alicia Ma; Guidos Foguelbach, Guillermo A; Tinajero Castañeda, Olga Adriana; Serrano Cuevas, Saúl

    2003-01-01

    Remodeling, understood as a new or different reconstruction, has been observed in every organ after a chronic inflammatory response. In allergy, it has very important clinical consequences. As an example, in asthma this process is responsible for functional deterioration. In this case, the myofibroblasts play a central role in the process, together with a succession of products that are involved. In this bibliographic review we analyze the most important factors.

  18. Right ventricular remodeling in pulmonary hypertension.

    PubMed

    Franco, Veronica

    2012-07-01

    The right ventricle (RV) is in charge of pumping blood to the lungs for oxygenation. Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance and vascular remodeling, which results in a striking increase in RV afterload and subsequent failure. There is still unexploited potential for therapies that directly target the RV with the aim of supporting and protecting the right side of the heart, striving to prolong survival in patients with PAH.

  19. Stepwise nucleosome translocation by RSC remodeling complexes.

    PubMed

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-02-19

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome.

  20. Retinal remodeling triggered by photoreceptor degenerations.

    PubMed

    Jones, Bryan W; Watt, Carl B; Frederick, Jeanne M; Baehr, Wolfgang; Chen, Ching-Kang; Levine, Edward M; Milam, Ann H; Lavail, Matthew M; Marc, Robert E

    2003-09-08

    Many photoreceptor degenerations initially affect rods, secondarily leading to cone death. It has long been assumed that the surviving neural retina is largely resistant to this sensory deafferentation. New evidence from fast retinal degenerations reveals that subtle plasticities in neuronal form and connectivity emerge early in disease. By screening mature natural, transgenic, and knockout retinal degeneration models with computational molecular phenotyping, we have found an extended late phase of negative remodeling that radically changes retinal structure. Three major transformations emerge: 1) Müller cell hypertrophy and elaboration of a distal glial seal between retina and the choroid/retinal pigmented epithelium; 2) apparent neuronal migration along glial surfaces to ectopic sites; and 3) rewiring through evolution of complex neurite fascicles, new synaptic foci in the remnant inner nuclear layer, and new connections throughout the retina. Although some neurons die, survivors express molecular signatures characteristic of normal bipolar, amacrine, and ganglion cells. Remodeling in human and rodent retinas is independent of the initial molecular targets of retinal degenerations, including defects in the retinal pigmented epithelium, rhodopsin, or downstream phototransduction elements. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, it suggests that the neural retina may be more plastic than previously believed.

  1. Psoriatic architecture constructed by epidermal remodeling.

    PubMed

    Iizuka, Hajime; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2004-08-01

    Epidermal remodeling is the concept that epidermal architecture is determined by a simple self-organizing mechanism; epidermal hyperproliferation constructs typical psoriatic architecture. This is based on the assumption that the enlargements in both the two-dimensional proliferative compartment (basal cell layer) and three-dimensional whole epidermal volume coexist. During this process, the dermal papillae become markedly, but passively, expanded by enlargement of the proliferative compartment. This creates a considerable shrinkage force against the crowded basal cell layer, which is forced to lose adherence to the dermal extracellular matrix (ECM). This results in anoikis, a type of apoptosis characterized by cell detachment, and, consequently, a markedly diminished epidermal turnover time in psoriasis. The papillary shrinkage force also explains the fact that dermal papillary height does not exceed a certain limit. At the cessation of hyperproliferation a normalisation remodeling takes place toward normal tissue architecture. Thus the concept of epidermal remodeling explains the self-organizing mechanism of the architectural change in psoriasis, which is essentially a reversible disorder depending on epidermal hyperproliferation.

  2. Role of Arginase in Vessel Wall Remodeling

    PubMed Central

    Durante, William

    2013-01-01

    Arginase metabolizes the semi-essential amino acid l-arginine to l-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and l-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages toward an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide (NO) synthesis by competing with NO synthase for substrate, l-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease. PMID:23717309

  3. Application of Petri nets in bone remodeling.

    PubMed

    Li, Lingxi; Yokota, Hiroki

    2009-07-06

    Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs) have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs), which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  4. Intestinal and multivisceral transplantation

    PubMed Central

    Meira, Sérgio Paiva; Guardia, Bianca Della; Evangelista, Andréia Silva; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Epstein, Marina Gabrielle; Pedroso, Pamella Tung; Salvalaggio, Paolo; Meirelles, Roberto Ferreira; Rocco, Rodrigo Andrey; de Almeida, Samira Scalso; de Rezende, Marcelo Bruno

    2015-01-01

    Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run. PMID:25993080

  5. Intestinal anisakidosis (anisakiosis).

    PubMed

    Takei, Hidehiro; Powell, Suzanne Z

    2007-10-01

    A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease.

  6. VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, P. A.; Chen, X.; Kelly, C. P.; Reinecker, H. C.

    2011-01-01

    Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major

  7. Intestinal microbiota and ulcerative colitis.

    PubMed

    Ohkusa, Toshifumi; Koido, Shigeo

    2015-11-01

    There is a close relationship between the human host and the intestinal microbiota, which is an assortment of microorganisms, protecting the intestine against colonization by exogenous pathogens. Moreover, the intestinal microbiota play a critical role in providing nutrition and the modulation of host immune homeostasis. Recent reports indicate that some strains of intestinal bacteria are responsible for intestinal ulceration and chronic inflammation in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). Understanding the interaction of the intestinal microbiota with pathogens and the human host might provide new strategies treating patients with IBD. This review focuses on the important role that the intestinal microbiota plays in maintaining innate immunity in the pathogenesis and etiology of UC and discusses new antibiotic therapies targeting the intestinal microbiota.

  8. Small intestine contrast injection (image)

    MedlinePlus

    ... and throat, through the stomach into the small intestine. When in place, contrast dye is introduced and ... means of demonstrating whether or not the small intestine is normal when abnormality is suspected.

  9. Intestinal Failure (Short Bowel Syndrome)

    MedlinePlus

    ... N Vitamin deficiencies as a result of poor absorption in the intestine N Electrolyte and mineral deficiencies ... N Kidney stones or gallstones due to poor absorption of calcium or bile How is intestinal failure ...

  10. Small intestine aspirate and culture

    MedlinePlus

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  11. [Intestinal microbiocenosis in children with intestinal enzymopathy].

    PubMed

    Kamilova, A T; Akhmedov, N N; Pulatova, D B; Nurmatov, B A

    2001-01-01

    141 children with different kinds of intestinal enzymopathy were examined; of these, 33 had celiac disease, 39--the syndrome of celiac disease, 12--congenital lactase deficiency and 57--the syndrome of disaccharidase insufficiency. In these patients a significant decrease in the average characteristics of the main protective flora and the growth of hemolytic and lactose-negative enterobacteria were established. In all groups of patients increased amounts of Proteus were detected, which was indicative of profound dysbiosis. The content of bifidobacteria was found to be decreased in 89.5-97% of the patients and the content of lactic acid bacteria, in 15.8-33.3%. The decreased content of Escherichia coli with normal enzymatic activity (less than 10(7) colony-forming units) was noted in one-third of the patients with the syndrome of celiac disease and congenital lactase deficiency, in about a half of the patients with the syndrome of disaccharidase insufficiency and least of all in patients with celiac disease (9.1%). The association of opportunistic microbes was detected in 15.6% of the patients, more often in those with celiac disease, the syndrome of celiac disease and congenital lactase deficiency. The severity of disturbances in intestinal eubiosis was found to depend on the gravity of the patients' state.

  12. Control of bone remodelling by applied dynamic loads

    NASA Technical Reports Server (NTRS)

    Lanyon, L. E.; Rubin, C. T.

    1984-01-01

    The data showing the relationship between bone mass and peak strain magnitude prepared and submitted for publication. The data from experiments relating remodelling activity with static or dynamic loads were prepared and submitted for publication. Development of programs to relate the location of remodelling activity with he natural and artificial dynamic strain distributions continued. Experiments on the effect of different strain rates on the remodelling response continued.

  13. Nucleosome remodelers in double-strand break repair.

    PubMed

    Seeber, Andrew; Hauer, Michael; Gasser, Susan M

    2013-04-01

    ATP-dependent nucleosome remodelers use ATP hydrolysis to shift, evict and exchange histone dimers or octamers and have well-established roles in transcription. Earlier work has suggested a role for nucleosome remodelers such as INO80 in double-strand break (DSB) repair. This review will begin with an update on recent studies that explore how remodelers are recruited to DSBs. We then examine their impact on various steps of repair, focusing on resection and the formation of the Rad51-ssDNA nucleofilament. Finally, we will explore new studies that implicate remodelers in the physical movement of chromatin in response to damage.

  14. Chromatin remodelling: the industrial revolution of DNA around histones.

    PubMed

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  15. LRP1 regulates remodeling of the extracellular matrix by fibroblasts

    PubMed Central

    Gaultier, Alban; Hollister, Margaret; Reynolds, Irene; Hsieh, En-hui; Gonias, Steven L.

    2009-01-01

    Low density lipoprotein receptor-related protein (LRP1) is an endocytic receptor for diverse proteases, protease inhibitors, and other plasma membrane proteins, including the urokinase receptor (uPAR). LRP1 also functions in cell-signaling and regulates gene expression. The goal of this study was to determine whether LRP1 regulates remodeling of provisional extracellular matrix (ECM) by fibroblasts. To address this problem, we utilized an in vitro model in which type I collagen was reconstituted and overlaid with fibronectin. Either the collagen or fibronectin was fluorescently-labeled. ECM remodeling by fibroblasts deficient in LRP1, uPAR, or MT1-MMP was studied. MT1-MMP was required for efficient remodeling of the deep collagen layer but not involved in fibronectin remodeling. Instead, fibronectin was remodeled by a system that required urokinase-type plasminogen activator (uPA), uPAR, and exogenously-added plasminogen. LRP1 markedly inhibited fibronectin remodeling by regulating cell-surface uPAR and plasminogen activation. LRP1 also regulated remodeling of the deep collagen layer but not by controlling MT1-MMP. Instead, LRP1 deficiency or inhibition de-repressed a secondary pathway for collagen remodeling, which was active in MT1-MMP-deficient cells but not in uPAR-deficient cells. These results demonstrate that LRP1 regulates ECM remodeling principally by repressing pathways that require plasminogen activation by uPA in association with uPAR. PMID:19699300

  16. CHD chromatin remodelers and the transcription cycle.

    PubMed

    Murawska, Magdalena; Brehm, Alexander

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by "opening" or "closing" chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts.

  17. Bacterial genome remodeling through bacteriophage recombination.

    PubMed

    Menouni, Rachid; Hutinet, Geoffrey; Petit, Marie-Agnès; Ansaldi, Mireille

    2015-01-01

    Bacteriophages co-exist and co-evolve with their hosts in natural environments. Virulent phages lyse infected cells through lytic cycles, whereas temperate phages often remain dormant and can undergo lysogenic or lytic cycles. In their lysogenic state, prophages are actually part of the host genome and replicate passively in rhythm with host division. However, prophages are far from being passive residents: they can modify or bring new properties to their host. In this review, we focus on two important phage-encoded recombination mechanisms, i.e. site-specific recombination and homologous recombination, and how they remodel bacterial genomes.

  18. Vascular remodeling underlies rebleeding in hemophilic arthropathy.

    PubMed

    Bhat, Vikas; Olmer, Merissa; Joshi, Shweta; Durden, Donald L; Cramer, Thomas J; Barnes, Richard Fw; Ball, Scott T; Hughes, Tudor H; Silva, Mauricio; Luck, James V; Moore, Randy E; Mosnier, Laurent O; von Drygalski, Annette

    2015-11-01

    Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

  19. Specific remodeling of splenic architecture by cytomegalovirus.

    PubMed

    Benedict, Chris A; De Trez, Carl; Schneider, Kirsten; Ha, Sukwon; Patterson, Ginelle; Ware, Carl F

    2006-03-01

    Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  20. Densitometric evaluation of periprosthetic bone remodeling

    PubMed Central

    Parchi, Paolo Domenico; Cervi, Valentina; Piolanti, Nicola; Ciapini, Gianluca; Andreani, Lorenzo; Castellini, Iacopo; Poggetti, Andrea; Lisanti, Michele

    2014-01-01

    Summary The application of Dual-energy X-ray absorptiometry (DEXA) in orthopaedic surgery gradually has been extended from the study of osteoporosis to different areas of interest like the study of the relation between bone and prosthetic implants. Aim of this review is to analyze changes that occur in periprosthetic bone after the implantation of a total hip arthroplasty (THA) or a total knee arthroplasty (TKA). In THA the pattern of adaptive bone remodeling with different cementless femoral stems varies and it appears to be strictly related to the design and more specifically to where the femoral stem is fixed on bone. Short stems with metaphyseal fixation allow the maintenance of a more physiologic load transfer to the proximal femur decreasing the entity of bone loss. Femoral bone loss after TKA seems to be related to the stress shielding induced by the implants while tibial bone remodeling seems to be related to postoperative changes in knee alignment (varus/valgus) and consequently in tibial load transfer. After both THA and TKA stress shielding seems to be an inevitable phenomenon that occurs mainly in the first year after surgery. PMID:25568658

  1. An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians

    PubMed Central

    Forsthoefel, David J.; James, Noelle P.; Escobar, David J.; Stary, Joel M.; Vieira, Ana P.; Waters, Forrest A.; Newmark, Phillip A.

    2012-01-01

    SUMMARY Planarians grow and regenerate organs by coordinating proliferation and differentiation of pluripotent stem cells with remodeling of post-mitotic tissues. Understanding how these processes are orchestrated requires characterizing cell type-specific gene expression programs and their regulation during regeneration and homeostasis. To this end, we analyzed the expression profile of planarian intestinal phagocytes, cells responsible for digestion and nutrient storage/distribution. Utilizing RNA interference, we identified cytoskeletal regulators required for intestinal branching morphogenesis, and a modulator of bioactive sphingolipid metabolism, ceramide synthase, required for the production of functional phagocytes. Additionally, we found that a gut-enriched homeobox transcription factor, nkx-2.2, is required for somatic stem cell proliferation, suggesting a niche-like role for phagocytes. Identification of evolutionarily conserved regulators of intestinal branching, differentiation, and stem cell dynamics demonstrates the utility of the planarian digestive system as a model for elucidating the mechanisms controlling post-embryonic organogenesis. PMID:23079596

  2. An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians.

    PubMed

    Forsthoefel, David J; James, Noëlle P; Escobar, David J; Stary, Joel M; Vieira, Ana P; Waters, Forrest A; Newmark, Phillip A

    2012-10-16

    Planarians grow and regenerate organs by coordinating proliferation and differentiation of pluripotent stem cells with remodeling of postmitotic tissues. Understanding how these processes are orchestrated requires characterizing cell-type-specific gene expression programs and their regulation during regeneration and homeostasis. To this end, we analyzed the expression profile of planarian intestinal phagocytes, cells responsible for digestion and nutrient storage/distribution. Utilizing RNA interference, we identified cytoskeletal regulators required for intestinal branching morphogenesis and a modulator of bioactive sphingolipid metabolism, ceramide synthase, required for the production of functional phagocytes. Additionally, we found that a gut-enriched homeobox transcription factor, nkx-2.2, is required for somatic stem cell proliferation, suggesting a niche-like role for phagocytes. Identification of evolutionarily conserved regulators of intestinal branching, differentiation, and stem cell dynamics demonstrates the utility of the planarian digestive system as a model for elucidating the mechanisms controlling postembryonic organogenesis.

  3. Evaluation of the National Remodelling Team: Year 3. Final Report

    ERIC Educational Resources Information Center

    Easton, Claire; Eames, Anna; Wilson, Rebekah; Walker, Matthew; Sharp, Caroline

    2006-01-01

    The aim of the National Foundation for Educational Research (NFER) evaluation was to examine the effectiveness and impact of the work of the National Remodelling Team (NRT) in completing the third phase of the remodeling program and its effectiveness in applying its model, tools and techniques to the extended schools program. This evaluation has…

  4. Unusual intestinal talcosis.

    PubMed

    Anani, P A; Ribaux, C; Gardiol, D

    1987-11-01

    A case of intestinal talcosis in a 46-year-old man is reported. At the age of 27, the patient was treated for pulmonary tuberculosis with tablets containing talc (183 g talc per 2,670 g total drug intake) over a period of 28 months. Eighteen years later, the patient was hospitalized for abdominal pain that remained refractory to antacids; he subsequently underwent a right hemicolectomy. Light-microscopic examination revealed a prominent fibrosis of the intestinal wall in which birefringent particles were demonstrated by polarized light. Using energy-dispersive spectroscopy, an analysis of these particles showed that they were predominantly composed of silicon and magnesium as well as small amounts of phosphorus, sulphur, calcium, and iron--the spectrum typically associated with talc. We believe that the source of this talc is the tablets ingested by the patient during prior antituberculosis therapy.

  5. Vessel remodelling, pregnancy hormones and extravillous trophoblast function.

    PubMed

    Chen, Jessie Z-J; Sheehan, Penelope M; Brennecke, Shaun P; Keogh, Rosemary J

    2012-02-26

    During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia.

  6. Proliferation and tissue remodeling in cancer: the hallmarks revisited.

    PubMed

    Markert, E K; Levine, A J; Vazquez, A

    2012-10-04

    Although cancers are highly heterogeneous at the genomic level, they can manifest common patterns of gene expression. Here, we use gene expression signatures to interrogate two major processes in cancer, proliferation and tissue remodeling. We demonstrate that proliferation and remodeling signatures are partially independent and result in four distinctive cancer subtypes. Cancers with the proliferation signature are characterized by signatures of p53 and PTEN inactivation and concomitant Myc activation. In contrast, remodeling correlates with RAS, HIF-1α and NFκB activation. From the metabolic point of view, proliferation is associated with upregulation of glycolysis and serine/glycine metabolism, whereas remodeling is characterized by a downregulation of oxidative phosphorylation. Notably, the proliferation signature correlates with poor outcome in lung, prostate, breast and brain cancer, whereas remodeling increases mortality rates in colorectal and ovarian cancer.

  7. Chromatin remodeling in DNA double-strand break repair.

    PubMed

    Bao, Yunhe; Shen, Xuetong

    2007-04-01

    ATP-dependent chromatin remodeling complexes use ATP hydrolysis to remodel nucleosomes and have well-established functions in transcription. However, emerging lines of evidence suggest that chromatin remodeling complexes are important players in DNA double-strand break (DSB) repair as well. The INO80 and SWI2 subfamilies of chromatin remodeling complexes have been found to be recruited to the double-strand lesions and to function directly in both homologous recombination and non-homologous end-joining, the two major conserved DSB repair pathways. Improperly repaired DSBs are implicated in cancer development in higher organisms. Understanding how chromatin remodeling complexes contribute to DSB repair should provide new insights into the mechanisms of carcinogenesis and might suggest new targets for cancer treatment.

  8. Left Atrial Reverse Remodeling: Mechanisms, Evaluation, and Clinical Significance.

    PubMed

    Thomas, Liza; Abhayaratna, Walter P

    2017-01-01

    The left atrium is considered a biomarker for adverse cardiovascular outcomes, particularly in patients with left ventricular diastolic dysfunction and atrial fibrillation in whom left atrial (LA) enlargement is of prognostic importance. LA enlargement with a consequent decrease in LA function represents maladaptive structural and functional "remodeling" that in turn promotes electrical remodeling and a milieu conducive for incident atrial fibrillation. Medical and nonmedical interventions may arrest this pathophysiologic process to the extent that subsequent reverse remodeling results in a reduction in LA size and improvement in LA function. This review examines cellular and basic mechanisms involved in LA remodeling, evaluates the noninvasive techniques that can assess these changes, and examines potential mechanisms that may initiate reverse remodeling.

  9. Elenoside increases intestinal motility

    PubMed Central

    Navarro, E; Alonso, SJ; Navarro, R; Trujillo, J; Jorge, E

    2006-01-01

    AIM: To study the effects of elenoside, an arylnaph-thalene lignan from Justicia hyssopifolia, on gastro-intestinal motility in vivo and in vitro in rats. METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses, intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanol-plant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg), cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2 x 10-4, 6.4 x 10-4 and 1.2 x 10-3 mol/L, and cisapride at 10-6 mol/L were investigated. RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase. Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride. CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs. Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain. PMID:17131476

  10. The allometry of rodent intestines.

    PubMed

    Lovegrove, Barry G

    2010-06-01

    This study examined the allometry of the small intestine, caecum, colon and large intestine of rodents (n = 51) using a phylogenetically informed approach. Strong phylogenetic signal was detected in the data for the caecum, colon and large intestine, but not for the small intestine. Most of the phylogenetic signal could be attributed to clade effects associated with herbivorous versus omnivorous rodents. The herbivorous rodents have longer caecums, colons and large intestines, but their small intestines, with the exception of the desert otomyine rodents, are no different to those of omnivorous rodents. Desert otomyine rodents have significantly shorter small intestines than all other rodents, reflecting a possible habitat effect and providing a partial explanation for the low basal metabolic rates of small desert mammals. However, the desert otomyines do not have shorter colons or large intestines, challenging claims for adaptation to water retention in arid environments. Data for the Arvicolidae revealed significantly larger caecums and colons, and hence longer large intestines, with no compensatory reduction in the length of the small intestine, which may explain how the smallest mammalian herbivores manage to meet the demands of a very high mass-specific metabolic rate. This study provides phylogenetically corrected allometries suitable for future prediction testing.

  11. Alcohol and the Intestine

    PubMed Central

    Patel, Sheena; Behara, Rama; Swanson, Garth R.; Forsyth, Christopher B.; Voigt, Robin M.; Keshavarzian, Ali

    2015-01-01

    Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches. PMID:26501334

  12. An essential and evolutionarily conserved role of protein arginine methyltransferase 1 for adult intestinal stem cells during postembryonic development.

    PubMed

    Matsuda, Hiroki; Shi, Yun-Bo

    2010-11-01

    Organ-specific adult stem cells are critical for the homeostasis of adult organs and organ repair and regeneration. Unfortunately, it has been difficult to investigate the origins of these stem cells and the mechanisms of their development, especially in mammals. Intestinal remodeling during frog metamorphosis offers a unique opportunity for such studies. During the transition from an herbivorous tadpole to a carnivorous frog, the intestine is completely remodeled as the larval epithelial cells undergo apoptotic degeneration and are replaced by adult epithelial cells developed de novo. The entire metamorphic process is under the control of thyroid hormone, making it possible to control the development of the adult intestinal stem cells. Here, we show that the thyroid hormone receptor-coactivator protein arginine methyltransferase 1 (PRMT1) is upregulated in a small number of larval epithelial cells and that these cells dedifferentiate to become the adult stem cells. More importantly, transgenic overexpression of PRMT1 leads to increased adult stem cells in the intestine, and conversely, knocking down the expression of endogenous PRMT1 reduces the adult stem cell population. In addition, PRMT1 expression pattern during zebrafish and mouse development suggests that PRMT1 may play an evolutionally conserved role in the development of adult intestinal stem cells throughout vertebrates. These findings are not only important for the understanding of organ-specific adult stem cell development but also have important implications in regenerative medicine of the digestive tract.

  13. Chondromodulin I Is a Bone Remodeling Factor

    PubMed Central

    Nakamichi, Yuko; Shukunami, Chisa; Yamada, Takashi; Aihara, Ken-ichi; Kawano, Hirotaka; Sato, Takashi; Nishizaki, Yuriko; Yamamoto, Yoko; Shindo, Masayo; Yoshimura, Kimihiro; Nakamura, Takashi; Takahashi, Naoyuki; Kawaguchi, Hiroshi; Hiraki, Yuji; Kato, Shigeaki

    2003-01-01

    Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage and its functions in cultured chondrocytes as a major regulator in cartilage development. Here, we generated mice deficient in ChM-I by targeted disruption of the ChM-I gene. No overt abnormality was detected in endochondral bone formation during embryogenesis and cartilage development during growth stages of ChM-I−/− mice. However, a significant increase in bone mineral density with lowered bone resorption with respect to formation was unexpectedly found in adult ChM-I−/− mice. Thus, the present study established that ChM-I is a bone remodeling factor. PMID:12509461

  14. Molecular mechanisms of synaptic remodeling in alcoholism.

    PubMed

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism.

  15. Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

    PubMed

    Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B; Gaggar, Amit; Thannickal, Victor J

    2016-06-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema.

  16. RNA helicase proteins as chaperones and remodelers

    PubMed Central

    Jarmoskaite, Inga; Russell, Rick

    2014-01-01

    Superfamily 2 helicase proteins are ubiquitous in RNA biology and have an extraordinarily broad set of functional roles. Central among these roles are to promote rearrangements of structured RNAs and to remodel RNA-protein complexes (RNPs), allowing formation of native RNA structure or progression through a functional cycle of structures. While all superfamily 2 helicases share a conserved helicase core, they are divided evolutionarily into several families, and it is principally proteins from three families, the DEAD-box, DEAH/RHA and Ski2-like families, that function to manipulate structured RNAs and RNPs. Strikingly, there are emerging differences in the mechanisms of these proteins, both between families and within the largest family (DEAD-box), and these differences appear to be tuned to their RNA or RNP substrates and their specific roles. This review outlines basic mechanistic features of the three families and surveys individual proteins and the current understanding of their biological substrates and mechanisms. PMID:24635478

  17. Cell wall remodeling under abiotic stress

    PubMed Central

    Tenhaken, Raimund

    2015-01-01

    Plants exposed to abiotic stress respond to unfavorable conditions on multiple levels. One challenge under drought stress is to reduce shoot growth while maintaining root growth, a process requiring differential cell wall synthesis and remodeling. Key players in this process are the formation of reactive oxygen species (ROS) and peroxidases, which initially cross-link phenolic compounds and glycoproteins of the cell walls causing stiffening. The function of ROS shifts after having converted all the peroxidase substrates in the cell wall. If ROS-levels remain high during prolonged stress, OH°-radicals are formed which lead to polymer cleavage. In concert with xyloglucan modifying enzymes and expansins, the resulting cell wall loosening allows further growth of stressed organs. PMID:25709610

  18. Bone Remodeling and Energy Metabolism: New Perspectives

    PubMed Central

    de Paula, Francisco J. A.; Rosen, Clifford J.

    2013-01-01

    Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications. PMID:26273493

  19. Chromatin remodeling: from transcription to cancer.

    PubMed

    Yaniv, Moshe

    2014-09-01

    In this short review article, I have tried to trace the path that led my laboratory from the early studies of the structure of papova minichromosomes and transcription control to the investigation of chromatin remodeling complexes of the SWI/SNF family. I discuss briefly the genetic and biochemical studies that lead to the discovery of the SWI/SNF complex in yeast and drosophila and summarize some of the studies on the developmental role of the murine complex. The discovery of the tumor suppressor function of the SNF5/INI1/SMARCB1 gene in humans and the identification of frequent mutations in other subunits of this complex in different human tumors opened a fascinating field of research on this epigenetic regulator. The hope is to better understand tumor development and to develop novel treatments.

  20. Remodeling of the fovea in Parkinson disease.

    PubMed

    Spund, B; Ding, Y; Liu, T; Selesnick, I; Glazman, S; Shrier, E M; Bodis-Wollner, I

    2013-05-01

    To quantify the thickness of the inner retinal layers in the foveal pit where the nerve fiber layer (NFL) is absent, and quantify changes in the ganglion cells and inner plexiform layer. Pixel-by-pixel volumetric measurements were obtained via Spectral-Domain optical coherence tomography (SD-OCT) from 50 eyes of Parkinson disease (PD) (n = 30) and 50 eyes of healthy control subjects (n = 27). Receiver operating characteristics (ROC) were used to classify individual subjects with respect to sensitivity and specificity calculations at each perifoveolar distance. Three-dimensional topographic maps of the healthy and PD foveal pit were created. The foveal pit is thinner and broader in PD. The difference becomes evident in an annular zone between 0.5 and 2 mm from the foveola and the optimal (ROC-defined) zone is from 0.75 to 1.5 mm. This zone is nearly devoid of NFL and partially overlaps the foveal avascular zone. About 78 % of PD eyes can be discriminated from HC eyes based on this zone. ROC applied to OCT pixel-by-pixel analysis helps to discriminate PD from HC retinae. Remodeling of the foveal architecture is significant because it may provide a visible and quantifiable signature of PD. The specific location of remodeling in the fovea raises a novel concept for exploring the mechanism of oxidative stress on retinal neurons in PD. OCT is a promising quantitative tool in PD research. However, larger scale studies are needed before the method can be applied to clinical follow-ups.

  1. How to make an intestine

    PubMed Central

    Wells, James M.; Spence, Jason R.

    2014-01-01

    With the high prevalence of gastrointestinal disorders, there is great interest in establishing in vitro models of human intestinal disease and in developing drug-screening platforms that more accurately represent the complex physiology of the intestine. We will review how recent advances in developmental and stem cell biology have made it possible to generate complex, three-dimensional, human intestinal tissues in vitro through directed differentiation of human pluripotent stem cells. These are currently being used to study human development, genetic forms of disease, intestinal pathogens, metabolic disease and cancer. PMID:24496613

  2. Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes.

    PubMed

    Brea, Roberto J; Rudd, Andrew K; Devaraj, Neal K

    2016-08-02

    Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.

  3. PECAM-1 is necessary for flow-induced vascular remodeling

    PubMed Central

    Chen, Zhongming; Tzima, Ellie

    2009-01-01

    OBJECTIVE Vascular remodeling is a physiological process that occurs in response to long-term changes in hemodynamic conditions, but may also contribute to the pathophysiology of intima-media thickening (IMT) and vascular disease. Shear stress detection by the endothelium is thought to be an important determinant of vascular remodeling. Previous work showed that Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a component of a mechanosensory complex that mediates endothelial cell (EC) responses to shear stress. METHODS AND RESULTS We tested the hypothesis that PECAM-1 contributes to vascular remodeling by analyzing the response to partial carotid artery ligation in PECAM-1 knockout mice and wild-type littermates. PECAM-1 deficiency resulted in impaired vascular remodeling and significantly reduced IMT in areas of low flow. Inward remodeling was associated with PECAM-1-dependent NFκB activation, surface adhesion molecule expression and leukocyte infiltration as well as Akt activation and vascular cell proliferation. CONCLUSIONS PECAM-1 plays a crucial role in the activation of the NFκB and Akt pathways and inflammatory cell accumulation during vascular remodeling and IMT. Elucidation of some of the signals that drive vascular remodeling represent pharmacologically tractable targets for the treatment of restenosis after balloon angioplasty or stent placement. PMID:19390054

  4. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    PubMed

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC.

  5. Synthetic Small Intestinal Scaffolds for Improved Studies of Intestinal Differentiation

    PubMed Central

    Costello, Cait M.; Hongpeng, Jia; Shaffiey, Shahab; Yu, Jiajie; Jain, Nina K.; Hackam, David

    2014-01-01

    In vitro intestinal models can provide new insights into small intestinal function, including cellular growth and proliferation mechanisms, drug absorption capabilities, and host-microbial interactions. These models are typically formed with cells cultured on 2D scaffolds or transwell inserts, but it is widely understood that epithelial cells cultured in 3D environments exhibit different phenotypes that are more reflective of native tissue. Our focus was to develop a porous, synthetic 3D tissue scaffold with villous features that could support the culture of epithelial cell types to mimic the natural microenvironment of the small intestine. We demonstrated that our scaffold could support the co-culture of Caco-2 cells with a mucus-producing cell line, HT29-MTX, as well as small intestinal crypts from mice for extended periods. By recreating the surface topography with accurately sized intestinal villi, we enable cellular differentiation along the villous axis in a similar manner to native intestines. In addition, we show that the biochemical microenvironments of the intestine can be further simulated via a combination of apical and basolateral feeding of intestinal cell types cultured on the 3D models. PMID:24390638

  6. Immunoglobulin in intestinal secretions.

    PubMed

    Cutropia de Guirao, C

    1977-12-01

    The objective of the present investigation is the study and interpretation of the role played by the immunoglobulins, especially IgA, during acute diarrhea in children. IgA, IGG and IgM values in serum and IgA in intestinal secretions were studied in a group of children (between 3 months and 5 years of age) during diarrhea, convalescence and in normals. The method of simple radial immunodiffusion according to Mancini was employed. IgA is the immunoglobulin which suffers the greastest alteration in acute diarrhea. The precipitation halos (the average values), were lower during the diarrhea than in convalescence and in normals.

  7. Polycyclic aromatic hydrocarbons, tobacco smoke, and epigenetic remodeling in asthma

    PubMed Central

    Klingbeil, E. C.; Hew, K. M.; Nygaard, U. C.; Nadeau, K. C.

    2014-01-01

    Environmental determinants including aerosolized pollutants such as polycyclic aromatic hydrocarbons (PAHs) and tobacco smoke have been associated with exacerbation and increased incidence of asthma. The influence of aerosolized pollutants on the development of immune dysfunction in asthmatics has been suggested to be mediated through epigenetic remodeling. Genome accessibility and transcription are regulated primarily through DNA methylation, histone modification, and microRNA transcript silencing. Epigenetic remodeling has been shown in studies to be associated with Th2 polarization and associated cytokine and chemokine regulation in the development of asthma. This review will present evidence for the contribution of the aerosolized pollutants PAH and environmental tobacco smoke to epigenetic remodeling in asthma. PMID:24760221

  8. Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment

    PubMed Central

    Azevedo, Paula S.; Polegato, Bertha F.; Minicucci, Marcos F.; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies. PMID:26647721

  9. Regulation of extracellular matrix remodeling and cell fate determination by matrix metalloproteinase stromelysin-3 during thyroid hormone-dependent post-embryonic development.

    PubMed

    Shi, Yun-Bo; Fu, Liezhen; Hasebe, Takashi; Ishizuya-Oka, Atsuko

    2007-12-01

    Interactions between cells and extracellular matrix (ECM), in particular the basement membrane (BM), are fundamentally important for the regulation of a wide variety of physiological and pathological processes. Matrix metalloproteinases (MMP) play critical roles in ECM remodeling and/or regulation of cell-ECM interactions because of their ability to cleave protein components of the ECM. Of particular interest among MMP is stromelysin-3 (ST3), which was first isolated from a human breast cancer and also shown to be correlated with apoptosis during development and invasion of tumor cells in mammals. We have been using intestinal remodeling during thyroid hormone (TH)-dependent amphibian metamorphosis as a model to study the role of ST3 during post-embryonic tissue remodeling and organ development in vertebrates. This process involves complete degeneration of the tadpole or larval epithelium through apoptosis and de novo development of the adult epithelium. Here, we will first summarize expression studies by us and others showing a tight spatial and temporal correlation of the expression of ST3 mRNA and protein with larval cell death and adult tissue development. We will then review in vitro and in vivo data supporting a critical role of ST3 in TH-induced larval epithelial cell death and ECM remodeling. We will further discuss the potential mechanisms of ST3 function during metamorphosis and its broader implications.

  10. Rapid changes in gene expression direct rapid shifts in intestinal form and function in the Burmese python after feeding.

    PubMed

    Andrew, Audra L; Card, Daren C; Ruggiero, Robert P; Schield, Drew R; Adams, Richard H; Pollock, David D; Secor, Stephen M; Castoe, Todd A

    2015-05-01

    Snakes provide a unique and valuable model system for studying the extremes of physiological remodeling because of the ability of some species to rapidly upregulate organ form and function upon feeding. The predominant model species used to study such extreme responses has been the Burmese python because of the extreme nature of postfeeding response in this species. We analyzed the Burmese python intestine across a time series, before, during, and after feeding to understand the patterns and timing of changes in gene expression and their relationship to changes in intestinal form and function upon feeding. Our results indicate that >2,000 genes show significant changes in expression in the small intestine following feeding, including genes involved in intestinal morphology and function (e.g., hydrolases, microvillus proteins, trafficking and transport proteins), as well as genes involved in cell division and apoptosis. Extensive changes in gene expression occur surprisingly rapidly, within the first 6 h of feeding, coincide with changes in intestinal morphology, and effectively return to prefeeding levels within 10 days. Collectively, our results provide an unprecedented portrait of parallel changes in gene expression and intestinal morphology and physiology on a scale that is extreme both in the magnitude of changes, as well as in the incredibly short time frame of these changes, with up- and downregulation of expression and function occurring in the span of 10 days. Our results also identify conserved vertebrate signaling pathways that modulate these responses, which may suggest pathways for therapeutic modulation of intestinal function in humans.

  11. Rapid changes in gene expression direct rapid shifts in intestinal form and function in the Burmese python after feeding

    PubMed Central

    Andrew, Audra L.; Card, Daren C.; Ruggiero, Robert P.; Schield, Drew R.; Adams, Richard H.; Pollock, David D.; Secor, Stephen M.

    2015-01-01

    Snakes provide a unique and valuable model system for studying the extremes of physiological remodeling because of the ability of some species to rapidly upregulate organ form and function upon feeding. The predominant model species used to study such extreme responses has been the Burmese python because of the extreme nature of postfeeding response in this species. We analyzed the Burmese python intestine across a time series, before, during, and after feeding to understand the patterns and timing of changes in gene expression and their relationship to changes in intestinal form and function upon feeding. Our results indicate that >2,000 genes show significant changes in expression in the small intestine following feeding, including genes involved in intestinal morphology and function (e.g., hydrolases, microvillus proteins, trafficking and transport proteins), as well as genes involved in cell division and apoptosis. Extensive changes in gene expression occur surprisingly rapidly, within the first 6 h of feeding, coincide with changes in intestinal morphology, and effectively return to prefeeding levels within 10 days. Collectively, our results provide an unprecedented portrait of parallel changes in gene expression and intestinal morphology and physiology on a scale that is extreme both in the magnitude of changes, as well as in the incredibly short time frame of these changes, with up- and downregulation of expression and function occurring in the span of 10 days. Our results also identify conserved vertebrate signaling pathways that modulate these responses, which may suggest pathways for therapeutic modulation of intestinal function in humans. PMID:25670730

  12. Direct Activation of Amidohydrolase Domain-Containing 1 Gene by Thyroid Hormone Implicates a Role in the Formation of Adult Intestinal Stem Cells During Xenopus Metamorphosis.

    PubMed

    Okada, Morihiro; Miller, Thomas C; Fu, Liezhen; Shi, Yun-Bo

    2015-09-01

    The T3-dependent anuran metamorphosis resembles postembryonic development in mammals, the period around birth when plasma T3 levels peak. In particular, the remodeling of the intestine during metamorphosis mimics neonatal intestinal maturation in mammals when the adult intestinal epithelial self-renewing system is established. We have been using intestinal metamorphosis to investigate how the organ-specific adult stem cells are formed during vertebrate development. Early studies in Xenopus laevis have shown that this process involves complete degeneration of the larval epithelium and de novo formation of adult stem cells. A tissue-specific microarray analysis of intestinal gene expression during Xenopus laevis metamorphosis has identified a number of candidate stem cell genes. Here we have carried out detailed analyses of one such gene, amidohydrolase domain containing 1 (AMDHD1) gene, which encodes an enzyme in the histidine catabolic pathway. We show that AMDHD1 is exclusively expressed in the proliferating adult epithelial stem cells during metamorphosis with little expression in other intestinal tissues. We further provide evidence that T3 activates AMDHD1 gene expression directly at the transcription level through T3 receptor binding to the AMDHD1 gene in the intestine. In addition, we have reported earlier that histidine ammonia-lyase gene, another gene in histidine catabolic pathway, is similarly regulated by T3 in the intestine. These results together suggest that histidine catabolism plays a critical role in the formation and/or proliferation of adult intestinal stem cells during metamorphosis.

  13. Intestinal microbiota and obesity.

    PubMed

    Blaut, Michael; Klaus, Susanne

    2012-01-01

    The human gut harbors a highly diverse microbial ecosystem of approximately 400 different species, which is characterized by a high interindividual variability. The intestinal microbiota has recently been suggested to contribute to the development of obesity and the metabolic syndrome. Transplantation of gut microbiota from obese mice to nonobese, germ-free mice resulted in transfer of metabolic syndrome-associated features from the donor to the recipient. Proposed mechanisms for the role of gut microbiota include the provision of additional energy by the conversion of dietary fiber to short-chain fatty acids, effects on gut-hormone production, and increased intestinal permeability causing elevated systemic levels of lipopolysaccharides (LPS). This metabolic endotoxemia is suggested to contribute to low-grade inflammation, a characteristic trait of obesity and the metabolic syndrome. Finally, activation of the endocannabinoid system by LPS and/or high-fat diets is discussed as another causal factor. In conclusion, there is ample evidence for a role of gut microbiota in the development of obesity in rodents. However, the magnitude of its contribution to human obesity is still unknown.

  14. Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis.

    PubMed

    Hasebe, Takashi; Fujimoto, Kenta; Kajita, Mitsuko; Fu, Liezhen; Shi, Yun-Bo; Ishizuya-Oka, Atsuko

    2016-11-21

    In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2016.

  15. Structural remodeling, trafficking and functions of glycosylphosphatidylinositol-anchored proteins.

    PubMed

    Maeda, Yusuke; Kinoshita, Taroh

    2011-10-01

    Glycosylphosphatidylinositol (GPI) is a glycolipid that is covalently attached to proteins as a post-translational modification. Such modification leads to the anchoring of the protein to the outer leaflet of the plasma membrane. Proteins that are decorated with GPIs have unique properties in terms of their physical nature. In particular, these proteins tend to accumulate in lipid rafts, which are critical for the functions and trafficking of GPI-anchored proteins (GPI-APs). Recent studies mainly using mutant cells revealed that various structural remodeling reactions occur to GPIs present in GPI-APs as they are transported from the endoplasmic reticulum to the cell surface. This review examines the recent progress describing the mechanisms of structural remodeling of mammalian GPI-anchors, such as inositol deacylation, glycan remodeling and fatty acid remodeling, with particular focus on their trafficking and functions, as well as the pathogenesis involving GPI-APs and their deficiency.

  16. Molecular Imaging of Angiogenesis and Vascular Remodeling in Cardiovascular Pathology

    PubMed Central

    Golestani, Reza; Jung, Jae-Joon; Sadeghi, Mehran M.

    2016-01-01

    Angiogenesis and vascular remodeling are involved in a wide array of cardiovascular diseases, from myocardial ischemia and peripheral arterial disease, to atherosclerosis and aortic aneurysm. Molecular imaging techniques to detect and quantify key molecular and cellular players in angiogenesis and vascular remodeling (e.g., vascular endothelial growth factor and its receptors, αvβ3 integrin, and matrix metalloproteinases) can advance vascular biology research and serve as clinical tools for early diagnosis, risk stratification, and selection of patients who would benefit most from therapeutic interventions. To target these key mediators, a number of molecular imaging techniques have been developed and evaluated in animal models of angiogenesis and vascular remodeling. This review of the state of the art molecular imaging of angiogenesis and vascular (and valvular) remodeling, will focus mostly on nuclear imaging techniques (positron emission tomography and single photon emission tomography) that offer high potential for clinical translation. PMID:27275836

  17. Prostacyclin receptor-dependent modulation of pulmonary vascular remodeling.

    PubMed

    Hoshikawa, Y; Voelkel, N F; Gesell, T L; Moore, M D; Morris, K G; Alger, L A; Narumiya, S; Geraci, M W

    2001-07-15

    Prostacyclin (PGI(2)) reduces pulmonary vascular resistance and attenuates vascular smooth muscle cell proliferation through signal transduction following ligand binding to its receptor. Because patients with severe pulmonary hypertension have a reduced PGI(2) receptor (PGI-R) expression in the remodeled pulmonary arterial smooth muscle, we hypothesized that pulmonary vascular remodeling may be modified PGI-R dependently. To test this hypothesis, PGI-R knockout (KO) and wild-type (WT) mice were subjected to a simulated altitude of 17,000 ft or Denver altitude for 3 wk, and right ventricular pressure and lung histology were assessed. The PGI-R KO mice developed more severe pulmonary hypertension and vascular remodeling after chronic hypoxic exposure when compared to the WT mice. Our results indicate that PGI(2) and its receptor play an important role in the regulation of hypoxia-induced pulmonary vascular remodeling, and that the absence of a functional receptor worsens pulmonary hypertension.

  18. Roles of chromatin remodellers in DNA double strand break repair.

    PubMed

    Jeggo, Penny A; Downs, Jessica A

    2014-11-15

    Now that we have a good understanding of the DNA double strand break (DSB) repair mechanisms and DSB-induced damage signalling, attention is focusing on the changes to the chromatin environment needed for efficient DSB repair. Mutations in chromatin remodelling complexes have been identified in cancers, making it important to evaluate how they impact upon genomic stability. Our current understanding of the DSB repair pathways suggests that each one has distinct requirements for chromatin remodelling. Moreover, restricting the extent of chromatin modifications could be a significant factor regulating the decision of pathway usage. In this review, we evaluate the distinct DSB repair pathways for their potential need for chromatin remodelling and review the roles of ATP-driven chromatin remodellers in the pathways.

  19. Determining School District Renovation/Remodeling/Repair Needs.

    ERIC Educational Resources Information Center

    MacKenzie, Donald G.; Phillips, Paul

    1991-01-01

    Bond issue funds were earmarked for remodeling 10 schools in a Florida school district. Describes a physical plant survey instrument used to examine each district school building to determine the district needs and the method that prioritizes those needs. (MLF)

  20. Balancing chromatin remodeling and histone modifications in transcription

    PubMed Central

    Petty, Emily; Pillus, Lorraine

    2013-01-01

    Chromatin remodelers use the energy of ATP hydrolysis to reposition or evict nucleosomes or to replace canonical histones with histone variants. By regulating nucleosome dynamics, remodelers gate access to the underlying DNA for replication, repair, and transcription. Nucleosomes are subject to extensive post-translational modifications that can recruit regulatory proteins or alter the local chromatin structure. Just as extensive cross-talk has been observed between different histone post-translational modifications, there is growing evidence for both coordinated and antagonistic functional relationships between nucleosome remodeling and modifying machineries. Defining the combined functions of the complexes that alter nucleosome interactions, position, and stability is key to understanding processes that require access to DNA, particularly with growing appreciation of their contributions to human health and disease. Here, we highlight recent advances in the interactions between histone modifications and the ISWI and CHD1 chromatin remodelers from studies in budding yeast, fission yeast, flies, and mammalian cells, with a focus on yeast. PMID:23870137

  1. Postinfarct Left Ventricular Remodelling: A Prevailing Cause of Heart Failure

    PubMed Central

    Galli, Alessio; Lombardi, Federico

    2016-01-01

    Heart failure is a chronic disease with high morbidity and mortality, which represents a growing challenge in medicine. A major risk factor for heart failure with reduced ejection fraction is a history of myocardial infarction. The expansion of a large infarct scar and subsequent regional ventricular dilatation can cause postinfarct remodelling, leading to significant enlargement of the left ventricular chamber. It has a negative prognostic value, because it precedes the clinical manifestations of heart failure. The characteristics of the infarcted myocardium predicting postinfarct remodelling can be studied with cardiac magnetic resonance and experimental imaging modalities such as diffusion tensor imaging can identify the changes in the architecture of myocardial fibers. This review discusses all the aspects related to postinfarct left ventricular remodelling: definition, pathogenesis, diagnosis, consequences, and available therapies, together with experimental interventions that show promising results against postinfarct remodelling and heart failure. PMID:26989555

  2. Roles and activities of chromatin remodeling ATPases in plants.

    PubMed

    Han, Soon-Ki; Wu, Miin-Feng; Cui, Sujuan; Wagner, Doris

    2015-07-01

    Chromatin remodeling ATPases and their associated complexes can alter the accessibility of the genome in the context of chromatin by using energy derived from the hydrolysis of ATP to change the positioning, occupancy and composition of nucleosomes. In animals and plants, these remodelers have been implicated in diverse processes ranging from stem cell maintenance and differentiation to developmental phase transitions and stress responses. Detailed investigation of their roles in individual processes has suggested a higher level of selectivity of chromatin remodeling ATPase activity than previously anticipated, and diverse mechanisms have been uncovered that can contribute to the selectivity. This review summarizes recent advances in understanding the roles and activities of chromatin remodeling ATPases in plants.

  3. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts.

    PubMed

    Kemi, Ole J; Hoydal, Morten A; Macquaide, Niall; Haram, Per M; Koch, Lauren G; Britton, Steven L; Ellingsen, Oyvind; Smith, Godfrey L; Wisloff, Ulrik

    2011-09-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T-tubule density. Thus, the T-tubules adapted to the physiologic hypertrophy. Next, we studied T-tubules in a rat model of metabolic syndrome with pressure overload-induced concentric left ventricle hypertrophy, evidenced by 15% (P < 0.01) increased cardiomyocyte size. These rats had only 85% (P < 0.01) of the T-tubule density of control rats. Exercise training further increased cardiomyocyte volume by 8% (P < 0.01); half to that in control rats, but the T-tubule density remained unchanged. Finally, post-myocardial infarction heart failure induced severe cardiac pathology, with a 70% (P < 0.01) increased cardiomyocyte volume that included both eccentric and concentric hypertrophy and 55% (P < 0.01) reduced T-tubule density. Exercise training reversed 50% (P < 0.01) of the pathologic hypertrophy, whereas the T-tubule density increased by 40% (P < 0.05) compared to sedentary heart failure, but remained at 60% of normal hearts (P < 0.01). Physiologic hypertrophy associated with conserved T-tubule spacing (~1.8-1.9 µm), whereas in pathologic hypertrophy, T-tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T-tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T-tubules; exercise training reverses the remodeling and partly corrects the T-tubule density.

  4. Cardiovascular remodeling and the peripheral serotonergic system.

    PubMed

    Ayme-Dietrich, Estelle; Aubertin-Kirch, Gaëlle; Maroteaux, Luc; Monassier, Laurent

    2017-01-01

    Plasma 5-hydroxytryptamine (5-HT; serotonin), released from blood platelets, plays a major role in the human cardiovascular system. Besides the effect of endogenous serotonin, many drugs targeting serotonergic receptors are widely used in the general population (antiobesity agents, antidepressants, antipsychotics, antimigraine agents), and may enhance the cardiovascular risk. Depending on the type of serotonin receptor activated and its location, the use of these compounds triggers acute and chronic effects. The acute cardiovascular response to 5-HT, named the Bezold-Jarish reflex, leads to intense bradycardia associated with atrioventricular block, and involves 5-HT3, 5-HT1B/1D, 5-HT7 and 5-HT2A/2B receptors. The chronic contribution of 5-HT and its receptors (5-HT4 and 5-HT2A/2B) in cardiovascular tissue remodeling, with a particular emphasis on cardiac hypertrophy, fibrosis and valve degeneration, will be explored in this review. Finally, through the analysis of the effects of sarpogrelate, some new aspects of 5-HT2A receptor pharmacology in vasomotor tone regulation and the interaction between endothelial and smooth muscle cells will also be discussed. The aim of this review is to emphasize the cardiac side effects caused by serotonin receptor activation, and to highlight their possible prevention by the development of new drugs targeting this system.

  5. Tissue remodeling investigation in varicose veins

    PubMed Central

    Ghaderian, Sayyed Mohammad Hossein; Khodaii, Zohreh

    2012-01-01

    Although the etiology of varicose veins remains unknown, recent studies have focused on endothelial cell integrity and function because the endothelium regulates vessel tone and synthesizes many pro- and anti-inflammatory factors. The aim of this study was to investigate the evidence involving the endothelium in the development of varicose vein disease. In addition, tissue remodeling was investigated in varicose veins to determine the expression of different types of collagen. Tissue specimens of superficial varicose veins and control saphenous vein were used for immunohistochemical and transmission electron microscope (TEM). α-smooth muscle actin, and collagen I, III, IV antibodies were applied for immunohistochemical investigation. Findings of this study showed alterations of the intima, such as focal intimal discontinuity and denudation of endothelium; and the media, such as irregular arrangements of smooth muscle cells and collagen fibres in varicose veins. Our findings showed some changes in terms of distribution of types I, III and IV collagen in the intima and media of varicose vein walls compared with controls. These alterations to the media suggest that the pathological abnormality in varicose veins may be due to the loss of muscle tone as a result of the breakup of its regular structure by the collagen fibres. These findings only described some changes in terms of distribution of these types of collagen in the intima and media of varicose vein walls which may result in venous wall dysfunction in varicosis. PMID:24551759

  6. What Happens After Treatment for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... After Treatment What Happens After Treatment for Small Intestine Adenocarcinoma? For some people with small intestine cancer, ... Small Intestine Adenocarcinoma Stops Working More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  7. KyoT2 downregulates airway remodeling in asthma.

    PubMed

    Hu, Mei; Ou-Yang, Hai-Feng; Han, Xing-Peng; Ti, Xin-Yu; Wu, Chang-Gui

    2015-01-01

    The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.

  8. FSTL1 PROMOTES ASTHMATIC AIRWAY REMODELING BY INDUCING ONCOSTATIN M

    PubMed Central

    Miller, Marina; Beppu, Andrew; Rosenthal, Peter; Pham, Alexa; Das, Sudipta; Karta, Maya; Song, Dae Jin; Vuong, Christine; Doherty, Taylor; Croft, Michael; Zuraw, Bruce; Zhang, Xu; Gao, Xiang; Aceves, Seema; Chouiali, Fazila; Hamid, Qutayba; Broide, David H.

    2016-01-01

    Chronic asthma is associated with airway remodeling and decline in lung function. Here we show that follistatin like 1 (Fstl1), a mediator not previously associated with asthma is highly expressed by macrophages in the lungs of severe human asthmatics. Chronic allergen challenged Lys-Cretg/Fstl1Δ/Δ mice in whom Fstl1 is inactivated in macrophages/myeloid cells had significantly reduced airway remodeling and reduced levels of oncostatin M (OSM) a cytokine previously not known to be regulated by Fstl1. The importance of the Fstl1 induction of OSM to airway remodeling was demonstrated in murine studies in which administration of Fstl1 induced airway remodeling and increased OSM, while administration of an anti-OSM antibody blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation, and airway hyperresponsiveness all cardinal features of asthma. Overall, these studies demonstrate that the Fstl1/oncostatin M pathway may be a novel pathway to inhibit airway remodeling in severe human asthma. PMID:26355153

  9. [Malaria and intestinal protozoa].

    PubMed

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately.

  10. The Intestinal Microbiome and Health

    PubMed Central

    Tuddenham, Susan; Sears, Cynthia L.

    2015-01-01

    Purpose of Review A diverse array of microbes colonizes the human intestine. In this review we seek to outline the current state of knowledge on what characterizes a “healthy” or “normal” intestinal microbiome, what factors modify the intestinal microbiome in the healthy state and how the intestinal microbiome affects normal host physiology Recent Findings What constitutes a “normal” or “healthy” intestinal microbiome is an area of active research, but key characteristics may include diversity, richness and a microbial community’s resilience and ability to resist change. A number of factors, including age, the host immune system, host genetics, diet and antibiotic use appear to modify the intestinal microbiome in the normal state. New research shows that the microbiome likely plays a critical role in the healthy human immune system and metabolism. Summary It is clear that there is a complicated bi-directional relationship between the intestinal microbiota and host which is vital to health. An enhanced understanding of this relationship will be critical not only to maximize and maintain human health but also to shape our understanding of disease and to foster new therapeutic approaches. PMID:26237547

  11. Intestinal flora, probiotics, and cirrhosis.

    PubMed

    Guerrero Hernández, Ignacio; Torre Delgadillo, Aldo; Vargas Vorackova, Florencia; Uribe, Misael

    2008-01-01

    Intestinal microflora constitutes a symbiotic ecosystem in permanent equilibrium, composed mainly of anaerobic bacteria. However, such equilibrium may be altered by daily conditions as drug use or pathologies interfering with intestinal physiology, generating an unfavorable environment for the organism. Besides, there are factors which may cause alterations in the intestinal wall, creating the conditions for translocation or permeation of substances or bacteria. In cirrhotic patients, there are many conditions that combine to alter the amount and populations of intestinal bacteria, as well as the functional capacity of the intestinal wall to prevent the permeation of substances and bacteria. Nowadays, numerous complications associated with cirrhosis have been identified, where such mechanisms could play an important role. There is evidence that some probiotic microorganisms could restore the microbiologic and immunologic equilibrium in the intestinal wall in cirrhotic patients and help in the treatment of complications due to cirrhosis. This article has the objective to review the interactions between intestinal flora, gut permeability, and the actual role of probiotics in the field of cirrhotic patients.

  12. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    NASA Astrophysics Data System (ADS)

    Sharma, Gulshan B.; Robertson, Douglas D.

    2013-07-01

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula's material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element's remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than actual

  13. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    SciTech Connect

    Sharma, Gulshan B.; Robertson, Douglas D.

    2013-07-01

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  14. Remodeling of alveolar septa after murine pneumonectomy

    PubMed Central

    Ysasi, Alexandra B.; Wagner, Willi L.; Bennett, Robert D.; Ackermann, Maximilian; Valenzuela, Cristian D.; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A.

    2015-01-01

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends (“E”). Septal retraction, observed in 20–30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P < 0.01) and returned to baseline levels within 3 wk. Consistent with septal retraction, the postpneumonectomy alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P < 0.001). To identify clumped capillaries predicted by septal retraction, vascular casting, analyzed by both scanning electron microscopy and synchrotron imaging, demonstrated matted capillaries that were most prominent 3 days after pneumonectomy. Numerical simulations suggested that septal retraction could reflect increased surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  15. Soluble Endoglin Modulates Aberrant Cerebral Vascular Remodeling

    PubMed Central

    Chen, Yongmei; Hao, Qi; Kim, Helen; Su, Hua; Letarte, Michelle; Karumanchi, S. Ananth; Lawton, Michael T.; Barbaro, Nicholas M.; Yang, Guo-Yuan; Young, William L.

    2009-01-01

    Objective Brain arteriovenous malformations (AVMs) are an important cause of neurological morbidity in young adults. The pathophysiology of these lesions is poorly understood. A soluble form of endoglin (sEng) has been shown to cause endothelial dysfunction and induce preeclampsia. We tested if sEng would be elevated in brain AVM tissues relative to epilepsy brain tissues, and also investigated whether sEng overexpression via gene transfer in the mouse brain would induce vascular dysplasia and associated changes in downstream signaling pathways. Methods Expression levels of sEng in surgical specimens were determined by Western blot assay and ELISA. Vascular dysplasia, levels of MMP and oxidative stress were determined by immunohistochemistry and gelatin zymography. Results Brain AVMs (n=33) had higher mean sEng levels (245 ± 175 vs 100 ± 60, % of control, P=0.04) compared with controls (n=8), as determined by Western blot. In contrast, membrane-bound Eng was not significantly different (108 ± 79 vs 100 ± 63, % of control, P=0.95). sEng gene transduction in the mouse brain induced abnormal vascular structures. It also increased matrix metalloproteinase (MMP) activity by 490 ± 30% (MMP-9), 220 ± 30% (MMP-2), and oxidants by 260 ± 20% (4-hydroxy-2-nonenal) at 2 weeks after injection, suggesting that MMPs and oxidative radicals may mediate sEng-induced pathological vascular remodeling. Interpretation The results suggest that elevated sEng may play a role in the generation of sporadic brain AVMs. Our findings may provide new targets for therapeutic intervention for patients with brain AVMs. PMID:19670444

  16. Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

    PubMed Central

    Shi, Mingjun; Cho, Han Jun; Adams-Huet, Beverley; Paek, Jean; Hill, Kathy; Shelton, John; Amaral, Ansel P.; Faul, Christian; Taniguchi, Masatomo; Wolf, Myles; Brand, Markus; Takahashi, Masaya; Kuro-o, Makoto; Hill, Joseph A.

    2015-01-01

    Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency—genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor–23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1–, angiotensin II–, or high phosphate–induced fibrosis and abolished TGF-β1– or angiotensin II–induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor–23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging. PMID:25326585

  17. Polarizing intestinal epithelial cells electrically through Ror2

    PubMed Central

    Cao, Lin; McCaig, Colin D.; Scott, Roderick H.; Zhao, Siwei; Milne, Gillian; Clevers, Hans; Zhao, Min; Pu, Jin

    2014-01-01

    ABSTRACT The apicobasal polarity of enterocytes determines where the brush border membrane (apical membrane) will form, but how this apical membrane faces the lumen is not well understood. The electrical signal across the epithelium could serve as a coordinating cue, orienting and polarizing enterocytes. Here, we show that applying a physiological electric field to intestinal epithelial cells, to mimic the natural electric field created by the transepithelial potential difference, polarized phosphorylation of the actin-binding protein ezrin, increased expression of intestinal alkaline phosphatase (ALPI, a differentiation marker) and remodeled the actin cytoskeleton selectively on the cathode side. In addition, an applied electric field also activated ERK1/2 and LKB1 (also known as STK11), key molecules in apical membrane formation. Disruption of the tyrosine protein kinase transmembrane receptor Ror2 suppressed activation of ERK1/2 and LKB1 significantly, and subsequently inhibited apical membrane formation in enterocytes. Our findings indicate that the endogenous electric field created by the transepithelial potential difference might act as an essential coordinating signal for apical membrane formation at a tissue level, through activation of LKB1 mediated by Ror2–ERK signaling. PMID:24928904

  18. Chronic intestinal pseudo-obstruction.

    PubMed

    Antonucci, Alexandra; Fronzoni, Lucia; Cogliandro, Laura; Cogliandro, Rosanna-F; Caputo, Carla; De Giorgio, Roberto; Pallotti, Francesca; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2008-05-21

    Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases.

  19. Chronic intestinal pseudo-obstruction

    PubMed Central

    Antonucci, Alexandra; Fronzoni, Lucia; Cogliandro, Laura; Cogliandro, Rosanna F; Caputo, Carla; Giorgio, Roberto De; Pallotti, Francesca; Barbara, Giovanni; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2008-01-01

    Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features intestinal pseudo-obstruction can be classified into three main categories: neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseudo-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases. PMID:18494042

  20. Intestinal Antigen-Presenting Cells

    PubMed Central

    Flannigan, Kyle L.; Geem, Duke; Harusato, Akihito; Denning, Timothy L.

    2016-01-01

    The microbiota that populate the mammalian intestine are critical for proper host physiology, yet simultaneously pose a potential danger. Intestinal antigen-presenting cells, namely macrophages and dendritic cells (DCs), are integral components of the mucosal innate immune system that maintain co-existence with the microbiota in face of this constant threat. Intestinal macrophages and DCs integrate signals from the microenvironment to orchestrate innate and adaptive immune responses that ultimately lead to durable tolerance of the microbiota. Tolerance is not a default response, however, because macrophages and DCs remain poised to vigorously respond to pathogens that breach the epithelial barrier. In this review, we summarize the salient features of macrophages and DCs in the healthy and inflamed intestine and discuss how signals from the microbiota can influence their function. PMID:25976247

  1. Small Intestine but Not Liver Lysophosphatidylcholine Acyltransferase 3 (Lpcat3) Deficiency Has a Dominant Effect on Plasma Lipid Metabolism.

    PubMed

    Kabir, Inamul; Li, Zhiqiang; Bui, Hai H; Kuo, Ming-Shang; Gao, Guangping; Jiang, Xian-Cheng

    2016-04-01

    Lysophosphatidylcholine acyltransferase 3 (Lpcat3) is involved in phosphatidylcholine remodeling in the small intestine and liver. We investigated lipid metabolism in inducible intestine-specific and liver-specificLpcat3gene knock-out mice. We producedLpcat3-Flox/villin-Cre-ER(T2)mice, which were treated with tamoxifen (at days 1, 3, 5, and 7), to deleteLpcat3specifically in the small intestine. At day 9 after the treatment, we found that Lpcat3 deficiency in enterocytes significantly reduced polyunsaturated phosphatidylcholines in the enterocyte plasma membrane and reduced Niemann-Pick C1-like 1 (NPC1L1), CD36, ATP-binding cassette transporter 1 (ABCA1), and ABCG8 levels on the membrane, thus significantly reducing lipid absorption, cholesterol secretion through apoB-dependent and apoB-independent pathways, and plasma triglyceride, cholesterol, and phospholipid levels, as well as body weight. Moreover, Lpcat3 deficiency does not cause significant lipid accumulation in the small intestine. We also utilized adenovirus-associated virus-Cre to depleteLpcat3in the liver. We found that liver deficiency only reduces plasma triglyceride levels but not other lipid levels. Furthermore, there is no significant lipid accumulation in the liver. Importantly, small intestine Lpcat3 deficiency has a much bigger effect on plasma lipid levels than that of liver deficiency. Thus, inhibition of small intestine Lpcat3 might constitute a novel approach for treating hyperlipidemia.

  2. iTRAQ reveals proteomic changes during intestine regeneration in the sea cucumber Apostichopus japonicus.

    PubMed

    Sun, Lina; Xu, Dongxue; Xu, Qinzeng; Sun, Jingchun; Xing, Lili; Zhang, Libin; Yang, Hongsheng

    2017-02-04

    Sea cucumbers have a striking capacity to regenerate most of their viscera after evisceration, which has drawn the interest of many researchers. In this study, the isobaric tag for relative and absolute quantitation (iTRAQ) was utilized to investigate protein abundance changes during intestine regeneration in sea cucumbers. A total of 4073 proteins were identified, and 2321 proteins exhibited significantly differential expressions, with 1100 upregulated and 1221 downregulated proteins. Our results suggest that intestine regeneration constitutes a complex life activity regulated by the cooperation of various biological processes, including cytoskeletal changes, extracellular matrix (ECM) remodeling and ECM-receptor interactions, protein synthesis, signal recognition and transduction, energy production and conversion, and substance transport and metabolism. Additionally, real-time PCR showed mRNA expression of differentially expressed genes correlated positively with their protein levels. Our results provided a basis for studying the regulatory mechanisms associated with sea cucumber regeneration.

  3. Patterns and Implications of Intracranial Arterial Remodeling in Stroke Patients

    PubMed Central

    Qiao, Ye; Anwar, Zeeshan; Intrapiromkul, Jarunee; liu, Li; Zeiler, Steven R.; Leigh, Richard; Zhang, Yiyi; Guallar, Eliseo; Wasserman, Bruce A.

    2015-01-01

    Background and Purpose Preliminary studies suggest ntracranial arteries are capable of accommodating plaque formation by remodeling. We sought to study the ability and extent of intracranial arteries to remodel using 3D high-resolution black blood MRI (BBMRI) and investigate its relation to ischemic events. Methods 42 patients with cerebrovascular ischemic events underwent 3D time-of-flight MRA and contrast-enhanced BBMRI examinations at 3T for intracranial atherosclerotic disease. Each plaque was classified by location (e.g., posterior vs. anterior circulation) and its likelihood to have caused a stroke identified on MRI (culprit, indeterminate, or non-culprit). Lumen area (LA), outer wall area (OWA), and wall area (WA) were measured at the lesion and reference sites. Plaque burden was calculated as WA divided by OWA. The arterial remodeling ratio (RR) was calculated as OWA at the lesion site divided by OWA at the reference site, after adjusting for vessel tapering. Arterial remodeling was categorized as positive if RR >1.05, intermediate if 0.95≤RR ≤ 1.05, and negative if RR <0.95. Results 137 plaques were identified in 42 patients (37% [50] posterior, 63% [87] anterior). Compared with anterior circulation plaques, posterior circulation plaques had a larger plaque burden (77.7±15.7 vs. 69.0±14.0, p=0.008), higher RR (1.14±0.38 vs. 0.95±0.32, p=0.002), and more often exhibited positive remodeling (54.0% vs.29.9%, p=0.011). Positive remodeling was marginally associated with downstream stroke presence when adjusted for plaque burden (OR 1.34, 95% CI: 0.99–1.81). Conclusions Intracranial arteries remodel in response to plaque formation, and posterior circulation arteries have a greater capacity for positive remodeling and, consequently, may more likely elude angiographic detection. Arterial remodeling may provide insight into stroke risk. PMID:26742795

  4. Intestinal angioedema mimicking Crohn's disease.

    PubMed

    Malcolm, A; Prather, C M

    1999-10-18

    Angioedema usually presents as episodic attacks of swelling of the face, airway and extremities, but it may also involve visceral tissues. A 58-year-old woman with repeated episodes of abdominal pain, nausea and vomiting had two laparotomies and was treated for Crohn's disease for two years before a diagnosis of acquired intestinal angioedema was made. This case provides important insights into the presentation of intestinal angioedema.

  5. [Early left ventricular remodelling following acute coronary accident].

    PubMed

    Gaertner, Roger; Logeart, Damien; Michel, Jean-Baptiste; Mercadier, Jean-Jacques

    2004-01-01

    Ventricular remodelling following acute coronary syndromes is both complex and multiform. It is due to the response of the myocardium to the different agressions associated with these syndromes, in particular the ischemia and necrosis downstream of the occluded artery. We must not however neglect the role of the remodelling of the lesions resulting from spontaneous reperfusion or provoked by the cells and tissues associated with coronary microcirculation embolisms and the no-reflow phenomenon. Acute post-infarct remodelling is dominated by early ventricular dilatation which largely affects late prognosis, necrosis elimination and its replacement by a fibrotic scar in parallel with a compensatory hypertrophy of the non-infarcted myocardium. The diverse cellular and molecular components of this remodelling are increasingly well-known, allowing us to better explain the beneficial effects of the currently available medications and providing us with new potential therapeutic targets. A grading of this knowledge associated with the identification of new risk factors and early therapeutic interventions should help us to further limit the deleterious aspects of this remodelling in the goal of preventing, or at least delaying, the devolution towards heart failure.

  6. Subtype-specific neuronal remodeling during Drosophila metamorphosis.

    PubMed

    Veverytsa, Lyubov; Allan, Douglas W

    2013-01-01

    During metamorphosis in holometabolous insects, the nervous system undergoes dramatic remodeling as it transitions from its larval to its adult form. Many neurons are generated through post-embryonic neurogenesis to have adult-specific roles, but perhaps more striking is the dramatic remodeling that occurs to transition neurons from functioning in the larval to the adult nervous system. These neurons exhibit a remarkable degree of plasticity during this transition; many subsets undergo programmed cell death, others remodel their axonal and dendritic arbors extensively, whereas others undergo trans-differentiation to alter their terminal differentiation gene expression profiles. Yet other neurons appear to be developmentally frozen in an immature state throughout larval life, to be awakened at metamorphosis by a process we term temporally-tuned differentiation. These multiple forms of remodeling arise from subtype-specific responses to a single metamorphic trigger, ecdysone. Here, we discuss recent progress in Drosophila melanogaster that is shedding light on how subtype-specific programs of neuronal remodeling are generated during metamorphosis.

  7. Wall tissue remodeling regulates longitudinal tension in arteries.

    PubMed

    Jackson, Zane S; Gotlieb, Avrum I; Langille, B Lowell

    2002-05-03

    Changes in blood pressure or flow induce arterial remodeling that normalizes mechanical loads that are imposed on arterial tissue. Arteries are also under substantial longitudinal stretch (axial strain) that may be altered by growth or atrophy of tissues to which they are attached. We therefore tested whether axial strain is also regulated in a negative feedback manner through arterial remodeling. Axial strain in rabbit carotid arteries was increased from 62+/-2% to 97+/-2% without altering other mechanical loads on wall tissues. Strain was reduced within 3 days and completely normalized by 7 days. Remodeling involved tissue elaboration, endothelial cell replication rates were increased by >50-fold and smooth muscle cell replication rates were increased by >15-fold, and substantially elevated DNA, elastin, and collagen contents were recorded. Also, increased rates of apoptosis were indicated by degradation of DNA into oligonucleosomes, and matrix remodeling was reflected in enlarged fenestrae in the internal elastic lamina and increased expression and activation of gelatinases, especially matrix metalloproteinase-2. Intriguingly, reduced axial strain was not normalized, presumably because remodeling processes, apart from cell contraction, are ineffective in decreasing strain, and arterial smooth muscle orientation precludes large effects of contraction on axial strain.

  8. Chemistry of bone remodelling preserved in extant and fossil Sirenia.

    PubMed

    Anné, Jennifer; Wogelius, Roy A; Edwards, Nicholas P; van Veelen, Arjen; Ignatyev, Konstantin; Manning, Phillip L

    2016-05-01

    Bone remodelling is a crucial biological process needed to maintain elemental homeostasis. It is important to understand the trace elemental inventories that govern these processes as malfunctions in bone remodelling can have devastating effects on an organism. In this study, we use a combination of X-ray techniques to map, quantify, and characterise the coordination chemistry of trace elements within the highly remodelled bone tissues of extant and extinct Sirenia (manatees and dugongs). The dense bone structure and unique body chemistry of sirenians represent ideal tissues for studying both high remodelling rates as well as unique fossilisation pathways. Here, elemental maps revealed uncorrelated patterning of Ca and Zn within secondary osteons in both extant and fossil sirenians, as well as elevated Sr within the connecting canals of fossil sirenians. Concentrations of these elements are comparable between extant and fossil material indicating geochemical processing of the fossil bone has been minimal. Zn was found to be bound in the same coordination within the apatite structure in both extant and fossil bone. Accurate quantification of trace elements in extant material was only possible when the organic constituents of the bone were included. The comparable distributions, concentrations, and chemical coordination of these physiologically important trace elements indicate the chemistry of bone remodelling has been preserved for 19 million years. This study signifies the powerful potential of merging histological and chemical techniques in the understanding of physiological processes in both extant and extinct vertebrates.

  9. Chromatin dynamics: Interplay between remodeling enzymes and histone modifications

    PubMed Central

    Swygert, Sarah G.; Peterson, Craig L.

    2014-01-01

    Chromatin dynamics play an essential role in regulating the accessibility of genomic DNA for a variety of nuclear processes, including gene transcription and DNA repair. The posttranslational modification of the core histones and the action of ATP-dependent chromatin remodeling enzymes represent two primary mechanisms by which chromatin dynamics are controlled and linked to nuclear events. Although there are examples in which a histone modification or a remodeling enzyme may be sufficient to drive a chromatin transition, these mechanisms typically work in concert to integrate regulatory inputs, leading to a coordinated alteration in chromatin structure and function. Indeed, site-specific histone modifications can facilitate the recruitment of chromatin remodeling enzymes to particular genomic regions, or they can regulate the efficiency or the outcome of a chromatin remodeling reaction. Conversely, chromatin remodeling enzymes can also influence, and sometimes directly modulate, the modification state of histones. These functional interactions are generally complex, frequently transient, and often require the association of myriad additional factors. PMID:24583555

  10. Biological remodelling: Stationary energy, configurational change, internal variables and dissipation

    NASA Astrophysics Data System (ADS)

    Garikipati, K.; Olberding, J. E.; Narayanan, H.; Arruda, E. M.; Grosh, K.; Calve, S.

    2006-07-01

    Remodelling is defined as an evolution of microstructure or variations in the configuration of the underlying manifold. The manner in which a biological tissue and its subsystems remodel their structure is treated in a continuum mechanical setting. While some examples of remodelling are conveniently modelled as evolution of the reference configuration—Case I—others are more suited to an internal variable description—Case II. In this paper, we explore the applicability of stationary energy states to remodelled systems. A variational treatment is introduced by assuming that stationary energy states are attained by changes in microstructure via one of the two mechanisms—Cases I and II. The configurational change of a long-chain molecule is presented as an example of Case I, and collagen fibre reorientation in in vitro tissue constructs as an example of Case II. The second example is further studied for its thermodynamic dissipation characteristics. This leads to an important finding on the limitation of purely mechanical treatments of some types of remodelling phenomena.

  11. Cortical remodeling during menopause, rheumatoid arthritis, glucocorticoid and bisphosphonate therapy.

    PubMed

    Aeberli, Daniel; Schett, Georg

    2013-03-21

    Bone mass, bone geometry and its changes are based on trabecular and cortical bone remodeling. Whereas the effects of estrogen loss, rheumatoid arthritis (RA), glucocorticoid (GC) and bisphosphonate (BP) on trabecular bone remodeling have been well described, the effects of these conditions on the cortical bone geometry are less known. The present review will report current knowledge on the effects of RA, GC and BP on cortical bone geometry and its clinical relevance. Estrogen deficiency, RA and systemic GC lead to enhanced endosteal bone resorption. While in estrogen deficiency and under GC therapy endosteal resorption is insufficiently compensated by periosteal apposition, RA is associated with some periosteal bone apposition resulting in a maintained load-bearing capacity and stiffness. In contrast, BP treatment leads to filling of endosteal bone cavities at the epiphysis; however, periosteal apposition at the bone shaft seems to be suppressed. In summary, estrogen loss, RA and GC show similar effects on endosteal bone remodeling with an increase in bone resorption, whereas their effect on periosteal bone remodeling may differ. Despite over 50 years of GC therapy and over 25 years of PB therapy, there is still need for better understanding of the skeletal effects of these drugs as well as of inflammatory disease such as RA on cortical bone remodeling.

  12. Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context

    PubMed Central

    Ajijola, Olujimi A.; Yagishita, Daigo; Patel, Krishan J.; Vaseghi, Marmar; Zhou, Wei; Yamakawa, Kentaro; So, Eileen; Lux, Robert L.; Mahajan, Aman

    2013-01-01

    Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine (n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms2, P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P = 0.0001), whereas left stellate ganglion stimulation showed the reverse (P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced. PMID:23893167

  13. Dynamical DNA accessibility induced by chromatin remodeling and protein binding

    NASA Astrophysics Data System (ADS)

    Montel, F.; Faivre-Moskalenko, C.; Castelnovo, M.

    2014-11-01

    Chromatin remodeling factors are enzymes being able to alter locally chromatin structure at the nucleosomal level and they actively participate in the regulation of gene expression. Using simple rules for individual nucleosome motion induced by a remodeling factor, we designed simulations of the remodeling of oligomeric chromatin, in order to address quantitatively collective effects in DNA accessibility upon nucleosome mobilization. Our results suggest that accessibility profiles are inhomogeneous thanks to borders effects like protein binding. Remarkably, we show that the accessibility lifetime of DNA sequence is roughly doubled in the vicinity of borders as compared to its value in bulk regions far from the borders. These results are quantitatively interpreted as resulting from the confined diffusion of a large nucleosome depleted region.

  14. Passive ventricular remodeling in cardiac disease: focus on heterogeneity

    PubMed Central

    Kessler, Elise L.; Boulaksil, Mohamed; van Rijen, Harold V. M.; Vos, Marc A.; van Veen, Toon A. B.

    2014-01-01

    Passive ventricular remodeling is defined by the process of molecular ventricular adaptation to different forms of cardiac pathophysiology. It includes changes in tissue architecture, such as hypertrophy, fiber disarray, alterations in cell size and fibrosis. Besides that, it also includes molecular remodeling of gap junctions, especially those composed by Connexin43 proteins (Cx43) in the ventricles that affect cell-to-cell propagation of the electrical impulse, and changes in the sodium channels that modify excitability. All those alterations appear mainly in a heterogeneous manner, creating irregular and inhomogeneous electrical and mechanical coupling throughout the heart. This can predispose to reentry arrhythmias and adds to a further deterioration into heart failure. In this review, passive ventricular remodeling is described in Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM), and Arrhythmogenic Cardiomyopathy (ACM), with a main focus on the heterogeneity of those alterations mentioned above. PMID:25566084

  15. Dynamic regulation of transcription factors by nucleosome remodeling.

    PubMed

    Li, Ming; Hada, Arjan; Sen, Payel; Olufemi, Lola; Hall, Michael A; Smith, Benjamin Y; Forth, Scott; McKnight, Jeffrey N; Patel, Ashok; Bowman, Gregory D; Bartholomew, Blaine; Wang, Michelle D

    2015-06-05

    The chromatin landscape and promoter architecture are dominated by the interplay of nucleosome and transcription factor (TF) binding to crucial DNA sequence elements. However, it remains unclear whether nucleosomes mobilized by chromatin remodelers can influence TFs that are already present on the DNA template. In this study, we investigated the interplay between nucleosome remodeling, by either yeast ISW1a or SWI/SNF, and a bound TF. We found that a TF serves as a major barrier to ISW1a remodeling, and acts as a boundary for nucleosome repositioning. In contrast, SWI/SNF was able to slide a nucleosome past a TF, with concurrent eviction of the TF from the DNA, and the TF did not significantly impact the nucleosome positioning. Our results provide direct evidence for a novel mechanism for both nucleosome positioning regulation by bound TFs and TF regulation via dynamic repositioning of nucleosomes.

  16. Regulation of the Golgi Complex by Phospholipid Remodeling Enzymes

    PubMed Central

    Ha, Kevin D.; Clarke, Benjamin A.; Brown, William J.

    2012-01-01

    The mammalian Golgi complex is a highly dynamic organelle consisting of stacks of flattened cisternae with associated coated vesicles and membrane tubules that contribute to cargo import and export, intra-cisternal trafficking, and overall Golgi architecture. At the morphological level, all of these structures are continuously remodeled to carry out these trafficking functions. Recent advances have shown that continual phospholipid remodeling by phospholipase A (PLA) and lysophospholipid acyltransferase (LPAT) enzymes, which deacylate and reacylate Golgi phospholipids, respectively, contributes to this morphological remodeling. Here we review the identification and characterization of four cytoplasmic PLA enzymes and one integral membrane LPAT that participate in the dynamic functional organization of the Golgi complex, and how some of these enzymes are integrated to determine the relative abundance of COPI vesicle and membrane tubule formation. PMID:22562055

  17. Diabetes mellitus and atrial remodeling: mechanisms and potential upstream therapies.

    PubMed

    Zhang, Qitong; Liu, Tong; Ng, Chee Y; Li, Guangping

    2014-10-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence has increasing substantially over the last decades. Recent data suggest that there is an increased risk of AF among the patients with diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM-related AF and diabetic atrial remodeling are not fully understood. In this comprehensive review, we would like to summarize the potential relationship between diabetes and atrial remodeling, including structural, electrical, and autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones, probucol, ACEI/ARBs, may play an important role in the prevention and treatment of AF. Therefore, large prospective randomized, controlled trials and further experimental studies should be challengingly continued.

  18. Remodeling of legacy systems in health care using UML.

    PubMed

    Garde, Sebastian; Knaup, Petra; Herold, Ralf

    2002-01-01

    Research projects in the field of Medical Informatics often involve the development of application systems. Usually they are developed over a longer period of time, so that at a certain point of time a systematically planned reimplementation is necessary. The first step of reimplementation should be a systematic and comprehensive remodeling. When using UML for this task a systematic approach for remodeling activities is missing. Therefore, we developed a method for remodeling of legacy systems (Qumquad) and applied it to DOSPO, a documentation and therapy planning system for pediatric oncology. Qumquad helps to systematically carry out three steps: the modeling of the current actual state of the application system, the systematic identification of weak points and the development of a target concept for reimplementation considering the identified weak points. Results show that this approach is valuable and feasible and could be applied to various application systems in health care.

  19. Synaptic activity and connective tissue remodeling in denervated frog muscle

    PubMed Central

    1994-01-01

    Denervation of skeletal muscle results in dramatic remodeling of the cellular and molecular composition of the muscle connective tissue. This remodeling is concentrated in muscle near neuromuscular junctions and involves the accumulation of interstitial cells and several extracellular matrix molecules. Given the role of extracellular matrix in neurite outgrowth and synaptogenesis, we predict that this remodeling of the junctional connective tissue directly influences the regeneration of the neuromuscular junction. As one step toward understanding the role of this denervation-induced remodeling in synapse formation, we have begun to look for the signals that are involved in initiating the junctional accumulations of interstitial cells and matrix molecules. Here, the role of muscle inactivity as a signal was examined. The distributions of interstitial cells, fibronectin, and tenascin were determined in muscles inactivated by presynaptic blockade of muscle activity with tetrodotoxin. We found that blockade of muscle activity for up to 4 wk produced neither the junctional accumulation of interstitial cells nor the junctional concentrations of tenascin and fibronectin normally present in denervated frog muscle. In contrast, the muscle inactivity induced the extrajunctional appearance of two synapse-specific molecules, the acetylcholine receptor and a muscle fiber antigen, mAb 3B6. These results demonstrate that the remodeling of the junctional connective tissue in response to nerve injury is a unique response of muscle to denervation in that it is initiated by a mechanism that is independent of muscle activity. Thus connective tissue remodeling in denervated skeletal muscle may be induced by signals released from or associated with the nerve other than the evoked release of neurotransmitter. PMID:7525607

  20. Epac2-mediated dendritic spine remodeling: implications for disease

    PubMed Central

    Woolfrey, Kevin M.; Srivastava, Deepak P.

    2010-01-01

    In the mammalian forebrain, most glutamatergic excitatory synapses occur on small dendritic protrusions called dendritic spines. Dendritic spines are highly plastic and can rapidly change morphology in response to numerous stimuli. This dynamic remodeling of dendritic spines is thought to be critical for information processing, memory and cognition. Conversely, multiple studies have revealed that neuropathologies such as autism spectrum disorders (ASDs) are linked with alterations in dendritic spine morphologies and miswiring of neural circuitry. One compelling hypothesis is that abnormal dendritic spine remodeling is a key contributing factor for this miswiring. Ongoing research has identified a number of mechanisms that are critical for the control of dendritic spine remodeling. Among these mechanisms, regulation of small GTPase signaling by guanine-nucleotide exchange factors (GEFs) is emerging as a critical mechanism for integrating physiological signals in the control of dendritic spine remodeling. Furthermore, multiple proteins associated with regulation of dendritic spine remodeling have also been implicated with multiple neuropathologies, including ASDs. Epac2, a GEF for the small GTPase Rap, has recently been described as a novel cAMP(yet PKA-independent) target localized to dendritic spines. Signaling via this protein in response to pharmacological stimulation or cAMP accumulation, via the dopamine D1/5 receptor, results in Rap activation, promotes structural destabilization, in the form of dendritic spine shrinkage, and functional depression due to removal of GluR2/3-containing AMPA receptors. In addition, Epac2 forms macromolecular complexes with ASD-associated proteins, which are sufficient to regulate Epac2 localization and function. Furthermore, rare nonsynonymous variants of the EPAC2 gene associated with the ASD phenotype alter protein function, synaptic protein distribution, and spine morphology. We review here the role of Epac2 in the remodeling

  1. Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

    PubMed

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara

    2016-08-01

    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  2. Nasomaxillary remodeling and facial form in robust Australopithecus: a reassessment.

    PubMed

    McCollum, Melanie A

    2008-01-01

    In a previous study of the patterns of facial growth remodeling characteristic of early hominid taxa, Bromage (1989) demonstrated that the nasoalveolar clivus of A. robustus was resorptive throughout ontogeny. Based upon the remodeling information provided by small samples (n=6 each) of chimpanzees and modern humans, he concluded that the clival resorption pattern characteristic of robust Australopithecus differed significantly from that of chimpanzees and was instead somewhat convergent upon that of modern humans, in that it served to emphasize a downward facial growth vector. The present study used the SEM/replica technique to assess nasomaxillary remodeling in larger, more age-varied samples of chimpanzee (n=33) and modern human crania (n=22). Results indicate far more intraspecific variability in nasomaxillary remodeling than suggested by Bromage's earlier study. In particular, results from an expanded sample demonstrate that the nasoalveolar clivus of chimpanzees is frequently resorptive, especially at later stages of ontogeny. However, the pattern of clival remodeling observed in chimpanzees is unlike that typical of robust Australopithecus, in which clival resorption occurs throughout ontogeny and in expansive fields that cover the entire clival surface. Although Bromage (1989) considered the pattern of nasomaxillary remodeling observed in robust Australopithecus to have been a byproduct of an extreme maxillary growth rotation, the failure of A. africanus to display a similar pattern suggests that some other factor(s) may have been involved. Regardless, it is unlikely that clival resorption in robust Australopithecus would have significantly impacted the overall vector of facial growth. Instead, the primary morphogenetic effect of this pattern of clival resorption would have been one of local surface sculpting.

  3. The pathophysiologic process of ventricular remodeling: from infarct to failure.

    PubMed

    Paul, S

    1995-05-01

    In the past, hypertensive heart disease was the principal cause of congestive heart failure, but currently ischemic heart disease is the major etiologic factor. In the last 20 years, the role of myocardial infarction (MI) and the subsequent alteration in ventricular architecture of the infarcted and noninfarcted myocardium have become increasingly associated with a phenomenon known as ventricular remodelling. This process consists of left ventricular wall thinning in the infarction area, ventricular chamber dilatation, and compensatory hypertrophy of the noninfarcted portion of the myocardium. This article describes the pathophysiologic transformation that begins with MI and ventricular remodeling and ends in congestive heart failure.

  4. Mechanisms of ATP-Dependent Chromatin Remodeling Motors.

    PubMed

    Zhou, Coral Y; Johnson, Stephanie L; Gamarra, Nathan I; Narlikar, Geeta J

    2016-07-05

    Chromatin remodeling motors play essential roles in all DNA-based processes. These motors catalyze diverse outcomes ranging from sliding the smallest units of chromatin, known as nucleosomes, to completely disassembling chromatin. The broad range of actions carried out by these motors on the complex template presented by chromatin raises many stimulating mechanistic questions. Other well-studied nucleic acid motors provide examples of the depth of mechanistic understanding that is achievable from detailed biophysical studies. We use these studies as a guiding framework to discuss the current state of knowledge of chromatin remodeling mechanisms and highlight exciting open questions that would continue to benefit from biophysical analyses.

  5. Remodeling of cell-cell junctions in arrhythmogenic cardiomyopathy.

    PubMed

    Asimaki, Angeliki; Saffitz, Jeffrey E

    2014-02-01

    Arrhythmogenic cardiomyopathy (AC) is a primary myocardial disorder characterized by a high incidence of ventricular arrhythmias often preceding the onset of ventricular remodeling and dysfunction. Approximately 50% of patients diagnosed with AC have one or more mutations in genes encoding desmosomal proteins, although non-desmosomal genes have also been associated with the disease. Increasing evidence implicates remodeling of intercalated disk proteins reflecting abnormal responses to mechanical load and aberrant cell signaling pathways in the pathogenesis of AC. This review summarizes recent advances in understanding disease mechanisms in AC that have come from studies of human myocardium and experimental models.

  6. Silent Synapse-Based Circuitry Remodeling in Drug Addiction

    PubMed Central

    2016-01-01

    Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. PMID:26721952

  7. Intestinal microbiota and overweight.

    PubMed

    Lyra, A; Lahtinen, S; Tiihonen, K; Ouwehand, A C

    2010-11-01

    The microbes in our gut can influence our weight by providing us with energy through the degradation of nondigestable carbohydrates and by affecting the cellular energy status of liver and muscle cells and the accumulation of lipids in adipose tissue. Thus, it is not surprising that in several studies the gastrointestinal microbiota of overweight and obese subjects has been found to differ from that of lean subjects. The initial findings linked obesity with proportionally decreased levels of the phylum Bacteroidetes and increased levels of the phylum Firmicutes. Later, several studies have assessed the association between overweight or obesity and the gastrointestinal microbiota, applying an array of molecular methods targeting the microbiota as a whole or specific bacterial groups or species within. However, at present it is difficult to draw conclusions on which of the observed microbiota alterations are relevant; essentially all of the bacterial groups that have been studied in more than one trial have given contradictory results in regard to their association with weight. Some of these discrepancies can result from methodological issues and some from the nature of the gastrointestinal microbiota, which is an extremely complex and dynamic microbial ecosystem with high subject specificity. In addition, selecting subjects purely based on weight may result in a largely heterogeneous group with several potentially confounding factors. While it may be premature to conclude which specific groups of bacteria are prominent in the intestinal tract of overweight and obese subjects, it appears clear that microbes contribute to weight gain and related health issues, such as the metabolic syndrome and type II diabetes. Therefore, it is important to continue to search for common microbial markers and predictors of obesity, and to study how these may be modulated with probiotics and prebiotics to promote health.

  8. Small intestinal physiology and pathophysiology.

    PubMed

    Sarna, S K; Otterson, M F

    1989-06-01

    The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents to uniformly and evenly expose them to the mucosal surface, and to propel them distally at a rate that allows optimal absorption of food components, and reabsorption of bile. Most of these functions are performed by individual phasic contractions. In humans, the phasic contractions are largely disorganized in time and space. These contractions may cause mixing and agitation of luminal contents with slow distal propulsion. Occasionally, an individual contraction of large amplitude and long duration migrates over several centimeters and may rapidly propel the contents over this distance. In general, the spatial and temporal relationships of individual phasic contractions become less organized distally, resulting in a slower propulsion rate in the distal small intestine than in the proximal small intestine. The migrating clustered contractions generated after a meal may also be propulsive, but because of their unpredictable and irregular occurrence, their precise role in postprandial propulsion is incompletely understood. Rapidly migrating contractions may occur when the electrical control activity is obliterated by pharmacologic agents or during parasitic infections. Their effects on motility are not known yet. Between meals, when digestion is complete, the small intestine generates migrating motor complexes that help keep the small intestine clean by dislodging debris from the villi and dumping them into the colon. This may prevent decay of these materials in the small intestine and limit their contribution to bacterial overgrowth. Giant migrating contractions may perform a similar function in the distal small intestine as well as return any refluxed fecal

  9. Intestinal ischemia in neonates and children.

    PubMed

    Jeican, Ionuţ Isaia; Ichim, Gabriela; Gheban, Dan

    2016-01-01

    The article reviews the intestinal ischemia theme on newborn and children. The intestinal ischemia may be either acute - intestinal infarction (by vascular obstruction or by reduced mesenteric blood flow besides the occlusive mechanism), either chronic. In neonates, acute intestinal ischemia may be caused by aortic thrombosis, volvulus or hypoplastic left heart syndrome. In children, acute intestinal ischemia may be caused by fibromuscular dysplasia, volvulus, abdominal compartment syndrome, Burkitt lymphoma, dermatomyositis (by vascular obstruction) or familial dysautonomia, Addison's disease, situs inversus abdominus (intraoperative), burns, chemotherapy administration (by nonocclusive mesenteric ischemia). Chronic intestinal ischemia is a rare condition in pediatrics and can be seen in abdominal aortic coarctation or hypoplasia, idiopathic infantile arterial calcinosis.

  10. Arterial Remodeling in B-Type Natriuretic Peptide Knock-Out Females

    PubMed Central

    Holditch, Sara J.; Schreiber, Claire A.; Burnett, John C.; Ikeda, Yasuhiro

    2016-01-01

    Sexual dimorphisms are recognized in cardiovascular conditions such as hypertension, stroke, thrombosis and vasculitis. B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. The anti-hypertensive, vasodilatory, anti-fibrotic, and anti-hypertrophic properties of BNP are well established in male animal models. Although circulating BNP levels are higher in women, when compared to age-matched men, the cardiovascular protective propensity of BNP in females is poorly understood. We assessed the cardiovascular consequences of BNP deletion in genetically null (Nppb−/−) female rat lines. Throughout the study, blood pressure (BP) remained uninfluenced by genotype, and cardiorenal consequences of BNP knock out remained minor. Unexpectedly, approximately 60% of Nppb−/− females developed mesenteric polyarteritis-nodosa (PAN)-like vasculitis in their life span, some as early as 4 months of age. Mesenteric lesions involved intense arterial remodeling, progressive inflammation, occluded lumens, and less frequently intestinal necrosis and multiple visceral arterial aneurysms. Cumulative pathologies resulted in a significant decline in survival of the Nppb−/− female. This study highlights BNP’s vasoprotective propensity, bringing to light a possible sex specific difference in the cardiovascular protection provided by BNP. Defects in the BNP/GC-A/cGMP pathway may play a role in arteriopathies in women, while GC-A agonists may provide effective therapy for arteritis. PMID:27162120

  11. [Chronic intestinal pseudo-obstruction].

    PubMed

    Muñoz, M T; Solís Herruzo, J A

    2007-02-01

    Chronic intestinal pseudo-obstruction (CIPO) is a syndrome characterized by the presence of recurrent episodes of clinical intestinal obstruction in the absence of obstructive lesions. Although this syndrome is rare, it causes a high morbidity. It is caused by a disturbance of the intestinal motility, that results in a failure of the progression of the intestinal content. Basically, the failure of the intestinal motility is a consequence of muscular disorder, neurological disorder or both. Usually, CIPO is secondary to other systemic disease; however, in the last years, many cases of primary CIPO have been described. The use of new manometric tecniques and specific histological procedures have allowed to clarify the pathogenesis of some of these entities including mitochondrial diseases and paraneoplasic syndromes. Clinical manifestations of CIPO are diverse, depending on the location and extension of the motility disorder. As the diagnosis of this disease is usually not an easy task, patients frecuently undergo unnecesary surgical interventions, are diagnosed of psyquiatric disorders, or the correct diagnosis is delayed several years after the first symptoms arise. The aims of the treatment are to maintain the nutritional condition and to improve symptoms using nutritional measures, drugs or, eventually, endoscopical or surgical procedures.

  12. Human intestinal capillariasis in Thailand

    PubMed Central

    Saichua, Prasert; Nithikathkul, Choosak; Kaewpitoon, Natthawut

    2008-01-01

    Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt and Taiwan; major outbreaks have occurred in the Philippines and Thailand. This article reviews the epidemiology, history and sources of C. philippinensis infection in Thailand. The annual epidemiological surveillance reports indicated that 82 accumulated cases of intestinal capillariasis were found in Thailand from 1994-2006. That made Thailand a Capillaria-prevalent area. Sisaket, in northeast Thailand, was the first province which has reported intestinal capillariasis. Moreover, Buri Ram presented a high prevalence of intestinal capillariasis, totaling 24 cases from 1994-2006. About half of all cases have consumed raw or undercooked fish. However, even if the numbers of the intestinal capillariasis cases in Thailand is reduced, C. philippinensis infection cases are still reported. The improvement of personal hygiene, specifically avoiding consumption of undercooked fish and promoting a health education campaign are required. These strategies may minimize or eliminate C. philippinensis infection in Thailand. PMID:18203280

  13. Intestinal Microbiota Metabolism and Atherosclerosis

    PubMed Central

    Liu, Tian-Xing; Niu, Hai-Tao; Zhang, Shu-Yang

    2015-01-01

    Objective: This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target. Data Sources: This study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: “Intestinal microbiota”, “trimethylamine N-oxide (TMAO)”, “trimethylamine (TMA)”, “cardiovascular”, and “atherosclerosis”. Study Selection: Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included. Results: A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear. Conclusions: Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management. PMID:26481750

  14. Therapeutic modulation of intestinal dysbiosis.

    PubMed

    Walker, Alan W; Lawley, Trevor D

    2013-03-01

    The human gastrointestinal tract is home to an extremely numerous and diverse collection of microbes, collectively termed the "intestinal microbiota". This microbiota is considered to play a number of key roles in the maintenance of host health, including aiding digestion of otherwise indigestible dietary compounds, synthesis of vitamins and other beneficial metabolites, immune system regulation and enhanced resistance against colonisation by pathogenic microorganisms. Conversely, the intestinal microbiota is also a potent source of antigens and potentially harmful compounds. In health, humans can therefore be considered to exist in a state of natural balance with their microbial inhabitants. A shift in the balance of microbiota composition such that it may become deleterious to host health is termed "dysbiosis". Dysbiosis of the gut microbiota has been implicated in numerous disorders, ranging from intestinal maladies such as inflammatory bowel diseases and colorectal cancer to disorders with more systemic effects such as diabetes, metabolic syndrome and atopy. Given the far reaching influence of the intestinal microbiota on human health a clear future goal must be to develop reliable means to alter the composition of the microbiota and restore a healthy balance of microbial species. While it is clear that much fundamental research remains to be done, potentially important therapeutic options include narrow spectrum antibiotics, novel probiotics, dietary interventions and more radical techniques such as faecal transplantation, all of which aim to suppress clinical dysbiosis, restore intestinal microbiota diversity and improve host health.

  15. Intestinal circulation during inhalation anesthesia

    SciTech Connect

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-04-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  16. Prebiotics in Chronic Intestinal Inflammation

    PubMed Central

    Looijer–van Langen, Mirjam A.C.; Dieleman, Levinus A.

    2016-01-01

    Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn’s disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials. PMID:18831524

  17. Campylobacter concisus pathotypes induce distinct global responses in intestinal epithelial cells

    PubMed Central

    Deshpande, Nandan P.; Wilkins, Marc R.; Castaño-Rodríguez, Natalia; Bainbridge, Emily; Sodhi, Nidhi; Riordan, Stephen M.; Mitchell, Hazel M.; Kaakoush, Nadeem O.

    2016-01-01

    The epithelial response to the opportunistic pathogen Campylobacter concisus is poorly characterised. Here, we assessed the intestinal epithelial responses to two C. concisus strains with different virulence characteristics in Caco-2 cells using RNAseq, and validated a subset of the response using qPCR arrays. C. concisus strains induced distinct response patterns from intestinal epithelial cells, with the toxigenic strain inducing a significantly more amplified response. A range of cellular functions were significantly regulated in a strain-specific manner, including epithelial-to-mesenchymal transition (NOTCH and Hedgehog), cytoskeletal remodeling, tight junctions, inflammatory responses and autophagy. Pattern recognition receptors were regulated, including TLR3 and IFI16, suggesting that nucleic acid sensing was important for epithelial recognition of C. concisus. C. concisus zonula occludens toxin (ZOT) was expressed and purified, and the epithelial response to the toxin was analysed using RNAseq. ZOT upregulated PAR2 expression, as well as processes related to tight junctions and cytoskeletal remodeling. C. concisus ZOT also induced upregulation of TLR3, pro-inflammatory cytokines IL6, IL8 and chemokine CXCL16, as well as the executioner caspase CASP7. Here, we characterise distinct global epithelial responses to C. concisus strains, and the virulence factor ZOT, and provide novel information on mechanisms by which this bacterium may affect the host. PMID:27677841

  18. The Intestinal Absorption of Folates

    PubMed Central

    Visentin, Michele; Diop-Bove, Ndeye; Zhao, Rongbao; Goldman, I. David

    2014-01-01

    The properties of intestinal folate absorption were documented decades ago. However, it was only recently that the proton-coupled folate transporter (PCFT) was identified and its critical role in folate transport across the apical brush-border membrane of the proximal small intestine established by the loss-of-function mutations identified in the PCFT gene in subjects with hereditary folate malabsorption and, more recently, by the Pcft-null mouse. This article reviews the current understanding of the properties of PCFT-mediated transport and how they differ from those of the reduced folate carrier. Other processes that contribute to the transport of folates across the enterocyte, along with the contribution of the enterohepatic circulation, are considered. Important unresolved issues are addressed, including the mechanism of intestinal folate absorption in the absence of PCFT and regulation of PCFT gene expression. The impact of a variety of ions, organic molecules, and drugs on PCFT-mediated folate transport is described. PMID:24512081

  19. Intestinal mycoplasma in Crohn's disease.

    PubMed

    Roediger, W E W

    2004-01-01

    Intestinal diversion with reconnection in active Crohn's disease (CD) indicates that luminal contents or bacteria contribute to the formation of CD lesions. Fluorescent staining for mycoplasma in freshly resected Crohn's tissue and electron microscopy reveal intracellular organisms akin to mycoplasma. Historically, tissue culture of CD has shown mycoplasma described as contaminants. Mycoplasma are surface epithelial parasites requiring exogenous cholesterol for membrane stability and cell entry. PCR of intestinal tissue has shown Mycoplasma pneumoniae to be detectable more significantly in CD. Oral M. iowae in experimental poultry localizes to the distal small bowel and colon. Hypothetically, lipopeptides of mycoplasmal membranes are proposed to cause chronicity and stronger immune responses than by other bacteria. 'Intestinal' mycoplasmas, from a number of observations, deserve consideration as organisms mediating inflammation of acute and chronic CD.

  20. Energy Efficiency Measures to Incorporate into Remodeling Projects

    SciTech Connect

    Liaukus, C.

    2014-12-01

    Energy improvements in a home are often approached as one concerted effort, beginning with a simple walk-through assessment or more in-depth energy audit and followed by the installation of recommended energy measures. While this approach allows for systems thinking to guide the efforts, comprehensive energy improvements of this nature are undertaken by a relatively small number of U.S. households compared to piecemeal remodeling efforts. In this report, the U.S Department of Energy Building America Retrofit Alliance research team examines the improvement of a home’s energy performance in an opportunistic way by examining what can be done to incorporate energy efficiency measures into general remodeling work and home repair projects. This allows for energy efficiency upgrades to occur at the same time as remodeling proejcts. There are challenges to this approach, not the least of which being that the work will take place over time in potentially many separate projects. The opportunity to improve a home’s energy efficiency at one time expands or contracts with the scope of the remodel. As such, guidance on how to do each piece thoughtfully and with consideration for potential future projects, is critical.

  1. CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

    ERIC Educational Resources Information Center

    Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

    2012-01-01

    The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

  2. Probing Nucleosome Remodeling by Unzipping Single DNA Molecules

    NASA Astrophysics Data System (ADS)

    Wang, Michelle

    2006-03-01

    At the core of eukaryotic chromatin is the nucleosome, which consists of 147 bp of DNA wrapped 1.65 turns around an octamer of histone proteins. Even this lowest level of genomic compaction presents a strong barrier to DNA-binding cellular factors that are required for essential processes such as transcription, DNA replication, recombination and repair. Chromatin remodeling enzymes use the energy of ATP hydrolysis to regulate accessibility of the genetic code by altering chromatin structure. While remodeling enzymes have been the subject of extensive research in recent years, their precise mechanism remains unclear. In order to probe the structure of individual nucleosomes and their remodeling, we assembled a histone octamer onto a DNA segment containing a strong nucleosome positioning sequence. As the DNA double helix was unzipped through the nucleosome using a feedback-enhanced optical trap, the presence of the nucleosome was detected as a series of dramatic increases in the tension in the DNA, followed by sudden tension reductions. Analysis of the unzipping force throughout the disruption accurately revealed the spatial location and fine structure of the nucleosome to near base pair precision. Using this approach, we investigate how remodeling enzymes may alter the location and structure of a nucleosome.

  3. Energy Efficiency Measures to Incorporate into Remodeling Projects

    SciTech Connect

    Liaukus, C.

    2014-12-01

    Energy improvements in a home are often approached as one concerted effort, beginning with a simple walk-through assessment or more in-depth energy audit and followed by the installation of recommended energy measures. While this approach allows for systems thinking to guide the efforts, comprehensive energy improvements of this nature are undertaken by a relatively small number of the households in our nation compared to more piecemeal remodeling efforts. Even when programs like the Weatherization Assistance Program and Home Performance with ENERGY STAR are considered, homes that have had a comprehensive energy makeover still represent a small fraction of the 111.1 million households. In this report, the U.S Department of Energy Building America Retrofit Alliance research team looks at the improvement of a home's energy performance in an opportunistic way: it examines what can be done to incorporate energy efficiency measures into general remodeling work and home repair projects. This allows for the possibility for people who would not normally pursue energy efficiency but will remodel their kitchen or re-side their home to improve their home's performance at the same time. There are challenges to this approach, not the least of which being that the work will take place over time in potentially many separate projects. The opportunity to improve a home's energy efficiency at one time expands or contracts with the scope of the remodel. As such, guidance on how to do each piece thoughtfully and with consideration for potential future projects, is critical.

  4. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  5. CRITERIA FOR DECIDING TO REMODEL THE EXISTING SCHOOL.

    ERIC Educational Resources Information Center

    SHOBE, EARL J.

    MODERNIZATION OF SCHOOL BUILDINGS REQUIRES ADAPTATION OF EDUCATIONAL AND ENVIRONMENTAL REQUIREMENTS. PRELIMINARY ANALYSIS OF--(1) CONSTRUCTION QUALITY, (2) ROOM SIZE, (3) SITE CAPABILITY, AND (4) ARCHITECTURAL REMODELING POTENTIAL HELPS TO DETERMINE FEASIBILITY AND APPROACH METHOD. ANALYSIS OF FIVE APPROACHES FOR CREATING ADDITIONS TO A SPECIFIC…

  6. Integrated mechanisms of CaMKII-dependent ventricular remodeling

    PubMed Central

    Kreusser, Michael M.; Backs, Johannes

    2014-01-01

    CaMKII has been shown to be activated during different cardiac pathological processes, and CaMKII-dependent mechanisms contribute to pathological cardiac remodeling, cardiac arrhythmias, and contractile dysfunction during heart failure. Activation of CaMKII during cardiac stress results in a broad number of biological effects such as, on the one hand, acute effects due to phosphorylation of distinct cellular proteins as ion channels and calcium handling proteins and, on the other hand, integrative mechanisms by changing gene expression. This review focuses on transcriptional and epigenetic effects of CaMKII activation during chronic cardiac remodeling. Multiple mechanisms have been described how CaMKII mediates changes in cardiac gene expression. CaMKII has been shown to directly phosphorylate components of the cardiac gene regulation machinery. CaMKII phosphorylates several transcription factors such as CREB that induces the activation of specific gene programs. CaMKII activates transcriptional regulators also indirectly by phosphorylating histone deacetylases, especially HDAC4, which in turn inhibits transcription factors that drive cardiac hypertrophy, fibrosis, and dysfunction. Recent studies demonstrate that CaMKII also phosphorylate directly histones, which may contribute to changes in gene expression. These findings of CaMKII-dependent gene regulation during cardiac remodeling processes suggest novel strategies for CaMKII-dependent “transcriptional or epigenetic therapies” to control cardiac gene expression and function. Manipulation of CaMKII-dependent signaling pathways in the settings of pathological cardiac growth, remodeling, and heart failure represents an auspicious therapeutic approach. PMID:24659967

  7. Regulator of calcineurin 1 mediates pathological vascular wall remodeling

    PubMed Central

    Esteban, Vanesa; Méndez-Barbero, Nerea; Jesús Jiménez-Borreguero, Luis; Roqué, Mercè; Novensá, Laura; Belén García-Redondo, Ana; Salaices, Mercedes; Vila, Luis; Arbonés, María L.

    2011-01-01

    Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. PMID:21930771

  8. Role of microRNAs in Vascular Remodeling

    PubMed Central

    Fang, Y.-C.; Yeh, C.-H.

    2015-01-01

    Besides being involved in the gradual formation of blood vessels during embryonic development, vascular remodeling also contributes to the progression of various cardiovascular diseases, such as; myocardial infarction, heart failure, atherosclerosis, pulmonary artery hypertension, restenosis, aneurysm, etc. The integrated mechanisms; proliferation of medial smooth muscle cell, dysregulation of intimal endothelial cell, activation of adventitial fibroblast, inflammation of macrophage, and the participation of extracellular matrix proteins are important factors in vascular remodeling. In the recent studies, microRNAs (miRs) have been shown to be expressed in all of these cell-types and play important roles in the mechanisms of vascular remodeling. Therefore, some miRs may be involved in prevention and others in the aggravation of the vascular lesions. miRs are small, endogenous, conserved, single-stranded, non-coding RNAs; which degrade target RNAs or inhibit translation post-transcriptionally. In this paper, we reviewed the function and mechanisms of miRs, which are highly expressed in various cells types, especially endothelial and smooth muscle cells, which are closely involved in the process of vascular remodeling. We also assess the functions of these miRs in the hope that they may provide new possibilities of diagnosis and treatment choices for the related diseases. PMID:26391551

  9. "New Professionalism," Workforce Remodeling and the Restructuring of Teachers' Work

    ERIC Educational Resources Information Center

    Stevenson, Howard; Carter, Bob; Passy, Rowena

    2007-01-01

    Since its election in 1997 the Labour government's policy has sought to promote a "new professionalism" amongst teachers. First mooted at the time when new performance management arrangements were introduced, the discourse of new professionalism has now become closely associated with the "workforce remodeling" agenda in which…

  10. Drosophila Brahma complex remodels nucleosome organizations in multiple aspects.

    PubMed

    Shi, Jiejun; Zheng, Meizhu; Ye, Youqiong; Li, Min; Chen, Xiaolong; Hu, Xinjie; Sun, Jin; Zhang, Xiaobai; Jiang, Cizhong

    2014-09-01

    ATP-dependent chromatin remodeling complexes regulate nucleosome organizations. In Drosophila, gene Brm encodes the core Brahma complex, the ATPase subunit of SWI/SNF class of chromatin remodelers. Its role in modulating the nucleosome landscape in vivo is unclear. In this study, we knocked down Brm in Drosophila third instar larvae to explore the changes in nucleosome profiles and global gene transcription. The results show that Brm knockdown leads to nucleosome occupancy changes throughout the entire genome with a bias in occupancy decrease. In contrast, the knockdown has limited impacts on nucleosome position shift. The knockdown also alters another important physical property of nucleosome positioning, fuzziness. Nucleosome position shift, gain or loss and fuzziness changes are all enriched in promoter regions. Nucleosome arrays around the 5' ends of genes are reorganized in five patterns as a result of Brm knockdown. Intriguingly, the concomitant changes in the genes adjacent to the Brahma-dependent remodeling regions have important roles in development and morphogenesis. Further analyses reveal abundance of AT-rich motifs for transcription factors in the remodeling regions.

  11. Remodelling the School Workforce in England: A Study in Tyranny

    ERIC Educational Resources Information Center

    Gunter, Helen

    2007-01-01

    Remodelling the school workforce is being rolled out across England with official purposes articulated around work-life balance, improving standards, and the need to efficiently and effectively deploy staffing. This is not new and can be related to ongoing policy thrusts designed to restructure the state as manifest in the haphazard construction…

  12. Analgesic Drugs Alter Connective Tissue Remodeling and Mechanical Properties

    PubMed Central

    Carroll, Chad C.

    2015-01-01

    Exercising individuals commonly consume analgesics but these medications alter tendon and skeletal muscle connective tissue properties, possibly limiting a person from realizing the full benefits of exercise training. I detail the novel hypothesis that analgesic medications alter connective tissue structure and mechanical properties by modifying fibroblast production of growth factors and matrix enzymes, which are responsible for extracellular matrix remodeling. PMID:26509485

  13. Protein-Remodeling Factors As Potential Therapeutics for Neurodegenerative Disease

    PubMed Central

    Jackrel, Meredith E.; Shorter, James

    2017-01-01

    Protein misfolding is implicated in numerous neurodegenerative disorders including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease. A unifying feature of patients with these disorders is the accumulation of deposits comprised of misfolded protein. Aberrant protein folding can cause toxicity through a loss or gain of protein function, or both. An intriguing therapeutic approach to counter these disorders is the application of protein-remodeling factors to resolve these misfolded conformers and return the proteins to their native fold and function. Here, we describe the application of protein-remodeling factors to alleviate protein misfolding in neurodegenerative disease. We focus on Hsp104, Hsp110/Hsp70/Hsp40, NMNAT, and HtrA1, which can prevent and reverse protein aggregation. While many of these protein-remodeling systems are highly promising, their activity can be limited. Thus, engineering protein-remodeling factors to enhance their activity could be therapeutically valuable. Indeed, engineered Hsp104 variants suppress neurodegeneration in animal models, which opens the way to novel therapeutics and mechanistic probes to help understand neurodegenerative disease. PMID:28293166

  14. Analgesic Drugs Alter Connective Tissue Remodeling and Mechanical Properties.

    PubMed

    Carroll, Chad C

    2016-01-01

    Exercising individuals commonly consume analgesics, but these medications alter tendon and skeletal muscle connective tissue properties, possibly limiting a person from realizing the full benefits of exercise training. I detail the novel hypothesis that analgesic medications alter connective tissue structure and mechanical properties by modifying fibroblast production of growth factors and matrix enzymes, which are responsible for extracellular matrix remodeling.

  15. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage.

    PubMed

    Rohner, Nathan Andrew; McClain, Jacob; Tuell, Sara Lydia; Warner, Alex; Smith, Blair; Yun, Youngho; Mohan, Abhinav; Sushnitha, Manuela; Thomas, Susan Napier

    2015-11-01

    Tissue remodeling is a characteristic of many solid tumor malignancies including melanoma. By virtue of tumor lymphatic transport, remodeling pathways active within the local tumor microenvironment have the potential to be operational within lymph nodes (LNs) draining the tumor interstitium. Here, we show that lymphatic drainage from murine B16 melanomas in syngeneic, immune-competent C57Bl/6 mice is associated with LN enlargement as well as nonuniform increases in bulk tissue elasticity and viscoelasticity, as measured by the response of whole LNs to compression. These remodeling responses, which quickly manifest in tumor-draining lymph nodes (TDLNs) after tumor inoculation and before apparent metastasis, were accompanied by changes in matrix composition, including up to 3-fold increases in the abundance of soluble collagen and hyaluronic acid. Intranodal pressures were also significantly increased in TDLNs (+1 cmH2O) relative to both non-tumor-draining LNs (-1 cmH2O) and LNs from naive animals (-1 to 2 cmH2O). These data suggest that the reorganization of matrix structure, composition, and fluid microenvironment within LNs associated with tumor lymphatic drainage parallels remodeling seen in primary malignancies and has the potential to regulate the adhesion, proliferation, and signaling function of LN-resident cells involved in directing melanoma disease progression.

  16. Systems analysis of bone remodelling as a homeostatic regulator.

    PubMed

    Chen, A; Hamamura, K; Zhang, P; Chen, Y; Yokota, H

    2010-01-01

    Bone remodelling in adult skeleton is a process of maintaining bone mass through combined activities of bone forming osteoblasts and bone resorbing osteoclasts. Focusing on a molecular pathway mediated by osteoprotegerin, the authors derived a mathematical formulation for molecular interactions and cellular behaviours. The authors also treated this remodelling process as a homeostatic regulator in a framework of linear quadratic problems. A primary question was: does a solution of a matrix Riccati equation provide a guideline for therapeutic interventions for prevention of bone loss? In order to elucidate the systems dynamics, the authors analysed the perturbed set of equations around a stable equilibrium state together with the original equations. The results demonstrate that a homeostatic regulator with the selected control variables effectively reduces bone degradation activities and restore a physiological remodelling process. To partially validate efficacy of the described intervention strategy, biological experiments were conducted with an osteoblast cell line using one of the control variables, salubrinal (chemical agent). The authors observed that administration of salubrinal activated mRNA levels of transcription factors and an osteogenic marker gene as well as enhancement of mineralisation. Taken together, the current study supports a potential usage of control theories in active regulation of bone remodelling homeostasis.

  17. Chd5 orchestrates chromatin remodeling during sperm development

    PubMed Central

    Li, Wangzhi; Wu, Jie; Kim, Sang-Yong; Zhao, Ming; Hearn, Stephen A.; Zhang, Michael Q.; Meistrich, Marvin L.

    2014-01-01

    One of the most remarkable chromatin remodeling processes occurs during spermiogenesis, the post-meiotic phase of sperm development during which histones are replaced with sperm-specific protamines to repackage the genome into the highly compact chromatin structure of mature sperm. Here we identify Chromodomain helicase DNA binding protein 5 (Chd5) as a master regulator of the histone-to-protamine chromatin remodeling process. Chd5 deficiency leads to defective sperm chromatin compaction and male infertility in mice, mirroring the observation of low CHD5 expression in testes of infertile men. Chd5 orchestrates a cascade of molecular events required for histone removal and replacement, including histone 4 (H4) hyperacetylation, histone variant expression, nucleosome eviction, and DNA damage repair. Chd5 deficiency also perturbs expression of transition proteins (Tnp1/Tnp2) and protamines (Prm1/2). These findings define Chd5 as a multi-faceted mediator of histone-to-protamine replacement and depict the cascade of molecular events underlying chromatin remodeling during this process of extensive chromatin remodeling. PMID:24818823

  18. What Should You Ask Your Doctor About Small Intestine Adenocarcinoma?

    MedlinePlus

    ... What Should You Ask Your Doctor About Small Intestine Adenocarcinoma? It’s important to have honest, open discussions ... Doctor About Small Intestine Adenocarcinoma? More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  19. Characterization of moose intestinal glycosphingolipids.

    PubMed

    Johansson, Miralda Madar; Dedic, Benjamin; Lundholm, Klara; Branzell, Filip Berner; Barone, Angela; Benktander, John; Teneberg, Susann

    2015-08-01

    As a part of a systematic investigation of the species-specific expression of glycosphingolipids, acid and non-acid glycosphingolipids were isolated from three small intestines and one large intestine of the moose (Alces alces). The glycosphingolipids were characterized by binding of monoclonal antibodies, lectins and bacteria in chromatogram binding assays, and by mass spectrometry. The non-acid fractions were complex mixtures, and all had glycosphingolipids belonging to the lacto- and neolactoseries (lactotriaosylceramide, lactotetraosylceramide, neolactotetraosylceramide, Galα3-Le(x) hexaosylceramide, and lacto-neolactohexaosylceramide), globo-series (globotriaosylceramide and globotetraosylceramide), and isogloboseries (isoglobotriaosylceramide). Penta- and heptaglycosylceramides with terminal Galili determinants were also characterized. Furthermore, glycosphingolipids with terminal blood group O determinants (H triaosylceramide, H type 2 pentaosylceramide, H type 1 penta- and heptaosylceramide) were characterized in two of the moose small intestines, and in the one large intestine, while the third small intestine had glycosphingolipids with terminal blood group A determinants (A tetraosylceramide, A type 1 hexa- and octaosylceramide, A dodecaosylceramide). The acid glycosphingolipid fractions of moose small and large intestine contained sulfatide, and the gangliosides GM3, GD3, GD1a, GD1b, and also NeuGc and NeuAc variants of the Sd(a) ganglioside and the sialyl-globopenta/SSEA-4 ganglioside. In humans, the NeuAc-globopenta/SSEA-4 ganglioside is a marker of embryonic and adult stem cells, and is also expressed in several human cancers. This is the first time sialyl-globopentaosylceramide/SSEA-4 has been characterized in a fully differentiated normal tissue, and also the first time NeuGc-globopentaosylceramide has been characterized.

  20. Regulation of intestinal blood flow.

    PubMed

    Matheson, P J; Wilson, M A; Garrison, R N

    2000-09-01

    The gastrointestinal system anatomically is positioned to perform two distinct functions: to digest and absorb ingested nutrients and to sustain barrier function to prevent transepithelial migration of bacteria and antigens. Alterations in these basic functions contribute to a variety of clinical scenarios. These primary functions intrinsically require splanchnic blood flow at both the macrovascular and microvascular levels of perfusion. Therefore, a greater understanding of the mechanisms that regulate intestinal vascular perfusion in the normal state and during pathophysiological conditions would be beneficial. The purpose of this review is to summarize the current understanding regarding the regulatory mechanisms of intestinal blood flow in fasted and fed conditions and during pathological stress.

  1. The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding

    PubMed Central

    Marchiando, Amanda M.; Shen, Le; Graham, W. Vallen; Edelblum, Karen L.; Duckworth, Carrie A.; Guan, Yanfang; Montrose, Marshall H.; Turner, Jerrold R.; Watson, Alastair J.M.

    2011-01-01

    BACKGROUND & AIMS Tumor necrosis factor (TNF) increases intestinal epithelial cell shedding and apoptosis, potentially challenging the barrier between the gastrointestinal lumen and internal tissues. We investigated the mechanism of tight junction remodeling and barrier maintenance, as well as the roles of cytoskeletal regulatory molecules during TNF-induced shedding. METHODS We studied wild-type and transgenic mice that express the fluorescent-tagged proteins enhanced green fluorescent protein–occludin or monomeric red fluorescent protein1–ZO-1. After injection of high doses of TNF (7.5µg, i.p.), laparotomies were performed and segments of small intestine were opened to visualize the mucosa by video confocal microscopy. Pharmacologic inhibitors and knockout mice were used to determine the roles of caspase activation, actomyosin, and microtubule remodeling and membrane trafficking in epithelial shedding. RESULTS Changes detected included redistribution of the tight junction proteins ZO-1 and occluding to lateral membranes of shedding cells. These proteins ultimately formed a funnel around the shedding cell that defined the site of barrier preservation. Claudins, E-cadherin, F-actin, myosin II, Rho-associated kinase (ROCK), and myosin light chain kinase (MLCK) were also recruited to lateral membranes. Caspase activity, myosin motor activity, and microtubules were required to initiate shedding, whereas completion of the process required microfilament remodeling and ROCK, MLCK, and dynamin II activities. CONCLUSIONS Maintenance of the epithelial barrier during TNF-induced cell shedding is a complex process that involves integration of microtubules, microfilaments, and membrane traffic to remove apoptotic cells. This process is accompanied by redistribution of apical junctional complex proteins to form intercellular barriers between lateral membranes and maintain mucosal function. PMID:21237166

  2. Galectin-3 and post-myocardial infarction cardiac remodeling.

    PubMed

    Meijers, Wouter C; van der Velde, A Rogier; Pascual-Figal, Domingo A; de Boer, Rudolf A

    2015-09-15

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in order to preserve cardiac function. A hallmark herein is fibrosis formation, both in the early and late phase following acute myocardial infarction. Galectin-3, a β-galactoside-binding lectin, which is a shared factor in fibrosis formation in multiple organs, has an established role in cardiac fibrosis in the setting of pressure overload, neuro-endocrine activation and hypertension, but its role in post- myocardial infarction remodeling has received less attention. However, accumulative experimental studies have shown that myocardial galectin-3 expression is upregulated after myocardial infarction, both on mRNA and protein level. This already occurs shortly after myocardial infarction in the infarcted and border zone area, and also at a later stage in the spared myocardium, contributing to tissue repair and fibrosis. This is associated with typical aspects of fibrosis formation, such as apposition of matricellular proteins and increased factors of collagen turnover. Interestingly, myocardial fibrosis in experimental post-myocardial infarction cardiac remodeling could be attenuated by galectin-3 inhibition. In clinical studies, circulating galectin-3 levels have been shown to identify patients at risk for new-onset heart failure and atrial fibrillation. Circulating galectin-3 levels also predict progressive left ventricular dilatation after myocardial infarction. From literature we conclude that galectin-3 is an active player in cardiac remodeling after myocardial infarction. Future studies should focus on the dynamics of galectin-3 activation after myocardial infarction, and study the possibilities to target galectin-3.

  3. Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology.

    PubMed

    Zachos, Nicholas C; Kovbasnjuk, Olga; Foulke-Abel, Jennifer; In, Julie; Blutt, Sarah E; de Jonge, Hugo R; Estes, Mary K; Donowitz, Mark

    2016-02-19

    Identification of Lgr5 as the intestinal stem cell marker as well as the growth factors necessary to replicate adult intestinal stem cell division has led to the establishment of the methods to generate "indefinite" ex vivo primary intestinal epithelial cultures, termed "mini-intestines." Primary cultures developed from isolated intestinal crypts or stem cells (termed enteroids/colonoids) and from inducible pluripotent stem cells (termed intestinal organoids) are being applied to study human intestinal physiology and pathophysiology with great expectations for translational applications, including regenerative medicine. Here we discuss the physiologic properties of these cultures, their current use in understanding diarrhea-causing host-pathogen interactions, and potential future applications.

  4. Intestinal disaccharidase activities in the chick

    PubMed Central

    Siddons, R. C.

    1969-01-01

    1. Disaccharidase activities of the small and large intestines of the chick were studied. 2. Homogenates of the small intestine readily hydrolysed maltose, sucrose and palatinose (6-O-α-d-glucopyranosyl-d-fructose), hydrolysed lactose slowly and did not hydrolyse trehalose and cellobiose. 3. Within the small intestine the disaccharidases were located mainly in the intestinal wall; the activity in the contents accounted for less than 5% of the total activity. 4. The disaccharidases were non-uniformly distributed along the small intestine, the activities being greatest in the middle section. 5. The disaccharidase activities increased with age between 1 and 43 days. 6. Homogenates of the large intestine and contents readily hydrolysed maltose, sucrose, palatinose and lactose and hydrolysed cellobiose and trehalose slowly. 7. The large-intestinal disaccharidases were located mainly in the contents. 8. Similar Km and pH optimum values were found for the maltase, sucrase and palatinase activities of the large and small intestines. 9. The lactase activity of the large intestine was markedly affected by diet and had different Km and pH values from the small intestinal lactase. 10. Low activities of intestinal disaccharidase were found in 12-day-old embryos and marked increases in the intestinal disaccharidases of the developing embryo occurred 2–3 days before hatching. PMID:5774506

  5. Remodeling of the residual gastric mucosa after roux-en-y gastric bypass or vertical sleeve gastrectomy in diet-induced obese rats.

    PubMed

    Arapis, Konstantinos; Cavin, Jean Baptiste; Gillard, Laura; Cluzeaud, Françoise; Lettéron, Philippe; Ducroc, Robert; Le Beyec, Johanne; Hourseau, Muriel; Couvelard, Anne; Marmuse, Jean-Pierre; Le Gall, Maude; Bado, André

    2015-01-01

    Whereas the remodeling of intestinal mucosa after bariatric surgeries has been the matter of numerous studies to our knowledge, very few reported on the remodeling of the residual gastric mucosa. In this study, we analyzed remodeling of gastric mucosa after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in rats. Diet-induced obese rats were subjected to RYGB, VSG or sham surgical procedures. All animals were assessed for food intake, body-weight, fasting blood, metabolites and hormones profiling, as well as insulin and glucose tolerance tests before and up to 5 weeks post-surgery. Remodeling of gastric tissues was analyzed by routine histology and immunohistochemistry studies, and qRT-PCR analyses of ghrelin and gastrin mRNA levels. In obese rats with impaired glucose tolerance, VSG and RYGB caused substantial weight loss and rats greatly improved their oral glucose tolerance. The remaining gastric mucosa after VSG and gastric pouch (GP) after RYGB revealed a hyperplasia of the mucous neck cells that displayed a strong immunoreactivity for parietal cell H+/K+-ATPase. Ghrelin mRNA levels were reduced by 2-fold in remaining fundic mucosa after VSG and 10-fold in GP after RYGB. In the antrum, gastrin mRNA levels were reduced after VSG in line with the reduced number of gastrin positive cells. This study reports novel and important observations dealing with the remaining gastric mucosa after RYGB and VSG. The data demonstrate, for the first time, a hyperplasia of the mucous neck cells, a transit cell population of the stomach bearing differentiating capacities into zymogenic and peptic cells.

  6. [Chronic intestinal pseudo-obstruction].

    PubMed

    Joly, Francisca; Amiot, Aurélien; Coffin, Benoît; Lavergne-Slove, Anne; Messing, Bernard; Bouhnik, Yoram

    2006-01-01

    Chronic intestinal pseudo-obstruction (CIPO) is a disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Pseudo-obstruction is an uncommon condition and can result from primary (40%) or secondary (60%) causes. The most common symptoms are nausea, vomiting, abdominal distension, abdominal pain and constipation or diarrhea. These symptoms are usually present many years before CIPO diagnosis. They can lead to severe electrolyte disorders and malnutrition. Principles for management of patients with CIPO are: to establish a correct clinical diagnosis in excluding mechanical obstruction; to perform a symptomatic and physiologic assessment of the gastrointestinal tract involved; to look for extra-intestinal manifestations, especially for myopathy and neuropathy; to discuss in some cases a surgery for full-thickness intestinal biopsies, and/or a neuromuscular biopsy in case of mitochondrial cytopathy suspicion. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. Treatment of CIPO includes prokinetic agents which may help to reduce gastrointestinal symptoms Courses of antibiotics may be needed in patients with symptoms suggestive of bacterial overgrowth. When necessary, enteral nutrition is preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Intestinal transplantation can be discussed in selected patients.

  7. Intestinal perfusion monitoring using photoplethysmography

    NASA Astrophysics Data System (ADS)

    Akl, Tony J.; Wilson, Mark A.; Ericson, M. Nance; Coté, Gerard L.

    2013-08-01

    In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.

  8. Circadian Disorganization Alters Intestinal Microbiota

    PubMed Central

    Voigt, Robin M.; Forsyth, Christopher B.; Green, Stefan J.; Mutlu, Ece; Engen, Phillip; Vitaterna, Martha H.; Turek, Fred W.; Keshavarzian, Ali

    2014-01-01

    Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases. PMID:24848969

  9. [Chronic intestinal pseudo-obstruction].

    PubMed

    Ohkubo, Hidenori; Inoh, Yumi; Fuyuki, Akiko; Nakajima, Atsushi

    2015-05-01

    Chronic intestinal pseudo-obstruction(CIPO) is a rare severe digestive disease in which clinical symptoms of intestinal obstruction appear without any mechanical cause. Pathophysiologically, CIPO shows ineffective intestinal propulsion due to an impairment of intestinal smooth muscle, enteric nervous system, and interstitial cells of Cajal(ICC). Sustained increased intra-bowel pressure often causes small intestinal malabsorption and bacterial translocation, and leads to malnutrition and blood stream infection (sepsis). Key points of the medical approach for CIPO are to improve nutritional status and reduce abdominal symptoms. Dietary cure and defecation control are the main options in mild cases, whereas home-parenteral-nutrition(HPN) and decompression therapy are often needed in severe cases. Stimulant laxatives, prokinetics and herbal medicine are usually used but often in fail. Percutaneous endoscopic gastrojejunostomy(PEG-J) tube may be burdenless compared to conventional ileus tube. Most important points in the management of this disease are to make a correct diagnosis as early as possible and avoid unnecessary surgery. However, no clear diagnostic criteria have been established so far. Manometry, scintigraphy, and full-thickness biopsy are the major examination for the CIPO diagnosis in the Western countries; however these specialized examinations are not popular in Japan. Therefore the Research Group(chief investigator, Atsushi Nakajima) proposed Japanese diagnostic criteria in 2009 to facilitate the diagnosis of this rare disease by the general physician. In 2013, we have reported that cine-MRI is a non-invasive diagnostic method for CIPO. Although further data are eagerly awaited, it can become a promising diagnostic tool in CIPO patients. Furthermore the Japanese criteria have been revised, and in 2014, the comprehensive criteria from a child to an adult have been devised. In 2015, CIPO is newly certified as Specified Rare and Intractable Disease which is

  10. SWI/SNF-dependent chromatin remodeling of RNR3 requires TAFIIs and the general transcription machinery

    PubMed Central

    Sharma, Vishva Mitra; Li, Bing; Reese, Joseph C.

    2003-01-01

    Gene expression requires the recruitment of chromatin remodeling activities and general transcription factors (GTFs) to promoters. Whereas the role of activators in recruiting chromatin remodeling activities has been clearly demonstrated, the contributions of the transcription machinery have not been firmly established. Here we demonstrate that the remodeling of the RNR3 promoter requires a number of GTFs, mediator and RNA polymerase II. We also show that remodeling is dependent upon the SWI/SNF complex, and that TFIID and RNA polymerase II are required for its recruitment to the promoter. In contrast, Gcn5p-dependent histone acetylation occurs independently of TFIID and RNA polymerase II function, and we provide evidence that acetylation increases the extent of nucleosome remodeling, but is not required for SWI/SNF recruitment. Thus, the general transcription machinery can contribute to nucleosome remodeling by mediating the association of SWI/SNF with promoters, thereby revealing a novel pathway for the recruitment of chromatin remodeling activities. PMID:12600943

  11. SUN4 is essential for nuclear remodeling during mammalian spermiogenesis.

    PubMed

    Calvi, Alessandra; Wong, Arnette Shi Wei; Wright, Graham; Wong, Esther Sook Miin; Loo, Tsui Han; Stewart, Colin L; Burke, Brian

    2015-11-15

    One of the more dramatic examples of cellular reorganization occurs during spermiogenesis in which a roughly spherical spermatid is transformed into a mature sperm cell. A highlight of this process involves nuclear remodeling whereby the round spermatid nucleus is sculpted into an elongated and polar structure. This transformation in nuclear architecture features chromatin condensation, changes in the composition and organization of the nuclear lamina and redistribution and elimination of nuclear pore complexes. The manchette, a cytoplasmic microtubule-based structure is thought to play a crucial role in the remodeling process. Here we show that SUN4, a spermatid nuclear membrane protein has an essential function in coupling the manchette to the nuclear periphery. In the absence of SUN4, manchette microtubules appear highly disorganized and the nucleus itself fails to elongate. Consequently, mice deficient in SUN4 display globozoospermia with associated infertility.

  12. Ventricular remodeling in heart failure: the role of myocardial collagen.

    PubMed

    Janicki, J S; Brower, G L; Henegar, J R; Wang, L

    1995-01-01

    Collagen which is present in the myocardium in relatively small amounts is the most abundant structural protein of the connective tissue network. Its structural organization consists of a complex weave of collagen fibers that surrounds and interconnects myocytes, groups of myocytes, muscle fibers and muscle bundles. The conformation of interstitial fibrillar collagen makes it highly resistant to degradation by all proteinases other than specific collagenases. In hearts with myocardial damage secondary to myocardial infarction, chronic ischemia, inflammation, or cardiomyopathy, a complex sequence of compensatory events occur that eventually result in an adverse left ventricular remodeling. This continual state of remodeling is characterized by persistent collagenase activity, fibrillar collagen degradation, and progressive myocyte loss. The net effect is a shift in the balance between collagen synthesis and degradation which leads to an inadequate fibrillar collagen matrix, progressive ventricular dilatation and sphericalization with wall thinning and eventual congestive heart failure.

  13. Physical principles of membrane remodelling during cell mechanoadaptation

    PubMed Central

    Kosmalska, Anita Joanna; Casares, Laura; Elosegui-Artola, Alberto; Thottacherry, Joseph Jose; Moreno-Vicente, Roberto; González-Tarragó, Víctor; del Pozo, Miguel Ángel; Mayor, Satyajit; Arroyo, Marino; Navajas, Daniel; Trepat, Xavier; Gauthier, Nils C.; Roca-Cusachs, Pere

    2015-01-01

    Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope—the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, before any active remodelling and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell–substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes. PMID:26073653

  14. The solid state environment orchestrates embryonic development and tissue remodeling

    NASA Technical Reports Server (NTRS)

    Damsky, C. H.; Moursi, A.; Zhou, Y.; Fisher, S. J.; Globus, R. K.

    1997-01-01

    Cell interactions with extracellular matrix and with other cells play critical roles in morphogenesis during development and in tissue homeostasis and remodeling throughout life. Extracellular matrix is information-rich, not only because it is comprised of multifunctional structural ligands for cell surface adhesion receptors, but also because it contains peptide signaling factors, and proteinases and their inhibitors. The functions of these groups of molecules are extensively interrelated. In this review, three primary cell culture models are described that focus on adhesion receptors and their roles in complex aspects of morphogenesis and remodeling: the regulation of proteinase expression by fibronectin and integrins in synovial fibroblasts; the regulation of osteoblast differentiation and survival by fibronectin, and the regulation of trophoblast differentiation and invasion by integrins, cadherins and immunoglobulin family adhesion receptors.

  15. Rapid formation and remodeling of postsynaptic densities in developing dendrites.

    PubMed

    Marrs, G S; Green, S H; Dailey, M E

    2001-10-01

    The dynamics of postsynaptic density (PSD) formation and remodeling were investigated in live developing hippocampal tissue slices. Time lapse imaging of transfected neurons expressing GFP-tagged PSD95, a prominent PSD protein, revealed that up to 40% of PSDs in developing dendrites are structurally dynamic; they rapidly (<15 min) appear or disappear, but also grow, shrink and move within shafts and spines. New spines containing PSDs were formed by conversion of dynamic filopodia-like spine precursors in which PSDs appeared de novo, or by direct extension of spines or spine precursors carrying preformed PSDs from the shaft. PSDs are therefore highly dynamic structures that can undergo rapid structural alteration within dendrite shafts, spines and spine precursors, permitting rapid formation and remodeling of synaptic connections in developing CNS tissues.

  16. Transcriptional regulation of bone and joint remodeling by NFAT

    PubMed Central

    Sitara, Despina; Aliprantis, Antonios O.

    2010-01-01

    Summary Osteoporosis and arthritis are highly prevalent diseases and a significant cause of morbidity and mortality worldwide. These diseases result from aberrant tissue remodeling leading to weak, fracture-prone bones or painful, dysfunctional joints. The nuclear factor of activated T cells (NFAT) transcription factor family controls diverse biologic processes in vertebrates. Here, we review the scientific evidence that links NFAT-regulated gene transcription to bone and joint pathology. A particular emphasis is placed on the role of NFATs in bone resorption and formation by osteoclasts and osteoblasts, respectively. In addition, emerging data that connect NFATs with cartilage biology, angiogenesis, nociception, and neurogenic inflammation are explored. The goal of this article is to highlight the importance of tissue remodeling in musculoskeletal disease and situate NFAT-driven cellular responses within this context to inspire future research endeavors. PMID:20193006

  17. ATP dependent chromatin remodeling enzymes in embryonic stem cells.

    PubMed

    Saladi, Srinivas Vinod; de la Serna, Ivana L

    2010-03-01

    Embryonic stem (ES) cells are pluripotent cells that can self renew or be induced to differentiate into multiple cell lineages, and thus have the potential to be utilized in regenerative medicine. Key pluripotency specific factors (Oct 4/Sox2/Nanog/Klf4) maintain the pluripotent state by activating expression of pluripotency specific genes and by inhibiting the expression of developmental regulators. Pluripotent ES cells are distinguished from differentiated cells by a specialized chromatin state that is required to epigenetically regulate the ES cell phenotype. Recent studies show that in addition to pluripotency specific factors, chromatin remodeling enzymes play an important role in regulating ES cell chromatin and the capacity to self-renew and to differentiate. Here we review recent studies that delineate the role of ATP dependent chromatin remodeling enzymes in regulating ES cell chromatin structure.

  18. Rapid remodeling of airway vascular architecture at birth.

    PubMed

    Ni, Amy; Lashnits, Erin; Yao, Li-Chin; Baluk, Peter; McDonald, Donald M

    2010-09-01

    Recent advances have documented the development of lung vasculature before and after birth, but less is known of the growth and maturation of airway vasculature. We sought to determine whether airway vasculature changes during the perinatal period and when the typical adult pattern develops. On embryonic day 16.5 mouse tracheas had a primitive vascular plexus unlike the adult airway vasculature, but instead resembling the yolk sac vasculature. Soon after birth (P0), the primitive vascular plexus underwent abrupt and extensive remodeling. Blood vessels overlying tracheal cartilage rings regressed from P1 to P3 but regrew from P4 to P7 to form the hierarchical, segmented, ladder-like adult pattern. Hypoxia and HIF-1α were present in tracheal epithelium over vessels that survived but not where they regressed. These findings reveal the plasticity of airway vasculature after birth and show that these vessels can be used to elucidate factors that promote postnatal vascular remodeling and maturation.

  19. Fat body remodeling and homeostasis control in Drosophila.

    PubMed

    Zheng, Huimei; Yang, Xiaohang; Xi, Yongmei

    2016-12-15

    Remarkable advances have been made in recent years in our understanding of the Drosophila fat body and its functions in energy storage, immune response and nutrient sensing. The fat body interplays with other tissues to respond to the physiological needs of the body's growth and coordinates various metabolic processes at different developmental stages and under different environmental conditions. The identification of various conserved genetic functions and signaling pathways relating to the Drosophila fat body may provide clues to lipometabolic disease and other aspects of tissue remodeling in humans. Here, we discuss recent insights into how regulation of fat body remodeling contributes to hemostasis with a special focus on how signaling networks and internal physiological states shape different aspects of the lipid metabolism in Drosophila.

  20. The role of microRNAs in bone remodeling

    PubMed Central

    Jing, Dian; Hao, Jin; Shen, Yu; Tang, Ge; Li, Mei-Le; Huang, Shi-Hu; Zhao, Zhi-He

    2015-01-01

    Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that microRNAs (miRNAs), known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression, and growing numbers of novel miRNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis, and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of miRNAs in regulating bone remodeling as well as novel applications for miRNAs in biomaterials for therapeutic purposes. PMID:26208037

  1. Structural remodeling of astrocytes in the injured CNS.

    PubMed

    Sun, Daniel; Jakobs, Tatjana C

    2012-12-01

    Astrocytes respond to all forms of CNS insult and disease by becoming reactive, a nonspecific but highly characteristic response that involves various morphological and molecular changes. Probably the most recognized aspect of reactive astrocytes is the formation of a glial scar that impedes axon regeneration. Although the reactive phenotype was first suggested more than 100 years ago based on morphological changes, the remodeling process is not well understood. We know little about the actual structure of a reactive astrocyte, how an astrocyte remodels during the progression of an insult, and how populations of these cells reorganize to form the glial scar. New methods of labeling astrocytes, along with transgenic mice, allow the complete morphology of reactive astrocytes to be visualized. Recent studies show that reactivity can induce a remarkable change in the shape of a single astrocyte, that not all astrocytes react in the same way, and that there is plasticity in the reactive response.

  2. Probabilistic Study of Bone Remodeling Using Finite Element Analysis

    NASA Astrophysics Data System (ADS)

    Werner, C.; Gorla, R. S. R.

    2013-08-01

    The dynamic bone remodeling process is a computationally challenging research area that struggles to understand the actual mechanisms. It has been observed that a mechanical stimulus in the bone greatly affects the remodeling process. A 3D finite element model of a femur is created and a probabilistic analysis is performed on the model. The probabilistic analysis measures the sensitivities of various parameters related to the material properties, geometric properties, and the three load cases defined as Single Leg Stance, Abduction, and Adduction. The sensitivity of each parameter is based on the calculated maximum mechanical stimulus and analyzed at various values of probabilities ranging from 0.001 to 0.999. The analysis showed that the parameters associated with the Single Leg Stance load case had the highest sensitivity with a probability of 0.99 and the angle of the force applied to the joint of the proximal femur had the overall highest sensitivity

  3. Engineered Split-TET2 Enzyme for Inducible Epigenetic Remodeling

    PubMed Central

    2017-01-01

    The Ten-eleven translocation (TET) family of 5-methylcytosine (5mC) dioxygenases catalyze the conversion of 5mC into 5-hydroxymethylcytosine (5hmC) and further oxidized species to promote active DNA demethylation. Here we engineered a split-TET2 enzyme to enable temporal control of 5mC oxidation and subsequent remodeling of epigenetic states in mammalian cells. We further demonstrate the use of this chemically inducible system to dissect the correlation between DNA hydroxymethylation and chromatin accessibility in the mammalian genome. This chemical-inducible epigenome remodeling tool will find broad use in interrogating cellular systems without altering the genetic code, as well as in probing the epigenotype–phenotype relations in various biological systems. PMID:28294608

  4. Notch signal integration in the vasculature during remodeling

    PubMed Central

    Rostama, Bahman; Peterson, Sarah M.; Vary, Calvin P. H.; Liaw, Lucy

    2014-01-01

    Notch signaling plays many important roles in homeostasis and remodeling in the vessel wall, and serves a critical role in the communication between endothelial cells and smooth muscle cells. Within blood vessels, Notch signaling integrates with multiple pathways by mechanisms including direct protein-protein interaction, cooperative or synergistic regulation of signal cascades, and co-regulation of transcriptional targets. After establishment of the mature blood vessel, the spectrum and intensity of Notch signaling changes during phases of active remodeling or disease progression. These changes can be mediated by regulation via microRNAs and protein stability or signaling, and corresponding changes in complementary signaling pathways. Notch also affects endothelial cells on a systems level by regulating key metabolic components. This review will outline the most recent findings of Notch activity in blood vessels, with a focus on how Notch signals integrate with other molecular signaling pathways controlling vascular phenotype. PMID:25464152

  5. Compensatory Effect between Aortic Stiffening and Remodelling during Ageing

    PubMed Central

    Guala, Andrea; Camporeale, Carlo; Ridolfi, Luca

    2015-01-01

    The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases. PMID:26426360

  6. [Intestinal-brain axis. Neuronal and immune-inflammatory mechanisms of brain and intestine pathology].

    PubMed

    Bondarenko, V M; Riabichenko, E V

    2013-01-01

    Mutually directed connections between intestine and brain are implemented by endocrine, neural and immune systems and nonspecific natural immunity. Intestine micro flora as an active participant of intestine-brain axis not only influences intestine functions but also stimulates the development of CNS in perinatal period and interacts with higher nervous centers causing depression and cognitive disorders in pathology. A special role belongs to intestine microglia. Apart from mechanic (protective) and trophic functions for intestine neurons, glia implements neurotransmitter, immunologic, barrier and motoric functions in the intestine. An interconnection between intestine barrier function and hematoencephalic barrier regulation exists. Chronic endotoxinemia as a result of intestine barrier dysfunction forms sustained inflammation state in periventricular zone of the brain with consequent destabilization of hematoencephalic barriers and spread oF inflammation to other parts of the brain resulting in neurodegradation development.

  7. Remodeling dynamics in the alveolar process in skeletally mature dogs.

    PubMed

    Huja, Sarandeep S; Fernandez, Soledad A; Hill, Kara J; Li, Yan

    2006-12-01

    Bone turnover rates can be altered by metabolic and mechanical demands. Due to the difference in the pattern of loading, we hypothesized that there are differences in bone remodeling rates between the maxillary and mandibular alveolar processes. Furthermore, in a canine model, the alveolar process of teeth that lack contact (e.g., second premolars) would have a different turnover rate than bone supporting teeth with functional contact (e.g., first molars). Six skeletally mature male dogs were given a pair of calcein labels. After sacrifice, specimens representing the anterior and posterior locations of both jaws were prepared for examination by histomorphometric methods to evaluate the bone volume/total volume (BV/TV; %), bone volume (mm2), mineral apposition rate (MAR; microm/day), and bone formation rate (BFR; %/year) in the alveolar process. There were no significant differences (P>0.05) in the BV/TV within the jaws. The bone volume within the alveolar process of the mandible was 2.8-fold greater than in the maxilla. The MAR was not significantly different between the jaws and anteroposterior locations. However, the BFR was significantly (P<0.0001) greater in the mandible than in the maxilla. The anterior location had higher (P=0.002) remodeling than the posterior location in the maxilla but not in the mandible. While there was a greater bone mass and increased remodeling in the mandible, no remodeling gradient in the coronal-apical direction was apparent in the alveolar process. Bone adaptation probably involves a complex interplay of bone turnover, mass, and architecture.

  8. Remodelling the vascular microenvironment of glioblastoma with alpha-particles

    PubMed Central

    Behling, Katja; Maguire, William F.; Di Gialleonardo, Valentina; Heeb, Lukas E.M.; Hassan, Iman F.; Veach, Darren R.; Keshari, Kayvan R.; Gutin, Philip H.; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    Rationale Tumors escape anti-angiogenic therapy by activation of pro-angiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We investigated targeted α-particle therapy with 225Ac-E4G10 as an anti-vascular approach and previously showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here we investigate changes in tumor-vascular morphology and functionality caused by 225Ac-E4G10. Methods We investigated remodeling of tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4 kBq dose of 225Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphological changes in the tumor blood brain barrier microenvironment. Multi-color flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted magnetic resonance imaged functional changes of the tumor vascular network. Results The mechanism of drug action is a combination of glioblastoma vascular microenvironment remodeling, edema relief, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis was lessened and resulted in increased perfusion and reduced diffusion. Pharmacological uptake of dasatinib into tumor was enhanced following α-particle therapy. Conclusion Targeted anti-vascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of Platelet-derived growth factor driven glioblastoma. PMID:27261519

  9. Intracortical remodeling parameters are associated with measures of bone robustness.

    PubMed

    Goldman, Haviva M; Hampson, Naomi A; Guth, J Jared; Lin, David; Jepsen, Karl J

    2014-10-01

    Prior work identified a novel association between bone robustness and porosity, which may be part of a broader interaction whereby the skeletal system compensates for the natural variation in robustness (bone width relative to length) by modulating tissue-level mechanical properties to increase stiffness of slender bones and to reduce mass of robust bones. To further understand this association, we tested the hypothesis that the relationship between robustness and porosity is mediated through intracortical, BMU-based (basic multicellular unit) remodeling. We quantified cortical porosity, mineralization, and histomorphometry at two sites (38% and 66% of the length) in human cadaveric tibiae. We found significant correlations between robustness and several histomorphometric variables (e.g., % secondary tissue [R(2)  = 0.68, P < 0.004], total osteon area [R(2)  = 0.42, P < 0.04]) at the 66% site. Although these associations were weaker at the 38% site, significant correlations between histological variables were identified between the two sites indicating that both respond to the same global effects and demonstrate a similar character at the whole bone level. Thus, robust bones tended to have larger and more numerous osteons with less infilling, resulting in bigger pores and more secondary bone area. These results suggest that local regulation of BMU-based remodeling may be further modulated by a global signal associated with robustness, such that remodeling is suppressed in slender bones but not in robust bones. Elucidating this mechanism further is crucial for better understanding the complex adaptive nature of the skeleton, and how interindividual variation in remodeling differentially impacts skeletal aging and an individuals' potential response to prophylactic treatments.

  10. Emphysema and mechanical stress-induced lung remodeling.

    PubMed

    Suki, Béla; Sato, Susumu; Parameswaran, Harikrishnan; Szabari, Margit V; Takahashi, Ayuko; Bartolák-Suki, Erzsébet

    2013-11-01

    Transpulmonary pressure and the mechanical stresses of breathing modulate many essential cell functions in the lung via mechanotransduction. We review how mechanical factors could influence the pathogenesis of emphysema. Although the progression of emphysema has been linked to mechanical rupture, little is known about how these stresses alter lung remodeling. We present possible new directions and an integrated multiscale view that may prove useful in finding solutions for this disease.

  11. Maximizing practice management in the newly remodeled practice.

    PubMed

    Moore, Virginia; Castagna, Debbie

    2010-07-01

    Embarking on the building of a new facility, or remodeling an existing space, can be an exciting time. In the midst of planning and decision-making, do not overlook two groups of people who represent driving forces behind the overall success of this investment--patients and staff. In rejuvenating a facility, it is important to remember that at every level, patients' needs must be taken into consideration, including a fundamental review--and potential "overhaul"--of internal systems.

  12. The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.

    PubMed

    Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark

    2017-02-10

    The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.

  13. Pulmonary arterial remodeling revealed by microfocal x-ray tomography

    NASA Astrophysics Data System (ADS)

    Karau, Kelly L.; Molthen, Robert C.; Johnson, Roger H.; Dhyani, Anita H.; Haworth, Steven T.; Dawson, Christopher A.

    2001-05-01

    Animal models and micro-CT imaging are useful for understanding the functional consequences of, and identifying the genes involved in, the remodeling of vascular structures that accompanies pulmonary vascular disease. Using a micro-CT scanner to image contrast-enhanced arteries in excised lungs from fawn hooded rats (a strain genetically susceptible to hypoxia induced pulmonary hypertension), we found that portions of the pulmonary arterial tree downstream from a given diameter were morphometrically indistinguishable. This 'self-consistency' property provided a means for summarizing the pulmonary arterial tree architecture and mechanical properties using a parameter vector obtained from measurements of the contiguous set of vessel segments comprising the longest (principal) pathway and its branches over a range of vascular pressures. This parameter vector was used to characterize the pulmonary vascular remodeling that occurred in rats exposed to a hypoxic (11.5% oxygen) environment and provided the input to a hemodynamic model relating structure to function. The major effect of the remodeling was a longitudinally (pulmonary artery to arterioles) uniform decrease in vessel distensibility that resulted in a 90% increase in arterial resistance. Despite the almost uniform change in vessel distensibility, over 50% of the resistance increase was attributable to vessels with unstressed diameters less than 125 microns.

  14. [Physiopathology of left ventricular remodeling after myocardial infarction].

    PubMed

    Bassand, J P; Anguenot, T

    1991-12-01

    The geometry of both the infarcted and non-infarcted zone of the left ventricle changes after myocardial infarction. Two mechanisms are involved: expansion of the infarcted zone and secondary dilatation of the non-infarcted zone. The necrosed area undergoes an inflammatory reaction followed by fibrosis which end up as a sca within a period of a few days to a few weeks. During this period if fibrous scarring the infarcted, thinned myocardium undergoes progressive expansion which starts in the first hours of the myocardial infarction. The loss of left ventricular systolic function related to the infarct and volumic overload created by expansion of the infarct influence the secondary development of dilatation of the non-infarcted zones. This dilatation results in restoration of left ventricular stroke volume but at the price of increased wall stress, which itself induces compensatory wall hypertrophy. These phenomena are more pronounced when the initial infarction is extensive and if they are sustained, they result in definitive myocardial failure. Several factors influence remodeling: the size of the infarct, arterial patency, wall stress and the quality of the scarring process itself. Therapeutic interventions of each of these factors can influence the remodeling. Limitation of infarct size by thrombolytic therapy, arterial revascularisation, even when performed late, seem capable of limiting expansion of the necrosed zone. Pharmacodynamic intervention of left ventricular afterload also affects ventricular remodeling. Nitrate derivatives, vasodilator therapy in general and converting enzyme inhibitors have been shown to be effective.

  15. Chromatin remodeling and bivalent histone modifications in embryonic stem cells.

    PubMed

    Harikumar, Arigela; Meshorer, Eran

    2015-12-01

    Pluripotent embryonic stem cells (ESCs) are characterized by distinct epigenetic features including a relative enrichment of histone modifications related to active chromatin. Among these is tri-methylation of lysine 4 on histone H3 (H3K4me3). Several thousands of the H3K4me3-enriched promoters in pluripotent cells also contain a repressive histone mark, namely H3K27me3, a situation referred to as "bivalency". While bivalent promoters are not unique to pluripotent cells, they are relatively enriched in these cell types, largely marking developmental and lineage-specific genes which are silent but poised for immediate action. The H3K4me3 and H3K27me3 modifications are catalyzed by lysine methyltransferases which are usually found within, although not entirely limited to, the Trithorax group (TrxG) and Polycomb group (PcG) protein complexes, respectively, but these do not provide selective bivalent specificity. Recent studies highlight the family of ATP-dependent chromatin remodeling proteins as regulators of bivalent domains. Here, we discuss bivalency in general, describe the machineries that catalyze bivalent chromatin domains, and portray the emerging connection between bivalency and the action of different families of chromatin remodelers, namely INO80, esBAF, and NuRD, in pluripotent cells. We posit that chromatin remodeling proteins may enable "bivalent specificity", often selectively acting on, or selectively depleted from, bivalent domains.

  16. Remodeling of the postsynaptic plasma membrane during neural development

    PubMed Central

    Tulodziecka, Karolina; Diaz-Rohrer, Barbara B.; Farley, Madeline M.; Chan, Robin B.; Di Paolo, Gilbert; Levental, Kandice R.; Waxham, M. Neal; Levental, Ilya

    2016-01-01

    Neuronal synapses are the fundamental units of neural signal transduction and must maintain exquisite signal fidelity while also accommodating the plasticity that underlies learning and development. To achieve these goals, the molecular composition and spatial organization of synaptic terminals must be tightly regulated; however, little is known about the regulation of lipid composition and organization in synaptic membranes. Here we quantify the comprehensive lipidome of rat synaptic membranes during postnatal development and observe dramatic developmental lipidomic remodeling during the first 60 postnatal days, including progressive accumulation of cholesterol, plasmalogens, and sphingolipids. Further analysis of membranes associated with isolated postsynaptic densities (PSDs) suggests the PSD-associated postsynaptic plasma membrane (PSD-PM) as one specific location of synaptic remodeling. We analyze the biophysical consequences of developmental remodeling in reconstituted synaptic membranes and observe remarkably stable microdomains, with the stability of domains increasing with developmental age. We rationalize the developmental accumulation of microdomain-forming lipids in synapses by proposing a mechanism by which palmitoylation of the immobilized scaffold protein PSD-95 nucleates domains at the postsynaptic plasma membrane. These results reveal developmental changes in lipid composition and palmitoylation that facilitate the formation of postsynaptic membrane microdomains, which may serve key roles in the function of the neuronal synapse. PMID:27535429

  17. Quantitative computed tomography imaging of airway remodeling in severe asthma

    PubMed Central

    Fetita, Catalin I.; Brillet, Pierre-Yves

    2016-01-01

    Asthma is a heterogeneous condition and approximately 5–10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively. PMID:26981458

  18. Quantitative computed tomography imaging of airway remodeling in severe asthma.

    PubMed

    Grenier, Philippe A; Fetita, Catalin I; Brillet, Pierre-Yves

    2016-02-01

    Asthma is a heterogeneous condition and approximately 5-10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively.

  19. Cerebral salt wasting syndrome after calvarial remodeling in craniosynostosis.

    PubMed

    Byeon, Jun-Hee; Yoo, Gyeol

    2005-10-01

    Hyponatremia and increased urine output after calvarial remodeling have been noted in pediatric patients with craniosynostosis. If not treated properly, patients develop hypoosmotic conditions that can lead to cerebral edema, increased intracranial pressure, and collapsed circulation. Postoperative hyponatremia after central nervous system surgery is considered as the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recently, however, cerebral salt wasting syndrome (CSWS) instead of SIADH has been reported frequently. CSWS is associated with a decreased serum sodium level, increased urinary sodium level, increased urine output, decreased ECF volume, increased atrial natriuretic peptide (ANP) level, and increased brain natriuretic peptide (BNP) level. We experienced nine patients with craniosynostosis who underwent calvarial remodeling. By postoperative day 1, the ANP and BNP levels increased by 3-6 folds compared with the preoperative levels. They returned to the normal levels by postoperative day 5. The ADH level was within the normal range even after operation. The urinary sodium level increased in all patients by postoperative day 1 and 3. But the serum sodium level, and serum and urine osmolarity were normal due to appropriate replacement of sodium and fluid. After calvarial remodeling, the potential development of CSWS should be considered and distinguished from SIADH. The patients with CSWS require normal saline resuscitation and should prophylactically receive normal saline.

  20. Purine receptor mediated actin cytoskeleton remodeling of human fibroblasts

    PubMed Central

    Goldman, Nanna; Chandler-Militello, Devin; Langevin, Helene; Nedergaard, Maiken; Takano, Takahiro

    2013-01-01

    Earlier studies have shown that activation of adenosine A1 receptors on peripheral pain fibers contributes to acupuncture-induced suppression of painful input. In addition to adenosine, acupuncture triggers the release of other purines, including ATP and ADP that may bind to purine receptors on nearby fibroblasts. We here show that purine agonists trigger increase in cytosolic Ca 2+ signaling in a cultured human fibroblasts cell line. The profile of agonist-induced Ca2+ increases indicates that the cells express functional P2yR2 and P2yR4 receptors, as well as P2yR1 and P2xR7 receptors. Unexpectedly, purine-induced Ca2+ signaling was associated with a remodeling of the actin cytoskeleton. ATP induced a transient loss in F-actin stress fiber. The changes of actin cytoskeleton occurred slowly and peaked at 10 min after agonist exposure. Inhibition of ATP-induced increases in Ca2+ by cyclopiazonic acid blocked receptor-mediated cytoskeleton remodeling. The Ca2+ ionophore failed to induce cytoskeletal remodeling despite triggering robust increases in cytosolic Ca2+. These observations indicate that purine signaling induces transient changes in fibroblast cytoarchitecture that could be related to the beneficial effects of acupuncture. PMID:23462235

  1. Senataxin controls meiotic silencing through ATR activation and chromatin remodeling.

    PubMed

    Yeo, Abrey J; Becherel, Olivier J; Luff, John E; Graham, Mark E; Richard, Derek; Lavin, Martin F

    2015-01-01

    Senataxin, defective in ataxia oculomotor apraxia type 2, protects the genome by facilitating the resolution of RNA-DNA hybrids (R-loops) and other aspects of RNA processing. Disruption of this gene in mice causes failure of meiotic recombination and defective meiotic sex chromosome inactivation, leading to male infertility. Here we provide evidence that the disruption of Setx leads to reduced SUMOylation and disruption of protein localization across the XY body during meiosis. We demonstrate that senataxin and other DNA damage repair proteins, including ataxia telangiectasia and Rad3-related protein-interacting partner, are SUMOylated, and a marked downregulation of both ataxia telangiectasia and Rad3-related protein-interacting partner and TopBP1 leading to defective activation and signaling through ataxia telangiectasia and Rad3-related protein occurs in the absence of senataxin. Furthermore, chromodomain helicase DNA-binding protein 4, a component of the nucleosome remodeling and deacetylase chromatin remodeler that interacts with both ataxia telangiectasia and Rad3-related protein and senataxin was not recruited efficiently to the XY body, triggering altered histone acetylation and chromatin conformation in Setx (-/-) pachytene-staged spermatocytes. These results demonstrate that senataxin has a critical role in ataxia telangiectasia and Rad3-related protein- and chromodomain helicase DNA-binding protein 4-mediated transcriptional silencing and chromatin remodeling during meiosis providing greater insight into its critical role in gene regulation to protect against neurodegeneration.

  2. Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling

    PubMed Central

    Mimura, Kallyne K. O.; Moraes, Andréia R.; Miranda, Aline C.; Greco, Rebecca; Ansari, Tahera; Sibbons, Paul; Greco, Karin V.; Oliani, Sonia M.

    2016-01-01

    Biocompatibility of two newly developed porcine skin scaffolds was assessed after 3, 14, 21 and 90 days of implantation in rats. Both scaffolds showed absence of cells, preservation of ECM and mechanical properties comparable to non-decellularised skin before implantation. Host cell infiltration was much prominent on both scaffolds when compared to Permacol (surgical control). At day 3, the grafts were surrounded by polymorphonuclear cells, which were replaced by a notable number of IL-6-positive cells at day 14. Simultaneously, the number of pro-inflammatory M1-macrophage was enhanced. Interestingly, a predominant pro-remodeling M2 response, with newly formed vessels, myofibroblasts activation and a shift on the type of collagen expression was sequentially delayed (around 21 days). The gene expression of some trophic factors involved in tissue remodeling was congruent with the cellular events. Our findings suggested that the responsiveness of macrophages after non-crosslinked skin scaffolds implantation seemed to intimately affect various cell responses and molecular events; and this range of mutually reinforcing actions was predictive of a positive tissue remodeling that was essential for the long-standing success of the implants. Furthermore, our study indicates that non-crosslinked biologic scaffold implantation is biocompatible to the host tissue and somehow underlying molecular events involved in tissue repair. PMID:27725772

  3. PDGFRα plays a crucial role in connective tissue remodeling.

    PubMed

    Horikawa, Shinjiro; Ishii, Yoko; Hamashima, Takeru; Yamamoto, Seiji; Mori, Hisashi; Fujimori, Toshihiko; Shen, Jie; Inoue, Ran; Nishizono, Hirofumi; Itoh, Hiroshi; Majima, Masataka; Abraham, David; Miyawaki, Toshio; Sasahara, Masakiyo

    2015-12-07

    Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.

  4. Senataxin controls meiotic silencing through ATR activation and chromatin remodeling

    PubMed Central

    Yeo, Abrey J; Becherel, Olivier J; Luff, John E; Graham, Mark E; Richard, Derek; Lavin, Martin F

    2015-01-01

    Senataxin, defective in ataxia oculomotor apraxia type 2, protects the genome by facilitating the resolution of RNA–DNA hybrids (R-loops) and other aspects of RNA processing. Disruption of this gene in mice causes failure of meiotic recombination and defective meiotic sex chromosome inactivation, leading to male infertility. Here we provide evidence that the disruption of Setx leads to reduced SUMOylation and disruption of protein localization across the XY body during meiosis. We demonstrate that senataxin and other DNA damage repair proteins, including ataxia telangiectasia and Rad3-related protein-interacting partner, are SUMOylated, and a marked downregulation of both ataxia telangiectasia and Rad3-related protein-interacting partner and TopBP1 leading to defective activation and signaling through ataxia telangiectasia and Rad3-related protein occurs in the absence of senataxin. Furthermore, chromodomain helicase DNA-binding protein 4, a component of the nucleosome remodeling and deacetylase chromatin remodeler that interacts with both ataxia telangiectasia and Rad3-related protein and senataxin was not recruited efficiently to the XY body, triggering altered histone acetylation and chromatin conformation in Setx−/− pachytene-staged spermatocytes. These results demonstrate that senataxin has a critical role in ataxia telangiectasia and Rad3-related protein- and chromodomain helicase DNA-binding protein 4-mediated transcriptional silencing and chromatin remodeling during meiosis providing greater insight into its critical role in gene regulation to protect against neurodegeneration. PMID:27462424

  5. Localized tissue mineralization regulated by bone remodelling: A computational approach

    PubMed Central

    Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

    2017-01-01

    Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

  6. Bone remodeling during prenatal morphogenesis of the human mental foramen.

    PubMed

    Radlanski, Ralf J; Renz, Herbert; Lajvardi, Souzan; Schneider, Richard A

    2004-08-01

    From a morphogenetic point of view, the mental foramen of the mandible is a highly suitable model to study the interactions of different tissues such as nerves, vessels, mesenchymal cells, cartilage, and bone. In previous work, we provided a three-dimensional description of the mental foramen at different developmental stages, and now we complement those studies with a three-dimensional visualization of different bone remodeling activities around the mental foramen. Histological serial sections of human embryos and fetuses, ranging in size from 25 to 117 mm crown-rump-length (CRL), were used to characterize the bone remodeling activity (apposition, inactivity, and resorption). We quantified and reconstructed this activity in three dimensions, and included information on the spatial relationship of the nerves, vessels, and dental primordia. In general, the mandible showed strong apposition at its outer surfaces. The brim of the mental foramen, however, displayed changing remodeling activity at different stages. In the depth of the bony gutter, which provides space for the nerve and the blood vessels, we found bone resorption beneath the inferior alveolar vein. Bone was also resorbed in proximity to the dental primordia. In future studies, we will relate gene expression data to these morphological findings in order to identify molecular mechanisms that regulate this complex system.

  7. Atrial Electrophysiological Remodeling and Fibrillation in Heart Failure

    PubMed Central

    Pandit, Sandeep V.; Workman, Antony J.

    2016-01-01

    Heart failure (HF) causes complex, chronic changes in atrial structure and function, which can cause substantial electrophysiological remodeling and predispose the individual to atrial fibrillation (AF). Pharmacological treatments for preventing AF in patients with HF are limited. Improved understanding of the atrial electrical and ionic/molecular mechanisms that promote AF in these patients could lead to the identification of novel therapeutic targets. Animal models of HF have identified numerous changes in atrial ion currents, intracellular calcium handling, action potential waveform and conduction, as well as expression and signaling of associated proteins. These studies have shown that the pattern of electrophysiological remodeling likely depends on the duration of HF, the underlying cardiac pathology, and the species studied. In atrial myocytes and tissues obtained from patients with HF or left ventricular systolic dysfunction, the data on changes in ion currents and action potentials are largely equivocal, probably owing mainly to difficulties in controlling for the confounding influences of multiple variables, such as patient’s age, sex, disease history, and drug treatments, as well as the technical challenges in obtaining such data. In this review, we provide a summary and comparison of the main animal and human electrophysiological studies to date, with the aim of highlighting the consistencies in some of the remodeling patterns, as well as identifying areas of contention and gaps in the knowledge, which warrant further investigation. PMID:27812293

  8. Nebivolol Attenuates Maladaptive Proximal Tubule Remodeling in Transgenic Rats

    PubMed Central

    Hayden, Melvin R.; Habibi, Javad; Whaley-Connell, Adam; Sowers, Dilek; Johnson, Megan; Tilmon, Roger; Jain, Deepika; Ferrario, Carlos; Sowers, James R.

    2010-01-01

    Background/Aims The impact of nebivolol therapy on the renal proximal tubular cell (PTC) structure and function was investigated in a transgenic (TG) rodent model of hypertension and the cardiometabolic syndrome. The TG Ren2 rat develops nephropathy with proteinuria, increased renal angiotensin II levels and oxidative stress, and PTC remodeling. Nebivolol, a β1-antagonist, has recently been shown to reduce albuminuria, in part, through reductions in renal oxidative stress. Accordingly, we hypothesized that nebivolol therapy would attenuate PTC damage and tubulointerstitial fibrosis. Methods Young Ren2 (R2-N) and SD (SD-N) rats were treated with nebivolol (10 mg/kg/day) or vehicle (R2-C; SD-C) for 3 weeks. PTC structure and function were tested using transmission electron microscopy and functional measurements. Results Nebivolol treatment decreased urinary N-acetyl-β-D-glucosaminidase, tubulointerstitial ultrastructural remodeling and fibrosis, NADPH oxidase activity, 3-nitrotyrosine levels, and increased megalin and lysosomal-associated membrane protein-2 immunostaining in PTCs. Ultrastructural abnormalities that were improved with therapy included altered canalicular structure, reduced endosomes/lysosomes and PTC vacuoles, basement membrane thickening, and mitochondrial remodeling/fragmentation. Conclusion These observations support the notion that nebivolol may improve PTC reabsorption of albumin and other glomerular filtered small molecular weight proteins in association with the attenuation of oxidative stress, tubulointerstitial injury and fibrosis in this rat model of metabolic kidney disease. PMID:20110666

  9. Inflammatory and bone remodeling responses to the cytolethal distending toxins.

    PubMed

    Belibasakis, Georgios N; Bostanci, Nagihan

    2014-04-04

    The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  10. Tension-dependent nucleosome remodeling at the pericentromere in yeast.

    PubMed

    Verdaasdonk, Jolien S; Gardner, Ryan; Stephens, Andrew D; Yeh, Elaine; Bloom, Kerry

    2012-07-01

    Nucleosome positioning is important for the structural integrity of chromosomes. During metaphase the mitotic spindle exerts physical force on pericentromeric chromatin. The cell must adjust the pericentromeric chromatin to accommodate the changing tension resulting from microtubule dynamics to maintain a stable metaphase spindle. Here we examine the effects of spindle-based tension on nucleosome dynamics by measuring the histone turnover of the chromosome arm and the pericentromere during metaphase in the budding yeast Saccharomyces cerevisiae. We find that both histones H2B and H4 exhibit greater turnover in the pericentromere during metaphase. Loss of spindle-based tension by treatment with the microtubule-depolymerizing drug nocodazole or compromising kinetochore function results in reduced histone turnover in the pericentromere. Pericentromeric histone dynamics are influenced by the chromatin-remodeling activities of STH1/NPS1 and ISW2. Sth1p is the ATPase component of the Remodels the Structure of Chromatin (RSC) complex, and Isw2p is an ATP-dependent DNA translocase member of the Imitation Switch (ISWI) subfamily of chromatin-remodeling factors. The balance between displacement and insertion of pericentromeric histones provides a mechanism to accommodate spindle-based tension while maintaining proper chromatin packaging during mitosis.

  11. Bortezomib protects from varicose-like venous remodeling.

    PubMed

    Pfisterer, Larissa; Meyer, Ralph; Feldner, Anja; Drews, Oliver; Hecker, Markus; Korff, Thomas

    2014-08-01

    Despite the high prevalence of venous diseases that are associated with and based on the structural reorganization of the venous vessel wall, not much is known about their mechanistic causes. In this context, we demonstrated that the quantity of myocardin, a transcriptional regulator of the contractile and quiescent smooth muscle cell phenotype, was diminished in proliferating synthetic venous smooth muscle cells (VSMCs) of human and mouse varicose veins by 51 and 60%, respectively. On the basis of the relevance of proteasomal activity for such phenotypic changes, we hypothesized that the observed VSMC activation is attenuated by the proteasome inhibitor bortezomib. This drug fully abolished VSMC proliferation and loss of myocardin in perfused mouse veins and blocked VSMC invasion in collagen gels by almost 80%. In line with this, topical transdermal treatment with bortezomib diminished VSMC proliferation by 80%, rescued 90% of VSMC myocardin abundance, and inhibited varicose-like venous remodeling by 67 to 72% in a mouse model. Collectively, our data indicate that the proteasome plays a pivotal role in VSMC phenotype changes during venous remodeling processes. Its inhibition protects from varicose-like vein remodeling in mice and may thus serve as a putative therapeutic strategy to treat human varicose veins.

  12. Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling

    PubMed Central

    Matsushima, Shouji; Kuroda, Junya; Zhai, Peiyong; Liu, Tong; Ikeda, Shohei; Nagarajan, Narayani; Yokota, Takashi; Kinugawa, Shintaro; Hsu, Chiao-Po; Li, Hong; Tsutsui, Hiroyuki

    2016-01-01

    NADPH oxidases (Noxes) produce ROS that regulate cell growth and death. NOX4 expression in cardiomyocytes (CMs) plays an important role in cardiac remodeling and injury, but the posttranslational mechanisms that modulate this enzyme are poorly understood. Here, we determined that FYN, a Src family tyrosine kinase, interacts with the C-terminal domain of NOX4. FYN and NOX4 colocalized in perinuclear mitochondria, ER, and nuclear fractions in CMs, and FYN expression negatively regulated NOX4-induced O2– production and apoptosis in CMs. Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. Transverse aortic constriction activated FYN in the left ventricle (LV), and FYN-deficient mice displayed exacerbated cardiac hypertrophy and dysfunction and increased ROS production and apoptosis. Deletion of Nox4 rescued the exaggerated LV remodeling in FYN-deficient mice. Furthermore, FYN expression was markedly decreased in failing human hearts, corroborating its role as a regulator of cardiac cell death and ROS production. In conclusion, FYN is activated by oxidative stress and serves as a negative feedback regulator of NOX4 in CMs during cardiac remodeling. PMID:27525436

  13. A Computational Model for Simulating Spaceflight Induced Bone Remodeling

    NASA Technical Reports Server (NTRS)

    Pennline, James A.; Mulugeta, Lealem

    2014-01-01

    An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

  14. Lung parenchyma remodeling in acute respiratory distress syndrome.

    PubMed

    Rocco, P R M; Dos Santos, C; Pelosi, P

    2009-12-01

    Acute respiratory distress syndrome (ARDS), the most severe manifestation of acute lung injury (ALI), is described as a stereotyped response to lung injury with a transition from alveolar capillary damage to a fibroproliferative phase. Most ARDS patients survive the acute initial phase of lung injury and progress to either reparation of the lesion or evolution of the syndrome. Despite advances in the management of ARDS, mortality remains high (40%) and autopsies show extended pulmonary fibrosis in 55% of patients, suggesting the importance of deregulated repair in the morbidity and mortality of these patients. Factors influencing progression to fibroproliferative ARDS versus resolution and reconstitution of the normal pulmonary parenchymal architecture are poorly understood. Abnormal repair and remodeling may be profoundly affected by both environmental and genetic factors. In this line, mechanical ventilation may affect the macromolecules that constitute the extracellular matrix (collagen, elastin, fibronectin, laminin, proteoglycan and glycosaminoglycans), suffer changes and impact the biomechanical behavior of lung parenchyma. Furthermore, evidence suggests that acute inflammation and fibrosis may be partially independent and/or interacting processes that are autonomously regulated, and thus amenable to individual and specific therapies. In this review, we explore recent advances in the field of fibroproliferative ARDS/ALI, with special emphasis on 1) the physiological properties of the extracellular matrix, 2) the mechanisms of remodeling, 3) the impact of mechanical ventilation on lung fibrotic response, and (4) therapeutic interventions in the remodeling process.

  15. PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

    PubMed Central

    Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

    2016-01-01

    Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

  16. Localized tissue mineralization regulated by bone remodelling: A computational approach.

    PubMed

    Berli, Marcelo; Borau, Carlos; Decco, Oscar; Adams, George; Cook, Richard B; García Aznar, José Manuel; Zioupos, Peter

    2017-01-01

    Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent-material density curve. Numerical results are discussed pointing to potential clinical applications.

  17. Surgical Aspects of Intestinal Ascariasis

    PubMed Central

    Ajao, Oluwole G.; Solanke, Toriola F.

    1977-01-01

    At the University College Hospital, Ibadan, Nigeria, a common differential diagnosis of acute abdomen is intestinal ascariasis. This condition mimics many causes of acute abdomen so that accurate pre-operative diagnosis depends mainly on a high index of suspicion. The purpose of this paper is to call attention to this condition which is prevalent in tropical countries, where preventive and social medicine have not reached their peak, and to review the pathological processes resulting from this disease. PMID:875064

  18. [Water and intestinal parasitic diseases].

    PubMed

    Romanenko, N A; Belova, E G; Baburina, L V; Novosil'tsev, G I; Chernyshenko, A I

    2004-01-01

    The paper presents data on the rates of Lamblia cyst dissemination of surface water sources in foreign countries, the Russian Federation, Moscow, and the Moscow Region. It shows a role of drinking water in the spread of intestinal parasitic diseases. In accordance with parasitological parameters, specific data on improvement of methodological control of water quality are presented. The dosages of ultraviolet radiation are given in relation to water decontamination of parasitic disease germs.

  19. Glycoprotein biosynthesis in small intestine

    PubMed Central

    Kim, Young S.; Perdomo, Jose

    1972-01-01

    Rat small intestinal mucosa was examined for ability to produce mucins with human blood group A, B, and H activity. Blood group activity of the mucins was compared to antigenic activity of red blood cells in individual rats and the enzymatic basis for differences was investigated. Red cells in all the rats examined contained human blood group A and B antigens. All rats synthesized intestinal mucins having B and H antigenic activity but 57% failed to produce mucins with blood group A activity (A-); the remaining 43% (A+) produced A substance. The activities of five glycosyltransferases including α(1→2) fucosyltransferase, the determinant of human secretor status, were measured in the intestine of A+ and A- rats. Four enzymes were the same in both groups, while the fifth, N-acetylgalactosaminyltransferase, was present only in A+ rats. The specificity of this latter enzyme, as found in the rat, appeared similar to that in humans, since it catalyzed addition of N-acetyl-D-galactosamine only to acceptors which had the H determinant structure. In the presence of the enzyme, A- mucin could be converted to A+ mucin; this was shown both by hemagglutination inhibition and immunoprecipitin studies of the products of incubation of A- mucin with UDP-N-acetyl-D-galactosamine and the enzyme. These studies indicate that the difference between A+ and A- rats is due to the apparent absence of N-acetylgalactosaminyltransferase in the intestinal mucosa of A- rats. These rats may provide experimental models for studies on the effect of ABO and secretor status on susceptibility to ulceration and carcinogenesis. Images PMID:4112001

  20. Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.

    PubMed

    de Dieuleveult, Maud; Yen, Kuangyu; Hmitou, Isabelle; Depaux, Arnaud; Boussouar, Fayçal; Bou Dargham, Daria; Jounier, Sylvie; Humbertclaude, Hélène; Ribierre, Florence; Baulard, Céline; Farrell, Nina P; Park, Bongsoo; Keime, Céline; Carrière, Lucie; Berlivet, Soizick; Gut, Marta; Gut, Ivo; Werner, Michel; Deleuze, Jean-François; Olaso, Robert; Aude, Jean-Christophe; Chantalat, Sophie; Pugh, B Franklin; Gérard, Matthieu

    2016-02-04

    ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.

  1. Microvasculature remodeling in the mouse lower gut during inflammaging.

    PubMed

    Jeong, Jae-Ho; Kim, KwangSoo; Lim, Daejin; Kim, Kun-Hee; Kim, Hyung-Seok; Lee, Sungsu; Song, Joo-Hye; Moon, Byoung-Gon; Choy, Hyon E; Park, Sang Chul

    2017-01-03

    Inflammaging is defined as low-grade, chronic, systemic inflammation in aging, in the absence of overt infection. Age-associated deterioration of gastrointestinal function could be ascribed to the inflammaging, although evidence is yet to emerge. Here we show that microvessels in aging mouse intestine were progressively deprived of supportive structures, microvessel-associated pericytes and adherens junction protein vascular endothelial (VE)-cadherin, and became leaky. This alteration was ascribed to up-regulation of angiopoetin-2 in microvascular endothelial cells. Up-regulation of the angiopoietin-2 was by TNF-α, originated from M2-like residential CD206(+) macrophages, proportion of which increases as animal ages. It was concluded that antigenic burdens encountered in intestine throughout life create the condition of chronic stage of inflammation, which accumulates M2-like macrophages expressing TNF-α. The TNF-α induces vascular leakage to facilitate recruitment of immune cells into intestine under the chronic inflammatory setting.

  2. Microvasculature remodeling in the mouse lower gut during inflammaging

    PubMed Central

    Jeong, Jae-Ho; Kim, KwangSoo; Lim, Daejin; Kim, Kun-Hee; Kim, Hyung-Seok; Lee, Sungsu; Song, Joo-Hye; Moon, Byoung-Gon; Choy, Hyon E.; Park, Sang Chul

    2017-01-01

    Inflammaging is defined as low-grade, chronic, systemic inflammation in aging, in the absence of overt infection. Age-associated deterioration of gastrointestinal function could be ascribed to the inflammaging, although evidence is yet to emerge. Here we show that microvessels in aging mouse intestine were progressively deprived of supportive structures, microvessel-associated pericytes and adherens junction protein vascular endothelial (VE)-cadherin, and became leaky. This alteration was ascribed to up-regulation of angiopoetin-2 in microvascular endothelial cells. Up-regulation of the angiopoietin-2 was by TNF-α, originated from M2-like residential CD206+ macrophages, proportion of which increases as animal ages. It was concluded that antigenic burdens encountered in intestine throughout life create the condition of chronic stage of inflammation, which accumulates M2-like macrophages expressing TNF-α. The TNF-α induces vascular leakage to facilitate recruitment of immune cells into intestine under the chronic inflammatory setting. PMID:28045067

  3. Periosteal response in translation-induced bone remodelling.

    PubMed Central

    Feik, S A; Ellender, G; Crowe, D M; Ramm-Anderson, S M

    1990-01-01

    Translation of transplanted bones induces strain in the periosteum and subsequent bone remodelling. This study examines the periosteal response on the leading and trailing sides of translated bones using an in vivo model where internal bone strain is virtually eliminated. Caudal vertebrae from 4 days old rats were threaded onto the arms of pre-stressed helical torsion springs and transplanted subcutaneously. In the experimental rats, the appliances were activated seven days later causing the bones to translate. Tissues were examined both optically and by transmission electron microscopy. A connective tissue sheath or capsule forms around the bones and, as the arms of the appliance move apart, traction on the enveloping soft tissues produces compression of the periosteum on the leading side and tension on the trailing side with remodelling occurring in a direction opposite to translation. The control periosteum has an ordered structure with well-delineated osteogenic, mid- and fibrous zones. During translation the periosteum on the leading side is consistently narrower than on the trailing side and shows a gradual reduction in formative activity followed by resorption in select areas. Cells and fibres are aligned predominantly parallel to the bone surface. Accelerated formation characterises the trailing side during the translation phase with increased activity and widening of all three periosteal layers. The fibrous layer merges with the connective tissue sheath which frequently is oriented approximately perpendicular to the bone surface. The direction of remodelling is reversed when translation ceases with corresponding changes visible in the periosteum, the osteoblastic layer being the last to show changes. A normal periosteal structure and remodelling pattern is regained when equilibrium of the bones within the soft tissues is attained. This study shows that the enveloping soft tissues profoundly influence the nature and rate of bone remodelling. The changes are

  4. Redox biology of the intestine

    PubMed Central

    Circu, Magdalena L.; Aw, Tak Yee

    2011-01-01

    The intestinal tract, known for its capability for self-renew, represents the first barrier of defense between the organism and its luminal environment. The thiol/disulfide redox systems comprising the glutathione/glutathione disulfide (GSH/GSSG), cysteine/cystine (Cys/CySS) and reduced and oxidized thioredoxin (Trx/TrxSS) redox couples play important roles in preserving tissue redox homeostasis, metabolic functions, and cellular integrity. Control of the thiol-disulfide status at the luminal surface is essential for maintaining mucus fluidity and absorption of nutrients, and protection against chemical-induced oxidant injury. Within intestinal cells, these redox couples preserve an environment that supports physiological processes and orchestrates networks of enzymatic reactions against oxidative stress. In this review, we focus on the intestinal redox and antioxidant systems, their subcellular compartmentation, redox signaling and epithelial turnover, and contribution of luminal microbiota, key aspects that are relevant to understanding redox-dependent processes in gut biology with implications for degenerative digestive disorders, such as inflammation and cancer. PMID:21831010

  5. Hirschsprung's disease - Postsurgical intestinal dysmotility

    PubMed Central

    Romaneli, Mariana Tresoldi das Neves; Ribeiro, Antonio Fernando; Bustorff-Silva, Joaquim Murray; de Carvalho, Rita Barbosa; Lomazi, Elizete Aparecida

    2016-01-01

    Abstract Objective: To describe the case of an infant with Hirschsprung's disease presenting as total colonic aganglionosis, which, after surgical resection of the aganglionic segment persisted with irreversible functional intestinal obstruction; discuss the difficulties in managing this form of congenital aganglionosis and discuss a plausible pathogenetic mechanism for this case. Case description: The diagnosis of Hirschsprung's disease presenting as total colonic aganglionosis was established in a two-month-old infant, after an episode of enterocolitis, hypovolemic shock and severe malnutrition. After colonic resection, the patient did not recover intestinal motor function that would allow enteral feeding. Postoperative examination of remnant ileum showed the presence of ganglionic plexus and a reduced number of interstitial cells of Cajal in the proximal bowel segments. At 12 months, the patient remains dependent on total parenteral nutrition. Comments: Hirschsprung's disease presenting as total colonic aganglionosis has clinical and surgical characteristics that differentiate it from the classic forms, complicating the diagnosis and the clinical and surgical management. The postoperative course may be associated with permanent morbidity due to intestinal dysmotility. The numerical reduction or alteration of neural connections in the interstitial cells of Cajal may represent a possible physiopathological basis for the condition. PMID:26979103

  6. [Chronic gastritis and intestinal metaplasia].

    PubMed

    Castillo, T; Navarrete, J; Celestina, A

    1989-01-01

    Much has been written about gastric mucosae behavior and the occurrence of intestinal metaplasia. The aim of this paper is to learn something more about these matters in peruvian population. We selected 100 patients with endoscopically no localized lesions between 30 to 70 years of age. We took 8 samples of gastric mucosae in each patient which were carefully examined for the presence of inflammatory changes, settle the line type between antral and fundic mucosae and the frequency of intestinal metaplasia finding. The results showed disagreement between endoscopic and histological findings, so we conclude it is better to diagnose chronic gastritis on the basis of histological parameters. The line between antral and fundic mucosae was of the close type one found in 87% of all cases and it advanced proximally with increasing age. Intestinal metaplasia was present in 46% of the whole number of patients and the rate of occurrence increased in 50% over 50 years age. These findings will let us compare future investigations of gastric mucosae behavior with localized benign or malign lesions.

  7. Epidermal Growth Factor and Intestinal Barrier Function

    PubMed Central

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  8. An intestinal Trojan horse for gene delivery

    NASA Astrophysics Data System (ADS)

    Peng, Haisheng; Wang, Chao; Xu, Xiaoyang; Yu, Chenxu; Wang, Qun

    2015-02-01

    The intestinal epithelium forms an essential element of the mucosal barrier and plays a critical role in the pathophysiological response to different enteric disorders and diseases. As a major enteric dysfunction of the intestinal tract, inflammatory bowel disease is a genetic disease which results from the inappropriate and exaggerated mucosal immune response to the normal constituents in the mucosal microbiota environment. An intestine targeted drug delivery system has unique advantages in the treatment of inflammatory bowel disease. As a new concept in drug delivery, the Trojan horse system with the synergy of nanotechnology and host cells can achieve better therapeutic efficacy in specific diseases. Here, we demonstrated the feasibility of encapsulating DNA-functionalized gold nanoparticles into primary isolated intestinal stem cells to form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel disease. This proof-of-concept intestinal Trojan horse will have a wide variety of applications in the diagnosis and therapy of enteric disorders and diseases.

  9. Epithelial stem cells and intestinal cancer.

    PubMed

    Tan, Shawna; Barker, Nick

    2015-06-01

    The mammalian intestine is comprised of an epithelial layer that serves multiple functions in order to maintain digestive activity as well as intestinal homeostasis. This epithelial layer contains highly proliferative stem cells which facilitate its characteristic rapid regeneration. How these stem cells contribute to tissue repair and normal homeostasis are actively studied, and while we have a greater understanding of the molecular mechanisms and cellular locations that underlie stem cell regulation in this tissue, much still remains undiscovered. This review describes epithelial stem cells in both intestinal and non-intestinal tissues, as well as the strategies that have been used to further characterize the cells. Through a discussion of the current understanding of intestinal self-renewal and tissue regeneration in response to injury, we focus on how dysregulation of critical signaling pathways results in potentially oncogenic aberrations, and highlight issues that should be addressed in order for effective intestinal cancer therapies to be devised.

  10. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  11. Glucocorticoid suppression of osteocyte perilacunar remodeling is associated with subchondral bone degeneration in osteonecrosis

    PubMed Central

    Fowler, Tristan W.; Acevedo, Claire; Mazur, Courtney M.; Hall-Glenn, Faith; Fields, Aaron J.; Bale, Hrishikesh A.; Ritchie, Robert O.; Lotz, Jeffrey C.; Vail, Thomas P.; Alliston, Tamara

    2017-01-01

    Through a process called perilacunar remodeling, bone-embedded osteocytes dynamically resorb and replace the surrounding perilacunar bone matrix to maintain mineral homeostasis. The vital canalicular networks required for osteocyte nourishment and communication, as well as the exquisitely organized bone extracellular matrix, also depend upon perilacunar remodeling. Nonetheless, many questions remain about the regulation of perilacunar remodeling and its role in skeletal disease. Here, we find that suppression of osteocyte-driven perilacunar remodeling, a fundamental cellular mechanism, plays a critical role in the glucocorticoid-induced osteonecrosis. In glucocorticoid-treated mice, we find that glucocorticoids coordinately suppress expression of several proteases required for perilacunar remodeling while causing degeneration of the osteocyte lacunocanalicular network, collagen disorganization, and matrix hypermineralization; all of which are apparent in human osteonecrotic lesions. Thus, osteocyte-mediated perilacunar remodeling maintains bone homeostasis, is dysregulated in skeletal disease, and may represent an attractive therapeutic target for the treatment of osteonecrosis. PMID:28327602

  12. Overlapping chromatin-remodeling systems collaborate genome wide at dynamic chromatin transitions.

    PubMed

    Morris, Stephanie A; Baek, Songjoon; Sung, Myong-Hee; John, Sam; Wiench, Malgorzata; Johnson, Thomas A; Schiltz, R Louis; Hager, Gordon L

    2014-01-01

    ATP-dependent chromatin remodeling is an essential process required for the dynamic organization of chromatin structure. Here we describe the genome-wide location and activity of three remodeler proteins with diverse physiological functions in the mouse genome: Brg1, Chd4 and Snf2h. The localization patterns of all three proteins substantially overlap with one another and with regions of accessible chromatin. Furthermore, using inducible mutant variants, we demonstrate that the catalytic activity of these proteins contributes to the remodeling of chromatin genome wide and that each of these remodelers can independently regulate chromatin reorganization at distinct sites. Many regions require the activity of more than one remodeler to regulate accessibility. These findings provide a dynamic view of chromatin organization and highlight the differential contributions of remodelers to chromatin maintenance in higher eukaryotes.

  13. Appendicular Tourniquet: A Cause of Intestinal Obstruction

    PubMed Central

    Shivashankar, Santhosh Chikkanayakanahalli; Gangappa, Rajashekara Babu; Varghese, Edison Vadakkenchery

    2016-01-01

    Intestinal obstruction is one of the common surgical emergencies seen in daily practice. Postoperative adhesions are notorious for being the most common cause for intestinal obstruction. Occasionally, laparotomy findings do come as a surprise to surgeons. Here one such case is discussed. A patient was operated on with suspicion of intestinal obstruction secondary to postoperative adhesions. However, laparotomy revealed the appendix to be inflamed, curled around the terminal ileum and acting as a tourniquet. PMID:27437300

  14. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    SciTech Connect

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  15. Segmental Dilatation of Intestine Presenting as Partial Intestinal Obstruction in a Child

    PubMed Central

    Khemakhem, Rachid; Elhassan, Elbager Othman

    2014-01-01

    Segmental dilatation of the intestine in pediatric age group is a rare entity. Patients usually present with partial intestinal obstruction which may delay surgical decision. Our case was an 18-month-old girl, who presented with partial intestinal obstruction, provisionally diagnosed as a case of Hirschsprung’s disease. Diagnostic evaluation with contrast study gave a clue of small intestinal obstruction with a dilated segment. PMID:25057472

  16. Diffuse intestinal ganglioneuromatosis in a child

    PubMed Central

    Matthews, Mika A.B.; Adler, Brent H.; Arnold, Michael A.; Kumar, Soma; Carvalho, Ryan; Besner, Gail E.

    2014-01-01

    A 7 year old male with a history of congenital neutropenia and growth hormone deficiency presented with abdominal pain, fevers, and diarrhea. Imaging and endoscopy revealed significant inflammation of the ascending colon with stenosis at the level of the hepatic flexure. A right hemicolectomy was performed, and pathologic findings were consistent with diffuse intestinal ganglioneuromatosis. Due to recurrent mass effect at the intestinal anastomotic site detected radiologically, a second intestinal resection was performed 7 months later. Genetic testing was negative for mutations in the RET protooncogene, NF1 and PTEN tumor suppressor genes. We report a case of diffuse intestinal ganglioneuromatosis in a child with congenital neutropenia. PMID:23701793

  17. A mathematical model of intestinal oedema formation.

    PubMed

    Young, Jennifer; Rivière, Béatrice; Cox, Charles S; Uray, Karen

    2014-03-01

    Intestinal oedema is a medical condition referring to the build-up of excess fluid in the interstitial spaces of the intestinal wall tissue. Intestinal oedema is known to produce a decrease in intestinal transit caused by a decrease in smooth muscle contractility, which can lead to numerous medical problems for the patient. Interstitial volume regulation has thus far been modelled with ordinary differential equations, or with a partial differential equation system where volume changes depend only on the current pressure and not on updated tissue stress. In this work, we present a computational, partial differential equation model of intestinal oedema formation that overcomes the limitations of past work to present a comprehensive model of the phenomenon. This model includes mass and momentum balance equations which give a time evolution of the interstitial pressure, intestinal volume changes and stress. The model also accounts for the spatially varying mechanical properties of the intestinal tissue and the inhomogeneous distribution of fluid-leaking capillaries that create oedema. The intestinal wall is modelled as a multi-layered, deforming, poroelastic medium, and the system of equations is solved using a discontinuous Galerkin method. To validate the model, simulation results are compared with results from four experimental scenarios. A sensitivity analysis is also provided. The model is able to capture the final submucosal interstitial pressure and total fluid volume change for all four experimental cases, and provide further insight into the distribution of these quantities across the intestinal wall.

  18. A mathematical model of intestinal oedema formation

    PubMed Central

    Young, Jennifer; Rivière, Béatrice; Cox, Charles S.; Uray, Karen

    2014-01-01

    Intestinal oedema is a medical condition referring to the build-up of excess fluid in the interstitial spaces of the intestinal wall tissue. Intestinal oedema is known to produce a decrease in intestinal transit caused by a decrease in smooth muscle contractility, which can lead to numerous medical problems for the patient. Interstitial volume regulation has thus far been modelled with ordinary differential equations, or with a partial differential equation system where volume changes depend only on the current pressure and not on updated tissue stress. In this work, we present a computational, partial differential equation model of intestinal oedema formation that overcomes the limitations of past work to present a comprehensive model of the phenomenon. This model includes mass and momentum balance equations which give a time evolution of the interstitial pressure, intestinal volume changes and stress. The model also accounts for the spatially varying mechanical properties of the intestinal tissue and the inhomogeneous distribution of fluid-leaking capillaries that create oedema. The intestinal wall is modelled as a multi-layered, deforming, poroelastic medium, and the system of equations is solved using a discontinuous Galerkin method. To validate the model, simulation results are compared with results from four experimental scenarios. A sensitivity analysis is also provided. The model is able to capture the final submucosal interstitial pressure and total fluid volume change for all four experimental cases, and provide further insight into the distribution of these quantities across the intestinal wall. PMID:23036806

  19. Intraoperative scintigraphy for active small intestinal bleeding

    SciTech Connect

    Biener, A.; Palestro, C.; Lewis, B.S.; Katz, L.B. )

    1990-11-01

    Localizing active sites of bleeding within the small intestine remains a difficult task. Endoscopic, angiographic or scintigraphic studies may point to the small intestine as the site of blood loss, but at operation, without a palpable lesion, the exact site of bleeding remains elusive. Patients are managed at laparotomy with intraoperative endoscopy, angiography, multiple enterotomies, blind resections, or placement of an enterostomy. We describe two patients in whom intraoperative scintigraphy accurately identified active sites of bleeding in the small intestine when other modalities failed. Intraoperative scintigraphy is rapid, easy to perform and is an effective means of identifying active sites of bleeding within the small intestine.

  20. Development of intestinal transport function in mammals.

    PubMed

    Pácha, J

    2000-10-01

    Considerable progress has been made over the last decade in the understanding of mechanisms responsible for the ontogenetic changes of mammalian intestine. This review presents the current knowledge about the development of intestinal transport function in the context of intestinal mucosa ontogeny. The review predominantly focuses on signals that trigger and/or modulate the developmental changes of intestinal transport. After an overview of the proliferation and differentiation of intestinal mucosa, data about the bidirectional traffic (absorption and secretion) across the developing intestinal epithelium are presented. The largest part of the review is devoted to the description of developmental patterns concerning the absorption of nutrients, ions, water, vitamins, trace elements, and milk-borne biologically active substances. Furthermore, the review examines the development of intestinal secretion that has a variety of functions including maintenance of the fluidity of the intestinal content, lubrication of mucosal surface, and mucosal protection. The age-dependent shifts of absorption and secretion are the subject of integrated regulatory mechanisms, and hence, the input of hormonal, nervous, immune, and dietary signals is reviewed. Finally, the utilization of energy for transport processes in the developing intestine is highlighted, and the interactions between various sources of energy are discussed. The review ends with suggestions concerning possible directions of future research.

  1. Intestinal barriers to bacteria and their toxins

    SciTech Connect

    Walker, R.I.; Owen, R.L. )

    1990-01-01

    Immunologic and nonimmunologic processes work together to protect the host from the multitude of microorganisms residing within the intestinal lumen. Mechanical integrity of the intestinal epithelium, mucus in combination with secretory antibody, antimicrobial metabolites of indigenous microorganisms, and peristalsis each limit proliferation and systemic dissemination of enteric pathogens. Uptake of microorganisms by Peyer's patches and other intestinal lymphoid structures and translocation circumvent the mucosal barrier, especially in immunosuppressed individuals. Improved understanding of the composition and limitation of the intestinal barrier, coupled with advances in genetic engineering of immunogenic bacteria, development of oral delivery systems, and immunomodulators, now make enhancement of mucosal barriers feasible. 32 references.

  2. Intestinal myiasis caused by Muscina stabulans.

    PubMed

    Shivekar, S; Senthil, K; Srinivasan, R; Sureshbabu, L; Chand, P; Shanmugam, J; Gopal, R

    2008-01-01

    Intestinal maggots were isolated from a patient, who had reported to the Department of General Medicine of Sri Manakula Vinayagar Medical College, Puducherry, in southern India with complaints of abdominal distress, bloating of abdomen and intestinal hurry following a meal. He was diagnosed as a case of intestinal myiasis. Maggots obtained from his stool were identified to be Muscina stabulans based on characteristic patterns of posterior spiracles. He was treated with purgatives and albendazole. This intestinal myiasis case caused by M. stabulans is reported here because of its rare occurrence and the need to establish a correct diagnosis.

  3. Update on small intestinal stem cells.

    PubMed

    Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

    2013-08-07

    Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

  4. Application of three-dimensional imaging to the intestinal crypt organoids and biopsied intestinal tissues.

    PubMed

    Chen, Yun; Tsai, Ya-Hui; Liu, Yuan-An; Lee, Shih-Hua; Tseng, Sheng-Hong; Tang, Shiue-Cheng

    2013-01-01

    Two-dimensional (2D) histopathology is the standard analytical method for intestinal biopsied tissues; however, the role of 3-dimensional (3D) imaging system in the analysis of the intestinal tissues is unclear. The 3D structure of the crypt organoids from the intestinal stem cell culture and intestinal tissues from the donors and recipients after intestinal transplantation was observed using a 3D imaging system and compared with 2D histopathology and immunohistochemistry. The crypt organoids and intestinal tissues showed well-defined 3D structures. The 3D images of the intestinal tissues with acute rejection revealed absence of villi and few crypts, which were consistent with the histopathological features. In the intestinal transplant for megacystis microcolon intestinal hypoperistalsis syndrome, the donor's intestinal tissues had well-developed nerve networks and interstitial cells of Cajal (ICCs) in the muscle layer, while the recipient's intestinal tissues had distorted nerve network and the ICCs were few and sparsely distributed, relative to those of the donor. The 3D images showed a clear spatial relationship between the microstructures of the small bowel and the features of graft rejection. In conclusion, integration of the 3D imaging and 2D histopathology provided a global view of the intestinal tissues from the transplant patients.

  5. Kinetic Control of Nucleosome Displacement by ISWI/ACF Chromatin Remodelers

    NASA Astrophysics Data System (ADS)

    Florescu, Ana-Maria; Schiessel, Helmut; Blossey, Ralf

    2012-09-01

    Chromatin structure is dynamically organized by chromatin remodelers, motor protein complexes which move and remove nucleosomes. The regulation of remodeler action has recently been proposed to underlie a kinetic proofreading scheme which combines the recognition of histone-tail states and the ATP-dependent loosening of DNA around nucleosomes. Members of the ISWI-family of remodelers additionally recognize linker length between nucleosomes. Here, we show that the additional proofreading step involving linker length alone is sufficient to promote the formation of regular arrays of nucleosomes. ATP-dependent remodeling by bidirectional motors is shown to reinforce positioning as compared to statistical positioning.

  6. Integrated remodeling-to-fracture finite element model of human proximal femur behavior.

    PubMed

    Hambli, Ridha; Lespessailles, Eric; Benhamou, Claude-Laurent

    2013-01-01

    The purpose of this work was to develop an integrated remodeling-to-fracture finite element model allowing for the combined simulation of (i) simulation of a human proximal femur remodeling under a given boundary conditions, (ii) followed by the simulation of its fracture behavior (force-displacement curve and fracture pattern) under quasi-static load. The combination of remodeling and fracture simulation into one unified model consists in considering that the femur properties resulting from the remodeling simulation correspond to the initial state for the fracture prediction. The remodeling model is based on phenomenological one based on a coupled strain and fatigue damage stimulus. The fracture model is based on continuum damage mechanics in order to predict the progressive fracturing process which allows to predict the fracture pattern and the complete force-displacement curve under quasi-static load. To prevent mesh-dependence that generally affects the damage propagation rate, regularization technique was applied in the current work. To investigate the potential of the proposed unified remodeling-to-fracture model, we performed remodeling simulations on a 3D proximal femur model for a duration of 365 days under five different daily loading conditions followed by a side fall fracture simulation reproducing previously published experimental tests (de Bakker et al. (2009), case C, male, 72 years old). We show here that the implementation of an integrated remodeling-to-fracture model provides more realistic prediction strategy to assess the bone remodeling effects on the fracture risk of bone.

  7. Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells

    PubMed Central

    de Dieuleveult, Maud; Yen, Kuangyu; Hmitou, Isabelle; Depaux, Arnaud; Boussouar, Fayçal; Dargham, Daria Bou; Jounier, Sylvie; Humbertclaude, Hélène; Ribierre, Florence; Baulard, Céline; Farrell, Nina P.; Park, Bongsoo; Keime, Céline; Carrière, Lucie; Berlivet, Soizick; Gut, Marta; Gut, Ivo; Werner, Michel; Deleuze, Jean-François; Olaso, Robert; Aude, Jean-Christophe; Chantalat, Sophie; Pugh, B. Franklin; Gérard, Matthieu

    2015-01-01

    Summary ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers1–3 target specific nucleosomes to regulate transcription is unclear. Here, we present genome-wide remodeller-nucleosome interaction profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank MNase-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites (TSSs) are nevertheless chromatinized with non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and modifications (H3K4me3 and H3K27ac). RNA polymerase (pol) II therefore navigates hundreds of bp of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3′ end of the NFR. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers play either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs. PMID:26814966

  8. Axonal remodeling in the corticospinal tract after stroke: how does rehabilitative training modulate it?

    PubMed Central

    Okabe, Naohiko; Narita, Kazuhiko; Miyamoto, Osamu

    2017-01-01

    Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstruct the remaining neural network. In the motor system, such neural network remodeling is observed as a motor map reorganization. Because of its significant correlation with functional recovery, motor map reorganization has been regarded as a key phenomenon for functional recovery after stroke. Although the mechanism underlying motor map reorganization remains unclear, increasing evidence has shown a critical role for axonal remodeling in the corticospinal tract. In this study, we review previous studies investigating axonal remodeling in the corticospinal tract after stroke and discuss which mechanisms may underlie the stimulatory effect of rehabilitative training. Axonal remodeling in the corticospinal tract can be classified into three types based on the location and the original targets of corticospinal neurons, and it seems that all the surviving corticospinal neurons in both ipsilesional and contralesional hemisphere can participate in axonal remodeling and motor map reorganization. Through axonal remodeling, corticospinal neurons alter their output selectivity from a single to multiple areas to compensate for the lost function. The remodeling of the corticospinal axon is influenced by the extent of tissue destruction and promoted by various therapeutic interventions, including rehabilitative training. Although the precise molecular mechanism underlying rehabilitation-promoted axonal remodeling remains elusive, previous data suggest that rehabilitative training promotes axonal remodeling by upregulating growth-promoting and downregulating growth-inhibiting signals.

  9. Sequence-targeted nucleosome sliding in vivo by a hybrid Chd1 chromatin remodeler

    PubMed Central

    Bowman, Gregory D.

    2016-01-01

    ATP-dependent chromatin remodelers regulate chromatin dynamics by modifying nucleosome positions and occupancy. DNA-dependent processes such as replication and transcription rely on chromatin to faithfully regulate DNA accessibility, yet how chromatin remodelers achieve well-defined nucleosome positioning in vivo is poorly understood. Here, we report a simple method for site-specifically altering nucleosome positions in live cells. By fusing the Chd1 remodeler to the DNA binding domain of the Saccharomyces cerevisiae Ume6 repressor, we have engineered a fusion remodeler that selectively positions nucleosomes on top of adjacent Ume6 binding motifs in a highly predictable and reproducible manner. Positioning of nucleosomes by the fusion remodeler recapitulates closed chromatin structure at Ume6-sensitive genes analogous to the endogenous Isw2 remodeler. Strikingly, highly precise positioning of single founder nucleosomes by either chimeric Chd1-Ume6 or endogenous Isw2 shifts phased chromatin arrays in cooperation with endogenous chromatin remodelers. Our results demonstrate feasibility of engineering precise nucleosome rearrangements through sequence-targeted chromatin remodeling and provide insight into targeted action and cooperation of endogenous chromatin remodelers in vivo. PMID:26993344

  10. Effects of loading frequency on the functional adaptation of trabeculae predicted by bone remodeling simulation.

    PubMed

    Kameo, Yoshitaka; Adachi, Taiji; Hojo, Masaki

    2011-08-01

    The process of bone remodeling is regulated by metabolic activities of many bone cells. While osteoclasts and osteoblasts are responsible for bone resorption and formation, respectively, activities of these cells are believed to be controlled by a mechanosensory system of osteocytes embedded in the extracellular bone matrix. Several experimental and theoretical studies have suggested that the strain-derived interstitial fluid flow in lacuno-canalicular porosity serves as the prime mover for bone remodeling. Previously, we constructed a mathematical model for trabecular bone remodeling that interconnects the microscopic cellular activities with the macroscopic morphological changes in trabeculae through the mechanical hierarchy. This model assumes that fluid-induced shear stress acting on osteocyte processes is a driving force for bone remodeling. The validity of this model has been demonstrated with a remodeling simulation using a two-dimensional trabecular model. In this study, to investigate the effects of loading frequency, which is thought to be a significant mechanical factor in bone remodeling, we simulated morphological changes of a three-dimensional single trabecula under cyclic uniaxial loading with various frequencies. The results of the simulation show the trabecula reoriented to the loading direction with the progress of bone remodeling. Furthermore, as the imposed loading frequency increased, the diameter of the trabecula in the equilibrium state was enlarged by remodeling. These results indicate that our simulation model can successfully evaluate the relationship between loading frequency and trabecular bone remodeling.

  11. Ghrelin signaling in heart remodeling of adult obese mice.

    PubMed

    Lacerda-Miranda, Glauciane; Soares, Vivian M; Vieira, Anatalia K G; Lessa, Juliana G; Rodrigues-Cunha, Alessandra C S; Cortez, Erika; Garcia-Souza, Erica P; Moura, Anibal S

    2012-05-01

    Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), has been suggested to be associated to obesity, insulin secretion, cardiovascular growth and homeostasis. GHS-R has been found in most of the tissues, and among the hormone action it is included the regulation of heart energy metabolism. Therefore, hypernutrition during early life leads to obesity, induces cardiac hypertrophy, compromises myocardial function, inducing heart failure in adulthood. We examined ghrelin signaling process in cardiac remodeling in these obese adult mice. The cardiomyocytes (cmy) of left ventricle were analyzed by light microscopy and stereology, content and phosphorilation of cardiac proteins: ghrelin receptor (growth hormone secretagogue receptor 1a, GHSR-1a), protein kinase B (AKT and pAKT), phosphatidil inositol 3 kinase (PI3K), AMP-activated protein kinase (AMPK and pAMPK) and actin were achieved by Western blotting. GHSR-1a gene expression was analyzed by Real Time-PCR. We observed hyperglycemia and higher liver and visceral fat weight in obese when compared to control group. Obese mice presented a marked increase in heart weight/tibia length, indicating an enlarged heart size or a remodeling process. Obese mice had increased GHSR-1a content and expression in the heart associated to PI3K content and increased AKT content and phosphorylation. In contrast, AMPK content and phosphorylation in heart was not different between experimental groups. Ghrelin plasma levels in obese group were decreased when compared to control group. Our data suggest that remodeled myocardial in adult obese mice overnourished in early life are associated with higher phosphorylation of GHSR-1a, PI3K and AKT but not with AMPK.

  12. Hypothyroidism and its rapid correction alter cardiac remodeling.

    PubMed

    Hajje, Georges; Saliba, Youakim; Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

    2014-01-01

    The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  13. Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity.

    PubMed

    Martínez-Martínez, Ernesto; López-Ándres, Natalia; Jurado-López, Raquel; Rousseau, Elodie; Bartolomé, Mará Visitación; Fernández-Celis, Amaya; Rossignol, Patrick; Islas, Fabian; Antequera, Alfonso; Prieto, Santiago; Luaces, María; Cachofeiro, Victoria

    2015-11-01

    Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity.

  14. The role of stem cells in vein graft remodelling.

    PubMed

    Xu, Q

    2007-11-01

    The vessel wall is a dynamic tissue that undergoes positive remodelling in response to altered mechanical stress. A typical example is vein graft remodelling, because veins do not develop arteriosclerosis until a vein segment is grafted on to arteries. In this process, it was observed that vascular endothelial and smooth muscle cells of vein grafts die due to suddenly elevated blood pressure. This cell death is followed by endothelial regeneration. Central to this theme is the essential role played by EPCs (endothelial progenitor cells) in regenerating the lost endothelium. The mechanisms by which EPCs attach to the vessel wall and differentiate into mature endothelial cells involve increased chemokine production and laminar shear flow stimulation on the vessel wall. It seems that neo-endothelial cells derived from EPCs lack mature cell functions and express high levels of adhesion molecules resulting in LDL (low-density lipoprotein) penetration and mononuclear cell infiltration into the sub-endothelial space. Among infiltrated mononuclear cells, there are smooth muscle progenitors that proliferate and differentiate into smooth muscle cells. Meanwhile, stem cells present in the media and adventitia may also migrate into arteriosclerotic lesions via the vasa vasorum that are abundant in the diseased vessels. However, the molecular events leading to the homing, differentiation and maturation of stem/progenitor cells still needs elucidation. The present review attempts to update the progress in stem cell research related to the pathogenesis of vein graft arteriosclerosis or remodelling, focusing on the mechanisms by which stem/progenitor cells participate in the development of lesions, and to discuss the controversial issues and the future perspectives surrounding this research area.

  15. Sclerostin Promotes Bone Remodeling in the Process of Tooth Movement

    PubMed Central

    Shu, Rui; Bai, Ding; Sheu, Tzongjen; He, Yao; Yang, Xianrui; Xue, Chaoran; He, Yiruo; Zhao, Mengyuan; Han, Xianglong

    2017-01-01

    Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 cells were cultured with recombinant human sclerostin (rhSCL) interference and then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP staining. During tooth movement, sclerostin was expressed differently in compression and tension sites. In SOST knock-out mice, there were significantly fewer TRAP-positive cells than in WT mice during tooth movement in compression sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 osteocyte-like cells was not different under a uniaxial compression and tension force, whereas hypoxia conditions significantly increased sclerostin expression in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 cells in experimental osteocyte-osteoclast co-culture. These data suggest that sclerostin plays an important role in the bone remodeling of tooth movement. PMID:28081119

  16. Sclerostin Promotes Bone Remodeling in the Process of Tooth Movement.

    PubMed

    Shu, Rui; Bai, Ding; Sheu, Tzongjen; He, Yao; Yang, Xianrui; Xue, Chaoran; He, Yiruo; Zhao, Mengyuan; Han, Xianglong

    2017-01-01

    Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 cells were cultured with recombinant human sclerostin (rhSCL) interference and then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP staining. During tooth movement, sclerostin was expressed differently in compression and tension sites. In SOST knock-out mice, there were significantly fewer TRAP-positive cells than in WT mice during tooth movement in compression sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 osteocyte-like cells was not different under a uniaxial compression and tension force, whereas hypoxia conditions significantly increased sclerostin expression in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 cells in experimental osteocyte-osteoclast co-culture. These data suggest that sclerostin plays an important role in the bone remodeling of tooth movement.

  17. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    NASA Technical Reports Server (NTRS)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  18. Mechanical force-induced midpalatal suture remodeling in mice

    PubMed Central

    Hou, Bo; Fukai, Naomi; Olsen, Bjorn R.

    2007-01-01

    Mechanical stress is an important epigenetic factor for regulating skeletal remodeling, and application of force can lead to remodeling of both bone and cartilage. Chondrocytes, osteoblasts and osteoclasts all participate and interact with each other in this remodeling process. To study cellular responses to mechanical stimuli in a system that can be genetically manipulated, we used mouse midpalatal suture expansion in vivo. 6-weeks-old male C57BL/6 mice were subjected to palatal suture expansion by opening loops with an initial force of 0.56N for periods of 1, 3, 7, 14 or 28 days. Periosteal cells in expanding sutures showed increased proliferation, with Ki67 positive cells representing 1.8±0.1% to 4.5±0.4% of total suture cells in control groups and 12.0±2.6% to 19.9±1.2% in experimental/expansion groups (p<0.05). Starting at day 1, cells expressing alkaline phosphatase and type I collagen were seen. New cartilage and bone formation was observed at the oral edges of the palatal bones at day 7; at the nasal edges only bone formation without cartilage appeared to occur. An increase in osteoclast numbers suggested increased bone remodeling, ranging from 60 to 160% throughout the experimental period. Decreased Saffranin O staining after day 3 suggested decreased proteoglycan content in the secondary cartilage. MicroCT showed a significant increase in maxillary width at days 14 and 28 (from 2334±4μm to 2485±3μm at day 14 and from 2383±5μm to 2574±7μm at day 28, p<0.001). The suture width was increased at days 14 and 28, except in the oral third region at day 28 (from 48±5μm to 36±4μm, p<0.05). Bone volume/total volume was significantly reduced at days 14 and 28 (50.2±0.7% vs. 68.0±3.7% and 56.5±1.0%vs. 60.9±1.3%, respectively, p<0.05), indicative of increased bone marrow space. These findings demonstrate that expansion forces across the midpalatal suture promote bone resorption through activation of osteoclasts and bone and cartilage formation via

  19. Expression of RANKL/OPG during bone remodeling in vivo

    SciTech Connect

    Tanaka, H.; Mine, T.; Ogasa, H.; Taguchi, T.; Liang, C.T.

    2011-08-12

    Highlights: {yields} This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. {yields} The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. {yields} Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. {yields} The present study confirmed that RANKL/OPG are key factors linking bone formation to resorption during the bone remodeling process. -- Abstract: The interaction between receptor activator of nuclear factor {kappa}B ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation. Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen {alpha}1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The

  20. [Intestinal giardiasis. Mini-review].

    PubMed

    Rivera, María; de la Parte, María A; Hurtado, Pilar; Magaldi, Luis; Collazo, María

    2002-06-01

    Giardia intestinalis is a common parasite in our country and the rest of the world and is responsible for several clinical disturbances that include dysentery type diarrheas, recurrent abdominal pain, duodenitis, jejunitis, cholecystitis and in some cases toxemias and convulsions. In this paper we review recent concepts of intestinal giardiasis, considering the basic aspects of the biology and physiology of Giardia intestinalis, its morphology and its relationship the parasite pathogenicity. We detail the physiopathological mechanisms responsible for the different clinic manifestations of giardiasis, the specific laboratory and endoscopic methods of diagnosis and the most recent advances in the treatment and prophylaxis of this disease.

  1. [Intestinal complications from vascular prostheses].

    PubMed

    Fernández, C; Calvete, J; García, J; Buch, E; Castells, P; Lledó, S

    1993-01-01

    Secondary FAE is a rare complication, usually located at the duodenum. The typical clinical presentation is like a digestive hemorrhage or a sepsis. We report two cases of FAE with atypical manifestations. The first case presented a lower digestive hemorrhage produced by the fistulization to the sigma. The second case appeared like an intestinal obliteration caused by the full emigration of a prosthesis to the jejunum. We wish to remark the importance of the clinical suspicion of a FAE (Key of diagnosis), and the sparing relevance of the complementary examinations and the urgency of a surgical treatment in order to avoid the high rate of morbi-mortality associated with this complication.

  2. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites.

    PubMed

    Gerbe, François; Sidot, Emmanuelle; Smyth, Danielle J; Ohmoto, Makoto; Matsumoto, Ichiro; Dardalhon, Valérie; Cesses, Pierre; Garnier, Laure; Pouzolles, Marie; Brulin, Bénédicte; Bruschi, Marco; Harcus, Yvonne; Zimmermann, Valérie S; Taylor, Naomi; Maizels, Rick M; Jay, Philippe

    2016-01-14

    Helminth parasitic infections are a major global health and social burden. The host defence against helminths such as Nippostrongylus brasiliensis is orchestrated by type 2 cell-mediated immunity. Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus production, ultimately resulting in worm expulsion. However, the mechanisms underlying the initiation of type 2 responses remain incompletely understood. Here we show that tuft cells, a rare epithelial cell type in the steady-state intestinal epithelium, are responsible for initiating type 2 responses to parasites by a cytokine-mediated cellular relay. Tuft cells have a Th2-related gene expression signature and we demonstrate that they undergo a rapid and extensive IL-4Rα-dependent amplification following infection with helminth parasites, owing to direct differentiation of epithelial crypt progenitor cells. We find that the Pou2f3 gene is essential for tuft cell specification. Pou2f3(-/-) mice lack intestinal tuft cells and have defective mucosal type 2 responses to helminth infection; goblet cell hyperplasia is abrogated and worm expulsion is compromised. Notably, IL-4Rα signalling is sufficient to induce expansion of the tuft cell lineage, and ectopic stimulation of this signalling cascade obviates the need for tuft cells in the epithelial cell remodelling of the intestine. Moreover, tuft cells secrete IL-25, thereby regulating type 2 immune responses. Our data reveal a novel function of intestinal epithelial tuft cells and demonstrate a cellular relay required for initiating mucosal type 2 immunity to helminth infection.

  3. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium.

    PubMed

    Purohit, Vishnudutt; Bode, J Christian; Bode, Christiane; Brenner, David A; Choudhry, Mashkoor A; Hamilton, Frank; Kang, Y James; Keshavarzian, Ali; Rao, Radhakrishna; Sartor, R Balfour; Swanson, Christine; Turner, Jerrold R

    2008-08-01

    This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram-negative bacteria in the intestine, which may result in accumulation of endotoxin. In addition, alcohol metabolism by Gram-negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan, which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram-negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, l-glutamine, oats supplementation, or zinc, thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram-negative bacteria

  4. Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits During Caenorhabditis elegans Development.

    PubMed

    Ertl, Iris; Porta-de-la-Riva, Montserrat; Gómez-Orte, Eva; Rubio-Peña, Karinna; Aristizábal-Corrales, David; Cornes, Eric; Fontrodona, Laura; Osteikoetxea, Xabier; Ayuso, Cristina; Askjaer, Peter; Cabello, Juan; Cerón, Julián

    2016-03-01

    SWI/SNF ATP-dependent chromatin-remodeling complexes have been related to several cellular processes such as transcription, regulation of chromosomal stability, and DNA repair. The Caenorhabditis elegans gene ham-3 (also known as swsn-2.1) and its paralog swsn-2.2 encode accessory subunits of SWI/SNF complexes. Using RNA interference (RNAi) assays and diverse alleles we investigated whether ham-3 and swsn-2.2 have different functions during C. elegans development since they encode proteins that are probably mutually exclusive in a given SWI/SNF complex. We found that ham-3 and swsn-2.2 display similar functions in vulva specification, germline development, and intestinal cell proliferation, but have distinct roles in embryonic development. Accordingly, we detected functional redundancy in some developmental processes and demonstrated by RNA sequencing of RNAi-treated L4 animals that ham-3 and swsn-2.2 regulate the expression of a common subset of genes but also have specific targets. Cell lineage analyses in the embryo revealed hyper-proliferation of intestinal cells in ham-3 null mutants whereas swsn-2.2 is required for proper cell divisions. Using a proteomic approach, we identified SWSN-2.2-interacting proteins needed for early cell divisions, such as SAO-1 and ATX-2, and also nuclear envelope proteins such as MEL-28. swsn-2.2 mutants phenocopy mel-28 loss-of-function, and we observed that SWSN-2.2 and MEL-28 colocalize in mitotic and meiotic chromosomes. Moreover, we demonstrated that SWSN-2.2 is required for correct chromosome segregation and nuclear reassembly after mitosis including recruitment of MEL-28 to the nuclear periphery.

  5. Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits During Caenorhabditis elegans Development

    PubMed Central

    Ertl, Iris; Porta-de-la-Riva, Montserrat; Gómez-Orte, Eva; Rubio-Peña, Karinna; Aristizábal-Corrales, David; Cornes, Eric; Fontrodona, Laura; Osteikoetxea, Xabier; Ayuso, Cristina; Askjaer, Peter; Cabello, Juan; Cerón, Julián

    2016-01-01

    SWI/SNF ATP-dependent chromatin-remodeling complexes have been related to several cellular processes such as transcription, regulation of chromosomal stability, and DNA repair. The Caenorhabditis elegans gene ham-3 (also known as swsn-2.1) and its paralog swsn-2.2 encode accessory subunits of SWI/SNF complexes. Using RNA interference (RNAi) assays and diverse alleles we investigated whether ham-3 and swsn-2.2 have different functions during C. elegans development since they encode proteins that are probably mutually exclusive in a given SWI/SNF complex. We found that ham-3 and swsn-2.2 display similar functions in vulva specification, germline development, and intestinal cell proliferation, but have distinct roles in embryonic development. Accordingly, we detected functional redundancy in some developmental processes and demonstrated by RNA sequencing of RNAi-treated L4 animals that ham-3 and swsn-2.2 regulate the expression of a common subset of genes but also have specific targets. Cell lineage analyses in the embryo revealed hyper-proliferation of intestinal cells in ham-3 null mutants whereas swsn-2.2 is required for proper cell divisions. Using a proteomic approach, we identified SWSN-2.2-interacting proteins needed for early cell divisions, such as SAO-1 and ATX-2, and also nuclear envelope proteins such as MEL-28. swsn-2.2 mutants phenocopy mel-28 loss-of-function, and we observed that SWSN-2.2 and MEL-28 colocalize in mitotic and meiotic chromosomes. Moreover, we demonstrated that SWSN-2.2 is required for correct chromosome segregation and nuclear reassembly after mitosis including recruitment of MEL-28 to the nuclear periphery. PMID:26739451

  6. Chronic intestinal pseudo-obstruction.

    PubMed

    Gabbard, Scott L; Lacy, Brian E

    2013-06-01

    Chronic intestinal pseudo-obstruction (CIP) is a rare and serious disorder of the gastrointestinal (GI) tract characterized as a motility disorder with the primary defect of impaired peristalsis; symptoms are consistent with a bowel obstruction, although mechanical obstruction cannot be identified. CIP is classified as a neuropathy, myopathy, or mesenchymopathy; it is a neuropathic process in the majority of patients. The natural history of CIP is generally that of a progressive disorder, although occasional patients with secondary CIP note significant symptomatic improvement when the underlying disorder is identified and treated. Symptoms vary from patient to patient depending on the location of the luminal GI tract involved and the degree of involvement; however, the small intestine is nearly always involved. Common symptoms include dysphagia, gastroesophageal reflux, abdominal pain, nausea, vomiting, bloating, abdominal distension, constipation or diarrhea, and involuntary weight loss. Unfortunately, these symptoms are nonspecific, which can contribute to misdiagnosis or a delay in diagnosis and treatment. Since many of the symptoms and signs suggest a mechanical bowel obstruction, diagnostic tests typically focus on uncovering a mechanical obstruction, although routine tests do not identify an obstructive process. Nutrition supplementation is required for many patients with CIP due to symptoms of dysphagia, nausea, vomiting, and weight loss. This review discusses the epidemiology, etiology, pathogenesis, diagnosis, and treatment of patients with CIP, with an emphasis on nutrition assessment and treatment options for patients with nutrition compromise.

  7. Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

    PubMed

    Tanaka, Leonardo Y; Laurindo, Francisco R M

    2017-01-18

    Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases.

  8. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

    PubMed

    Langdahl, Bente; Ferrari, Serge; Dempster, David W

    2016-12-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  9. Left Ventricular Remodeling and Function in Children with Biventricular Circulation After Fetal Aortic Valvuloplasty.

    PubMed

    Friedman, Kevin G; Freud, Lindsay; Escobar-Diaz, Maria; Banka, Puja; Emani, Sitaram; Tworetzky, Wayne

    2015-10-01

    Fetal aortic valvuloplasty (FAV) has shown promise in averting the progression of fetal aortic stenosis to hypoplastic left-heart syndrome. Altered loading conditions due to valvar disease, intrinsic endomyocardial abnormalities, and procedures that alter endomyocardial mechanics may place patients with biventricular circulation (BiV) after FAV at risk of abnormal LV remodeling and function. Using the most recent echo data on BiV patients after technically successful FAV (n = 34), we evaluated LV remodeling pattern, risk factors for pathologic LV remodeling, and the association between LV remodeling pattern and LV function. Median age at follow-up was 4.7 years (range 1.0-12.5). Cardiac interventions were common. At latest follow-up, no patient had hypoplastic LV. Nineteen patients (55 %) had dilated LV, and five (16 %) patients had severely dilated LV. LV remodeling patterns were as follows: 12 (35 %) normal ventricle, 11 (32 %) mixed hypertrophy, 8 (24 %) eccentric hypertrophy or remodeling, and 3 (9 %) concentric hypertrophy. Univariate factors associated with pathologic LV remodeling were long-standing AR, ≥2 cardiac interventions, EFE resection, and aortic or mitral regurgitation ≥ moderate at most recent follow-up. In multivariate analysis, only long-standing AR fraction remained associated with pathologic remodeling. Pathologic LV remodeling was associated with depressed ejection fraction, lower septal E´, and higher E/E´. Pathologic LV remodeling, primarily eccentric or mixed hypertrophy, is common in BiV patients after FAV and is related to LV loading conditions imposed by valvar disease. Pathologic remodeling is associated with both systolic and diastolic dysfunction in this population.

  10. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis

    PubMed Central

    Langdahl, Bente; Ferrari, Serge; Dempster, David W.

    2016-01-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20–30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  11. The genomics of probiotic intestinal microorganisms

    PubMed Central

    Salminen, Seppo; Nurmi, Jussi; Gueimonde, Miguel

    2005-01-01

    An intestinal population of beneficial commensal microorganisms helps maintain human health, and some of these bacteria have been found to significantly reduce the risk of gut-associated disease and to alleviate disease symptoms. The genomic characterization of probiotic bacteria and other commensal intestinal bacteria that is now under way will help to deepen our understanding of their beneficial effects. PMID:15998456

  12. Autonomic Modification of Intestinal Smooth Muscle Contractility

    ERIC Educational Resources Information Center

    Montgomery, Laura E. A.; Tansey, Etain A.; Johnson, Chris D.; Roe, Sean M.; Quinn, Joe G.

    2016-01-01

    Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe…

  13. Intestinal radiation syndrome: sepsis and endotoxin

    SciTech Connect

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1985-03-01

    Rats were whole-body irradiated with 8-MeV cyclotron-produced neutrons and /sup 137/Cs ..gamma.. rays to study the role of enteric bacteria and endotoxin in the intestinal radiation syndrome. Decrease in intestinal weight was used as an index of radiation-induced breakdown of the mucosa. Neutron and ..gamma..-ray doses that were sublethal for intestinal death resulted in a dose-dependent decrease in intestinal weight, reaching minimal values 2 to 3 days after exposure, followed by recovery within 5 days after irradiation. Neutron and photon doses that caused intestinal death resulted in greater mucosal breakdown with little or no evidence of mucosal recovery. The presence of fluid in the intestine and diarrhea, but not bacteremia or endotoxemia, were related to mucosal breakdown and recovery. Neither sepsis nor endotoxin could be detected in liver samples taken at autopsy from animals which died a short time earlier from intestinal injury. These results suggest that overt sepsis and endotoxemia do not play a significant role in the intestinal radiation syndrome.

  14. Schlafen 3 changes during rat intestinal maturation

    PubMed Central

    Walsh, Mary F.; Hermann, Rebecca; Sun, Kelian; Basson, Marc D.

    2015-01-01

    BACKGROUND Understanding gut development may illuminate the adaptive response to massive small-bowel resection and facilitate enteral nutrition. We reported that Schlafen-3 (Slfn3) mediates differentiation in vitro in rat intestinal epithelial. We hypothesized that Slfn3 is involved in intestinal development in vivo. METHODS We removed fetal intestines, liver, and lungs on day 20 of gestation, at birth, and on postnatal days 1 and 5. Expression of Slfn3, markers of intestinal differentiation, and Slfn5, to address specificity, were determined by quantitative reverse-transcription polymerase chain reaction. RESULTS Villin expression increased on days 1 and 5 (8.7 ± .6 and 5.4 ± .4, respectively; P < .01). Intestinal Slfn3 expression was increased substantially after birth (2.1- ± .5-fold) and on days 1 and 5 (P < .02). Slfn3 was higher after birth in liver and lung but decreased sharply thereafter. Slfn5 expression was mostly unchanged. CONCLUSIONS The data suggest that the developmental/maturation effects we observed correlate with Slfn3 but not Slfn5 and are more relevant to the intestines. A better understanding of how Slfn3 promotes intestinal differentiation could help promote intestinal maturation, improving outcomes in children or adults with short-gut syndrome. PMID:22906252

  15. Regulation and impairments of dynamic desmosome and corneodesmosome remodeling.

    PubMed

    Kitajima, Yasuo

    2013-04-30

    Desmosomes and corneodesmosomes are the most important adhering junctions to provide strength for the epidermal sheet structure made of living keratinocytes and enucleated corneocytes, respectively. These junctions are connected directly with transmembrane desmosomal cadherins, desmogleins (Dsgs) and desmocollins (Dscs), mainly Dsg1/Dsc1 and Dsg3/Dsc3 in desmosomes and Dsg1/Dsc1 with corneodesmosin in corneodesmosomes. Dsgs and Dscs are associated with several proteins at their inner cytoplasmic domains to anchor keratin intermediate filaments. Desmosomes are not static, but dynamic units that undergo regular remodeling to allow for keratinocyte outward-migration in the epidermis. Recently, two mutually-reversible desmosomal adhesion states have been recognized, i.e., "stable hyper-adhesion (Ca(2+)-independent)" and "dynamic weak-adhesion (Ca(2+)-dependent)". A remarkable impairment of this remodeling is observed in pemphigus vulgaris (an autoimmune blistering disease), caused by anti-Dsg3 antibodies, generating a weak-adhesion desmosome state. Immediately after formation, corneodesmosomes normally commit to degradation, which is complicatedly regulated by proteolytic cleavage of their respective extracellular portion(s), via kallikrein-regulated peptidases and cathepsins. This proteolytic activity is in turn controlled by a variety of inhibitory agents, including protease inhibitors, cholesterol sulfate, and an acidic gradient. The impairment of protease control causes keratinization disorders. This review focuses on the dynamic regulation of desmosomes and corneodesmosomes in relation to keratinization disorders.

  16. Remodeling of chromatin under low intensity diffuse ultrasound.

    PubMed

    Noriega, Sandra; Budhiraja, Gaurav; Subramanian, Anuradha

    2012-08-01

    A variety of mechanotransduction pathways mediate the response of fibroblasts or chondrocytes to ultrasound stimulation. In addition, regulatory pathways that co-ordinate stimulus-specific cellular responses are likely to exist. In this study, analysis was confined to the hypothesis that ultrasound stimulation (US) influences the chromatin structure, and that these changes may reflect a regulatory pathway that connects nuclear architecture, chromatin structure and gene expression. Murine fibroblasts seeded on tissue culture plates were stimulated with US (5.0 MHz (14 kPa), 51-s per application) and the thermal denaturation profiles of nuclei isolated from fibroblasts were assessed by dynamic scanning calorimetry (DSC). When compared to the thermal profiles obtained from the nuclei of non-stimulated cells, the nuclei obtained from stimulated cells showed a change in peak profiles and peak areas, which is indicative of chromatin remodeling. Independently, US was also observed to impact the histone (H1):chromatin association as measured indirectly by DAPI staining. Based on our work, it appears plausible that US can produce a remodeling of chromatin, thus triggering signal cascade and other intracellular mechanisms.

  17. Structural Stability and Functional Remodeling of High-Density Lipoproteins

    PubMed Central

    Gursky, Olga

    2015-01-01

    Lipoproteins are protein-lipid nanoparticles that transport lipids in circulation and are central in atherosclerosis and other disorders of lipid metabolism. Apolipoproteins form flexible structural scaffolds and important functional ligands on the particle surface and direct lipoprotein metabolism. Lipoproteins undergo multiple rounds of metabolic remodeling that is crucial to lipid transport. Important aspects of this remodeling, including apolipoprotein dissociation and particle fusion, are mimicked in thermal or chemical denaturation and are modulated by free energy barriers. Here we review our biophysical studies that revealed kinetic mechanism of lipoprotein stabilization and unraveled its structural basis. The main focus is on high-density lipoprotein (HDL). An inverse correlation between stability and functions of various HDLs in cholesterol transport suggests functional role of structural disorder. A mechanism for conformational adaptation of the major HDL proteins, apoA-I and apoA-II, to the increasing lipid load is proposed. Together, these studies help understand why HDL form discrete subclasses separated by kinetic barriers, which have distinct composition, conformation and functional properties. Understanding these properties may help improve HDL quality and develop novel therapies for cardiovascular disease. PMID:25749369

  18. Epigenetic regulation and chromatin remodeling in learning and memory

    PubMed Central

    Kim, Somi; Kaang, Bong-Kiun

    2017-01-01

    Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms. PMID:28082740

  19. Remodeling patterns of occipital growth: a preliminary report.

    PubMed

    Kranioti, Elena F; Rosas, Antonio; García-Vargas, Samuel; Estalrrich, Almudena; Bastir, Markus; Peña-Melián, Angel

    2009-11-01

    Occipital growth depends on coordinated deposition and resorption on the external and internal surface and includes interrelated processes of movement: cortical drift, displacement, and relocation. The current work aspires to map patterns of remodeling activity on the endocranial surface of the occipital bone from childhood to adulthood using a larger study sample compared with previous studies. The study sample consists of 5 adult and 10 immature (2(1/4) to 8 years old) occipital bones from skeletal remains from the eighteenth and nineteenth century. Preparation of the samples includes the elaboration of negative impressions, positive replicas coated with gold, and observed with the reflected light microscope. Cerebellar fossae are typically resorptive in both immature and adult specimens. Cerebral fossae, on the other hand, exhibit a resorptive surface in early childhood and turn into depository around the age of 7 years, which places this transition within the age interval of the completion of cerebral development. Depository fields are also observed in adult cerebral fossae. The remodeling map presented here is consistent with the results of Mowbray (Anat Rec B New Anat 2005;283B:14-22) and differs from cellular patterns described by Enlow. Future research implicating more elements of the neurocapsule can shed light on the factors affecting and driving occipital growth.

  20. Multiple modes of chromatin remodeling by Forkhead box proteins.

    PubMed

    Lalmansingh, Avin S; Karmakar, Sudipan; Jin, Yetao; Nagaich, Akhilesh K

    2012-07-01

    Forkhead box (FOX) proteins represent a large family of transcriptional regulators unified by their DNA binding domain (DBD) known as a 'forkhead' or 'winged helix' domain. Over 40 FOX genes have been identified in the mammalian genome. FOX proteins share significant sequence similarities in the DBD which allow them to bind to a consensus DNA response element. However, their modes of action are quite diverse as they regulate gene expression by acting as pioneer factors, transcription factors, or both. This review focuses on the mechanisms of chromatin remodeling with an emphasis on three sub-classes-FOXA, FOXO, and FOXP members. FOXA proteins serve as pioneer factors to open up local chromatin structure and thereby increase accessibility of chromatin to factors regulating transcription. FOXP proteins, in contrast, function as classic transcription factors to recruit a variety of chromatin modifying enzymes to regulate gene expression. FOXO proteins represent a hybrid subclass having dual roles as pioneering factors and transcription factors. A subset of FOX proteins interacts with condensed mitotic chromatin and may function as 'bookmarking' agents to maintain transcriptional competence at specific genomic sites. The overall diversity in chromatin remodeling function by FOX proteins is related to unique structural motifs present within the DBD flanking regions that govern selective interactions with core histones and/or chromatin coregulatory proteins. This article is part of a Special Issue entitled: Chromatin in time and space.

  1. Respiratory muscle fiber remodeling in chronic hyperinflation: dysfunction or adaptation?

    PubMed

    Clanton, Thomas L; Levine, Sanford

    2009-07-01

    The diaphragm and other respiratory muscles undergo extensive remodeling in both animal models of emphysema and in human chronic obstructive pulmonary disease, but the nature of the remodeling is different in many respects. One common feature is a shift toward improved endurance characteristics and increased oxidative capacity. Furthermore, both animals and humans respond to chronic hyperinflation by diaphragm shortening. Although in rodent models this clearly arises by deletion of sarcomeres in series, the mechanism has not been proven conclusively in human chronic obstructive pulmonary disease. Unique characteristics of the adaptation in human diaphragms include shifts to more predominant slow, type I fibers, expressing slower myosin heavy chain isoforms, and type I and type II fiber atrophy. Although some laboratories report reductions in specific force, this may be accounted for by decreases in myosin heavy chain content as the muscles become more oxidative and more efficient. More recent findings have reported reductions in Ca(2+) sensitivity and reduced myofibrillar elastic recoil. In contrast, in rodent models of disease, there is no consistent evidence for loss of specific force, no consistent shift in fiber populations, and atrophy is predominantly seen only in fast, type IIX fibers. This review challenges the hypothesis that the adaptations in human diaphragm represent a form of dysfunction, secondary to systemic disease, and suggest that most findings can as well be attributed to adaptive processes of a complex muscle responding to unique alterations in its working environment.

  2. Regulation of tyrosine phosphatases in the adventitia during vascular remodelling

    SciTech Connect

    Micke, Patrick; Hackbusch, Daniel; Mercan, Sibel; Stawowy, Philipp; Ostman, Arne; Kappert, Kai

    2009-05-15

    Protein tyrosine phosphatases (PTPs) are regulators of growth factor signalling in vascular remodelling. The aim of this study was to evaluate PTP expression in the context of PDGF-signalling in the adventitia after angioplasty. Utilising a rat carotid artery model, the adventitial layers of injured and non-injured vessels were laser microdissected. The mRNA expression of the PDGF {beta}-receptor, the ligands PDGF-A/B/C/D and the receptor-antagonising PTPs (DEP-1, TC-PTP, SHP-2, PTP1B) were determined and correlated to vascular morphometrics, proliferation markers and PDGF {beta}-receptor phosphorylation. The levels of the PDGF {beta}-receptor, PDGF-C and PDGF-D were upregulated concurrently with the antagonising PTPs DEP-1 and TC-PTP at day 8, and normalised at day 14 after vessel injury. Although the proliferation parameters were time-dependently altered in the adventitial layer, the phosphorylation of the PDGF {beta}-receptor remained unchanged. The expression dynamics of specific PTPs indicate a regulatory role of PDGF-signalling also in the adventitia during vascular remodelling.

  3. Danger control programs cause tissue injury and remodeling.

    PubMed

    Hagemann, Jan H; Haegele, Holger; Müller, Susanna; Anders, Hans-Joachim

    2013-05-28

    Are there common pathways underlying the broad spectrum of tissue pathologies that develop upon injuries and from subsequent tissue remodeling? Here, we explain the pathophysiological impact of a set of evolutionary conserved danger control programs for tissue pathology. These programs date back to the survival benefits of the first multicellular organisms upon traumatic injuries by launching a series of danger control responses, i.e., 1. Haemostasis, or clotting to control bleeding; 2. Host defense, to control pathogen entry and spreading; 3. Re-epithelialisation, to recover barrier functions; and 4. Mesenchymal, to repair to regain tissue stability. Taking kidney pathology as an example, we discuss how clotting, inflammation, epithelial healing, and fibrosis/sclerosis determine the spectrum of kidney pathology, especially when they are insufficiently activated or present in an overshooting and deregulated manner. Understanding the evolutionary benefits of these response programs may refine the search for novel therapeutic targets to limit organ dysfunction in acute injuries and in progressive chronic tissue remodeling.

  4. Coupling Circadian Rhythms of Metabolism and Chromatin Remodeling

    PubMed Central

    Masri, Selma; Orozco-Solis, Ricardo; Aguilar-Arnal, Lorena; Cervantes, Marlene; Sassone-Corsi, Paolo

    2015-01-01

    The circadian clock controls a large variety of neuronal, endocrine, behavioral and physiological responses in mammals. This control is exerted in large part at the transcriptional level on genes expressed in a cyclic manner. A highly specialized transcriptional machinery based on clock regulatory factors organized in feedback autoregulatory loops governs a significant portion of the genome. These oscillations in gene expression are paralleled by critical events of chromatin remodeling that appear to provide plasticity to circadian regulation. Specifically, the NAD+-dependent deacetylases SIRT1 and SIRT6 have been linked to circadian control of gene expression. This, and additional accumulating evidence, shows that the circadian epigenome appears to share intimate links with cellular metabolic processes and has remarkable plasticity showing reprogramming in response to nutritional challenges. In addition to SIRT1 and SIRT6, a number of chromatin remodelers have been implicated in clock control, including the histone H3K4 tri-methyltransferase MLL1. Deciphering the molecular mechanisms that link metabolism, epigenetic control and circadian responses will provide valauble insights towards innovative strategies of therapeutic intervention. PMID:26332964

  5. Structural remodeling and mechanical function in heart failure.

    PubMed

    Leonard, Bridget Louise; Smaill, Bruce Henry; LeGrice, Ian John

    2012-02-01

    The cardiac extracellular matrix (ECM) is the three-dimensional scaffold that defines the geometry and muscular architecture of the cardiac chambers and transmits forces produced during the cardiac cycle throughout the heart wall. The cardiac ECM is an active system that responds to the stresses to which it is exposed and in the normal heart is adapted to facilitate efficient mechanical function. There are marked differences in the short- and medium-term changes in ventricular geometry and cardiac ECM that occur as a result of volume overload, hypertension, and ischemic cardiomyopathy. Despite this, there is a widespread view that a common remodeling "phenotype" governs the final progression to end-stage heart failure in different forms of heart disease. In this review article, we make the case that this interpretation is not consistent with the clinical and experimental data on the topic. We argue that there is a need for new theoretical and experimental models that will enable stresses acting on the ECM and resultant deformations to be estimated more accurately and provide better spatial resolution of local signaling mechanisms that are activated as a result. These developments are necessary to link the effects of structural remodeling with altered cardiac mechanical function.

  6. Transcriptome Remodeling of Acinetobacter baumannii during Infection and Treatment

    PubMed Central

    Wright, Meredith S.; Jacobs, Michael R.; Bonomo, Robert A.

    2017-01-01

    ABSTRACT Acinetobacter baumannii is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infections. Genetic changes that occur during host infection and treatment have the potential to remodel gene expression patterns related to resistance and pathogenesis. Longitudinal sets of multidrug-resistant A. baumannii isolates from eight patients were analyzed by RNA sequencing (RNA-seq) to identify differentially expressed genes and link them to genetic changes contributing to transcriptional variation at both within-patient and population levels. The number of differentially expressed genes among isolates from the same patient ranged from 26 (patient 588) to 145 (patient 475). Multiple patients had isolates with differential gene expression patterns related to mutations in the pmrAB and adeRS two-component regulatory system genes, as well as significant differences in genes related to antibiotic resistance, iron acquisition, amino acid metabolism, and surface-associated proteins. Population level analysis revealed 39 genetic regions with clade-specific differentially expressed genes, for which 19, 8, and 3 of these could be explained by insertion sequence mobilization, recombination-driven sequence variation, and intergenic mutations, respectively. Multiple types of mutations that arise during infection can significantly remodel the expression of genes that are known to be important in pathogenesis. PMID:28270585

  7. Reverse remodeling and recovery from cachexia in rats with aldosteronism.

    PubMed

    Cheema, Yaser; Zhao, Wenyuan; Zhao, Tieqiang; Khan, M Usman; Green, Kelly D; Ahokas, Robert A; Gerling, Ivan C; Bhattacharya, Syamal K; Weber, Karl T

    2012-08-15

    The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal.

  8. Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

    PubMed Central

    Muller, Jean; Laporte, Jocelyn

    2012-01-01

    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1) a common molecular pathway underlying these different neuromuscular diseases, and (2) tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches. PMID:22496665

  9. Integrative models of vascular remodeling during tumor growth

    PubMed Central

    Rieger, Heiko; Welter, Michael

    2015-01-01

    Malignant solid tumors recruit the blood vessel network of the host tissue for nutrient supply, continuous growth, and gain of metastatic potential. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature that is in many respects different from the hierarchically organized arterio-venous blood vessel network of the host tissues. Integrative models based on detailed experimental data and physical laws implement in silico the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. In this review, we give an overview over the current status of integrative models describing tumor growth, vascular remodeling, blood and interstitial fluid flow, drug delivery, and concomitant transformations of the microenvironment. © 2015 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. PMID:25808551

  10. LPS Remodeling Triggers Formation of Outer Membrane Vesicles in Salmonella

    PubMed Central

    Elhenawy, Wael; Bording-Jorgensen, Michael; Valguarnera, Ezequiel; Haurat, M. Florencia; Wine, Eytan

    2016-01-01

    ABSTRACT Outer membrane vesicles (OMV) are proposed to mediate multiple functions during pathogenesis and symbiosis. However, the mechanisms responsible for OMV formation remain poorly understood. It has been shown in eukaryotic membranes that lipids with an inverted-cone shape favor the formation of positive membrane curvatures. Based on these studies, we formulated the hypothesis that lipid A deacylation might impose shape modifications that result in the curvature of the outer membrane (OM) and subsequent OMV formation. We tested the effect of lipid A remodeling on OMV biogenesis employing Salmonella enterica serovar Typhimurium as a model organism. Expression of the lipid A deacylase PagL resulted in increased vesiculation, without inducing an envelope stress response. Mass spectrometry analysis revealed profound differences in the patterns of lipid A in OM and OMV, with accumulation of deacylated lipid A forms exclusively in OMV. OMV biogenesis by intracellular bacteria upon macrophage infection was drastically reduced in a pagL mutant strain. We propose a novel mechanism for OMV biogenesis requiring lipid A deacylation in the context of a multifactorial process that involves the orchestrated remodeling of the outer membrane. PMID:27406567

  11. Retinal Remodeling and Metabolic Alterations in Human AMD.

    PubMed

    Jones, Bryan W; Pfeiffer, Rebecca L; Ferrell, William D; Watt, Carl B; Tucker, James; Marc, Robert E

    2016-01-01

    Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease.

  12. Early remodeling of the neocortex upon episodic memory encoding.

    PubMed

    Bero, Adam W; Meng, Jia; Cho, Sukhee; Shen, Abra H; Canter, Rebecca G; Ericsson, Maria; Tsai, Li-Huei

    2014-08-12

    Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, whereas reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural, and functional remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal-hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states.

  13. Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution

    PubMed Central

    Baiocchini, Andrea; Montaldo, Claudia; Conigliaro, Alice; Grimaldi, Alessio; Correani, Virginia; Mura, Francesco; Ciccosanti, Fabiola; Rotiroti, Nicolina; Brenna, Alessia; Montalbano, Marzia; D’Offizi, Gianpiero; Capobianchi, Maria Rosaria; Alessandro, Riccardo; Piacentini, Mauro; Schininà, Maria Eugenia; Maras, Bruno; Del Nonno, Franca; Tripodi, Marco; Mancone, Carmine

    2016-01-01

    Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis). Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies. PMID:26998606

  14. Steroid control of muscle remodeling during metamorphosis in Manduca sexta.

    PubMed

    Hegstrom, C D; Truman, J W

    1996-04-01

    During metamorphosis in the tobacco hornworm, Manduca sexta, the abdominal body-wall muscle DEO1 is remodeled to form the adult muscle DE5. The degeneration of muscle DEO1 involves the dismantling of its contractile apparatus followed by the degeneration of muscle nuclei. As some nuclei are degenerating, others begin to incorporate 5-bromodeoxyuridine (BrdU), indicating the onset of nuclear proliferation. This proliferation is initially most evident at the site where the motoneuron contacts the muscle remnant. The developmental events involved in muscle remodeling are under the control of the steroid hormones, the ecdysteroids. The loss of the contractile elements of the larval muscle requires the rise and fall of the prepupal peak of ecdysteroids, whereas the subsequent loss of muscle nuclei is influenced by the slight rise in ecdysteroids seen after pupal ecdysis. Incorporation of BrdU by muscle nuclei depends on both the adult peak of the ecdysteroids and contact with the motoneuron. Unilateral axotomy blocks proliferation within the rudiment, but it does not block its subsequent differentiation into a very thin muscle in the adult.

  15. LKB1 and AMPK regulate synaptic remodeling in old age

    PubMed Central

    Samuel, Melanie A; Voinescu, P Emanuela; Lilley, Brendan N; de Cabo, Rafa; Foretz, Marc; Viollet, Benoit; Pawlyk, Basil; Sandberg, Michael A; Vavvas, Demetrios G; Sanes, Joshua R

    2015-01-01

    Age-related decreases in neural function result in part from alterations in synapses. To identify molecular defects that lead to such changes, we focused on the outer retina, in which synapses are markedly altered in old rodents and humans. We found that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate this process. In old mice, synaptic remodeling was accompanied by specific decreases in the levels of total LKB1 and active (phosphorylated) AMPK. In the absence of either kinase, young adult mice developed retinal defects similar to those that occurred in old wild-type animals. LKB1 and AMPK function in rod photoreceptors where their loss leads to aberrant axonal retraction, the extension of postsynaptic dendrites and the formation of ectopic synapses. Conversely, increasing AMPK activity genetically or pharmacologically attenuates and may reverse age-related synaptic alterations. Together, these results identify molecular determinants of age-related synaptic remodeling and suggest strategies for attenuating these changes. PMID:25086610

  16. Mediators of inflammation and bone remodeling in rheumatic disease

    PubMed Central

    Shaw, Anita T.; Gravallese, Ellen M.

    2015-01-01

    Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure the proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis (RA) and spondyloarthritis (SpA), a disease category that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases. PMID:26481971

  17. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    PubMed Central

    Nicolosi, Pier Andrea; Tombetti, Enrico; Maugeri, Norma; Rovere-Querini, Patrizia; Brunelli, Silvia; Manfredi, Angelo A.

    2016-01-01

    Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment. PMID:27069480

  18. Adrenal Androgen Dehydroepiandrosterone Sulfate Inhibits Vascular Remodeling Following Arterial Injury

    PubMed Central

    Ii, Masaaki; Hoshiga, Masaaki; Negoro, Nobuyuki; Fukui, Ryosuke; Nakakoji, Takahiro; Kohbayashi, Eiko; Shibata, Nobuhiko; Furutama, Daisuke; Ishihara, Tadashi; Hanafusa, Toshiaki; Losordo, Douglas W.; Ohsawa, Nakaaki

    2009-01-01

    Recent epidemiologic studies have suggested that serum dehydroepiandrosterone sulfate (DHEAS) levels have a significant inverse correlation with the incidence of cardiovascular diseases. However, direct evidence for the association with DHEAS and vascular disorders has not yet been explored. DHEAS significantly reduced neointima formation 28 days after surgery without altering other serum metabolite levels in a rabbit carotid balloon injury model. Immunohistochemical analyses revealed the reduction of proliferating cell nuclear antigen (PCNA) index and increase of TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) index, expressing differentiated vascular smooth muscle cell (VSMC) markers in the media 7 days after surgery. In vitro, DHEAS exhibited inhibitory effects on VSMC proliferation and migration activities, inducing G1 cell cycle arrest with upregulation of one of the cyclin dependent kinase (CDK) inhibitors p16INK4a and apoptosis with activating peroxisome proliferator-activated receptor (PPAR)-α in VSMCs. DHEAS inhibits vascular remodeling reducing neointima formation after vascular injury via its effects on VSMC phenotypic modulation, functions and apoptosis upregulating p16INK4a/activating PPARα. DHEAS may play a pathophysiological role for vascular remodeling in cardiovascular disease. PMID:19298964

  19. Membrane Remodeling by a Bacterial Phospholipid-Methylating Enzyme

    PubMed Central

    Danne, Linna; Aktas, Meriyem; Unger, Andreas; Linke, Wolfgang A.; Erdmann, Ralf

    2017-01-01

    ABSTRACT Membrane deformation by proteins is a universal phenomenon that has been studied extensively in eukaryotes but much less in prokaryotes. In this study, we discovered a membrane-deforming activity of the phospholipid N-methyltransferase PmtA from the plant-pathogenic bacterium Agrobacterium tumefaciens. PmtA catalyzes the successive three-step N-methylation of phosphatidylethanolamine to phosphatidylcholine. Here, we defined the lipid and protein requirements for the membrane-remodeling activity of PmtA by a combination of transmission electron microscopy and liposome interaction studies. Dependent on the lipid composition, PmtA changes the shape of spherical liposomes either into filaments or small vesicles. Upon overproduction of PmtA in A. tumefaciens, vesicle-like structures occur in the cytoplasm, dependent on the presence of the anionic lipid cardiolipin. The N-terminal lipid-binding α-helix (αA) is involved in membrane deformation by PmtA. Two functionally distinct and spatially separated regions in αA can be distinguished. Anionic interactions by positively charged amino acids on one face of the helix are responsible for membrane recruitment of the enzyme. The opposite hydrophobic face of the helix is required for membrane remodeling, presumably by shallow insertion into the lipid bilayer. PMID:28196959

  20. Microscale mechanisms of agarose-induced disruption of collagen remodeling.

    PubMed

    Ulrich, Theresa A; Lee, Tae Geol; Shon, Hyun Kyong; Moon, Dae Won; Kumar, Sanjay

    2011-08-01

    Cells are strongly influenced by the local structure and mechanics of the extracellular matrix (ECM). We recently showed that adding agarose to soft collagen ECMs can mechanically stiffen these hydrogels by two orders of magnitude while limiting 3D cell motility, which we speculated might derive from agarose-mediated inhibition of collagen fiber deformation and remodeling. Here, we directly address this hypothesis by investigating the effects of agarose on cell-collagen interactions at the microscale. Addition of agarose progressively restricts cell spreading, reduces stress fiber and focal adhesion assembly, and inhibits macroscopic gel compaction. While time-of-flight secondary ion mass spectrometry and scanning electron microscopy fail to reveal agarose-induced alterations in collagen ligand presentation, the latter modality shows that agarose strongly impairs cell-directed assembly of large collagen bundles. Agarose-mediated inhibition of cell spreading and cytoarchitecture can be rescued by β-agarase digestion or by covalently crosslinking the matrix with glutaraldehyde. Based on these results, we argue that cell spreading and motility on collagen requires local matrix stiffening, which can be achieved via cell-mediated fiber remodeling or by chemically crosslinking the fibers. These findings provide new mechanistic insights into the regulatory function of agarose and bear general implications for cell adhesion and motility in fibrous ECMs.

  1. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function

    PubMed Central

    Isaac, R Stefan; Jiang, Fuguo; Doudna, Jennifer A; Lim, Wendell A; Narlikar, Geeta J; Almeida, Ricardo

    2016-01-01

    The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo. DOI: http://dx.doi.org/10.7554/eLife.13450.001 PMID:27130520

  2. Intestinal Organoids: New Frontiers in the Study of Intestinal Disease and Physiology.

    PubMed

    Wallach, Thomas E; Bayrer, James R

    2017-02-01

    The development of sustainable intestinal organoid cell culture has emerged as a new modality for the study of intestinal function and cellular processes. Organoid culture is providing a new testbed for therapeutic research and development. Intestinal organoids, self-renewing 3-dimensional structures comprised intestinal stem cells and their differentiated epithelial progeny allow for more facile and robust exploration of cellular activity, cell organization and structure, genetic manipulation, and vastly more physiologic modeling of intestinal response to stimuli as compared to traditional 2-dimensional cell line cultures. Intestinal organoids are affecting a wide variety of research into gastrointestinal pathology. The purpose of this review is to discuss the current state-of-the-art and future effect of research using enteroids and colonoids (organoids grown from the small and large intestines, respectively).

  3. Intestinal bile acid physiology and pathophysiology

    PubMed Central

    Martínez-Augustin, Olga; de Medina, Fermín Sánchez

    2008-01-01

    Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipathic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology. PMID:18837078

  4. Multispectral tissue characterization for intestinal anastomosis optimization

    NASA Astrophysics Data System (ADS)

    Cha, Jaepyeong; Shademan, Azad; Le, Hanh N. D.; Decker, Ryan; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

    2015-10-01

    Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement.

  5. Mercury methylation by fish intestinal contents.

    PubMed Central

    Rudd, J W; Furutani, A; Turner, M A

    1980-01-01

    A new radiochemical method has been applied to the examination of mercury methylation in fish intestinal contents. Intestinal contents of six freshwater fish species were found capable of converting 203Hg2+ to CH3203Hg+. This activity was observed in fish from five of six lakes tested whether or not there was mercury pollution. Bacterial activity in the intestinal contents is most likely responsible for this methylation. Methylating activity of piscivors increased with decreasing quantity of intestinal contents. Generally, pike and walleye intestinal contents methylated a larger fraction of 203Hg2+ than those of whitefish and suckers. These data contradict the previous general conclusion that there is no mercury methylation in fish. PMID:7425625

  6. The intestinal lesion of autistic spectrum disorder.

    PubMed

    Jass, Jeremy R

    2005-08-01

    This editorial briefly reviews the significance of lymphoid nodular hyperplasia in the intestinal tract of children with autistic spectrum disorder. The distinction between physiological and pathological lymphoid hyperplasia of the intestinal tract is of importance in the context of a possible causative link with autism. A primary intestinal lesion may occur as part of the broad spectrum of immunological disorders to which autistic children are prone. This could result in increased intestinal permeability to peptides of dietary origin which may then lead to disruption of neuroregulatory mechanisms required for normal brain development. Alternatively, there could be a primary defect in the translocation and processing of factors derived from the intestinal lumen. These possibilities deserve further investigation and should not be lost in the fog of the controversy regarding the role of measles/mumps/rubella vaccination in the aetiology of autistic spectrum disorder.

  7. Relationship between Left Ventricular Structural and Metabolic Remodelling in Type 2 Diabetes Mellitus

    PubMed Central

    Levelt, Eylem; Mahmod, Masliza; Piechnik, Stefan K.; Ariga, Rina; Francis, Jane M.; Rodgers, Christopher T.; Clarke, William T.; Sabharwal, Nikant; Schneider, Jurgen E.; Karamitsos, Theodoros D.; Clarke, Kieran; Rider, Oliver J.; Neubauer, Stefan

    2016-01-01

    Concentric left ventricular (LV) remodelling is associated with adverse cardiovascular events and is frequently observed in patients with type 2 diabetes mellitus (T2DM). Despite this, the cause of concentric remodelling in diabetes, per se, is unclear, but may be related to cardiac steatosis and impaired myocardial energetics. Thus, we investigated the relationship amongst myocardial metabolic changes and LV remodelling in T2DM. Forty-six non-hypertensive T2DM patients and twenty matched controls underwent cardiovascular magnetic resonance to assess LV remodelling (LV mass to LV end diastolic volume ratio-LVMVR), function, pre- and post-contrast tissue characterisation using T1 mapping, 1H-, 31P-magnetic resonance spectroscopy for myocardial triglyceride content (MTG) and phosphocreatine to ATP ratio (PCr/ATP) respectively. When compared to body mass index and blood pressure matched controls, diabetes was associated with: concentric LV remodelling, higher MTG, impaired myocardial energetics and impaired systolic strain indicating a subtle contractile dysfunction. Importantly, cardiac steatosis independently predicted concentric remodelling and systolic strain. Extracellular volume fraction was unchanged, indicating absence of fibrosis. In conclusion, cardiac steatosis may contribute to LV concentric remodelling and contractile dysfunction in diabetes. As cardiac steatosis is modifiable, strategies aimed at reducing myocardial triglyceride may be beneficial in reversing concentric remodelling and improving contractile function in the diabetic heart. PMID:26438611

  8. 16 CFR 301.24 - Repairing, restyling and remodeling fur products for consumer.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Repairing, restyling and remodeling fur... UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.24 Repairing, restyling and remodeling fur products for consumer. When fur products owned by and...

  9. 16 CFR 301.24 - Repairing, restyling and remodeling fur products for consumer.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Repairing, restyling and remodeling fur... UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.24 Repairing, restyling and remodeling fur products for consumer. When fur products owned by and...

  10. 16 CFR 301.24 - Repairing, restyling and remodeling fur products for consumer.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Repairing, restyling and remodeling fur... UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.24 Repairing, restyling and remodeling fur products for consumer. When fur products owned by and...

  11. 16 CFR 301.24 - Repairing, restyling and remodeling fur products for consumer.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Repairing, restyling and remodeling fur... UNDER SPECIFIC ACTS OF CONGRESS RULES AND REGULATIONS UNDER FUR PRODUCTS LABELING ACT Regulations § 301.24 Repairing, restyling and remodeling fur products for consumer. When fur products owned by and...

  12. 16 CFR 301.24 - Repairing, restyling and remodeling fur products for consumer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Repairing, restyling and remodeling fur products for consumer. 301.24 Section 301.24 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS....24 Repairing, restyling and remodeling fur products for consumer. When fur products owned by and...

  13. Giving Your Building a Second Chance -- Guidelines for Remodeling Your Center.

    ERIC Educational Resources Information Center

    Wardle, Francis

    2001-01-01

    Discusses (1) factors supporting day care center remodeling; (2) assessing building suitability for remodeling; (3) documents to help in assessment; (4) creating a team; (5) cost and funding; and (6) overall design considerations. Emphasizes unique children's needs. Includes tips on indoor environments, individual classrooms, the playground, and…

  14. Relationship Between Left Ventricular Structural and Metabolic Remodeling in Type 2 Diabetes.

    PubMed

    Levelt, Eylem; Mahmod, Masliza; Piechnik, Stefan K; Ariga, Rina; Francis, Jane M; Rodgers, Christopher T; Clarke, William T; Sabharwal, Nikant; Schneider, Jurgen E; Karamitsos, Theodoros D; Clarke, Kieran; Rider, Oliver J; Neubauer, Stefan

    2016-01-01

    Concentric left ventricular (LV) remodeling is associated with adverse cardiovascular events and is frequently observed in patients with type 2 diabetes mellitus (T2DM). Despite this, the cause of concentric remodeling in diabetes per se is unclear, but it may be related to cardiac steatosis and impaired myocardial energetics. Thus, we investigated the relationship between myocardial metabolic changes and LV remodeling in T2DM. Forty-six nonhypertensive patients with T2DM and 20 matched control subjects underwent cardiovascular magnetic resonance to assess LV remodeling (LV mass-to-LV end diastolic volume ratio), function, tissue characterization before and after contrast using T1 mapping, and (1)H and (31)P magnetic resonance spectroscopy for myocardial triglyceride content (MTG) and phosphocreatine-to-ATP ratio, respectively. When compared with BMI- and blood pressure-matched control subjects, subjects with diabetes were associated with concentric LV remodeling, higher MTG, impaired myocardial energetics, and impaired systolic strain indicating a subtle contractile dysfunction. Importantly, cardiac steatosis independently predicted concentric remodeling and systolic strain. Extracellular volume fraction was unchanged, indicating the absence of fibrosis. In conclusion, cardiac steatosis may contribute to concentric remodeling and contractile dysfunction of the LV in diabetes. Because cardiac steatosis is modifiable, strategies aimed at reducing MTG may be beneficial in reversing concentric remodeling and improving contractile function in the hearts of patients with diabetes.

  15. Downregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR.

    PubMed

    Yin, Qian; Yang, Chengzhi; Wu, Jimin; Lu, Haiyan; Zheng, Xiaohui; Zhang, Youyi; Lv, Zhizhen; Zheng, Xiaopu; Li, Zijian

    2016-01-01

    β-adrenergic receptors (β-ARs) play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO) at the dose of 0.25 mg·kg(-1)·d(-1) for 7 days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB) is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR), a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling.

  16. Remodeling and Tenacity of Inhibitory Synapses: Relationships with Network Activity and Neighboring Excitatory Synapses.

    PubMed

    Rubinski, Anna; Ziv, Noam E

    2015-11-01

    Glutamatergic synapse size remodeling is governed not only by specific activity forms but also by apparently stochastic processes with well-defined statistics. These spontaneous remodeling processes can give rise to skewed and stable synaptic size distributions, underlie scaling of these distributions and drive changes in glutamatergic synapse size "configurations". Where inhibitory synapses are concerned, however, little is known on spontaneous remodeling dynamics, their statistics, their activity dependence or their long-term consequences. Here we followed individual inhibitory synapses for days, and analyzed their size remodeling dynamics within the statistical framework previously developed for glutamatergic synapses. Similar to glutamatergic synapses, size distributions of inhibitory synapses were skewed and stable; at the same time, however, sizes of individual synapses changed considerably, leading to gradual changes in synaptic size configurations. The suppression of network activity only transiently affected spontaneous remodeling dynamics, did not affect synaptic size configuration change rates and was not followed by the scaling of inhibitory synapse size distributions. Comparisons with glutamatergic synapses within the same dendrites revealed a degree of coupling between nearby inhibitory and excitatory synapse remodeling, but also revealed that inhibitory synapse size configurations changed at considerably slower rates than those of their glutamatergic neighbors. These findings point to quantitative differences in spontaneous remodeling dynamics of inhibitory and excitatory synapses but also reveal deep qualitative similarities in the processes that control their sizes and govern their remodeling dynamics.

  17. Interstitial fluid flow in canaliculi as a mechanical stimulus for cancellous bone remodeling: in silico validation.

    PubMed

    Kameo, Yoshitaka; Adachi, Taiji

    2014-08-01

    Cancellous bone has a dynamic 3-dimensional architecture of trabeculae, the arrangement of which is continually reorganized via bone remodeling to adapt to the mechanical environment. Osteocytes are currently believed to be the major mechanosensory cells and to regulate osteoclastic bone resorption and osteoblastic bone formation in response to mechanical stimuli. We previously developed a mathematical model of trabecular bone remodeling incorporating the possible mechanisms of cellular mechanosensing and intercellular communication in which we assumed that interstitial fluid flow activates the osteocytes to regulate bone remodeling. While the proposed model has been validated by the simulation of remodeling of a single trabecula, it remains unclear whether it can successfully represent in silico the functional adaptation of cancellous bone with its multiple trabeculae. In the present study, we demonstrated the response of cancellous bone morphology to uniaxial or bending loads using a combination of our remodeling model with the voxel finite element method. In this simulation, cancellous bone with randomly arranged trabeculae remodeled to form a well-organized architecture oriented parallel to the direction of loading, in agreement with the previous simulation results and experimental findings. These results suggested that our mathematical model for trabecular bone remodeling enables us to predict the reorganization of cancellous bone architecture from cellular activities. Furthermore, our remodeling model can represent the phenomenological law of bone transformation toward a locally uniform state of stress or strain at the trabecular level.

  18. Remodeling and Tenacity of Inhibitory Synapses: Relationships with Network Activity and Neighboring Excitatory Synapses

    PubMed Central

    Rubinski, Anna; Ziv, Noam E.

    2015-01-01

    Glutamatergic synapse size remodeling is governed not only by specific activity forms but also by apparently stochastic processes with well-defined statistics. These spontaneous remodeling processes can give rise to skewed and stable synaptic size distributions, underlie scaling of these distributions and drive changes in glutamatergic synapse size “configurations”. Where inhibitory synapses are concerned, however, little is known on spontaneous remodeling dynamics, their statistics, their activity dependence or their long-term consequences. Here we followed individual inhibitory synapses for days, and analyzed their size remodeling dynamics within the statistical framework previously developed for glutamatergic synapses. Similar to glutamatergic synapses, size distributions of inhibitory synapses were skewed and stable; at the same time, however, sizes of individual synapses changed considerably, leading to gradual changes in synaptic size configurations. The suppression of network activity only transiently affected spontaneous remodeling dynamics, did not affect synaptic size configuration change rates and was not followed by the scaling of inhibitory synapse size distributions. Comparisons with glutamatergic synapses within the same dendrites revealed a degree of coupling between nearby inhibitory and excitatory synapse remodeling, but also revealed that inhibitory synapse size configurations changed at considerably slower rates than those of their glutamatergic neighbors. These findings point to quantitative differences in spontaneous remodeling dynamics of inhibitory and excitatory synapses but also reveal deep qualitative similarities in the processes that control their sizes and govern their remodeling dynamics. PMID:26599330

  19. Costs of a more spacious home after remodelling by hermit crabs.

    PubMed

    Laidre, Mark E; Patten, Eli; Pruitt, Lisa

    2012-12-07

    Architectural creations occur throughout the animal kingdom, with invertebrates and vertebrates building structures such as homes to maximize their Darwinian fitness. Animal architects face many trade-offs in building optimally designed structures. But what about animals that do not build, and those that only remodel the original creations of others: do such secondary architects face similar trade-offs? Recent evidence has revealed that hermit crabs-animals well known for opportunistically moving into remnant gastropod shells-can also act as secondary architects, remodelling the shells they inherit from gastropods. Remodelling has only been found among terrestrial hermits (Coenobita spp.), not marine hermits. Here we investigate the potential trade-offs Coenobita compressus faces from remodelling by subjecting its remodelled and unremodelled homes to controlled engineering crush tests, which parallel the homes being crushed by predators. While remodelled homes are significantly more spacious and lightweight than unremodelled homes, we find that the homes attain these beneficial qualities at a cost: a reduced resistance to being crushed. Hermit crabs may therefore only remodel their homes to thresholds set by the bite force of their predators. Our results suggest that, like primary animal architects, which face trade-offs when optimizing architectural designs, secondary animal architects face trade-offs when remodelling such designs.

  20. Relationship between self-reported residential indoor remodeling and semen quality: a case-control study.

    PubMed

    Miao, Mao-Hua; Li, Zheng; Li, De-Kun; Yan, Bei; Liang, Hong; Zhi, Er-Lei; Du, Hong-Wei; Yuan, Wei

    2015-01-01

    The present study examined the association between residential indoor remodeling and poor semen quality. Sperm donors aged 18-45 years old were recruited in Shanghai, China. Semen specimens were collected and analyzed. An in-person interview was conducted to obtain information on the history of indoor remodeling and potential confounders. A total of 70 participants with abnormal semen quality (case group) and 68 controls were examined. A total of 20 subjects reported indoor remodeling in the recent 24 months, and among them 17 subjects reported indoor remodeling in the recent 12 months. Compared with participants with no history of indoor remodeling, participants with a history of indoor remodeling in the recent 24 months were more than three times as likely to have poor sperm quality (adjusted odds ratio = 3.8, 95% confidence interval: 1.3-12.0) after controlling for potential confounders. The association was strengthened when the analysis was restricted to those who had indoor remodeling in the recent 12 months. Our findings provide preliminary evidence that indoor remodeling has an adverse effect on semen quality.

  1. Successful Endothelialization and Remodeling of a Cell-Free Small-Diameter Arterial Graft in a Large Animal Model

    PubMed Central

    Koobatian, Maxwell T.; Row, Sindhu; Smith, Randall; Koenigsknecht, Carmon; Andreadis, Stelios T.; Swartz, Daniel D.

    2015-01-01

    The large number of coronary artery bypass procedures necessitates development of off-the-shelf vascular grafts that do not require cell or tissue harvest from patients. However, immediate thrombus formation after implantation due to the absence of a healthy endothelium is very likely. Here we present the successful development of an Acellular Tissue Engineered Vessel (A-TEV) based on small intestinal submucosa that was functionalized sequentially with heparin and VEGF. A-TEVs were implanted into the carotid artery of an ovine model demonstrating high patency rates and significant host cell infiltration as early as one week post-implantation. At one month, a confluent and functional endothelium was present and the vascular wall showed significant infiltration of host smooth muscle cells exhibiting vascular contractility in response to vaso-agonists. After three months the endothelium aligned in the direction of flow and the medial layer comprised of circumferentially aligned smooth muscle cells. A-TEVs demonstrated high elastin and collagen content as well as impressive mechanical properties and vascular contractility comparable to native arteries. This is the first demonstration of successful endothelialization, remodeling, and development of vascular function of a cell-free vascular graft that was implanted in the arterial circulation of a pre-clinical animal model. PMID:26561932

  2. Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells

    PubMed Central

    Robinson, Benjamin K.; Cortes, Ernesto; Rice, Alistair J.; Sarper, Muge

    2016-01-01

    ABSTRACT Extracellular matrix (ECM) remodelling is integral to numerous physiological and pathological processes in biology, such as embryogenesis, wound healing, fibrosis and cancer. Until recently, most cellular studies have been conducted on 2D environments where mechanical cues significantly differ from physiologically relevant 3D environments, impacting cellular behaviour and masking the interpretation of cellular function in health and disease. We present an integrated methodology where cell-ECM interactions can be investigated in 3D environments via ECM remodelling. Monitoring and quantification of collagen-I structure in remodelled matrices, through designated algorithms, show that 3D matrices can be used to correlate remodelling with increased ECM stiffness observed in fibrosis. Pancreatic stellate cells (PSCs) are the key effectors of the stromal fibrosis associated to pancreatic cancer. We use PSCs to implement our methodology and demonstrate that PSC matrix remodelling capabilities depend on their contractile machinery and β1 integrin-mediated cell-ECM attachment. PMID:27170254

  3. Intestinal mucosal atrophy and adaptation.

    PubMed

    Shaw, Darcy; Gohil, Kartik; Basson, Marc D

    2012-11-28

    Mucosal adaptation is an essential process in gut homeostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation. This review will summarize current understanding of the basic science surrounding adaptation, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes.

  4. Intestinal mucosal atrophy and adaptation

    PubMed Central

    Shaw, Darcy; Gohil, Kartik; Basson, Marc D

    2012-01-01

    Mucosal adaptation is an essential process in gut homeostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation. This review will summarize current understanding of the basic science surrounding adaptation, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes. PMID:23197881

  5. Rutaecarpine attenuates hypoxia-induced right ventricular remodeling in rats.

    PubMed

    Li, Wen-Qun; Li, Xiao-Hui; Du, Jie; Zhang, Wang; Li, Dai; Xiong, Xiao-Ming; Li, Yuan-Jian

    2016-07-01

    Rutaecarpine has been shown to exhibit wide pharmacological effects in the cardiovascular system via stimulation of calcitonin gene-related peptide (CGRP) release. In the present study, the effect of rutaecarpine on hypoxia-induced right ventricular (RV) remodeling and the underlying mechanisms were evaluated. RV remodeling was induced by hypoxia (10 % O2, 3 weeks) in rats. Rats were treated with rutaecarpine (20 or 40 mg/kg) by intragastric administration. Proliferation of cardiac fibroblasts was induced by TGF-β1 (5 ng/mL) and determined by MTS and EdU incorporation method. Cardiac fibroblasts were treated with exogenous CGRP (10 or 100 nM). The concentrations of CGRP and TGF-β1 in plasma were measured by ELISA. The expression of eIF3a, p27, α-SMA, collagen-I/III, ANP, and BNP were measured by real-time PCR or western blot. Hypoxia induced an increase of right ventricle systolic pressure (RVSP), ration of RV/LV+S, and RV/tibial length in rats, while cardiac hypertrophy, apoptosis, and fibrosis were detected. The expression of ANP, BNP, α-SMA, collagen-I, collagen-III, eIF3a, and TGF-β1 was up-regulated, and the expression of p27 was down-regulated in the right ventricle of hypoxia-treated rats. The plasma concentration of CGRP was decreased and TGF-β1 was increased in hypoxia-treated rats. All of these effects induced by hypoxia were attenuated by rutaecarpine in a dose-dependent manner. In cultured cardiac fibroblasts, TGF-β1 significantly promoted the proliferation and up-regulated the expression of α-SMA and collagen-I/III, while the expression of eIF3a was up-regulated and the expression of p27 was down-regulated. The effects of TGF-β1 were attenuated by CGRP. CGRP8-37, a selective CGRP receptor antagonist, abolished the effects of CGRP. Rutaecarpine attenuates hypoxia-induced RV remodeling via stimulation of CGRP release, and the effects of rutaecarpine involve the eIF3a/p27 pathway.

  6. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.

    PubMed

    Obrowsky, Sascha; Chandak, Prakash G; Patankar, Jay V; Povoden, Silvia; Schlager, Stefanie; Kershaw, Erin E; Bogner-Strauss, Juliane G; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar

    2013-02-01

    Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor α (PPARα). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [(3)H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [(3)H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPARα target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPARα-dependent processes also in the small intestine.

  7. Intestinal lymphangiectasia and thymic hypoplasia.

    PubMed Central

    Sorensen, R U; Halpin, T C; Abramowsky, C R; Hornick, D L; Miller, K M; Naylor, P; Incefy, G S

    1985-01-01

    We have evaluated the immunological abnormalities present in a 6 year old patient with primary intestinal and generalized lymphangiectasia confirmed by intestinal, lung and lymph node biopsies. Lymphocyte loss through the gut was confirmed by the detection of lymphocytes in her stool. An increased enteric protein loss was suggested by hypoproteinaemia, peripheral oedema, and a very short half-life for i.v. immune serum globulin (3 days). Lymphocyte subpopulation analysis revealed a selective loss of T lymphocytes, with a proportionally increased loss of the OKT4 positive helper/inducer subpopulation. Functionally, there was a decrease in proliferative responses to some mitogens and to allogeneic cells, and a lack of T cell help for in vitro B lymphocyte differentiation into immunoglobulin secreting cells. Natural killer function was normal. In this patient, a concomitant thymic deficiency was documented by failure to identify thymic tissue on a thymus biopsy and by an absence or decrease of the serum thymic factor (thymulin) and thymosin alpha 1. No compensatory lymphopoiesis was detected in the bone marrow. In an attempt to increase T lymphocyte development, the patient was treated with thymosin fraction 5. Daily treatment with this preparation resulted in a transient clinical improvement which could not be sustained on a weekly thymosin treatment schedule. However, lymphocyte numbers did not increase during this treatment. The findings in this patient support the notion that T lymphocytes are needed to stimulate thymic epithelium. In situations of excessive loss of long lived T lymphocytes a secondary thymic atrophy may occur and further contribute to the development of a deficiency in cell-mediated immunity. Images Fig. 1 Fig. 2 PMID:3971596

  8. Intestinal microbiota, diet and health.

    PubMed

    Power, Susan E; O'Toole, Paul W; Stanton, Catherine; Ross, R Paul; Fitzgerald, Gerald F

    2014-02-01

    The human intestine is colonised by 10¹³ to 10¹⁴ micro-organisms, the vast majority of which belong to the phyla Firmicutes and Bacteroidetes. Although highly stable over time, the composition and activities of the microbiota may be influenced by a number of factors including age, diet and antibiotic treatment. Although perturbations in the composition or functions of the microbiota are linked to inflammatory and metabolic disorders (e.g. inflammatory bowel diseases, irritable bowel syndrome and obesity), it is unclear at this point whether these changes are a symptom of the disease or a contributing factor. A better knowledge of the mechanisms through which changes in microbiota composition (dysbiosis) promote disease states is needed to improve our understanding of the causal relationship between the gut microbiota and disease. While evidence of the preventive and therapeutic effects of probiotic strains on diarrhoeal illness and other intestinal conditions is promising, the exact mechanisms of the beneficial effects are not fully understood. Recent studies have raised the question of whether non-viable probiotic strains can confer health benefits on the host by influencing the immune system. As the potential health effect of these non-viable bacteria depends on whether the mechanism of this effect is dependent on viability, future research needs to consider each probiotic strain on a case-by-case basis. The present review provides a comprehensive, updated overview of the human gut microbiota, the factors influencing its composition and the role of probiotics as a therapeutic modality in the treatment and prevention of diseases and/or restoration of human health.

  9. Vitamin D and intestinal calcium absorption.

    PubMed

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J; Seth, Tanya

    2011-12-05

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed.

  10. The Circadian Clock Mutation Promotes Intestinal Dysbiosis

    PubMed Central

    Voigt, Robin M.; Summa, Keith C.; Forsyth, Christopher B.; Green, Stefan J.; Engen, Phillip; Naqib, Ankur; Vitaterna, Martha H.; Turek, Fred W; Keshavarzian, Ali

    2016-01-01

    Background Circadian rhythm disruption is a prevalent feature of modern day society that is associated with an increase in pro-inflammatory diseases and there is a clear need for a better understanding of the mechanism(s) underlying this phenomenon. We have previously demonstrated that both environmental and genetic circadian rhythm disruption causes intestinal hyperpermeability and exacerbates alcohol-induced intestinal hyperpermeability and liver pathology. The intestinal microbiota can influence intestinal barrier integrity and impact immune system function; thus, in the current study, we sought to determine if genetic alteration of the core circadian clock gene, Clock, altered the intestinal microbiota community. Methods Male ClockΔ19 mutant mice (mice homozygous for a dominant-negative mutant allele) or littermate wild-type mice were fed one of three experimental diets: (1) a standard chow diet, (2) an alcohol-containing diet, or (3) an alcohol-control diet in which the alcohol calories were replaced with dextrose. Stool microbiota was assessed with 16S ribosomal RNA gene amplicon sequencing. Results The fecal microbial community of Clock mutant mice had lower taxonomic diversity, relative to wild type mice and the ClockΔ19 mutation was associated with intestinal dysbiosis when mice were fed either the alcohol-containing or the control diet. We found that alcohol consumption significantly altered the intestinal microbiota in both wild type and Clock mutant mice. Conclusion Our data support a model by which circadian rhythm disruption by the ClockΔ19 mutation perturbs normal intestinal microbial communities and this trend was exacerbated in the context of a secondary dietary intestinal stressor. PMID:26842252

  11. Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis

    PubMed Central

    Swinehart, Ilea T.; Badylak, Stephen F.

    2016-01-01

    During normal morphogenesis the extracellular matrix (ECM) influences cell motility, proliferation, apoptosis, and differentiation. Tissue engineers have attempted to harness the cell signaling potential of ECM to promote the functional reconstruction, if not regeneration, of injured or missing adult tissues that otherwise heal by the formation of scar tissue. ECM bioscaffolds, derived from decellularized tissues, have been used to promote the formation of site appropriate, functional tissues in many clinical applications including skeletal muscle, fibrocartilage, lower urinary tract, and esophageal reconstruction, among others. These scaffolds function by the release or exposure of growth factors and cryptic peptides, modulation of the immune response, and recruitment of progenitor cells. Herein, we describe this process of ECM induced constructive remodeling and examine similarities to normal tissue morphogenesis. PMID:26699796

  12. DNA methylation remodeling in vitro and in vivo

    PubMed Central

    Clark, Amander T

    2015-01-01

    In mammals, global DNA demethylation in vivo occurs in the pre-implantation embryo and in primordial germ cells (PGCs) where it is hypothesized to create a blank slate or “tabula rasa” upon which new DNA methylation patterns are written. However, global DNA demethylation in vivo is far from complete with a small number of loci protected from demethylation. Failure to demethylate, or overt demethylation results in compromised differentiation. Recent work has shown that reversion of primed human pluripotent stem cells to the naïve state leads to unbridled DNA demethylation which has unknown consequences on the quality differentiated cells created in vitro. Taken together understanding DNA methylation remodeling is critical for understanding the epigenetic foundations of life, and the quality of stem cells for regenerative medicine. PMID:26451496

  13. Effects of mechanical stimuli on adaptive remodeling of condylar cartilage.

    PubMed

    Sriram, D; Jones, A; Alatli-Burt, I; Darendeliler, M A

    2009-05-01

    Trabecular bone has been shown to be responsive to low-magnitude, high-frequency mechanical stimuli. This study aimed to assess the effects of these stimuli on condylar cartilage and its endochondral bone. Forty female 12-week-old C3H mice were divided into 3 groups: baseline control (killed at day 0), sham (killed at day 28 without exposure to mechanical stimuli), and experimental (killed following 28 days of exposure to mechanical stimuli). The experimental group was subjected to mechanical vibration of 30 Hz, for 20 minutes per day, 5 days per week, for 28 days. The specimens were analyzed by micro-computed tomography. The experimental group demonstrated a significant decrease in the volume of condylar cartilage and also a significant increase in bone histomorphometric parameters. The results suggest that the low-magnitude, high-frequency mechanical stimuli enhance adaptive remodeling of condylar cartilage, evidenced by the advent of endochondral bone replacing the hypertrophic cartilage.

  14. Promoting brain remodeling to aid in stroke recovery

    PubMed Central

    Zhang, Zheng Gang; Chopp, Michael

    2015-01-01

    Endogenous brain repair after stroke involves a set of highly interactive processes, such as angiogenesis, neurogenesis, oligodendrogenesis, synaptogenesis and axonal outgrowth, which together orchestrate neurological recovery. During the past several years, there have been advances in our understanding of miRNAs and histone deacetylases (HDACs) in brain repair processes after stroke. Emerging data indicate the important role of exosomes for intercellular communication in promoting coupled brain remodeling processes. These advances will likely have a major impact on development of restorative therapies for ischemic brain repair, consequently leading to improvement of neurological function. In this review, we provide an update on our current understanding of cellular and molecular mechanisms of miRNAs, exosomes, and HDACs in brain restorative processes after stroke. PMID:26278490

  15. Metabolic Remodeling in early development and cardiomyocyte maturation

    PubMed Central

    Kreipke, Rebecca; Wang, Yuliang; Miklas, Jason Wayne; Mathieu, Julie; Ruohola-Baker, Hannele

    2016-01-01

    Aberrations in metabolism contribute to a large number of diseases, such as diabetes, obesity, cancer, and cardiovascular diseases, that have a substantial impact on the mortality rates and quality of life worldwide. However, the mechanisms leading to these changes in metabolic state – and whether they are conserved between diseases – is not well understood. Changes in metabolism similar to those seen in pathological conditions are observed during normal development in a number of different cell types. This provides hope that understanding the mechanism of these metabolic switches in normal development may provide useful insight in correcting them in pathological cases. Here, we focus on the metabolic remodeling observed both in early stage embryonic stem cells and during the maturation of cardiomyocytes. PMID:26912118

  16. JOINING THE DOTS: FROM CHROMATIN REMODELING TO NEURONAL PLASTICITY

    PubMed Central

    Zocchi, Loredana; Sassone-Corsi, Paolo

    2010-01-01

    SUMMARY In recent years spectacular advances in the field of epigenetics have taken place. Multiple lines of evidence that connect epigenetic regulation to brain functions have been accumulating. Neurons daily convert a variety of external stimuli into rapid or long-lasting changes in gene expression. Control is achieved through several post-translational modifications that occur both on DNA and chromatin. Specific modifications mediate many developmental processes and adult brain functions, such as synaptic plasticity and memory. In this review, we focus on critical chromatin remodeling events that mediate long-lasting neuronal responses. The challenging goal is to reach sufficient understanding of these epigenetic pathways in the brain so that they may be useful for future development of specific pharmacological strategies. PMID:20471240

  17. Alternative lengthening of telomeres: remodeling the telomere architecture.

    PubMed

    Conomos, Dimitri; Pickett, Hilda A; Reddel, Roger R

    2013-01-01

    To escape from the normal limits on proliferative potential, cancer cells must employ a means to counteract the gradual telomere attrition that accompanies semi-conservative DNA replication. While the majority of human cancers do this by up-regulating telomerase enzyme activity, most of the remainder use a homologous recombination-mediated mechanism of telomere elongation known as alternative lengthening of telomeres (ALT). Many molecular details of the ALT pathway are unknown, and even less is known regarding the mechanisms by which this pathway is activated. Here, we review current findings about telomere structure in ALT cells, including DNA sequence, shelterin content, and heterochromatic state. We speculate that remodeling of the telomere architecture may contribute to the emergence and maintenance of the ALT phenotype.

  18. Minireview: Nuclear Receptor Regulation of Osteoclast and Bone Remodeling

    PubMed Central

    Jin, Zixue; Li, Xiaoxiao

    2015-01-01

    Osteoclasts are bone-resorbing cells essential for skeletal remodeling and regeneration. However, excessive osteoclasts often contribute to prevalent bone degenerative diseases such as osteoporosis, arthritis, and cancer bone metastasis. Osteoclast dysregulation is also associated with rare disorders such as osteopetrosis, pycnodysostosis, Paget's disease, and Gorham-Stout syndrome. The nuclear receptor (NR) family of transcription factors functions as metabolic sensors that control a variety of physiological processes including skeletal homeostasis and serves as attractive therapeutic targets for many diseases. In this review, we highlight recent findings on the new players and the new mechanisms for how NRs regulate osteoclast differentiation and bone resorption. An enhanced understanding of NR functions in osteoclastogenesis will facilitate the development of not only novel osteoprotective medicine but also prudent strategies to minimize the adverse skeletal effects of certain NR-targeting drugs for a better treatment of cancer and metabolic diseases. PMID:25549044

  19. The Role of Semaphorin 3A in Bone Remodeling

    PubMed Central

    Li, Zhenxia; Hao, Jin; Duan, Xin; Wu, Nan; Zhou, Zongke; Yang, Fan; Li, Juan; Zhao, Zhihe; Huang, Shishu

    2017-01-01

    Bone remodeling occurs at the bone surface throughout adult life and associates bony quantity and quality. This process is a balance between the osteoblastic bone formation and osteoclastic bone resorption, which cross-talks together. Semaphorin 3A is a membrane-associated secreted protein and regarded as a diffusible axonal chemorepellent, which has been identified in the involvement of bone resorption and formation synchronously. However, the role of Semaphorin 3A in bone homeostasis and diseases remains elusive, in particular the association to osteoblasts and osteoclasts. In this review article, we summarize recent progress of Semaphorin 3A in the bone mass, homeostasis, and diseases and discuss the novel application of nerve-based bone regeneration. This will facilitate the understanding of Semaphorin 3A in skeletal biology and shed new light on the modulation and potential treatment in the bone disorders. PMID:28293171

  20. mAKAP – A Master Scaffold for Cardiac Remodeling

    PubMed Central

    Passariello, Catherine L.; Li, Jinliang; Dodge-Kafka, Kimberly; Kapiloff, Michael S.

    2014-01-01

    Cardiac remodeling is regulated by an extensive intracellular signal transduction network. Each of the many signaling pathways in this network contributes uniquely to the control of cellular adaptation. In the last few years, it has become apparent that multimolecular signaling complexes or ‘signalosomes’ are important for fidelity in intracellular signaling and for mediating crosstalk between the different signaling pathways. These complexes integrate upstream signals and control downstream effectors. In the cardiac myocyte, the protein mAKAPβ serves as a scaffold for a large signalosome that is responsive to cAMP, calcium, hypoxia, and mitogen-activated protein kinase signaling. The main function of mAKAPβ signalosomes is to modulate stress-related gene expression regulated by the transcription factors NFATc, MEF2 and HIF-1α and type II histone deacetylases that control pathological cardiac hypertrophy. PMID:25551320

  1. RSK3 – A Regulator of Pathological Cardiac Remodeling

    PubMed Central

    Martinez, Eliana C.; Passariello, Catherine L.; Li, Jinliang; Matheson, Christopher J.; Dodge-Kafka, Kimberly; Reigan, Philip; Kapiloff, Michael S.

    2015-01-01

    Summary The family of p90 ribosomal S6 kinases (RSK) are pleiotropic effectors for extracellular signal-regulated kinase (ERK) signaling pathways. Recently, RSK3 was shown to be important for pathological remodeling of the heart. While cardiac myocyte hypertrophy can be compensatory for increased wall stress, in chronic heart diseases this non-mitotic cell growth is usually associated with interstitial fibrosis, increased cell death, and decreased cardiac function. Although RSK3 is less abundant in the cardiac myocyte than other RSK family members, RSK3 appears to serve a unique role in cardiac myocyte stress responses. A potential mechanism conferring RSK3’s unique function in the heart is anchoring by the scaffold protein muscle A-kinase Anchoring Protein β (mAKAPβ). Recent findings suggest that RSK3 should be considered as a therapeutic target for the prevention of heart failure, a clinical syndrome of major public health significance. PMID:25988524

  2. Neural plasticity and network remodeling: From concepts to pathology.

    PubMed

    Cohen, Erez James; Quarta, Eros; Bravi, Riccardo; Granato, Alberto; Minciacchi, Diego

    2017-03-06

    Neuroplasticity has been subject to a great deal of research in the last century. Recently, significant emphasis has been placed on the global effect of localized plastic changes throughout the central nervous system, and on how these changes integrate in a pathological context. Specifically, alterations of network functionality have been described in various pathological contexts to which corresponding structural alterations have been proposed. However, considering the amount of literature and the different pathological contexts, an integration of this information is still lacking. In this paper we will review the concepts of neural plasticity as well as their repercussions on network remodeling and provide a possible explanation to how these two concepts relate to each other. We will further examine how alterations in different pathological contexts may relate to each other and will discuss the concept of plasticity diseases, its models and implications.

  3. Re-modelled CT unit quickly up to speed.

    PubMed

    2011-06-01

    Medical turnkey pre-installation specialist Canute International Medical Services (CIMS) recently supported provider of managed equipment services Asteral in a project to re-model the Rowan Bentall wing of Surrey's Kingston Hospital. The new CT scanning facility was developed by Asteral via an MES agreement, elements of which included two new CT scanners, major refurbishment of the existing building, and ongoing maintenance and finance. As HEJ editor Jonathan Baillie reports, despite a tight two-month schedule, the project team's expertise, and meticulous co-ordination and planning, enabled the delivery of a significantly enhanced facility on time and on budget with minimal disruption and without a single day's scanning being lost.

  4. Pharmacological induction of transforming growth factor-beta1 in rat models enhances radiation injury in the intestine and the heart.

    PubMed

    Boerma, Marjan; Wang, Junru; Sridharan, Vijayalakshmi; Herbert, Jean-Marc; Hauer-Jensen, Martin

    2013-01-01

    Radiation therapy in the treatment of cancer is dose limited by radiation injury in normal tissues such as the intestine and the heart. To identify the mechanistic involvement of transforming growth factor-beta 1 (TGF-β1) in intestinal and cardiac radiation injury, we studied the influence of pharmacological induction of TGF-β1 with xaliproden (SR 57746A) in rat models of radiation enteropathy and radiation-induced heart disease (RIHD). Because it was uncertain to what extent TGF-β induction may enhance radiation injury in heart and intestine, animals were exposed to irradiation schedules that cause mild to moderate (acute) radiation injury. In the radiation enteropathy model, male Sprague-Dawley rats received local irradiation of a 4-cm loop of rat ileum with 7 once-daily fractions of 5.6 Gy, and intestinal injury was assessed at 2 weeks and 12 weeks after irradiation. In the RIHD model, male Sprague-Dawley rats received local heart irradiation with a single dose of 18 Gy and were followed for 6 months after irradiation. Rats were treated orally with xaliproden starting 3 days before irradiation until the end of the experiments. Treatment with xaliproden increased circulating TGF-β1 levels by 300% and significantly induced expression of TGF-β1 and TGF-β1 target genes in the irradiated intestine and heart. Various radiation-induced structural changes in the intestine at 2 and 12 weeks were significantly enhanced with TGF-β1 induction. Similarly, in the RIHD model induction of TGF-β1 augmented radiation-induced changes in cardiac function and myocardial fibrosis. These results lend further support for the direct involvement of TGF-β1 in biological mechanisms of radiation-induced adverse remodeling in the intestine and the heart.

  5. Intestinal pseudo-obstruction associated with amyloidosis.

    PubMed

    Liapis, Konstantinos; Michelis, Fotios V; Delimpasi, Sosanna; Karmiris, Themistoklis

    2011-06-01

    Intestinal pseudo-obstruction is a condition characterised by clinical manifestations of mechanical obstruction of the intestine in the absence of any organic occlusion of the lumen. This syndrome has rarely been reported to complicate the course of systemic amyloidosis. We describe the case of a 64-year-old man who presented with the syndrome of small bowel pseudo-obstruction secondary to AL amyloid infiltration of the gastrointestinal tract. We comment on the pathophysiology and on the clinical importance of amyloidosis-associated intestinal pseudo-obstruction.

  6. Cytoskeletal Expression and Remodeling in Pluripotent Stem Cells

    PubMed Central

    Boraas, Liana C.; Guidry, Julia B.; Pineda, Emma T.; Ahsan, Tabassum

    2016-01-01

    Many emerging cell-based therapies are based on pluripotent stem cells, though complete understanding of the properties of these cells is lacking. In these cells, much is still unknown about the cytoskeletal network, which governs the mechanoresponse. The objective of this study was to determine the cytoskeletal state in undifferentiated pluripotent stem cells and remodeling with differentiation. Mouse embryonic stem cells (ESCs) and reprogrammed induced pluripotent stem cells (iPSCs), as well as the original un-reprogrammed embryonic fibroblasts (MEFs), were evaluated for expression of cytoskeletal markers. We found that pluripotent stem cells overall have a less developed cytoskeleton compared to fibroblasts. Gene and protein expression of smooth muscle cell actin, vimentin, lamin A, and nestin were markedly lower for ESCs than MEFs. Whereas, iPSC samples were heterogeneous with most cells expressing patterns of cytoskeletal proteins similar to ESCs with a small subpopulation similar to MEFs. This indicates that dedifferentiation during reprogramming is associated with cytoskeletal remodeling to a less developed state. In differentiation studies, it was found that shear stress-mediated differentiation resulted in an increase in expression of cytoskeletal intermediate filaments in ESCs, but not in iPSC samples. In the embryoid body model of spontaneous differentiation of pluripotent stem cells, however, both ESCs and iPSCs had similar gene expression for cytoskeletal proteins during early differentiation. With further differentiation, however, gene levels were significantly higher for iPSCs compared to ESCs. These results indicate that reprogrammed iPSCs more readily reacquire cytoskeletal proteins compared to the ESCs that need to form the network de novo. The strategic selection of the parental phenotype is thus critical not only in the context of reprogramming but also the ultimate functionality of the iPSC-differentiated cell population. Overall, this

  7. Maternal Nutrient Restriction Predisposes Ventricular Remodeling in Adult Sheep Offspring

    PubMed Central

    Ge, Wei; Hu, Nan; George, Lindsey A.; Ford, Stephen P.; Nathanielsz, Peter W.; Wang, Xiaoming; Ren, Jun

    2012-01-01

    Maternal nutrient restriction during pregnancy is associated with the development of a “thrifty phenotype” in offspring, conferring increased prevalence of metabolic diseases in adulthood. To explore the possible mechanisms behind heart diseases in adulthood following maternal nutrient restriction, dams were fed a nutrient restricted (NR: 50%) or control (100%) diet from 28 to 78 d of gestation. Both groups were then fed 100% of requirements to lambing. At 6 yrs of age, female offspring of NR and control ewes of similar weight and body condition were subject to ad libitum feeding of a highly palatable diet for 12 wks. Cardiac geometry, post-insulin receptor signaling, autophagy and pro-inflammatory cytokines were evaluated in hearts from adult offspring. Our results indicated that maternal nutrient restriction overtly increased body weight gain and triggered cardiac remodeling in offspring following the 12-week ad libitum feeding. Phosphorylation of IRS1 was increased in left but not right ventricles from NR offspring. Levels of STAT3 were upregulated in left ventricles whereas expression of TNFα and TLR4 was enhanced in right ventricles in adult offspring of maternal nutrition restricted ewes. No significant differences were found in pan IRS-1, pan AMPK, pan Akt, pAMPK, pAkt, GLUT4, phosphorylated mTOR, Beclin-1 and LC3 II proteins in left and right ventricle between the control and NR offspring. These data revealed that maternal nutrient restriction during early to mid gestation may predispose adult offspring to cardiac remodeling possibly associated with phosphorylation of IRS1 as well as proinflammatory cytokines but not autophagy. PMID:23333094

  8. Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis.

    PubMed

    Lund, Amie K; Knuckles, Travis L; Obot Akata, Chrys; Shohet, Ralph; McDonald, Jacob D; Gigliotti, Andrew; Seagrave, Jean Clare; Campen, Matthew J

    2007-02-01

    Epidemiological evidence indicates that environmental air pollutants are positively associated with the development of chronic vascular disease; however, the mechanisms involved have not been fully elucidated. In the present study we examined molecular pathways associated with chronic vascular disease in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice, including markers of vascular remodeling and oxidative stress, in response to exposure to the ubiquitous environmental pollutant, gasoline engine emissions. ApoE(-/-) mice, on a high-fat diet, were exposed by inhalation to either filtered air; 8, 40, or 60 mug/m(3) particulate matter whole exhaust; or filtered exhaust with gases matching the 60-mug/m(3) concentration, for 7 weeks. Aortas and plasma were collected and assayed for changes in histochemical markers, real-time reverse transcriptase-polymerase chain reaction, and indicators of oxidative damage. Inhalational exposure to gasoline engine emissions resulted in increased aortic mRNA expression of matrix metalloproteinase-3 (MMP-3), MMP-7, and MMP-9, tissue inhibitor of metalloproteinases-2, endothelin-1 and heme oxygenase-1 in ApoE(-/-) mice; increased aortic MMP-9 protein levels were confirmed through immunohistochemistry. Elevated reactive oxygen species were also observed in arteries from exposed animals, despite absence of plasma markers. Similar findings were also observed in the aortas of ApoE(-/-) mice exposed to particle-filtered atmosphere, implicating the gaseous components of the whole exhaust in mediating the expression of markers associated with the vasculopathy. These findings demonstrate that exposure to gasoline engine emissions results in the transcriptional upregulation of factors associated with vascular remodeling, as well as increased markers of vascular oxidative stress, which may contribute to the progression of atherosclerosis and reduced stability of vulnerable plaques.

  9. Left ventricular structure and remodeling in patients with COPD

    PubMed Central

    Pelà, Giovanna; Li Calzi, Mauro; Pinelli, Silvana; Andreoli, Roberta; Sverzellati, Nicola; Bertorelli, Giuseppina; Goldoni, Matteo; Chetta, Alfredo

    2016-01-01

    Background Data on cardiac alterations such as left ventricular (LV) hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features. Methods Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score. Results Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT), suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that – after multivariate analysis – significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42) predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59–0.81). Patients with COPD showed right ventricular to be functional but no structural changes. Conclusion Patients with COPD without evident cardiovascular disease exhibit significant changes in LV geometry, resulting in concentric remodeling. In all individuals, RWT was significantly and independently related to COPD. However, its prognostic role should be determined in future studies. PMID:27257378

  10. Tie1 controls angiopoietin function in vascular remodeling and inflammation

    PubMed Central

    Korhonen, Emilia A.; Lampinen, Anita; Giri, Hemant; Kim, Minah; Allen, Breanna; D’Amico, Gabriela; Sipilä, Tuomas J.; Lohela, Marja; Vaheri, Antti; Ylä-Herttuala, Seppo; Koh, Gou Young; McDonald, Donald M.

    2016-01-01

    The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin–dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability. PMID:27548530

  11. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    PubMed Central

    Garcia, Larissa Ferraz; Mataveli, Fábio D’Aguiar; Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell; Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva

    2015-01-01

    Objective Evaluate the effects of VEGF165 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Methods Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF165 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. Results There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF165. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF165, suggesting greater tissue differentiation. Conclusion The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF165 seems to provide a protective effect in the treatment of acute myocardial infarct. PMID:25993074

  12. Bone remodelling analysis of the humerus after a shoulder arthroplasty.

    PubMed

    Quental, Carlos; Folgado, João; Fernandes, Paulo R; Monteiro, Jacinto

    2012-10-01

    The shoulder arthroplasty has become an efficient treatment for some pathologies. However there are complications that can compromise its success. Among them, the stress shielding effect on the humerus has been reported as a possible cause of failure. The objective of this work was to investigate the bone remodelling in the humerus after a shoulder arthroplasty. For this purpose, computational models were developed to analyse the stress shielding contribution to the humeral component failure of shoulder arthroplasties, with a cemented and an uncemented prosthesis. A computational remodelling model was used to characterize the bone apparent density at each site of the humerus. The density distribution was obtained by the solution of a problem that takes into account both structural stiffness and the metabolic cost of bone maintenance. Bone was subjected to 6 load cases that include the glenohumeral reaction force and the action of 10 muscles. In the implanted models, different interface conditions were tested for the bone-implant and the cement-implant interfaces. Moreover, a pathological case defined by a poorer quality of bone was considered. In the healthy situation, the models that better model in vivo conditions showed no significant changes in bone mass. However, the results for the pathological case showed some bone resorption which supports the importance given to the quality of bone in the success of the joint replacement. Bearing in mind the conditions addressed, the results lead to conclude that the stress shielding is not a key factor for the humeral component failure of shoulder arthroplasties in a healthy situation though several issues, including muscle function and bone quality, may heighten its effect.

  13. Left ventricular remodeling after experimental myocardial cryoinjury in rats.

    PubMed

    Ciulla, Michele M; Paliotti, Roberta; Ferrero, Stefano; Braidotti, Paola; Esposito, Arturo; Gianelli, Umberto; Busca, Giuseppe; Cioffi, Ugo; Bulfamante, Gaetano; Magrini, Fabio

    2004-01-01

    The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was documented on echocardiograms, with an average size of about 21%. Macroscopic examination reflected closely the stamp of the instrument used, without transition zones to viable myocardium. Histological examination, during the acute setting, revealed an extensive area of coagulation necrosis and hemorrhage in the subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas the reparative phase started within the first week, with proliferation of fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of collagen fibers was reported with a reparative scar completed at the 30th day. Ultrastructural study revealed vascular capillary damage and irreversible alterations of the myocytes in the acute setting and confirmed the histological findings of the later phases. The damage was associated with a progressive left ventricular (LV) remodeling, including thinning of the infarcted area, hypertrophy of the noninfarcted myocardium, and significant LV dilation. This process started from the 60th day and progressed over the subsequent 120 days period; at 180 days, a significant increase in LV filling pressure, indicative of heart failure, was found. In conclusion, myocardial cryodamage, although different in respect to ischemic damage, causes a standardized injury reproducing the cellular patterns of coagulation necrosis, early microvascular reperfusion, hemorrhage, inflammation

  14. Retinal Remodeling and Metabolic Alterations in Human AMD

    PubMed Central

    Jones, Bryan W.; Pfeiffer, Rebecca L.; Ferrell, William D.; Watt, Carl B.; Tucker, James; Marc, Robert E.

    2016-01-01

    Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease. PMID:27199657

  15. Circulating microparticles enhanced rat vascular wall remodeling following endothelial denudation

    PubMed Central

    Lee, Fan-Yen; Lu, Hung-I; Chai, Han-Tan; Sheu, Jiunn-Jye; Chen, Yi-Ling; Huang, Tein-Hung; Kao, Gour-Shenq; Chen, Sheng-Yi; Chung, Sheng-Ying; Sung, Pei-Hsun; Chang, Hsueh-Wen; Lee, Mel S; Yip, Hon-Kan

    2016-01-01

    This study tested the hypothesis that circulating microparticles (MPs) exacerbated vascular wall (VW) remodeling after endothelial denudation by 0.014 wire in a rat model. Adult male Sprague Dawley rats (n = 40) were equally categorized into group 1 [sham-control (SC); 3.0 mL saline intravenous injection], group 2 [SC + intravenous MPs (1.0 × 107) derived from patients with carotid artery stenosis (CAS)], group 3 [femoral arterial endothelial denudation (FAED)], group 4 (FAED + MPs derived from healthy subjects), and group 5 (FAED + CAS-derived MPs). Animals were euthanized by day 28 after FAED procedure. The results demonstrated that neointimal area (NIA) (mm2), medial area, and number of infiltrated cells in medial layer were highest in group 5 and lowest in groups 1 and 2, and significantly higher in group 4 than those in group 3 (all P<0.0001), but no differences were noted between groups 1 and 2. However, the ratio of luminal area to VW area showed an opposite pattern compared to that of NIA among five groups (P<0.0001). Immunofluorescent study showed an identical pattern of changes in the numbers of inflammatory (F4/80, CD14, CD40, IL-β) and proliferative (Ki-67, Cx43) cells in VW compared to that of NIA among the five groups (all P<0.00). The mNRA expressions of inflammatory (MMP-9, NF-κB, TNF-α, IL-1β, iNOS, PDGF) and cell activation (c-Fos, c-Myc, osteopontin, PCNA) biomarkers showed an identical pattern compared to that of NIA among all groups (all P<0.001). Take altogether, CAS-derived MPs further aggravated MP-mediated VW remodeling after endothelial damage compared to that observed after administration of MPS derived from healthy subjects. PMID:27904658

  16. Erythrocyte Stiffness during Morphological Remodeling Induced by Carbon Ion Radiation

    PubMed Central

    Zhang, Baoping; Liu, Bin; Zhang, Hong; Wang, Jizeng

    2014-01-01

    The adverse effect induced by carbon ion radiation (CIR) is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy) or X-rays (2, 4, 6, and 12 Gy) for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy). The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study provides a new

  17. Phase field approaches of bone remodeling based on TIP

    NASA Astrophysics Data System (ADS)

    Ganghoffer, Jean-François; Rahouadj, Rachid; Boisse, Julien; Forest, Samuel

    2016-01-01

    The process of bone remodeling includes a cycle of repair, renewal, and optimization. This adaptation process, in response to variations in external loads and chemical driving factors, involves three main types of bone cells: osteoclasts, which remove the old pre-existing bone; osteoblasts, which form the new bone in a second phase; osteocytes, which are sensing cells embedded into the bone matrix, trigger the aforementioned sequence of events. The remodeling process involves mineralization of the bone in the diffuse interface separating the marrow, which contains all specialized cells, from the newly formed bone. The main objective advocated in this contribution is the setting up of a modeling and simulation framework relying on the phase field method to capture the evolution of the diffuse interface between the new bone and the marrow at the scale of individual trabeculae. The phase field describes the degree of mineralization of this diffuse interface; it varies continuously between the lower value (no mineral) and unity (fully mineralized phase, e.g. new bone), allowing the consideration of a diffuse moving interface. The modeling framework is the theory of continuous media, for which field equations for the mechanical, chemical, and interfacial phenomena are written, based on the thermodynamics of irreversible processes. Additional models for the cellular activity are formulated to describe the coupling of the cell activity responsible for bone production/resorption to the kinetics of the internal variables. Kinetic equations for the internal variables are obtained from a pseudo-potential of dissipation. The combination of the balance equations for the microforce associated to the phase field and the kinetic equations lead to the Ginzburg-Landau equation satisfied by the phase field with a source term accounting for the dissipative microforce. Simulations illustrating the proposed framework are performed in a one-dimensional situation showing the evolution of

  18. OPTN/SRTR 2015 Annual Data Report: Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2017-01-01

    Intestine and intestine-liver transplant remains important in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2015, 196 new patients were added to the intestine transplant waiting list, with equal numbers waiting for intestine and intestine-liver transplant. Among prevalent patients on the list at the end of 2015, 63.3% were waiting for an intestine transplant and 36.7% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was notably higher for intestine-liver than for intestine transplant candidates (respectively, 19.9 vs. 2.8 deaths per 100 waitlist years in 2014-2015). By age, pretransplant mortality was highest for adult candidates, at 19.6 per 100 waitlist years, and lowest for children aged younger than 6 years, at 3.6 per 100 waitlist years. Pretransplant mortality by etiology was highest for candidates with non-congenital types of short-gut syndrome. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 70 in 2015. Intestine-liver transplants increased from a low of 44 in 2012 to 71 in 2015. Short-gut syndrome (congenital and non-congenital) was the main cause of disease leading to intestine and to intestine-liver transplant. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

  19. Starving for more: Nutrient sensing by LIN-28 in adult intestinal progenitor cells.

    PubMed

    Luhur, Arthur; Sokol, Nicholas

    2015-01-01

    In this Extra View, we extend our recent work on the protein LIN-28 and its role in adult stem cell divisions. LIN-28 is an mRNA- and microRNA-binding protein that is conserved from worms to humans. When expressed ectopically, it promotes the reprogramming of differentiated vertebrate cells into pluripotent stem cells as well as the regeneration of vertebrate tissues after injury. However, its endogenous function in stem cell populations is less clear. We recently reported that LIN-28 is specifically expressed in progenitor cells in the adult Drosophila intestine and enhances insulin signaling within this population. Loss of lin-28 alters the division patterns of these progenitor cells, limiting the growth of the intestinal epithelium that is ordinarily caused by feeding. Thus, LIN-28 is part of an uncharacterized circuit used to remodel a tissue in response to environmental cues like nutrition. Here, we extend this analysis by reporting that the levels of LIN-28 in progenitor cells are sensitive to nutrient availability. In addition, we speculate about the role of LIN-28 in the translational control of target mRNAs such as Insulin Receptor (InR) and how such translational control may be an important mechanism that underlies the stem cell dynamics needed for tissue homeostasis and growth.

  20. Ultrastructural and Molecular Changes in the Developing Small Intestine of the Toad Bufo regularis

    PubMed Central

    Sakr, S. A.; Badawy, G. M.; El-Borm, H. T.

    2014-01-01

    The ontogenetic development of the small intestine of the toad Bufo regularis was investigated using twofold approaches, namely, ultrastructural and molecular. The former has been done using transmission electron microscope and utilizing the developmental stages 42, 50, 55, 60, 63, and 66. The most prominent ultrastructural changes were recorded at stage 60 and were more evident at stage 63. These included the appearance of apoptotic bodies/nuclei within the larval epithelium, the presence of macrophages, swollen mitochondria, distorted rough endoplasmic reticulum, chromatin condensation, and irregular nuclear envelop, and the presence of large vacuoles and lysosomes. The molecular investigation involved examining DNA content and fragmentation. The results showed that the DNA content decreased significantly during the metamorphic stages 60 and 63 compared with both larval (50 and 55) and postmetamorphic (66) stages. The metamorphic stages (60 and 63) displayed extensive DNA laddering compared with stages 50, 55, and 66. The percentage of DNA damage was 0.00%, 12.91%, 57.26%, 45.48%, and 4.43% for the developmental stages 50, 55, 60, 63, and 66, respectively. In conclusion, the recorded remodeling of the small intestine represents a model for clarifying the mechanism whereby cell death and proliferation are controlled. PMID:24715821

  1. Protein-engineered scaffolds for in vitro 3D culture of primary adult intestinal organoids.

    PubMed

    DiMarco, Rebecca L; Dewi, Ruby E; Bernal, Gabriela; Kuo, Calvin; Heilshorn, Sarah C

    2015-10-15

    Though in vitro culture of primary intestinal organoids has gained significant momentum in recent years, little has been done to investigate the impact of microenvironmental cues provided by the encapsulating matrix on the growth and development of these fragile cultures. In this work, the impact of various in vitro culture parameters on primary adult murine organoid formation and growth are analyzed with a focus on matrix properties and geometric culture configuration. The air-liquid interface culture configuration was found to result in enhanced organoid formation relative to a traditional submerged configuration. Additionally, through use of a recombinantly engineered extracellular matrix (eECM), the effects of biochemical and biomechanical cues were independently studied. Decreasing mechanical stiffness and increasing cell adhesivity were found to increase organoid yield. Tuning of eECM properties was used to obtain organoid formation efficiency values identical to those observed in naturally harvested collagen I matrices but within a stiffer construct with improved ease of physical manipulation. Increased ability to remodel the surrounding matrix through mechanical or enzymatic means was also shown to enhance organoid formation. As the engineering and tunability of recombinant matrices is essentially limitless, continued property optimization may result in further improved matrix performance and may help to identify additional microenvironmental cues that directly impact organoid formation, development, differentiation, and functional behavior. Continued culture of primary organoids in recombinant matrices could therefore prove to be largely advantageous in the field of intestinal tissue engineering for applications in regenerative medicine and in vitro tissue mimics.

  2. Ultrastructural and molecular changes in the developing small intestine of the toad Bufo regularis.

    PubMed

    Sakr, S A; Badawy, G M; El-Borm, H T

    2014-01-01

    The ontogenetic development of the small intestine of the toad Bufo regularis was investigated using twofold approaches, namely, ultrastructural and molecular. The former has been done using transmission electron microscope and utilizing the developmental stages 42, 50, 55, 60, 63, and 66. The most prominent ultrastructural changes were recorded at stage 60 and were more evident at stage 63. These included the appearance of apoptotic bodies/nuclei within the larval epithelium, the presence of macrophages, swollen mitochondria, distorted rough endoplasmic reticulum, chromatin condensation, and irregular nuclear envelop, and the presence of large vacuoles and lysosomes. The molecular investigation involved examining DNA content and fragmentation. The results showed that the DNA content decreased significantly during the metamorphic stages 60 and 63 compared with both larval (50 and 55) and postmetamorphic (66) stages. The metamorphic stages (60 and 63) displayed extensive DNA laddering compared with stages 50, 55, and 66. The percentage of DNA damage was 0.00%, 12.91%, 57.26%, 45.48%, and 4.43% for the developmental stages 50, 55, 60, 63, and 66, respectively. In conclusion, the recorded remodeling of the small intestine represents a model for clarifying the mechanism whereby cell death and proliferation are controlled.

  3. Impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen metabolism

    SciTech Connect

    Kirfel, Jutta Pantelis, Dimitrios; Kabba, Mustapha; Kahl, Philip; Roeper, Anke; Kalff, Joerg C.; Buettner, Reinhard

    2008-12-10

    Four and one half LIM domain protein FHL2 participates in many cellular processes involved in tissue repair such as regulation of gene expression, cytoarchitecture, cell adhesion, migration and signal transduction. The repair process after wounding is initiated by the release of peptides and bioactive lipids. These molecules induce synthesis and deposition of a provisional extracellular matrix. We showed previously that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of FHL2 in response to activation of the RhoA GTPase. Our present study shows that FHL2 is an important signal transducer influencing the outcome of intestinal anastomotic healing. Early wound healing is accompanied by reconstitution and remodelling of the extracellular matrix and collagen is primarily responsible for wound strength. Our results show that impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen III metabolism. Impaired collagen III synthesis reduced the mechanical stability of the anastomoses and led to lower bursting pressure in Fhl2-deficient mice after surgery. Our data confirm that FHL2 is an important factor regulating collagen expression in the early phase of wound healing, and thereby is critically involved in the physiologic process of anastomosis healing after bowel surgery and thus may represent a new therapeutic target.

  4. Peptidases Compartmentalized to the Ascaris suum Intestinal Lumen and Apical Intestinal Membrane

    PubMed Central

    Rosa, Bruce A.

    2015-01-01

    The nematode intestine is a tissue of interest for developing new methods of therapy and control of parasitic nematodes. However, biological details of intestinal cell functions remain obscure, as do the proteins and molecular functions located on the apical intestinal membrane (AIM), and within the intestinal lumen (IL) of nematodes. Accordingly, methods were developed to gain a comprehensive identification of peptidases that function in the intestinal tract of adult female Ascaris suum. Peptidase activity was detected in multiple fractions of the A. suum intestine under pH conditions ranging from 5.0 to 8.0. Peptidase class inhibitors were used to characterize these activities. The fractions included whole lysates, membrane enriched fractions, and physiological- and 4 molar urea-perfusates of the intestinal lumen. Concanavalin A (ConA) was confirmed to bind to the AIM, and intestinal proteins affinity isolated on ConA-beads were compared to proteins from membrane and perfusate fractions by mass spectrometry. Twenty-nine predicted peptidases were identified including aspartic, cysteine, and serine peptidases, and an unexpectedly high number (16) of metallopeptidases. Many of these proteins co-localized to multiple fractions, providing independent support for localization to specific intestinal compartments, including the IL and AIM. This unique perfusion model produced the most comprehensive view of likely digestive peptidases that function in these intestinal compartments of A. suum, or any nematode. This model offers a means to directly determine functions of these proteins in the A. suum intestine and, more generally, deduce the wide array functions that exist in these cellular compartments of the nematode intestine. PMID:25569475

  5. Chronic intestinal pseudo-obstruction due to lymphocytic intestinal leiomyositis: Case report and literature review.

    PubMed

    Uchida, Keiichi; Otake, Kohei; Inoue, Mikihiro; Koike, Yuhki; Matsushita, Kohei; Araki, Toshimitsu; Okita, Yoshiki; Tanaka, Koji; Uchida, Katsunori; Yodoya, Noriko; Iwamoto, Shotaro; Arai, Katsuhiro; Kusunoki, Masato

    2012-02-01

    Lymphocytic intestinal leiomyositis is a rare entity, which causes chronic intestinal pseudo-obstruction (CIPO) in children. We present the first case of a boy who had pure red cell anemia 1 year before onset. Prolonged ileus developed after gastroenteritis and the patient was diagnosed using a biopsy of the intestinal wall. Findings from the present case indicate that there are three important factors for accurate diagnosis: history of enteritis, positive serum smooth muscle antibody, and lymphocyte infiltration with muscle destruction in the muscularis propria in the intestinal wall. Earlier diagnosis and induction of immunosuppressive therapy may be essential for a better outcome.

  6. Ovariectomy Stimulates and Bisphosphonates Inhibit Intracortical Remodeling in the Mouse Mandible

    PubMed Central

    Kubek, Daniel J.; Burr, David B.; Allen, Matthew R.

    2010-01-01

    Objective The pathophysiology of osteonecrosis of the jaw (ONJ) is thought to be linked to suppression of intracortical remodeling. Aim of this study was to determine whether mice, which normally do not undergo appreciable amounts of intracortical remodeling, could be stimulated by ovariectomy to remodel within the cortex of the mandible and if bisphosphonates (BPs) would suppress this intracortical remodeling. Material and Methods Skeletally mature female C3H mice were either ovariectomized (OVX) or SHAM operated and treated with two intravenous doses of zoledronic acid (ZOL, 0.06 mg/kg body weight) or vehicle (VEH). This ZOL dose corresponds to the dose given to cancer patients on a mg/kg basis, adjusted for body weight. Calcein was administered prior to sacrifice to label active formation sites. Dynamic histomorphometry of the mandible and femur were performed. Results Vehicle-treated OVX animals had significantly higher (8-fold) intracortical remodeling of the alveolar portion of the mandible compared to sham – this was significantly suppressed by ZOL treatment. At all skeletal sites, overall bone formation rate (BFR) was lower with ZOL treatment compared to the corresponding VEH group. Conclusions Under normal conditions the level of intracortical remodeling in the mouse mandible is minimal but in C3H mice can be stimulated to appreciable levels with ovariectomy. Based on this, if the suppression of intracortical remodeling is found to be part of the pathophysiology of ONJ, the ovariectomized C3H mouse could serve as a useful tool for studying this condition. PMID:21040464

  7. Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis.

    PubMed

    Rego, Bruno V; Wells, Sarah M; Lee, Chung-Hao; Sacks, Michael S

    2016-12-01

    Little is known about how valvular tissues grow and remodel in response to altered loading. In this work, we used the pregnancy state to represent a non-pathological cardiac volume overload that distends the mitral valve (MV), using both extant and new experimental data and a modified form of our MV structural constitutive model. We determined that there was an initial period of permanent set-like deformation where no remodelling occurs, followed by a remodelling phase that resulted in near-complete restoration of homeostatic tissue-level behaviour. In addition, we observed that changes in the underlying MV interstitial cell (MVIC) geometry closely paralleled the tissue-level remodelling events, undergoing an initial passive perturbation followed by a gradual recovery to the pre-pregnant state. Collectively, these results suggest that valvular remodelling is actively mediated by average MVIC deformations (i.e. not cycle to cycle, but over a period of weeks). Moreover, tissue-level remodelling is likely to be accomplished by serial and parallel additions of fibrillar material to restore the mean homeostatic fibre stress and MVIC geometries. This finding has significant implications in efforts to understand and predict MV growth and remodelling following such events as myocardial infarction and surgical repair, which also place the valve under altered loading conditions.

  8. A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues.

    PubMed

    Comellas, Ester; Gasser, T Christian; Bellomo, Facundo J; Oller, Sergio

    2016-03-01

    Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data.

  9. Intrapulmonary vascular remodeling: MSCT-based evaluation in COPD and alpha-1 antitrypsin deficient subjects

    NASA Astrophysics Data System (ADS)

    Crosnier, Adeline; Fetita, Catalin; Thabut, Gabriel; Brillet, Pierre-Yves

    2016-03-01

    Whether COPD is generally known as a small airway disease, recent investigations suggest that vascular remodeling could play a key role in disease progression. This paper develops a specific investigation framework in order to evaluate the remodeling of the intrapulmonary vascular network and its correlation with other image or clinical parameters (emphysema score or FEV1) in patients with smoking- or genetic- (alpha-1 antitrypsin deficiency - AATD) related COPD. The developed approach evaluates the vessel caliber distribution per lung or lung region (upper, lower, 10%- and 20%- periphery) in relation with the severity of the disease and computes a remodeling marker given by the area under the caliber distribution curve for radii less than 1.6mm, AUC16. It exploits a medial axis analysis in relation with local caliber information computed in the segmented vascular network, with values normalized with respect to the lung volume (for which a robust segmentation is developed). The first results obtained on a 34-patient database (13 COPD, 13 AATD and 8 controls) showed significant vascular remodeling for COPD and AATD versus controls, with a negative correlation with the emphysema degree for COPD, but not for AATD. Significant vascular remodeling at 20% lung periphery was found both for the severe COPD and AATD patients, but not for the moderate groups. Also the vascular remodeling in AATD did not correlate with the FEV1, nor with DLCO, which might suggest independent mechanisms for bronchial and vascular remodeling in the lung.

  10. The Effect of Hemodynamic Remodeling on the Survival of Arterialized Venous Flaps

    PubMed Central

    Yan, Hede; Kolkin, Jon; Zhao, Bin; Li, Zhefeng; Jiang, Shichao; Wang, Wei; Xia, Zhen; Fan, Cunyi

    2013-01-01

    Objective To evaluate the effect of hemodynamic remodeling on the survival status of the arterialized venous flaps (AVFs) and investigate the mechanism of this procedure. Materials and Methods Two 7 x 9 cm skin flaps in each rabbit (n=36) were designed symmetrically in the abdomen. The thoracoepigastric pedicle and one femoral artery were used as vascular sources. Four groups were included: Composite skin grafts group and arterial perfusion group were designed in one rabbit; AVF group and hemodynamic remodeling group by ligation of the thoracoepigastric vein in the middle were outlined in another rabbit. Flap viability, status of vascular perfusion and microvasculature, levels of epidermal metabolite and water content in each group were assessed. Results Highly congested veins and simple trunk veins were found using angiography in the AVF group; while a fairly uniform staining and plenty of small vessels were observed in the hemodynamic remodeling group. The metabolite levels of the remodeling group are comparable with those in the arterial perfusion group. There was no statistically significant difference in the percentage of flap survival between the arterial perfusion group and hemodynamic remodeling group; however, significant difference was seen between the AVF group and the hemodynamic remodeling group. Conclusions Under the integrated perfusion mode, the AVFs are in an over-perfusion and non-physiological hemodynamic state, resulting in unreliability and unpredictability in flap survival; under the separated perfusion mode produced by remodeling, a physiological-like circulation will be created and therefore, better flap survival can be expected. PMID:24265782

  11. PICKLE is a CHD subfamily II ATP-dependent chromatin remodeling factor.

    PubMed

    Ho, Kwok Ki; Zhang, Heng; Golden, Barbara L; Ogas, Joe

    2013-02-01

    PICKLE plays a critical role in repression of genes that regulate development identity in Arabidopsis thaliana. PICKLE codes for a putative ATP-dependent chromatin remodeler that exhibits sequence similarity to members of subfamily II of animal CHD remodelers, which includes remodelers such as CHD3/Mi-2 that also restrict expression of developmental regulators. Whereas animal CHD3 remodelers are a component of the Mi-2/NuRD complex that promotes histone deacetylation, PICKLE promotes trimethylation of histone H3 lysine 27 suggesting that it acts via a distinct epigenetic pathway. Here, we examine whether PICKLE is also a member of a multisubunit complex and characterize the biochemical properties of recombinant PICKLE protein. Phylogenetic analysis indicates that PICKLE-related proteins in plants share a common ancestor with members of subfamily II of animal CHD remodelers. Biochemical characterization of PICKLE in planta, however, reveals that PICKLE primarily exists as a monomer. Recombinant PICKLE protein is an ATPase that is stimulated by ssDNA and mononucleosomes and binds to both naked DNA and mononucleosomes. Furthermore, recombinant PICKLE exhibits ATP-dependent chromatin remodeling activity. These studies demonstrate that subfamily II CHD proteins in plants, such as PICKLE, retain ATP-dependent chromatin remodeling activity but act through a mechanism that does not involve the ubiquitous Mi-2/NuRD complex.

  12. [Recurrent intestinal ischemia due to factor VIII].

    PubMed

    Castellanos Monedero, Jesús Javier; Legaz Huidobro, María Luisa; Galindo Andugar, María Angeles; Rodríguez Pérez, Alvaro; Mantrana del Valle, José María

    2008-01-01

    Intestinal ischemia is difficult to diagnose and can be caused by several etiologic processes. We report the case of a female patient with recurrent bowel ischemia due to small vessel thrombosis, which is caused by factor VIII, a procoagulant factor.

  13. Psychological Effects of Intestinal Bypass Surgery.

    ERIC Educational Resources Information Center

    Wampler, Richard S.; And Others

    1980-01-01

    Preoperative and postoperative intestinal bypass patients were evaluated. Results suggest that postoperative bypass patients have improved psychological health and an increased sense of freedom and well-being but may need assistance in improving self-concepts. (Author)

  14. How Is Small Intestine Adenocarcinoma Diagnosed?

    MedlinePlus

    ... the intestine a foot at a time. An advantage of this over capsule endoscopy is that the ... Life Events College Relay For Life Donate a Car Ways to Give Memorial Giving Planned Giving Leadership ...

  15. [THE INTESTINAL BARRIER, THE MICROBIOTA, MICROBIOME].

    PubMed

    Mar'yanovich, A T

    2016-01-01

    The review examined modern condition of development directions physiology of digestion, like structure and function of the intestinal barrier, the microbiota of the digestive tract in its relations with the microorganism.

  16. [Antioxidant therapy in combined treatment of postoperative intestinal paresis].

    PubMed

    Magomedov, M A

    2004-01-01

    Method of treatment of postoperative intestinal paresis with antioxidant emoxipin in experiment demonstrated that stabilization of redox processes and antioxidant systems in intestinal tissues leads to compensation of energy deficiency and recovery of intestinal peristalsis. Clinical use of this method in combined treatment of patients with postoperative intestinal paresis in acute generalized peritonitis reduces time of postoperative intestinal paresis and intoxication, lethality reduced 1,7-fold.

  17. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    SciTech Connect

    Ostrup, Olga; Hyttel, Poul; Klaerke, Dan A.; Collas, Philippe

    2011-09-02

    Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression. This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.

  18. Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

    SciTech Connect

    Gao, Fu; Chambon, Pierre; Tellides, George; Kong, Wei; Zhang, Xiaoming; Li, Wei

    2014-11-07

    Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

  19. Pulmonary Vein Remodeling Following Atrial Fibrillation Ablation: Implications For The Radiographic Diagnosis Of Pulmonary Vein Stenosis.

    PubMed

    Merchant Md, Faisal M; Levy Bs, Mathew R; Iravanian Md, Shahriar; Weragoda Md, Ramal M; Clermont Md, Edward C; Kelli Md, Heval M; Eisner PhD, Robert L; Vadnais Md, David; El-Chami Md, Mikhael F; Leon Md, Angel R; Delurgio Md, David B

    2016-01-01

    Background: Pulmonary vein (PV) reverse remodeling has been recognized following atrial fibrillation (AF) ablation. However, the extent of physiologic reverse remodeling after AF ablation and the potential impact of reverse remodeling on the radiographic diagnosis of PV stenosis have not been well characterized. Methods: From January 2004 to February 2014, 186 patients underwent paired cardiac magnetic resonance imaging (MRI) to delineate PV orifice dimensions before and after (mean 109 ± 61 days) an initial AF ablation. Results: Negative remodeling of the PV orifice cross sectional area occurred in 67.8% of veins with a mean reduction in area of 21.0 ± 14.1%, and positive remodeling was seen in the remaining PVs with an increase in area of 22.1 ± 23.4% compared to baseline. No PVs demonstrated a reduction in cross-sectional area of > 75% (maximum reduction observed was 58%). Negative remodeling of the PV long axis dimension was observed in 55.2% of veins with a mean reduction of 14.6 ± 9.2% compared to pre-ablation and positive remodeling was observed in 25.3% of PVs with a mean increase in diameter of 14.7 ± 12.6%. Only 1 PV demonstrated a reduction in orifice diameter of > 50%. There were no clinically evident or suspected cases of PV stenosis in this cohort. Conclusions: Negative remodeling of the PV orifice area was noted in the majority of PVs following AF ablation. However, in almost all cases, the extent of negative remodeling was well below commonly used thresholds for the radiographic diagnosis of PV stenosis.

  20. Small intestine dysfunction in Parkinson's disease.

    PubMed

    Dutkiewicz, Justyna; Szlufik, Stanisław; Nieciecki, Michał; Charzyńska, Ingeborga; Królicki, Leszek; Smektała, Piotr; Friedman, Andrzej

    2015-12-01

    The aim of this study was to assess the small bowel transit time in patients with Parkinson's disease (PD). Ten patients with PD with no gastrointestinal complaints and ten healthy control subjects were investigated using single photon emission computed tomography fused with computed tomography after swallowing of a specially prepared capsule containing technetium 99m, which allowed visualization of the passage in the intestines. Preliminary results show that the small intestine passage in PD patients was prolonged compared to controls.

  1. Neural regulation of intestinal nutrient absorption.

    PubMed

    Mourad, Fadi H; Saadé, Nayef E

    2011-10-01

    The nervous system and the gastrointestinal (GI) tract share several common features including reciprocal interconnections and several neurotransmitters and peptides known as gut peptides, neuropeptides or hormones. The processes of digestion, secretion of digestive enzymes and then absorption are regulated by the neuro-endocrine system. Luminal glucose enhances its own absorption through a neuronal reflex that involves capsaicin sensitive primary afferent (CSPA) fibres. Absorbed glucose stimulates insulin release that activates hepatoenteric neural pathways leading to an increase in the expression of glucose transporters. Adrenergic innervation increases glucose absorption through α1 and β receptors and decreases absorption through activation of α2 receptors. The vagus nerve plays an important role in the regulation of diurnal variation in transporter expression and in anticipation to food intake. Vagal CSPAs exert tonic inhibitory effects on amino acid absorption. It also plays an important role in the mediation of the inhibitory effect of intestinal amino acids on their own absorption at the level of proximal or distal segment. However, chronic extrinsic denervation leads to a decrease in intestinal amino acid absorption. Conversely, adrenergic agonists as well as activation of CSPA fibres enhance peptides uptake through the peptide transporter PEPT1. Finally, intestinal innervation plays a minimal role in the absorption of fat digestion products. Intestinal absorption of nutrients is a basic vital mechanism that depends essentially on the function of intestinal mucosa. However, intrinsic and extrinsic neural mechanisms that rely on several redundant loops are involved in immediate and long-term control of the outcome of intestinal function.

  2. Circadian regulators of intestinal lipid absorption

    PubMed Central

    Hussain, M. Mahmood; Pan, Xiaoyue

    2015-01-01

    Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption. PMID:25057097

  3. Regulation of intestinal lactase in adult hypolactasia.

    PubMed Central

    Lloyd, M; Mevissen, G; Fischer, M; Olsen, W; Goodspeed, D; Genini, M; Boll, W; Semenza, G; Mantei, N

    1992-01-01

    Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine. Images PMID:1737843

  4. Autonomic modification of intestinal smooth muscle contractility.

    PubMed

    Montgomery, Laura E A; Tansey, Etain A; Johnson, Chris D; Roe, Sean M; Quinn, Joe G

    2016-03-01

    Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe this spontaneous activity and its modification by agents associated with parasympathetic and sympathetic nerve activity. A section of the rabbit small intestine is suspended in an organ bath, and the use of a pressure transducer and data-acquisition software allows the measurement of tension generated by the smooth muscle of intestinal walls. The application of the parasympathetic neurotransmitter ACh at varying concentrations allows students to observe an increase in intestinal smooth muscle tone with increasing concentrations of this muscarinic receptor agonist. Construction of a concentration-effect curve allows students to calculate an EC50 value for ACh and consider some basic concepts surrounding receptor occupancy and activation. Application of the hormone epinephrine to the precontracted intestine allows students to observe the inhibitory effects associated with sympathetic nerve activation. Introduction of the drug atropine to the preparation before a maximal concentration of ACh is applied allows students to observe the inhibitory effect of a competitive antagonist on the physiological response to a receptor agonist. The final experiment involves the observation of the depolarizing effect of K(+) on smooth muscle. Students are also invited to consider why the drugs atropine, codeine, loperamide, and botulinum toxin have medicinal uses in the management of gastrointestinal problems.

  5. Epigenetic Regulation of the Intestinal Epithelium

    PubMed Central

    Elliott, Ellen N.; Kaestner, Klaus H.

    2015-01-01

    The intestinal epithelium is an ideal model system for the study of normal and pathological differentiation processes. The mammalian intestinal epithelium is a single cell layer comprised of proliferative crypts and differentiated villi. The crypts contain both proliferating and quiescent stem cell populations that self-renew and produce all the differentiated cell types, which are replaced every 3 to 5 days. The genetics of intestinal development, homeostasis, and disease are well defined, but less is known about the contribution of epigenetics in modulating these processes. Epigenetics refers to heritable phenotypic traits, including gene expression, which are independent of mutations in the DNA sequence. We have known for several decades that human colorectal cancers contain hypomethylated DNA, but the causes and consequences of this phenomenon are not fully understood. In contrast, tumor suppressor gene promoters are often hypermethylated in colorectal cancer, resulting in decreased expression of the associated gene. In this review, we describe the role that epigenetics plays in intestinal homeostasis and disease, with an emphasis on results from mouse models. We highlight the importance of producing and analyzing next-generation sequencing data detailing the epigenome from intestinal stem cell to differentiated intestinal villus cell. PMID:26220502

  6. Exercise, intestinal barrier dysfunction and probiotic supplementation.

    PubMed

    Lamprecht, Manfred; Frauwallner, Anita

    2012-01-01

    Athletes exposed to high-intensity exercise show an increased occurrence of gastrointestinal (GI) symptoms like cramps, diarrhea, bloating, nausea, and bleeding. These problems have been associated with alterations in intestinal permeability and decreased gut barrier function. The increased GI permeability, a so-called 'leaky gut', also leads to endotoxemia, and results in increased susceptibility to infectious and autoimmune diseases, due to absorption of pathogens/toxins into tissue and the bloodstream. Key components that determine intestinal barrier function and GI permeability are tight junctions, protein structures located in the paracellular channels between epithelial cells of the intestinal wall. The integrity of tight junctions depends on sophisticated interactions between the gut residents and their expressed substances, the intestinal epithelial cell metabolism and the activities of the gut-associated lymphoid tissue. Probiotic supplements are an upcoming group of nutraceuticals that could offer positive effects on athlete's gut and entire health. Some results demonstrate promising benefits for probiotic use on the athlete's immune system. There is also evidence that probiotic supplementation can beneficially influence intestinal barrier integrity in acute diseases. With regard to exercise-induced GI permeability problems, there is still a lack of studies with appropriate data and a gap to understand the underlying mechanisms to support such health beneficial statements implicitly. This article refers (i) to exercise-induced intestinal barrier dysfunction, (ii) provides suggestions to estimate increased gut barrier permeability in athletes, and (iii) discusses the potential of probiotic supplementation to counteract an exercise-induced leaky gut.

  7. Current understanding concerning intestinal stem cells

    PubMed Central

    Cui, Shuang; Chang, Peng-Yu

    2016-01-01

    In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same. PMID:27610020

  8. Intestinal perforation by an ingested foreign body*

    PubMed Central

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F. S.; de Castro, Francisco Gomes; Miller, Wagner Peitl; de Lima, Raphael Rodrigues; Tazima, Leandro; Geraldo, Jamylle

    2016-01-01

    Objective To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). Conclusion In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation. PMID:27818542

  9. Nutritional Keys for Intestinal Barrier Modulation

    PubMed Central

    De Santis, Stefania; Cavalcanti, Elisabetta; Mastronardi, Mauro; Jirillo, Emilio; Chieppa, Marcello

    2015-01-01

    The intestinal tract represents the largest interface between the external environment and the human body. Nutrient uptake mostly happens in the intestinal tract, where the epithelial surface is constantly exposed to dietary antigens. Since inflammatory response toward these antigens may be deleterious for the host, a plethora of protective mechanisms take place to avoid or attenuate local damage. For instance, the intestinal barrier is able to elicit a dynamic response that either promotes or impairs luminal antigens adhesion and crossing. Regulation of intestinal barrier is crucial to control intestinal permeability whose increase is associated with chronic inflammatory conditions. The cross talk among bacteria, immune, and dietary factors is able to modulate the mucosal barrier function, as well as the intestinal permeability. Several nutritional products have recently been proposed as regulators of the epithelial barrier, even if their effects are in part contradictory. At the same time, the metabolic function of the microbiota generates new products with different effects based on the dietary content. Besides conventional treatments, novel therapies based on complementary nutrients are now growing. Fecal therapy has been recently used for the clinical treatment of refractory Clostridium difficile infection instead of the classical antibiotic therapy. In the present review, we will outline the epithelial response to nutritional components derived from dietary intake and microbial fermentation focusing on the consequent effects on the integrity of the epithelial barrier. PMID:26697008

  10. Bone remodelling in Neanderthal mandibles from the El Sidrón site (Asturias, Spain)

    PubMed Central

    Martinez-Maza, Cayetana; Rosas, Antonio; García-Vargas, Samuel; Estalrrich, Almudena; de la Rasilla, Marco

    2011-01-01

    Skull morphology results from the bone remodelling mechanism that underlies the specific bone growth dynamics. Histological study of the bone surface from Neanderthal mandible specimens of El Sidrón (Spain) provides information about the distribution of the remodelling fields (bone remodelling patterns or BRP) indicative of the bone growth directions. In comparison with other primate species, BRP shows that Neanderthal mandibles from the El Sidrón (Spain) sample present a specific BRP. The interpretation of this map allows inferences concerning the growth directions that explain specific morphological traits of the Neanderthal mandible, such as its quadrangular shape and the posterior location of the mental foramen. PMID:21307043

  11. Bone remodelling in Neanderthal mandibles from the El Sidrón site (Asturias, Spain).

    PubMed

    Martinez-Maza, Cayetana; Rosas, Antonio; García-Vargas, Samuel; Estalrrich, Almudena; de la Rasilla, Marco

    2011-08-23

    Skull morphology results from the bone remodelling mechanism that underlies the specific bone growth dynamics. Histological study of the bone surface from Neanderthal mandible specimens of El Sidrón (Spain) provides information about the distribution of the remodelling fields (bone remodelling patterns or BRP) indicative of the bone growth directions. In comparison with other primate species, BRP shows that Neanderthal mandibles from the El Sidrón (Spain) sample present a specific BRP. The interpretation of this map allows inferences concerning the growth directions that explain specific morphological traits of the Neanderthal mandible, such as its quadrangular shape and the posterior location of the mental foramen.

  12. Vitamin D receptor (VDR) promoter targeting through a novel chromatin remodeling complex.

    PubMed

    Kato, Shigeaki; Fujiki, Ryoji; Kitagawa, Hirochika

    2004-05-01

    We have purified nuclear complexes for Vitamin D receptor (VDR), and identified one of them as a novel ATP-dependent chromatine remodeling containing Williams syndrome transcription factor (WSTF), that is supposed to be responsible for Williams syndrome. This complex (WSTF including nucleosome assembly complex (WINAC)) exhibited an ATP-dependent chromatin remodeling activity in vitro. Transient expression assays revealed that WINAC potentiates ligand-induced function of VDR in gene activation and repression. Thus, this study describes a molecular basis of the VDR function on chromosomal DNA through chromatine remodeling.

  13. Nivalenol and deoxynivalenol affect rat intestinal epithelial cells: a concentration related study.

    PubMed

    Bianco, Giuseppe; Fontanella, Bianca; Severino, Lorella; Quaroni, Andrea; Autore, Giuseppina; Marzocco, Stefania

    2012-01-01

    The integrity of the gastrointestinal tract represents a crucial first level defence against ingested toxins. Among them, Nivalenol is a trichotecenes mycotoxin frequently found on cereals and processed grains; when it contaminates human food and animal feed it is often associated with another widespread contaminant, Deoxynivalenol. Following their ingestion, intestinal epithelial cells are exposed to concentrations of these trichothecenes high enough to cause mycotoxicosis. In this study we have investigated the effects of Nivalenol and Deoxynivalenol on intestinal cells in an in vitro model system utilizing the non-tumorigenic rat intestinal epithelial cell line IEC-6. Both Nivalenol and Deoxynivalenol (5-80 µM) significantly affected IEC-6 viability through a pro-apoptotic process which mainly involved the following steps: (i) Bax induction; (ii) Bcl-2 inhibition, and (iii) caspase-3 activation. Moreover, treatment with Nivalenol produced a significant cell cycle arrest of IEC-6 cells, primarily at the G(0)/G(1) interphase and in the S phase, with a concomitant reduction in the fraction of cells in G(2). Interestingly, when administered at lower concentrations (0.1-2.5 µM), both Nivalenol and Deoxynivalenol affected epithelial cell migration (restitution), representing the initial step in gastrointestinal wound healing in the gut. This reduced motility was associated with significant remodelling of the actin cytoskeleton, and changes in expression of connexin-43 and focal adhesion kinase. The concentration range of Nivalenol or Deoxynivalenol we have tested is comparable with the mean estimated daily intake of consumers eating contaminated food. Thus, our results further highlight the risks associated with intake of even low levels of these toxins.

  14. Hepatic and Intestinal Schistosomiasis: Review

    PubMed Central

    Elbaz, Tamer; Esmat, Gamal

    2013-01-01

    Schistosomiasis is an endemic disease in Egypt caused by the trematode Schistosoma which has different species. Hepatic schistosomiasis represents the best known form of chronic disease with a wide range of clinical manifestations. The pathogenesis of schistosomiasis is related to the host cellular immune response. This leads to granuloma formation and neo angiogenesis with subsequent periportal fibrosis manifested as portal hypertension, splenomegaly and esophageal varices. Intestinal schistosomiasis is another well identified form of chronic schistosomal affection. Egg deposition and granuloma formation eventually leads to acute then chronic schistosomal colitis and is commonly associated with polyp formation. It frequently presents as abdominal pain, diarrhea, tenesmus and anal pain. Definite diagnosis of schistosomiasis disease depends on microscopy and egg identification. Marked progress regarding serologic diagnosis occurred with development of recent PCR techniques that can confirm schistosomal affection at any stage. Many antischistosomal drugs have been described for treatment, praziquantel being the most safe and efficient drug. Still ongoing studies try to develop effective vaccines with identification of many target antigens. Preventive programs are highly needed to control the disease morbidity and to break the cycle of transmission. PMID:25685451

  15. Incomplete intestinal absorption of fructose.

    PubMed Central

    Kneepkens, C M; Vonk, R J; Fernandes, J

    1984-01-01

    Intestinal D-fructose absorption in 31 children was investigated using measurements of breath hydrogen. Twenty five children had no abdominal symptoms and six had functional bowel disorders. After ingestion of fructose (2 g/kg bodyweight), 22 children (71%) showed a breath hydrogen increase of more than 10 ppm over basal values, indicating incomplete absorption: the increase averaged 53 ppm, range 12 to 250 ppm. Four of these children experienced abdominal symptoms. Three of the six children with bowel disorders showed incomplete absorption. Seven children were tested again with an equal amount of glucose, and in three of them also of galactose, added to the fructose. The mean maximum breath hydrogen increases were 5 and 10 ppm, respectively, compared with 103 ppm after fructose alone. In one boy several tests were performed with various sugars; fructose was the only sugar incompletely absorbed, and the effect of glucose on fructose absorption was shown to be dependent on the amount added. It is concluded that children have a limited absorptive capacity for fructose. We speculate that the enhancing effect of glucose and galactose on fructose absorption may be due to activation of the fructose carrier. Apple juice in particular contains fructose in excess of glucose and could lead to abdominal symptoms in susceptible children. PMID:6476870

  16. MicroRNAs dynamically remodel gastrointestinal smooth muscle cells.

    PubMed

    Park, Chanjae; Yan, Wei; Ward, Sean M; Hwang, Sung Jin; Wu, Qiuxia; Hatton, William J; Park, Jong Kun; Sanders, Kenton M; Ro, Seungil

    2011-04-14

    Smooth muscle cells (SMCs) express a unique set of microRNAs (miRNAs) which regulate and maintain the differentiation state of SMCs. The goal of this study was to investigate the role of miRNAs during the development of gastrointestinal (GI) SMCs in a transgenic animal model. We generated SMC-specific Dicer null animals that express the reporter, green fluorescence protein, in a SMC-specific manner. SMC-specific knockout of Dicer prevented SMC miRNA biogenesis, causing dramatic changes in phenotype, function, and global gene expression in SMCs: the mutant mice developed severe dilation of the intestinal tract associated with the thinning and destruction of the smooth muscle (SM) layers; contractile motility in the mutant intestine was dramatically decreased; and SM contractile genes and transcriptional regulators were extensively down-regulated in the mutant SMCs. Profiling and bioinformatic analyses showed that SMC phenotype is regulated by a complex network of positive and negative feedback by SMC miRNAs, serum response factor (SRF), and other transcriptional factors. Taken together, our data suggest that SMC miRNAs are required for the development and survival of SMCs in the GI tract.

  17. New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering

    PubMed Central

    Shirafkan, Ali; Montalbano, Mauro; McGuire, Joshua; Rastellini, Cristiana; Cicalese, Luca

    2016-01-01

    Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option. PMID:27011901

  18. Relation between baseline plaque features and subsequent coronary artery remodeling determined by optical coherence tomography and intravascular ultrasound.

    PubMed

    Xie, Zulong; Dong, Nana; Sun, Rong; Liu, Xinxin; Gu, Xia; Sun, Yong; Du, Hongwei; Dai, Jiannan; Liu, Youbin; Hou, Jingbo; Tian, Jinwei; Yu, Bo

    2017-01-17

    Atherosclerosis often leads to myocardial infarction and stroke. We examined the influence of baseline plaque characteristics on subsequent vascular remodeling in response to changes in plaque size. Using optical coherence tomography (OCT) and intravascular ultrasound (IVUS), we examined 213 plaques from 138 patients with acute coronary syndrome at baseline and repeated IVUS at the 12-month follow-up. The change in external elastic membrane (EEM) area for each 1 mm2 change in plaque area (i.e., the slope of the regression line) was calculated as a measure of vascular remodeling capacity. In plaques with static positive remodeling, the slope was smaller than in plaques without static positive remodeling. In addition, the slope of the regression line for lesions with a large plaque burden was much smaller than that for lesions with a small plaque burden. Multivariate linear regression analysis showed that diabetes, calcification and static positive remodeling were inversely and independently associated with the level of change in EEM area/change in plaque area. Lesions with a large plaque burden, calcifications or static positive remodeling had less remodeling capacity, and calcification and static positive remodeling were independent predictors of reduced subsequent remodeling. Therefore, calcifications and static positive remodeling could be used as morphological biomarkers to predict decreased subsequent arterial remodeling.

  19. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  20. Lung remodeling in aging surfactant protein D deficient mice.

    PubMed

    Schneider, Jan Philipp; Arkenau, Martina; Knudsen, Lars; Wedekind, Dirk; Ochs, Matthias

    2017-02-07

    Pulmonary surfactant, a mixture of lipids and proteins at the air-liquid interface of alveoli, prevents the lungs from collapsing due to surface tension. One constituent is surfactant-associated protein-D (SP-D), a protein involved in surfactant homeostasis and innate immunity. Mice deficient in SP-D (SP-D (-/-)) has been described as developing a characteristic phenotype which affects the surfactant system (including changes in the intra-cellular and intra-alveolar surfactant pool, alveolar epithelial type II cells and alveolar macrophages), lung architecture and its inflammatory state (development of an emphysema-like pathology, inflammatory cell infiltration). Furthermore, it has been described that these mice develop sub-pleural fibrosis and a thickening of alveolar septal walls. The aim of the present study was to systematically investigate the long term progression of this phenotype with special focus on parenchymal remodeling, whether there are progressive emphysematous changes and whether there is progressive septal wall thickening which might indicate the development of pulmonary fibrosis. By means of design-based stereology and light microscopy, lungs of wild type (wt) and SP-D (-/-) mice of four age groups (3, 6, 12 and ∼18 months) were investigated. The data do not suggest a relevant spontaneous pro-fibrotic remodeling or a destructive process in the aging SP-D (-/-) mice. We demonstrated neither a significant destructive emphysema nor significant thickening of alveolar septal walls, but the data suggest an increase in the number weighted mean alveolar volume in aging SP-D (-/-) mice without loss of alveoli or alveolar epithelial surface area per lung. This increase may reflect over-distension due to altered mechanical properties of alveoli. In the light of our findings and data from the literature, the question arises as to whether a lack of SP-D promotes structural changes in the lung which have been described as being associated with aging lungs