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Sample records for double major papilla

  1. Endoscopic sphincterotomy of the major duodenal papilla in acute relapsing pancreatitis associated with pancreas divisum: a case report.

    PubMed

    Spaziani, E; Trentino, P; Picchio, M; Di Filippo, A; Briganti, M; Pietricola, G; Elisei, W; Ceci, F; Coda, S; Pattaro, G; Parisella, F; De Angelis, F; Pecchia, M; Stagnitti, F

    2010-05-01

    We report a case of acute relapsing pancreatitis associated with pancreas divisum, who underwent major papilla sphincterotomy after failed minor papilla cannulation. Long-term results were satisfactory. The possible explanations of the efficacy of major papilla endoscopic resection in this particular case are discussed. PMID:20615366

  2. Effect of the manipulation of the duodenal papilla during double balloon enteroscopy

    PubMed Central

    Latorre, Rafael; López-Albors, Octavio; Soria, Federico; Candanosa, Eugenia; Pérez-Cuadrado, Enrique

    2016-01-01

    AIM: To determine the hypothesis that inflating the balloons in the duodenal papilla determines changes in the biochemical markers of pancreatitis. METHODS: Four groups of pigs were used: Group papilla (GP), the overtube’s balloon was inflated in the area of the papilla; GP + double balloon enteroscopy (GP + DBE), the overtube’s balloon was kept inflated in the area of the papilla for 20 min before a DBE; Group DBE (GDBE), DBE was carried out after insuring the balloon’s inflation far from the pancreatic papilla; and Group control (GC). Serum concentrations of amylase, lipase and C-reactive protein (CRP) were evaluated. Pancreases were processed for histopathology examination. RESULTS: Main changes occurred 24 h after the procedure compared with baseline levels. Amylase levels increased significantly in GP (59.2% higher) and were moderately higher in groups GP + DBE and GDBE (22.7% and 20%, respectively). Lipase increased in GP and GP + DBE, whereas it hardly changed in GDBE and in GC. CRP increased significantly in GP, GP + DBE and GDBE, while no changes were reported for GC. No statistically significant difference between groups GP and GP + DBE was found for the histopathological findings, except for vacuolization and necrosis of the pancreatic parenchyma that was higher in GP than in GP + DBE. CONCLUSION: The manipulation of the duodenal papilla by the inflated overtube’s balloon during DBE causes pancreatic structural damage and increased biochemical markers associated with pancreatitis. PMID:27158201

  3. Widespread lymph node recurrence of major duodenal papilla cancer following pancreaticoduodenectomy

    PubMed Central

    Li, Bai-Sen; Shi, Hui; Wen, Min; Xiao, Ming-Yong; Wang, Jian

    2015-01-01

    Major duodenal papilla cancer (MDPC) represents the primary type of duodenal cancer, and is typically considered a periampullary carcinoma as most tumors arise in this region. This report describes an extremely rare case involving a patient with rapidly and extensively recurrent MDPC following pancreaticoduodenectomy, who achieved complete response by concurrent image-guided radiation and intravenous oxaliplatin plus oral capecitabine therapies. The patient was a 50-year-old female who was admitted to our hospital 6 wk after resection for MDPC for evaluation of a nontender and enlarged node in the left side of her neck. After clinical work-up, the patient was diagnosed with postoperatively recurrent MDPC with widespread lymph node metastases at the bilateral cervix, mediastinum, abdominal cavity, and retroperitoneal area. She was administered whole field image-guided radiation therapy along with four cycles of the intravenous oxaliplatin plus oral capecitabine regimen. A complete response by positron emission tomography with 18-fluorodeoxyglucose was observed 4 months after treatment. The patient continues to be disease-free 2 years after the diagnosis of recurrence. PMID:26730173

  4. Topography and morphometry of the common bile duct and major duodenal papilla of man and principal domesticated animals.

    PubMed

    Khalil, M M; Islam, M N; Khalil, M M; Khan, Z I; Adiluzzaman, A A; Hossain, M I

    2005-01-01

    A comparative topography and morphometry of the common bile duct and major duodenal papilla was studied on the extrahepatic biliary apparatus of human and major domesticated animals such as horse, ox, Black Bengal (BB) goat, sheep, dog and cat of local breed. In Black Bengal goat, sheep, dog and cat, the extrahepatic biliary system seemed to be the continuation of the cystic duct, which was found to continue as the common hepatic/common bile duct into which all the hepatic/lobar ducts open. In man, the mean length and the mean diameter of the common bile duct were 7.67+/-0.58 cm. and 7.27+/-0.77 mm. respectively. In the ox, these values were 1.57+/-0.72 cm. and 11.82+/-0.79 mm. respectively; in the Black Bengal goat, 7.23+/-0.74 cm. and 4.45+/-0.72 mm. respectively; in the sheep, 5.27+/-0.66 cm. and 3.75+/-0.79 mm. respectively; in the dog, 4.72+/-0.67 cm. and 6.43+/-0.55 mm. respectively and in the cat, 3.26+/-0.87 cm. and 5.63+/-0.43 mm. respectively. In man, the mean length and the mean diameter at the base of the MDP were 4.37+/-0.56 mm. and 3.97+/-0.72 mm. respectively. In horse, these were 52.36+/-0.67 mm. and 12.47+/-0.63 mm. respectively; in ox, 12.53+/-0.73 mm. and 8.83+/-0.68 mm. respectively; in Black Bengal goat, 14.36+/-0.55 mm. and 5.23+/-0.57 mm. respectively; in sheep, 11.27+/-0.69 mm. and 4.51+/-0.74 mm. respectively; in dog, 17.43+/-0.82 mm. and 6.72+/-0.64 mm. respectively and in cat, these values were 12.36+/-0.47 mm. and 7.12+/-0.87 mm. The distance of the Major Duodenal Papilla (MDP) form the pyloric end of the stomach was proportionately shorter in the meat-eaters, i.e., the omnivorous man (9.76+/-0.88 cm), and the carnivores, dog (6.37+/-0.73 cm) and cat (2.75+/-0.87 cm.) when compared to that of the herbivores, i.e., ox (55.37+/-0.68 cm.), BB goat (23.27+/-0.89 cm.) and sheep (25.62+/-0.77 cm.). In the horse, the major duodenal papilla was perpendicular to the duodenal mucosal surface with the largest mean length and the mean diameter. In

  5. Ultrasonographic appearance of the major duodenal papilla in dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease.

    PubMed

    Mortier, Jeremy R; Maddox, Thomas W; White, Gillian M; Blundell, Richard J; Monné, Josep M; Lillis, Susannah M

    2016-06-01

    OBJECTIVE To determine the ultrasonographic appearance of the major duodenal papilla (MDP) in dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease. ANIMALS 40 adult client-owned dogs examined because of conditions that did not include hepatobiliary, pancreatic, or gastrointestinal tract disease. PROCEDURES Ultrasonographic examination of the MDP was performed. Each MDP was measured in 3 planes. Intraobserver reliability of measurements was determined, and associations between MDP dimensions and characteristics of the dogs were investigated. Histologic examination of longitudinal sections of the MDP was performed for 1 dog to compare the ultrasonographic and histologic appearance. RESULTS The MDP appeared as a layered structure with a hyperechoic outer layer, hypoechoic middle layer, and hyperechoic inner layer that corresponded to the duodenal serosa, duodenal muscularis, and duodenal submucosa, respectively. Layers visible during ultrasonographic examinations were consistent with layers identified histologically. Intraobserver reliability was substantial for each plane of measurement. Mean ± SD length, width, and height of the MDP were 15.2 ± 3.5 mm, 6.3 ± 1.6 mm, and 4.3 ± 1.0 mm, respectively. An increase in body weight of dogs was significantly associated with increased values for all measurements. CONCLUSIONS AND CLINICAL RELEVANCE The ultrasonographic appearance and approximate dimensions of the MDP of dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease were determined. Additional studies are needed to evaluate possible ultrasonographic lesions of the MDP in dogs with hepatobiliary, pancreatic, or intestinal diseases and to investigate clinical implications of these lesions with regard to diagnosis and prognosis. PMID:27227497

  6. The College Double Major and Subsequent Earnings

    ERIC Educational Resources Information Center

    Hemelt, Steven W.

    2010-01-01

    In this study I examine the relationship between graduating from college with two majors rather than one and labor market earnings using the 2003 National Survey of College Graduates. Because institutions are heterogeneous both in terms of overall quality and in the availability of opportunities to double major, I attempt to control for such…

  7. Comparative morphology of changeable skin papillae in octopus and cuttlefish.

    PubMed

    Allen, Justine J; Bell, George R R; Kuzirian, Alan M; Velankar, Sachin S; Hanlon, Roger T

    2014-04-01

    A major component of cephalopod adaptive camouflage behavior has rarely been studied: their ability to change the three-dimensionality of their skin by morphing their malleable dermal papillae. Recent work has established that simple, conical papillae in cuttlefish (Sepia officinalis) function as muscular hydrostats; that is, the muscles that extend a papilla also provide its structural support. We used brightfield and scanning electron microscopy to investigate and compare the functional morphology of nine types of papillae of different shapes, sizes and complexity in six species: S. officinalis small dorsal papillae, Octopus vulgaris small dorsal and ventral eye papillae, Macrotritopus defilippi dorsal eye papillae, Abdopus aculeatus major mantle papillae, O. bimaculoides arm, minor mantle, and dorsal eye papillae, and S. apama face ridge papillae. Most papillae have two sets of muscles responsible for extension: circular dermal erector muscles arranged in a concentric pattern to lift the papilla away from the body surface and horizontal dermal erector muscles to pull the papilla's perimeter toward its core and determine shape. A third set of muscles, retractors, appears to be responsible for pulling a papilla's apex down toward the body surface while stretching out its base. Connective tissue infiltrated with mucopolysaccharides assists with structural support. S. apama face ridge papillae are different: the contraction of erector muscles perpendicular to the ridge causes overlying tissues to buckle. In this case, mucopolysaccharide-rich connective tissue provides structural support. These six species possess changeable papillae that are diverse in size and shape, yet with one exception they share somewhat similar functional morphologies. Future research on papilla morphology, biomechanics and neural control in the many unexamined species of octopus and cuttlefish may uncover new principles of actuation in soft, flexible tissue. PMID:24741712

  8. Undergraduate Double Majors' Perceptions of Performer and Teacher Identity Development

    ERIC Educational Resources Information Center

    Sieger, Crystal

    2016-01-01

    The purpose of this research was to investigate music performer/music teacher identity by examining double majors in various stages of their programs of study aspiring to become a performer and music educator. Unlike their single-major peers, double majors cope with additional challenges as they simultaneously develop both identities, determining…

  9. Double Majors Produce Dynamic Thinkers, Study Finds

    ERIC Educational Resources Information Center

    Berrett, Dan

    2013-01-01

    An undergraduate education is traditionally supposed to provide students with both breadth and depth of knowledge, which derive from their general-education requirements and major, respectively. Increasingly, education experts also want students to develop a third skill, integrative thinking. It entails learning the deeper, underlying meaning of a…

  10. Denver Papillae Protocol for Objective Analysis of Fungiform Papillae

    PubMed Central

    Nuessle, Tiffany M.; Garneau, Nicole L.; Sloan, Meghan M.; Santorico, Stephanie A.

    2015-01-01

    The goal of the Denver Papillae Protocol is to use a dichotomous key to define and prioritize the characteristics of fungiform papillae (FP) to ensure consistent scoring between scorers. This protocol builds off of a need that has arisen from the last two decades of taste research using FP as a proxy for taste pore density. FP density has historically been analyzed using Miller & Reedy’s 1990 characterizations of their morphology: round, stained lighter, large, and elevated. In this work, the authors forewarned that stricter definitions of FP morphology needed to be outlined. Despite this call to action, follow up literature has been scarce, with most studies continuing to cite Miller & Reedy’s original work. Consequently, FP density reports have been highly variable and, combined with small sample sizes, may contribute to the discrepant conclusions on the role of FP in taste sensitivity. The Genetics of Taste Lab explored this apparent inconsistency in counting and found that scorers were individually prioritizing the importance of these characteristics differently and had no guidance for when a papilla had some, but not all, of the reported qualities of FP. The result of this subjectivity is highly variable FP counts of the same tongue image. The Denver Papillae Protocol has been developed to remedy this consequence through use of a dichotomous key that further defines and prioritizes the importance of the characteristics put forth by Miller & Reedy. The proposed method could help create a standard way to quantify FP for researchers in the field of taste and nutritional studies. PMID:26131644

  11. How to double the number of undergraduate physics majors

    NASA Astrophysics Data System (ADS)

    Kopp, Sacha

    2015-03-01

    Many colleges and universities around the country have a solid physics program that prepares students bound for graduate physics study. For a variety of reasons, the number of students choosing to major in physics may be small, typically <1% of the student body. When compared to other majors, this population is experiencing negligible growth. I will describe a campaign launched while at the University of Texas at Austin aimed at recruiting and retention of majors. This campaign includes actual programmatic changes in the curriculum and instruction of majors. Additionally, it includes a direct marketing campaign that attempted to change student attitudes about physics and its relation to their current major. Finally, it includes a program to reach out to local high schools and engage students in a discussion about their career choices before they apply for college. I will share some numerical and attitudinal data that suggests positive changes in the student population.

  12. Morphology of the lingual papillae in the giraffe.

    PubMed

    Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

    2013-01-01

    We examined the dorsal lingual surfaces of an adult giraffe (giraffa camelopardalis) by scanning electron microscopy. The filiform papillae on the lingual apex consisted of slender and thick conical papillae. The connective tissue core of the filiform papilla was flower-bud-like in shape. The filiform papillae on the lingual body consisted of large conical papillae and the fungiform papillae were round in shape. The connective tissue core of the fungiform papilla was rose-like in shape. The filiform papillae on the lingual prominence consisted of more large conical papillae than that of the lingual body. The connective tissue core of the filiform papilla was trianglar in shape. The large lenticular papillae were limited on the lingual prominence. The connective tissue core of the lenticular papilla consisted of small spines. The vallate papillae were located on both sides of the posterolateral aspects. The vallate papillae were flattened-oval in shape and the papillae were surrounded by a semicircular trench. The top of the connective tissue core of the vallate papilla had a rough surface with no spines. PMID:23614981

  13. Osmoprotective proteome adjustments in mouse kidney papilla

    PubMed Central

    Gabert, B. J.; Kültz, D.

    2011-01-01

    The papilla of the mammalian kidney must tolerate greatly varying degrees of hyperosmotic stress during urine concentration and depending on whole organism hydration state. To identify proteome adaptations supporting cell function and survival in such a harsh environment we compared the proteome of a) the hyperosmotic renal papilla with that of adjacent iso-osmotic cortex tissue and b) the renal papilla of diuretic versus that of anti-diuretic mice. Though functionally distinct the papilla is in close physical proximity to the renal cortex, an iso-osmotic region. Proteomic differences between the papilla and cortex of C57BL6 mice were identified using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry. We found 37 different proteins characteristic of the cortex and 16 proteins over-represented in the papilla. Regional specificity was confirmed by Western Blot and further substantiated by immunohistochemistry for selected proteins. Proteins that are characteristic of the renal papilla include αB crystallin, Hsp beta-1, Hsp90, 14-3-3 protein, glutathione S-transferase, aldose reductase, actin and tropomyosin. Gene ontology analysis confirmed a significant increase in molecular functions associated with protein chaperoning and cell stabilization. Proteins over-represented in the cortex were largely related to routine metabolism. During antidiuresis 15 different proteins changed significantly while 18 different proteins changed significantly during diuresis relative to normally hydrated controls. Changes were confirmed by Western blot for selected proteins. Proteins that are significantly altered by diuretic state are associated with cell structure (actin, tubulin), signaling (Rho GDP dissociation inhibitor, abhydrolase domain-containing protein 14B), chaperone functioning (Hsp beta-1, αB crystallin, T complex protein-1) and anti-oxidant functions (α-enolase, GAPDH and LDH). Taken together our study reveals that specific proteins involved in

  14. Spacing patterns on tongue surface-gustatory papilla.

    PubMed

    Jung, Han-Sung; Akita, Keiichi; Kim, Jae-Young

    2004-01-01

    The dorsal surface of the mammalian tongue is covered with four kinds of papillae, fungiform, circumvallate, foliate and filiform papillae. With the exception of the filiform papillae, these types of papillae contain taste buds and are known as the gustatory papillae. The gustatory papillae are distributed over the tongue surface in a distinct spatial pattern. The circumvallate and foliate papillae are positioned in the central and lateral regions respectively and the fungiform papillae are distributed on the anterior part of the tongue in a stereotyped array. The patterned distribution and developmental processes of the fungiform papillae indicate some similarity between the fungiform papillae and the other epithelial appendages, including the teeth, feathers and hair. This is because 1) prior to the morphological changes, the signaling molecules are expressed in the fungiform papillae forming area with a stereotyped pattern; 2) the morphogenesis of the fungiform papillae showed specific structures in early development, such as epithelial thickening and mesenchymal condensation and 3) the fungiform papillae develop through reciprocal interactions between the epithelium and mesenchymal tissue. These results led us to examine whether or not the early organogenesis of the fungiform papillae is a good model system for understanding both the spacing pattern and the epithelial-mesenchymal interaction during embryogenesis. PMID:15272380

  15. Abutment-Supported Papilla: A Combined Surgical and Prosthetic Approach to Papilla Reformation.

    PubMed

    Urban, Istvan A; Klokkevold, Perry R; Takei, Henry H

    2016-01-01

    Restoration of lost interdental papilla remains one of the most challenging goals for clinicians. When a single tooth is replaced with an implant, the papilla between the tooth and the implant can often be maintained or predictably reconstructed as long as the periodontal attachment and bone of the adjacent tooth is preserved. However, if the periodontal support is compromised on the neighboring natural tooth, the papilla will often be deficient or missing. This article presents a multidisciplinary treatment approach to regenerate the interdental papilla between an implant and a periodontally compromised tooth using surgical procedures and a customized abutment. Specifically, an abutment with modified subgingival contours is used to enhance support of the surgically reformed papilla. PMID:27560670

  16. Morphology of Floral Papillae in Maxillaria Ruiz & Pav. (Orchidaceae)

    PubMed Central

    DAVIES, K. L.; TURNER, M. P.

    2004-01-01

    • Background and Aims The labellar papillae and trichomes of Maxillaria Ruiz & Pav. show great diversity. Although papillae also occur upon other parts of the flower (e.g. column and anther cap), these have not yet been studied. Labellar trichomes of Maxillaria are useful in taxonomy, but hitherto the taxonomic value of floral papillae has not been assessed. The aim of this paper is to describe the range of floral papillae found in Maxillaria and to determine whether papillae are useful as taxonomic characters. • Methods Light microscopy, histochemistry, low‐vacuum scanning and transmission electron microscopy. • Key Results A total of 75 taxa were studied. Conical papillae with rounded or pointed tips were the most common. The column and anther cap usually bear conical, obpyriform or villiform papillae, whereas those around the stigmatic surface and at the base of the anther are often larger and swollen. Labellar papillae show greater diversity, and may be conical, obpyriform, villiform, fusiform or clavate. Papillae may also occur on multiseriate trichomes that perhaps function as pseudostamens. Labellar papillae contain protein but most lack lipid. The occurrence of starch, however, is more variable. Many papillae contain pigment or act as osmophores, thereby attracting insects. Rewards such as nectar or a protein‐rich, wax‐like, lipoidal substance may be secreted by papillae onto the labellar surface. Some papillae may have a protective role in preventing desiccation. Species of diverse vegetative morphology may have identical floral papillae, whereas others of similar vegetative morphology may not. • Conclusions Generally, floral papillae in Maxillaria have little taxonomic value. Nevertheless, the absence of papillae from members of the M. cucullata alliance, the occurrence of clavate papillae with distended apices in the M. rufescens alliance and the presence of papillose trichomes in some species may yet prove to be useful. PMID:14630691

  17. Androgen action in cultured dermal papilla cells from human hair follicles.

    PubMed

    Randall, V A; Thornton, M J; Hamada, K; Messenger, A G

    1994-01-01

    Androgens are major regulators of human hair growth with paradoxically different effects on hair follicles depending on their body site. They stimulate terminal growth in many regions including the face, have no effect on eyelashes, but may cause inhibition and balding on the scalp in genetically disposed individuals. How this occurs is unknown. However, androgens may act on the hair follicle via the cells of the dermal papilla; these would then influence the other cells of the hair follicle by altering the production of regulatory substances such as growth factors and/or extracellular matrix components. Therefore, primary lines of dermal papilla cells have been established from androgen-sensitive hair follicles, such as beard, and control, relatively androgen-independent, non-balding scalp cells and their mechanism of androgen action has been compared. Isolated beard dermal papillae were larger than those from scalp follicles. Although dermal papilla cells did not respond to in vitro androgens by alterations in growth, androgen-dependent dermal papilla cells contained higher levels of specific, low capacity, high affinity androgen receptors than non-balding scalp cells. The ability of the cells to metabolise testosterone to 5 alpha-dihydrotestosterone in culture also varied in parallel to that predicted from studies of hair growth in the 5 alpha-reductase deficiency syndrome. These results support the hypothesis that androgens act via the dermal papilla. They also show that dermal papilla cells retain differences in gene expression in culture which appear to correspond with their androgenic response in vivo. Further studies of such cells should help elucidate why bald men can grow beards! PMID:8003318

  18. A case of carcinoma in an adenoma of the duodenal minor papilla successfully treated with endoscopic mucosal resection

    PubMed Central

    Matsui, Toru; Matsubayashi, Hiroyuki; Hotta, Kinichi; Sasaki, Keiko; Ito, Hiroaki; Ono, Hiroyuki

    2016-01-01

    Background and study aims: Endoscopic papillectomy is currently used to treat noninvasive tumors of the papilla of Vater, but it is seldom reported for treatment of similar tumors of the minor papilla. This report describes the case of a 69-year-old female with a tumor located at the duodenal minor papilla. Findings of duodenoscopy, biopsy, and pancreatography indicated that her noninvasive tumor of the minor papilla was suitable for treatment with endoscopic resection. Glycerol-injected endoscopic mucosal resection (EMR) was performed, and the resected material histologically showed carcinoma in the adenoma, negative for neoplastic extension at the cut margin. No complications occurred during the treatment course, and no recurrence has been recognized for 80 months. Unlike the major papilla of Vater, the minor papilla can be lifted up by submucosal injection. Noninvasive epithelial tumors of the duodenal minor papilla without extension to the pancreatic duct can be successfully treated with EMR, as the technique is easy, it is minimally invasive, and it is curative. PMID:27004240

  19. Morphological variations of the vallate papillae in some mammalian species.

    PubMed

    El Sharaby, Ashraf A; El-Gendy, Samir A; Alsafy, Mohamed A; Nomir, Ahmed G; Wakisaka, Satoshi

    2014-06-01

    The morpho-structural characteristics of the vallate papillae of the tongue of rat, dog, donkey and buffalo were investigated by macroscopy and their microstructure by light and scanning electron microscopy (SEM). The numbers of vallate papillae varied among the different species. In rat, a single vallate papilla surrounded by incomplete groove and an annular fold was observed. Taste buds were detected along the entire length of the medial and lateral groove epithelium, but not in the papillary dome. In dog, some papillae lacking the annular pad had irregular ridges and grooves toward the center of the papillary surface, while other papillae had small secondary papillary grooves arising from the center of the papilla. Taste buds were located in the medial and lateral epithelium of both primary and secondary grooves as well as in the dome epithelium. In donkey, two papillae were frequently observed around the midline of the tongue root, and an additional papilla was found occasionally in the middle and associated with secondary papilla. In buffalo, several papillae were relatively small and variable in shape. With SEM, small ridges and grooves were found in the papillae of donkey and buffalo. In both species, taste buds were constantly observed along the medial wall epithelium, but no taste buds were found in the lateral wall. We conclude that the vallate papillae exhibited peculiar characteristics, which are species specific and might have a correlation with the variable feeding habits among these animals. PMID:24242871

  20. Morphology of the lingual papillae in the Patagonian cavy.

    PubMed

    Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

    2011-11-01

    We examined the dorsal lingual surfaces of an adult Patagonian cavy (Dolichotis patagonum) by scanning electron microscopy. The tongue of the Patagonian cavy is about 8 cm long and the lingual body had lingual prominence on the posterior third. There were no fungiform papillae in the lingual dorsal surface. The fungiform papillae were observed in both lateral sides of the lingual apex. The filiform papilla of the lingual body consisted of a large conical papilla. The connective tissue core of the filiform papilla showed many slender processes. The fungiform papillae were round in shape. The connective tissue core of the fungiform papilla was flower-bud shaped. Two vallate papillae were located on between lingual body and root, and insert in two grooves. The connective tissue core of the vallate papilla was covered with numerous small spines. Many foliate papillae were observed on the posterolateral regions of the tongue. After removing epithelium from the foliate papillae many vertical depressions became apparent. These findings suggest that in the structure of the lingual papillae of the Patagonian cavy there is similar to that of the capybara. PMID:22519071

  1. Characterization of Ovine Dermal Papilla Cell Aggregation

    PubMed Central

    Sari, Agnes Rosarina Prita; Rufaut, Nicholas Wolfgang; Jones, Leslie Norman; Sinclair, Rodney Daniel

    2016-01-01

    Context: The dermal papilla (DP) is a condensation of mesenchymal cells at the proximal end of the hair follicle, which determines hair shaft size and regulates matrix cell proliferation and differentiation. DP cells have the ability to regenerate new hair follicles. These cells tend to aggregate both in vitro and in vivo. This tendency is associated with the ability of papilla cells to induce hair growth. However, human papilla cells lose their hair-inducing activity in later passage number. Ovine DP cells are different from human DP cells since they do not lose their aggregative behavior or hair-inducing activity in culture. Nonetheless, our understanding of ovine DP cells is still limited. Aim: The aim of this study was to observe the expression of established DP markers in ovine cells and their association with aggregation. Subjects and Methods: Ovine DP cells from three different sheep were compared. Histochemistry, immunoflourescence, and polymerase chain reaction experiments were done to analyze the DP markers. Results: We found that ovine DP aggregates expressed all the 16 markers evaluated, including alkaline phosphatase and versican. Expression of the versican V0 and V3 isoforms, neural cell adhesion molecule, and corin was increased significantly with aggregation, while hey-1 expression was significantly decreased. Conclusions: Overall, the stable expression of numerous markers suggests that aggregating ovine DP cells have a similar phenotype to papillae in vivo. The stability of their molecular phenotype is consistent with their robust aggregative behavior and retained follicle-inducing activity after prolonged culture. Their phenotypic stability in culture contrasts with DP cells from other species, and suggests that a better understanding of ovine DP cells might provide opportunities to improve the hair-inducing activity and therapeutic potential of human cells. PMID:27625564

  2. Oxidative stress-associated senescence in dermal papilla cells of men with androgenetic alopecia.

    PubMed

    Upton, James H; Hannen, Rosalind F; Bahta, Adiam W; Farjo, Nilofer; Farjo, Bessam; Philpott, Michael P

    2015-05-01

    Dermal papilla cells (DPCs) taken from male androgenetic alopecia (AGA) patients undergo premature senescence in vitro in association with the expression of p16(INK4a), suggesting that DPCs from balding scalp are more sensitive to environmental stress than nonbalding cells. As one of the major triggers of senescence in vitro stems from the cell "culture shock" owing to oxidative stress, we have further investigated the effects of oxidative stress on balding and occipital scalp DPCs. Patient-matched DPCs from balding and occipital scalp were cultured at atmospheric (21%) or physiologically normal (2%) O2. At 21% O2, DPCs showed flattened morphology and a significant reduction in mobility, population doubling, increased levels of reactive oxygen species and senescence-associated β-Gal activity, and increased expression of p16(INK4a) and pRB. Balding DPCs secreted higher levels of the negative hair growth regulators transforming growth factor beta 1 and 2 in response to H2O2 but not cell culture-associated oxidative stress. Balding DPCs had higher levels of catalase and total glutathione but appear to be less able to handle oxidative stress compared with occipital DPCs. These in vitro findings suggest that there may be a role for oxidative stress in the pathogenesis of AGA both in relation to cell senescence and migration but also secretion of known hair follicle inhibitory factors. PMID:25647436

  3. Morphology of the filiform lingual papillae in porcupine (Hystrix cristata).

    PubMed

    Karan, M; Yilmaz, S; Aydin, A

    2011-04-01

    The light and scanning electron microscopic structure of the filiform lingual papillae was studied in five adult porcupine (three males and two females). The tongue was characterised by a round tip, a rostral median sulcus and a deep lingual fossa which was situated just rostral to a prominent inter-molar eminence corresponding to a torus linguae. The filiform papillae were curved, enclosed a large connective tissue core and were separated by wide inter-papillary zones covered by a thick epithelium. Most filiform papillae had a cylindrical shape, but the rostral and central parts of the tongue contained a number of flat, comb-shaped papillae with rounded tips. PMID:21105901

  4. Characterization of Apical Papilla and its Residing Stem Cells from Human Immature Permanent Teeth –A Pilot Study

    PubMed Central

    Sonoyama, Wataru; Liu, Yi; Yamaza, Takayoshi; Tuan, Rocky S.; Wang, Songlin; Shi, Songtao; Huang, George T.-J.

    2009-01-01

    Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells or DPSCs) and deciduous teeth (stem cells from human exfoliated deciduous teeth or SHED). We recently discovered another type of MSCs in the apical papilla of human immature permanent teeth termed stem cells from apical papilla (SCAP). Here we further characterized the apical papilla tissue and stem cell properties of SCAP using histological, immunohistochemical and immunocytofluorescent analyses. We found that apical papilla is distinctive to pulp in terms of containing less cellular and vascular components than those in pulp. Cells in apical papilla proliferated 2- to 3-fold greater than those in pulp in organ cultures. Both SCAP and DPSCs were as potent in osteo/dentinogenic differentiation as MSCs from bone marrows while weaker in adipogenic potential. The immunophenotype of SCAP is similar to that of DPSCs on the osteo/dentinogenic and growth factor receptor gene profiles. Double staining experiments showed that STRO-1 co-expressed with dentinogenic markers such as bone sialophosphoprotein (BSP), osteocalcin (OCN) and growth factors FGFR1 and TGFβRI in cultured SCAP. Additionally, SCAP express a wide variety of neurogenic markers such as nestin and neurofilament M upon stimulation with a neurogenic medium. We conclude that SCAP are similar to DPSCs but a distinct source of potent dental stem/progenitor cells. Their implications in root development and apexogenesis are discussed. PMID:18215674

  5. Morphology of the lingual papillae in the brush-tailed rat kangaroo.

    PubMed

    Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

    2014-01-01

    We examined the dorsal lingual surface of an adult brush-tailed rat kangaroo (Bettongia penicillata) by scanning electron microscopy. The filiform and fungiform papillae on the lingual apex and body consisted of a main papilla and secondary papillae. The connective tissue core of the filiform papillae on the lingual apex was cylindrical in shape with a crushed top. The connective tissue core of the filiform papillae on the lingual body had one large and several small processes. The fungiform papillae were round in shape. The connective tissue core of the fungiform papillae had several depressions on its top. The surface of the vallate papillae was rough and the papillae were surrounded by a groove and a pad. Several long conical papillae derived from the posterolateral margin of the tongue where foliate papillae have been shown to be distributed in many other animal species. The long conical papillae were very similar to those of the koala and opossum. PMID:24815106

  6. Surgical augmentation of interdental papilla - A case series

    PubMed Central

    Muthukumar, Santhanakrishnan; Rangarao, Suresh

    2015-01-01

    Formation of black triangles between teeth due to loss of interdental palpilla is one of the common problems encountered in routine clinical practice, as extreme importance is given to esthetics. This paper discusses two different surgical approaches in treating three cases with papillary loss in the first case the reconstruction of papilla was achieved by using a semilunar coronally repositioned papilla technique and in second and the third case reconstruction of the papilla was achieved by modification of Nodland's microsurgical technique. In all the three cases a free connective tissue graft was used to reconstruct the lost volume of interdental papilla. Complete reconstruction of the lost papilla was achieved in all the three cases 6 months postoperatively. PMID:26604592

  7. Changes in fungiform papillae density during development in humans.

    PubMed

    Correa, Maryam; Hutchinson, Ian; Laing, David G; Jinks, Anthony L

    2013-07-01

    The anterior region of the human tongue ceases to grow by 8-10 years of age and the posterior region at 15-16 years. This study was conducted with 30 adults and 85 children (7-12 year olds) to determine whether the cessation of growth in the anterior tongue coincides with the stabilization of the number and distribution of fungiform papillae (FP) on this region of the tongue. This is important for understanding when the human sense of taste becomes adult in function. This study also aimed to determine whether a small subpopulation of papillae could be used to predict the total number of papillae. FP were photographed and analyzed using a digital camera. The results indicated that the number of papillae stabilized at 9-10 years of age, whereas the distribution and growth of papillae stabilized at 11-12 years of age. One subpopulation of papillae predicted the density of papillae on the whole anterior tongue of 7-10 year olds, whereas another was the best predictor for the older children and adults. Overall, the population, size, and distribution of FP stabilized by 11-12 years of age, which is very close to the age that cessation of growth of the anterior tongue occurs. PMID:23709647

  8. Double-Blinding and Bias in Medication and Cognitive-Behavioral Therapy Trials for Major Depressive Disorder

    PubMed Central

    Berger, Douglas

    2016-01-01

    While double-blinding is a crucial aspect of study design in an interventional clinical trial of medication for a disorder with subjective endpoints such as major depressive disorder, psychotherapy clinical trials, particularly cognitive-behavioral therapy trials, cannot be double-blinded. This paper highlights the evidence-based medicine problem of double-blinding in the outcome research of a psychotherapy and opines that psychotherapy clinical trials should be called, “partially-controlled clinical data” because they are not double-blinded. The implications for practice are, 1. For practitioners to be clear with patients the level of rigor to which interventions have been studied, 2. For authors of psychotherapy outcome studies to be clear that the problem in the inability to blind a psychotherapy trial severely restricts the validity of any conclusions that can be drawn, and 3. To petition National Health Insurance plans to use caution in approving interventions studied without double-blinded confirmatory trials as they may lead patients to avoid other treatments shown to be effective in double-blinded trials. PMID:26870318

  9. Clinical Evaluation of Papilla Reconstruction Using Subepithelial Connective Tissue Graft

    PubMed Central

    Kaushik, Alka; PK, Pal; Chopra, Deepak; Chaurasia, Vishwajit Rampratap; Masamatti, Vinaykumar S; DK, Suresh; Babaji, Prashant

    2014-01-01

    Objective: The aesthetics of the patient can be improved by surgical reconstruction of interdental papilla by using an advanced papillary flap interposed with subepithelial connective tissue graft. Materials and Methods: A total of fifteen sites from ten patients having black triangles/papilla recession in the maxillary anterior region were selected and subjected to presurgical evaluation. The sites were treated with interposed subepithelial connective tissue graft placed under a coronally advance flap. The integrity of the papilla was maintained by moving the whole of gingivopapillary unit coronally. The various parameters were analysed at different intervals. Results: There was a mean decrease in the papilla presence index score and distance from contact point to gingival margin, but it was statistically not significant. Also, there is increase in the width of the keratinized gingiva which was statistically highly significant. Conclusion: Advanced papillary flap with interposed sub–epithelial connective tissue graft can offer predictable results for the reconstruction of interdental papilla. If papilla loss occurs solely due to soft-tissue damage, reconstructive techniques can completely restore it; but if due to periodontal disease involving bone loss, reconstruction is generally incomplete and multiple surgical procedures may be required. PMID:25386529

  10. Morphology of the lingual papillae of the black-backed jackal (Canis mesomelas).

    PubMed

    Emura, Shoichi; Sugiyama, Kazue

    2014-01-01

    We examined the dorsal lingual surface of an adult black-backed jackal (Canis mesomelas) by using scanning electron microscopy. The filiform papilla on the lingual apex exhibited a crown-like shape with several pointed processes. The connective tissue core of the filiform papilla was U-shaped. The filiform papillae on the lingual body had several pointed processes. The connective tissue core of the filiform papillae consisted of one large and several small conical papillae. The fungiform papillae on the lingual apex and body had a smooth surface. The connective tissue core of the fungiform papillae was not hollow and did not have processes. The vallate papillae were surrounded by a groove and pad with many processes on the surface. The connective tissue core of the vallate papillae had many ditches. Thus, the tongue of the black-backed jackal more closely resembles that of the bush dog than those of the raccoon dog or fox. PMID:25274405

  11. Morphology of the Lingual and Buccal Papillae in Alpaca (Vicugna pacos) - Light and Scanning Electron Microscopy.

    PubMed

    Goździewska-Harłajczuk, K; Klećkowska-Nawrot, J; Janeczek, M; Zawadzki, M

    2015-10-01

    The aim of this study was the description of the lingual and buccal papillae in adult alpaca (Vicugna pacos) by light and scanning electron microscopy (SEM). The tongue consisted of apex, body and root. Four types of lingual papillae (filiform, fungiform, conical and circumvallate) in addition to two types of buccal papillae were observed. The filiform papillae, some with secondary papillae, were distributed on both the corpus and apex of the tongue, with stratified epithelium, and layer of keratin coat were recognized. The short (small) cone papillae had pointed top, while bunoform papillae were wide with smooth apex. The much less numerous circumvallate papillae with pseudopapillae on the each rim of the caudal lingual body were present with weak layer of keratin and intra-epithelial taste buds. The small fungiform papillae were found on the dorsal lingual surface, while the large fungiform papillae were situated on the ventral surface of the tongue, especially, in rostral part and were round in shape with numerous gustatory pores and very thin keratin coat. Pseudopapillae were present on the buccal conical 'bunoform' papillae surface, while 'elongate' buccal papillae surface was rather softly folded with thin coat of keratin. Microridges were observed in the less keratinized parts of each type of papillae. The orientation of either lingual or buccal papillae into the throat side facilitates the emptying of oral cavity from nutrient and swallowing of food. In conclusion, the anatomical features of the alpaca tongue are an adaptation to the feeding habits. PMID:25223623

  12. Transcriptome Sequencing Reveals Differences between Primary and Secondary Hair Follicle-derived Dermal Papilla Cells of the Cashmere Goat (Capra hircus)

    PubMed Central

    Yuan, Jianlong; Guo, Xudong; Liu, Dongjun

    2013-01-01

    The dermal papilla is thought to establish the character and control the size of hair follicles. Inner Mongolia Cashmere goats (Capra hircus) have a double coat comprising the primary and secondary hair follicles, which have dramatically different sizes and textures. The Cashmere goat is rapidly becoming a potent model for hair follicle morphogenesis research. In this study, we established two dermal papilla cell lines during the anagen phase of the hair growth cycle from the primary and secondary hair follicles and clarified the similarities and differences in their morphology and growth characteristics. High-throughput transcriptome sequencing was used to identify gene expression differences between the two dermal papilla cell lines. Many of the differentially expressed genes are involved in vascularization, ECM-receptor interaction and Wnt/β-catenin/Lef1 signaling pathways, which intimately associated with hair follicle morphogenesis. These findings provide valuable information for research on postnatal morphogenesis of hair follicles. PMID:24069460

  13. Ciprofloxacin Improves the Stemness of Human Dermal Papilla Cells

    PubMed Central

    Kiratipaiboon, Chayanin; Tengamnuay, Parkpoom; Chanvorachote, Pithi

    2016-01-01

    Improvement in the expansion method of adult stem cells may augment their use in regenerative therapy. Using human dermal papilla cell line as well as primary dermal papilla cells as model systems, the present study demonstrated that ciprofloxacin treatment could prevent the loss of stemness during culture. Clonogenicity and stem cell markers of dermal papilla cells were shown to gradually decrease in the culture in a time-dependent manner. Treatment of the cells with nontoxic concentrations of ciprofloxacin could maintain both stem cell morphology and clonogenicity, as well as all stem cells markers. We found that ciprofloxacin exerted its effect through ATP-dependent tyrosine kinase/glycogen synthase kinase3β dependent mechanism which in turn upregulated β-catenin. Besides, ciprofloxacin was shown to induce epithelial-mesenchymal transition in DPCs as the transcription factors ZEB1 and Snail were significantly increased. Furthermore, the self-renewal proteins of Wnt/β-catenin pathway, namely, Nanog and Oct-4 were significantly upregulated in the ciprofloxacin-treated cells. The effects of ciprofloxacin in preserving stem cell features were confirmed in the primary dermal papilla cells directly obtained from human hair follicles. Together, these results revealed a novel application of ciprofloxacin for stem cell maintenance and provided the underlying mechanisms that are responsible for the stemness in dermal papilla cells. PMID:26649051

  14. Ampullary Adenoma Treated by Endoscopic Double-Snare Retracting Papillectomy.

    PubMed

    Soma, Hiromitsu; Miyata, Naoteru; Hozawa, Shigenari; Higuchi, Hajime; Yamagishi, Yoshiyuki; Nakamura, Yuji; Saeki, Keita; Kameyama, Kaori; Masugi, Yohei; Yahagi, Naohisa; Kanai, Takanori

    2015-09-23

    We report herein improved methods for the safe and successful completion of endoscopic papillectomy (EP). Between January 2008 and November 2011, 12 patients underwent double-snare retracting papillectomy for the treatment of lesions of the major duodenal papilla. The main outcomes were en bloc resection rates, pathological findings, and adverse events. All of the patients (mean age, 60.1 years; range, 38 to 80 years) were diagnosed with ampullary adenoma by endoscopic forceps biopsies prior to endoscopic snare papillectomy. En bloc resection by double-snare retracting papillectomy was successfully performed for all lesions (median size, 12.3 mm), comprising six tubular adenomas, one tubulovillous adenoma, three cases of epithelial atypia, one hamartomatous polyp, and one case of duodenitis with regenerative change. Significant hemorrhage and pancreatitis were observed in one case after EP. Adenoma recurrence occurred in three patients during follow-up (median, 28.5 months) at a mean interval of 2 months postoperatively (range, 1 to 3 months). No serious adverse events were observed. Double-snare retracting papillectomy is effective and feasible for treating lesions of the major duodenal papilla. Further treatment experience, including a single-arm phase II study, needs to be accumulated before conducting a randomized controlled study. PMID:26087781

  15. Separate and distinctive roles for Wnt5a in tongue, lingual tissue and taste papilla development

    PubMed Central

    Liu, Hong-Xiang; Grosse, Ann S.; Iwatsuki, Ken; Mishina, Yuji; Gumucio, Deborah L.; Mistretta, Charlotte M.

    2012-01-01

    Although canonical Wnt signaling is known to regulate taste papilla induction and numbers, roles for noncanonical Wnt pathways in tongue and taste papilla development have not been explored. With mutant mice and whole tongue organ cultures we demonstrate that Wnt5a protein and message are within anterior tongue mesenchyme across embryo stages from the initiation of tongue formation, through papilla placode appearance and taste papilla development. The Wnt5a mutant tongue is severely shortened, with an ankyloglossia, and lingual mesenchyme is disorganized. However, fungiform papilla morphology, number and innervation are preserved, as is expression of the papilla marker, Shh. These data demonstrate that the genetic regulation for tongue size and shape can be separated from that directing lingual papilla development. Preserved number of papillae in a shortened tongue results in an increased density of fungiform papillae in the mutant tongues. In tongue organ cultures, exogenous Wnt5a profoundly suppresses papilla formation and simultaneously decreases canonical Wnt signaling as measured by the TOPGAL reporter. These findings suggest that Wnt5a antagonizes canonical Wnt signaling to dictate papilla number and spacing. In all, distinctive roles for Wnt5a in tongue size, fungiform papilla patterning and development are shown and a necessary balance between non-canonical and canonical Wnt paths in regulating tongue growth and fungiform papillae is proposed in a model, through the Ror2 receptor. PMID:22024319

  16. Osteogenic differentiation of human dental papilla mesenchymal cells

    SciTech Connect

    Ikeda, Etsuko; Hirose, Motohiro . E-mail: motohiro-hirose@aist.go.jp; Kotobuki, Noriko; Shimaoka, Hideki; Tadokoro, Mika; Maeda, Masahiko; Hayashi, Yoshiko; Kirita, Tadaaki; Ohgushi, Hajime

    2006-04-21

    We isolated dental papilla from impacted human molar and proliferated adherent fibroblastic cells after collagenase treatment of the papilla. The cells were negative for hematopoietic markers but positive for CD29, CD44, CD90, CD105, and CD166. When the cells were further cultured in the presence of {beta}-glycerophosphate, ascorbic acid, and dexamethasone for 14 days, mineralized areas together with osteogenic differentiation evidenced by high alkaline phosphatase activity and osteocalcin contents were observed. The differentiation was confirmed at both protein and gene expression levels. The cells can also be cryopreserved and, after thawing, could show in vivo bone-forming capability. These results indicate that mesenchymal type cells localize in dental papilla and that the cells can be culture expanded/utilized for bone tissue engineering.

  17. "Restoratively driven papilla regeneration: correcting the dreaded 'black triangle'".

    PubMed

    Clark, David

    2008-11-01

    Until now there were very few dedicated tools or techniques for restoratively driven papilla regeneration. Previous attempts at both diastema closure and papilla regeneration using direct composites often ended with significant compromise in periodontal health. The interdental papilla serves as both an esthetic and functional asset, and anatomically ideal interproximal composite shapes can serve as a predictable scaffold to regain this valuable gingival architecture. The reader is strongly cautioned that to attempt this elective procedure using no magnification and without appropriate materials may not be in the patient's best interest, and that non treatment or referral is recommended. This extremely rounded, injection molded composite filling technique is new. Once again, technological advancements allow changes to perform techniques that were previously unthinkable. Slowly, the profession will change their thought patterns, retrain their hands and minds, and allow this substantial clinical evolution in restorative dentistry. PMID:19180945

  18. Dental Apical Papilla as Therapy for Spinal Cord Injury.

    PubMed

    De Berdt, P; Vanacker, J; Ucakar, B; Elens, L; Diogenes, A; Leprince, J G; Deumens, R; des Rieux, A

    2015-11-01

    Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the neural crest, express numerous neurogenic markers, and mediate neurite outgrowth and axonal targeting. The goal of the present work was to investigate for the first time their potential to promote motor recovery after SCI in a rat hemisection model when delivered in their original stem cell niche-that is, by transplantation of the human apical papilla tissue itself into the lesion. Control groups consisted of animals subjected to laminectomy only (shams) and to lesion either untreated or injected with a fibrin hydrogel with or without human SCAP. Basso-Beattie-Bresnahan locomotor scores at 1 and 3 d postsurgery confirmed early functional decline in all SCI groups. This significant impairment was reversed, as seen in CatWalk analyses, after transplantation of apical papilla into the injured spinal cord wound, whereas the other groups demonstrated persistent functional impairment. Moreover, tactile allodynia did not develop as an unwanted side effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the microglial marker Iba-1, which has been frequently associated with allodynia. Notably, the apical papilla transplant group presented with reduced Iba-1 expression level. Masson trichrome and human mitochondria staining showed the preservation of the apical papilla integrity and the presence of numerous human cells, while human cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point. Altogether, our data suggest that the transplantation of a human apical papilla at the lesion site improves gait in spinally injured rats and reduces glial reactivity. It also underlines the potential interest for the application of delivering SCAP in their original niche, as compared with use of a fibrin hydrogel. PMID:26341974

  19. Morphology and morphometry of lingual papillae in adult and newborn Egyptian fruit bats (Rousettus aegyptiacus).

    PubMed

    Trzcielińska-Lorych, J; Jackowiak, H; Skieresz-Szewczyk, K; Godynicki, S

    2009-10-01

    The paper presents a comparison of the microscopic structure and morphometric traits of gustatory and mechanical lingual papillae in newborn and adult frugivorous Egyptian fruit bats (Rousettus aegyptiacus). All of the four types of lingual papillae found in adult animals were observed on the tongue surface in the newborn Egyptian fruit bats. After the birth, the gustatory papillae (fungiform and vallate papillae) were especially well-developed, as their structural characteristics, such as morphology of the epithelium and presence of the taste buds, indicate that they have reached almost complete functional traits. Mechanical papillae, particularly filiform papillae, in newborns are still fetal in character. Keratinization processes in the epithelium of these papillae are not advanced and specific structures, such as elongated processes, are missing. The morphometric analysis of the size of papillae and thickness of the mucosal epithelium showed that a complete development of keratinized structures in Egyptian fruit bats occurs at later stages of postnatal development. PMID:19681832

  20. Adenocarcinoma of the minor duodenal papilla and its precursor lesions: a clinical and pathologic study.

    PubMed

    Shia, Jinru; Agaram, Narasimhan P; Olgac, Semra; Cobanov, Brando; Adsay, Volkan; Klimstra, David S

    2014-04-01

    The minor duodenal papilla drains the accessory pancreatic duct of Santorini and lies proximal to the ampulla of Vater. Adenocarcinoma and its precursor lesions arising in the minor papilla are rare. Literature data thus far are limited to a few individual case reports, and the condition is consequently poorly defined. Our study cases were composed of carcinomas fulfilling all of the following criteria: location at 1.5 to 2.5 cm proximal to the major papilla; presence of associated submucosal pancreatobiliary-type ducts with periductal glands or acinar tissue; a predominant submucosal location of the tumor; and lack of an intestinal-type adenoma in the adjacent duodenal mucosa. Tumors were studied morphologically, immunohistochemically, and clinically. Nine cases fulfilling the inclusion criteria were identified. There were 5 men and 4 women with an age range of 50 to 76 years (median, 72 y). The tumor size ranged from 1.2 to 4.4 cm (median, 3 cm). The carcinomas were of colloid type (3 tumors), pancreatobiliary type (4), or nonmucinous intestinal type (2). Five cases were associated with an intraductal papillary mucinous neoplasm (IPMN)-like precursor lesion within the residual structures of the minor papilla in the duodenal submucosa. Immunohistochemically, the intestinal-type and mucinous-type tumors tended to be positive for CK20, CDX2, MUC2, and B72.3, and pancreatobiliary-type tumors tended to be positive for CK7, MUC1, B72.3, and CA125. Loss of DPC4 (Smad4) expression was found in the pancreatobiliary-type carcinomas only. Two tumors showed loss of DNA mismatch-repair protein expression, one losing MLH1 and PMS2 and the other losing MSH6. Both patients were older than 60 years, and neither had germline mutation testing. Follow-up information was available for 6 patients (median follow-up time, 67.5 mo): 3 of the 6 patients died of disease at 60, 75, and 85 months after surgery, respectively, and all 3 patients had an intestinal-type carcinoma (1 colloid and

  1. A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepin in patients with major depression.

    PubMed

    Marttila, M; Jääskeläinen, J; Järvi, R; Romanov, M; Miettinen, E; Sorri, P; Ahlfors, U; Zivkov, M

    1995-12-01

    One hundred and sixty-three patients with major depression were randomly assigned to treatment with mirtazapine or doxepin for 6 weeks in a double-blind clinical trial. Initially, patients received mirtazapine 20 mg/day or doxepin 75 mg/day; dosages were then titrated up to a maximum of 60 mg/day and 300 mg/day, respectively. Both drugs produced considerable improvement in depressive symptoms with no statistically significant differences between the two patient groups. In the mirtazapine group only two patients prematurely terminated the study due to adverse drug experiences, as compared to six in the doxepin-treated group. Moreover, doxepin-treated patients complained more frequently of dry mouth and movement disorders. In conclusion, mirtazapine is an effective treatment for major depression and appears to offer advantages in tolerability over doxepin. PMID:8998395

  2. The Effect of Ovine Secreted Soluble Factors on Human Dermal Papilla Cell Aggregation

    PubMed Central

    Sari, Agnes Rosarina Prita; Rufaut, Nicholas Wolfgang; Jones, Leslie Norman; Sinclair, Rodney Daniel

    2016-01-01

    Context: In androgenetic alopecia, follicular miniaturization and dynamic changes to the hair cycle produce patterned baldness. The most effective treatment for baldness is hair transplantation surgery. The major limitation to hair transplantation is the availability of donor hair from the relatively unaffected occipital scalp. Hair induction with in vitro expansion of donor follicle populations has the potential to overcome this. The major obstacle to this is that in vitro expansion of human dermal papilla cell (DPC) colonies is associated with irreversible loss of aggregative behavior and hair follicle-inductive potential. In contrast, cultured ovine DPCs maintain these properties after extensive proliferation. Aims: To determine whether aggregating ovine DPC secrete factors that enhance the aggregative behavior or inductive potential of human DPC. Subjects and Methods: Fluorescently-labelled ovine DPC were mixed in culture with human DPC at passage number seven-nine, which had lost their aggregative behavior. The effects of different culture substrates and medium compositions on aggregative behavior were determined. Ovine and human papilla cells were co-cultured, separated by a permeable membrane to determine whether the ovine cells secrete soluble factors that affect human papilla cells. Results: In direct co-culture experiments, well-formed aggregates were produced by 90:10 human:ovine and 50:50 human:ovine DPC mixtures. In contrast, unmixed human DPC remained in a monolayer state after 18 days. Both human and ovine DPC had a higher tendency to aggregate in medium containing 20% (v/v) lamb serum (LS) compared to 10% (v/v) fetal calf serum (FCS). In co-culture experiments separated with permeable membrane, the human DPC aggregates were bigger and more rapidly formed with the addition of ovine secreted soluble factors. Conclusions: Soluble factors secreted by ovine DPC and present in LS increase the aggregative behavior of human DPC. These molecules might

  3. Groove pancreatitis and pancreatic heterotopia in the minor duodenal papilla.

    PubMed

    Chatelain, Denis; Vibert, Eric; Yzet, Thierry; Geslin, Guillaume; Bartoli, Eric; Manaouil, David; Delcenserie, Richard; Brevet, Marie; Dupas, Jean-Louis; Regimbeau, Jean-Marc

    2005-05-01

    Groove pancreatitis is a rare form of segmental chronic pancreatitis that involves the anatomic space between the head of the pancreas, the duodenum, and the common bile duct. We report 2 cases of groove pancreatitis with pancreatic heterotopia in the minor papilla. Patients were a 44-year-old woman and a 47-year-old man. Both had a past history of alcohol consumption and presented with abdominal pain, vomiting, and weight loss caused by duodenal stenosis. Abdominal computed tomography revealed thickening of the duodenal wall and enlargement of the pancreatic head in both patients. In 1 patient, ultrasound endoscopy showed a dilated duct in the head of the pancreas. Pancreaticoduodenectomy was performed to rule out pancreatic adenocarcinoma and because of the severity of the symptoms. In both cases, gross and microscopic examinations showed fibrous scar of the groove area. The Santorini duct was dilated and contained protein plugs in both patients, with abscesses in 1 of them. In both cases, there were microscopic foci of heterotopic pancreas with mild fibrosis in the wall of the minor papilla. Groove pancreatitis is often diagnosed in middle-aged alcoholic men presenting with clinical symptoms caused by duodenal stenosis. The pathogenesis of this rare entity could be because of disturbance of the pancreatic secretion through the minor papilla. Pancreatitis in heterotopic pancreas located in the minor papilla and chronic consumption of alcohol seem to be important pathogenic factors. PMID:15841034

  4. Biosynthesis of major histocompatibility complex molecules and generation of T cells in Ii TAP1 double-mutant mice.

    PubMed Central

    Tourne, S; van Santen, H M; van Roon, M; Berns, A; Benoist, C; Mathis, D; Ploegh, H

    1996-01-01

    Major histocompatibility complex (MHC) class I and II molecules are loaded with peptides in distinct subcellular compartments. The transporter associated with antigen processing (TAP) is responsible for delivering peptides derived from cytosolic proteins to the endoplasmic reticulum, where they bind to class I molecules, while the invariant chain (Ii) directs class II molecules to endosomal compartments, where they bind peptides originating mostly from exogenous sources. Mice carrying null mutations of the TAP1 or Ii genes (TAP10) or Ii0, respectively) have been useful tools for elucidating the two MHC/peptide loading pathways. To evaluate to what extent these pathways functionally intersect, we have studied the biosynthesis of MHC molecules and the generation of T cells in Ii0TAP10 double-mutant mice. We find that the assembly and expression of class II molecules in Ii0 and Ii0TAP10 animals are indistinguishable and that formation and display of class I molecules is the same in TAP10 and Ii0TAP10 animals. Thymic selection in the double mutants is as expected, with reduced numbers of both CD4+ CD8- and CD4- CD8+ thymocyte compartments. Surprisingly, lymph node T-cell populations look almost normal; we propose that population expansion of peripheral T cells normalizes the numbers of CD4+ and CD8+ cells in Ii0TAP10 mice. Images Fig. 1 Fig. 2 PMID:8643655

  5. Treatment of major depressive disorders with generic duloxetine and paroxetine: a multi-centered, double-blind, double-dummy, randomized controlled clinical trial

    PubMed Central

    WANG, Zhiyang; XU, Xiufeng; TAN, Qingrong; LI, Keqing; MA, Cui; XIE, Shiping; GAO, Chengge; WANG, Gang; LI, Huafang

    2015-01-01

    Background This study is a pre-registration trial of generic duloxetine that was approved by the China Food and Drug Administration (approval number: 2006L01603). Aims Compare the treatment efficacy and safety of generic duloxetine to that of paroxetine in patients with major depressive disorders (MDD). Methods This was a double-dummy, double-blind, multicenter, positive drug (paroxetine), parallel randomized controlled clinical trial. The 299 patients with MDD recruited for the study were randomly assigned to use duloxetine (n=149; 40–60 mg/d) or paroxetine (n=150; 20 mg/d) for 8 weeks. The Hamilton Depression rating scale (HAMD-17) was administered at baseline and 1, 2, 4, 6, and 8 weeks after starting treatment. Remission was defined as a HAMD-17 score below 8 at the end of the trial, and treatment effectiveness was defined as a decrease in baseline HAMD-17 score of at least 50% by the end of the trial. Safety was assessed based on the reported prevalence and severity of side effects and changes in laboratory and electrocardiographic findings. Three patients in the duloxetine group dropped out before starting medication, so results were analyzed using a modified intention-to-treat (ITT) method with 146 in the experimental group and 150 in the control group. Results Both groups experienced 29 dropouts during the 8-week trial. HAMD-17 scores decreased significantly from baseline throughout the trial in both groups. Based on the ITT analysis, at the end of the trial there was no significant difference between the duloxetine group and the paroxetine group in effectiveness (67.1% v. 71.3%, X2=0.62 p=0.433), remission rate (41.1% v. 51.3%, X2=3.12, p=0.077), or in the incidence of side effects (56.8% v. 54.7%, X2=0.14, p=0.705). Conclusions Generic duloxetine is as effective and safe as paroxetine in the acute treatment of patients with MDD who seek care at psychiatric outpatient departments in China. PMID:26549959

  6. Adenoma of the Papillae of Vater. Report of Eleven Cases

    PubMed Central

    Mäkelä, Jyrki; Palm, Jukka; Saarela, Arto

    2000-01-01

    Eleven patients with a preoperative diagnosis of adenoma of the papillae of Vater were followed up during the fifteen-year period from 1984 till 1998 in the Oulu University Hospital. Seven patients were treated primarily by transduodenal excision without any recurrences so far. One of these seven patients was found to have adenocarcinoma in a histological examination. Active surgery for adenoma of the papillae of Vater is recommended because of the precancerous nature of the lesion, and because malignancy cannot always be detected by endoscopic biopsies. Transduodenal excision could be recommend for patients at high operative risk, especially in cases with small adenomas and low-grade dysplasia, where histologically free resection margins can be achieved, but pancreaticoduodenectomy should still be performed on patients at low operative risk. PMID:10674750

  7. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results from a Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Papakostas, George I.; Fava, Maurizio; Baer, Lee; Swee, Michaela B.; Jaeger, Adrienne; Bobo, William V.; Shelton, Richard C.

    2016-01-01

    Objective To test the efficacy of adjunctive ziprasidone in adults with non-psychotic unipolar major depression experiencing persistent symptoms following 8 weeks of open-label escitalopram. Method This was a multi-center, parallel randomized, double-blind, placebo-controlled trial conducted at three academic medical centers in the United States. The participant pool consisted of 139 outpatients with persistent symptoms of major depressive disorder following an 8-week open label trial of escitalopram (phase 1). Subjects were randomized (1:1, n=139) to adjunctive ziprasidone (escitalopram+ziprasidone, n=71) or adjunctive placebo (escitalopram+placebo, n=68), with 8 weekly follow-up assessments. Primary outcome was defined by clinical response according to the 17-item Hamilton Depression Rating Scale (HAMD-17) and determined by a 50% or greater reduction in scale scores. The Hamilton Anxiety Rating scale (HAM-A) and Visual Analogue Scale for Pain were defined a priori as key secondary outcome measures. Results Rates of clinical response (35.2% vs. 20.5%, p=0.04) and mean improvement in HAMD-17 total scores (−6.4 ± 6.4 vs. −3.3 ± 6.2, p=0.04) were significantly greater for the escitalopram+ziprasidone group. Several secondary measures of antidepressant efficacy were also in favor of adjunctive ziprasidone. Escitalopram+ziprasidone also resulted in significantly greater improvement in HAM-A, but not Visual Analogue Scale for Pain scores. Ten (14%) patients discontinued escitalopram+ziprasidone due to intolerance versus none for escitalopram+placebo (p<0.01 versus placebo). Conclusions Adjunctive ziprasidone, when added to escitalopram, demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms following 8 weeks of open-label escitalopram. PMID:26085041

  8. Scanning Electron Microscopic Structure of the Lingual Papillae of the Common Opossum (Didelphis marsupialis)

    NASA Astrophysics Data System (ADS)

    Okada, Shigenori; Schraufnagel, Dean E.

    2005-08-01

    The mammalian tongue has evolved for specialized functions in different species. The structure of its papillae tells about the animal's diet, habit, and taxonomy. The opossum has four kinds of lingual papillae (filiform, conical, fungiform, vallate). Scanning electron microscopy of the external features, connective tissue cores, and corrosion casts of the microvasculature show the filiform papillae have a spearhead-like main process and spiny accessory processes around the apical part of the main process. The shape and number of both processes depend on their position on the tongue. On the apex, the main processes have shovel-like capillary networks and the accessory processes have small conical networks. On the lingual radix, the processes have small capillary loops. In the patch region, conical papillae have capillaries arranged as a full sail curving posteriorly. The fungiform papillae are scattered among the filiform papillae and have capillary baskets beneath each taste bud. Giant fungiform papillae on the tongue tip are three to four times larger than the ones on the lingual body. Capillaries of giant papillae form a fan-shaped network. The opossum has three vallate papillae arranged in a triangle. Their tops have secondary capillary loops but not their lateral surfaces. Mucosal folds on the posterolateral border have irregular, fingerlike projections with cylindrical capillary networks. These findings and the structure of the rest of the masticatory apparatus suggest the lingual papillae of opossum have kept their ancestral carnivorous features but also developed the herbivore characteristics of other marsupials.

  9. Scanning electron microscopic structure of the lingual papillae of the common opossum (Didelphis marsupialis).

    PubMed

    Okada, Shigenori; Schraufnagel, Dean E

    2005-08-01

    The mammalian tongue has evolved for specialized functions in different species. The structure of its papillae tells about the animal's diet, habit, and taxonomy. The opossum has four kinds of lingual papillae (filiform, conical, fungiform, vallate). Scanning electron microscopy of the external features, connective tissue cores, and corrosion casts of the microvasculature show the filiform papillae have a spearhead-like main process and spiny accessory processes around the apical part of the main process. The shape and number of both processes depend on their position on the tongue. On the apex, the main processes have shovel-like capillary networks and the accessory processes have small conical networks. On the lingual radix, the processes have small capillary loops. In the patch region, conical papillae have capillaries arranged as a full sail curving posteriorly. The fungiform papillae are scattered among the filiform papillae and have capillary baskets beneath each taste bud. Giant fungiform papillae on the tongue tip are three to four times larger than the ones on the lingual body. Capillaries of giant papillae form a fan-shaped network. The opossum has three vallate papillae arranged in a triangle. Their tops have secondary capillary loops but not their lateral surfaces. Mucosal folds on the posterolateral border have irregular, fingerlike projections with cylindrical capillary networks. These findings and the structure of the rest of the masticatory apparatus suggest the lingual papillae of opossum have kept their ancestral carnivorous features but also developed the herbivore characteristics of other marsupials. PMID:16079016

  10. Hair bundle profiles along the chick basilar papilla

    PubMed Central

    DUNCAN, R. K.; ILE, K. E.; DUBIN, M. G.; SAUNDERS, J. C.

    2001-01-01

    Cochlear hair cells play a central role in the transduction of sound into neural output. Anatomical descriptions of these cells, and their protruding hair bundles, are of fundamental interest since hair cell transduction is dependent on hair bundle micromechanics and hair bundle micromechanics depends on hair bundle morphology. In this paper, we describe quantitatively changes in the staircase profile of the hair bundle along the apical portion of the chick's basilar papilla. Images of hair cells from 8 discretely dissected segments of the apical 3rd of the basilar papilla were archived, and the profile contour outlined by the tips of the stereocilia was digitised and curves were fitted by linear and power equations. The hair bundles of tall hair cells exhibited both linear and curvilinear profiles, which were equally distributed along the papilla. All short hair cells in our sample had straight contours. The differences in hair bundle shape among the tall hair cells may lead to differential susceptibility to injury and some variance in the current-displacement transduction curves due to differences in the translation of forces throughout the hair bundle. PMID:11215761

  11. Characteristics of filiform, fungiform and vallate papillae and surface of interface epithelium-connective tissue of the maned sloth tongue mucosa (Bradypus torquatus, Iliger, 1811): Light and Scanning Electron Microscopy Study.

    PubMed

    Benetti, E J; Pícoli, L C; Guimarães, J P; Motoyama, A A; Miglino, M A; Watanabe, L-S

    2009-02-01

    The study of lingual surfaces and the surface of interface epithelium-connective tissue of the tongue of Bradypus torquatus was performed by employing the light and scanning electron microscopy (SEM) techniques. The results revealed that the rostral part of the tongue presents a round apex and covered by filiform and fungiform lingual papillae and a ventral smooth surface. It was observed that the epithelial layer of the dorsal surface possesses the basal, spinosum, granular and cornified epithelial cells. The lamina propria is characterized by a dense connective tissue forming the long, short and round papillae. Numerous typical filiform papillae are located especially in the rostral part intermingled for few fungiform papillae, which were revealed in three-dimensional SEM images. Usually, the fungiform papillae are located in the border of rostral apex of the tongue exhibiting the rounded form. They are covered by keratinized epithelial cells. In the fungiform papillae, several taste pores were observed on the surface. The vallate papillae presented numerous taste buds in the wall of epithelial cells, being that the major number of taste buds is located on the superior half of vallate papilla. The taste pores are surrounded by several laminae of keratinized epithelial cells. The samples treated with NaOH solution and examined by SEM revealed, after removal of the epithelial layer, the dense connective core in original disposition, presenting different sizes and shapes. The specimens stained with Picrosirius and examined by polarized light microscopy revealed the connective tissue, indicating the collagen fibres type I and type III. PMID:19143682

  12. Mirtazapine in comorbid major depression and an alcohol use disorder: A double-blind placebo-controlled pilot trial.

    PubMed

    Cornelius, Jack R; Chung, Tammy; Douaihy, Antoine B; Kirisci, Levent; Glance, Jody; Kmiec, Julie; FitzGerald, Douglas; Wesesky, Maribeth A; Salloum, Ihsan

    2016-08-30

    This was a first double-blind, placebo-controlled pilot study to evaluate the efficacy of the novel antidepressant medication mirtazapine for treating both the depressive symptoms and the level of alcohol consumption of subjects with comorbid major depressive disorder and an alcohol use disorder (MDD/AUD). The results of two previous studies of mirtazapine in MDD/AUD subjects had suggested efficacy for mirtazapine for decreasing their level of depressive symptoms, but level of alcohol consumption had not been assessed in those studies. All subjects in this 12-week pilot study were randomized to either mirtazapine or placebo, and also received motivational enhancement therapy. Between-group analyses involving the outcome measures of depressive symptoms, level of alcohol consumption, and level of alcohol craving indicated no significant differences between groups, possibly because of limited sample size. However, within-group t tests in the mirtazapine group showed a significant decrease in depressive symptoms by week 2, also noted at all subsequent assessments (weeks 3, 4, 6, 8, 10, and 12) during the 12-week study. In contrast, no significant decrease in depressive symptoms was noted in the placebo group until week 8. No evidence of efficacy was found for mirtazapine for decreasing level of alcohol consumption in MDD /AUD subjects. PMID:27327217

  13. Morphology of the lingual papillae in the Egyptian rousette bat (Rousettus aegyptiacus).

    PubMed

    Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

    2012-01-01

    The dorsal lingual surface of the Egyptian rousette bat was examined by scanning electron microscopy. Filiform, fungiform and vallate papillae were observed. The filiform papillae were distributed over the entire dorsal surface of the tongue. The filiform papillae notably differed in morphology by their location on the tongue and could be classified into 5 types: 1) scalelike, 2) small crown-like, 3) giant trifid, 4) large crown-like, 5) conical papillae. The fungiform papillae were present rounded bodies on the anterior 2/3 of the tongue. The Egyptian rousette bat showed the a triangular arrangement of the three vallate papillae, with the apex of the triangle directed posteriorly. These findings indicate that the tongue of the Egyptian rousette bat is similar to that of the large flying fox. PMID:23429050

  14. Angiotensin II regulates growth of the developing papillas ex vivo

    PubMed Central

    Song, Renfang; Preston, Graeme; Khalili, Ali; El-Dahr, Samir S.

    2012-01-01

    We tested the hypothesis that lack of angiotensin (ANG) II production in angiotensinogen (AGT)-deficient mice or pharmacologic antagonism of ANG II AT1 receptor (AT1R) impairs growth of the developing papillas ex vivo, thus contributing to the hypoplastic renal medulla phenotype observed in AGT- or AT1R-null mice. Papillas were dissected from Hoxb7GFP+ or AGT+/+, +/−, −/− mouse metanephroi on postnatal day P3 and grown in three-dimentional collagen matrix gels in the presence of media (control), ANG II (10−5 M), or the specific AT1R antagonist candesartan (10−6 M) for 24 h. Percent reduction in papillary length was attenuated in AGT+/+ and in AGT+/− compared with AGT−/− (−18.4 ± 1.3 vs. −32.2 ± 1.6%, P < 0.05, −22.8 ± 1.3 vs. −32.2 ± 1.6%, P < 0.05, respectively). ANG II blunted the decrease in papilla length observed in respective media-treated controls in Hoxb7GFP+ (−1.5 ± 0.3 vs. −10.0 ± 1.4%, P < 0.05) or AGT+/+, +/−, and −/− papillas (−12.8 ± 0.7 vs. −18.4 ± 1.3%, P < 0.05, −16.8 ± 1.1 vs. −23 ± 1.2%, P < 0.05; −26.2 ± 1.6 vs. −32.2 ± 1.6%, P < 0.05, respectively). In contrast, percent decrease in the length of Hoxb7GFP+ papillas in the presence of the AT1R antagonist candesartan was higher compared with control (−24.3 ± 2.1 vs. −10.5 ± 1.8%, P < 0.05). The number of proliferating phospho-histone H3 (pH3)-positive collecting duct cells was lower, whereas the number of caspase 3-positive cells undergoing apoptosis was higher in candesartan- vs. media-treated papillas (pH3: 12 ± 1.4 vs. 21 ± 2.1, P < 0.01; caspase 3: 3.8 ± 0.5 vs. 1.7 ± 0.2, P < 0.01). Using quantitative RT-PCR, we demonstrate that AT1R signaling regulates the expression of genes implicated in morphogenesis of the renal medulla. We conclude that AT1R prevents shrinkage of the developing papillas observed ex vivo via control of Wnt7b, FGF7, β-catenin, calcineurin B1, and α3 integrin gene expression, collecting duct cell

  15. Cuttlefish skin papilla morphology suggests a muscular hydrostatic function for rapid changeability.

    PubMed

    Allen, Justine J; Bell, George R R; Kuzirian, Alan M; Hanlon, Roger T

    2013-06-01

    Coleoid cephalopods adaptively change their body patterns (color, contrast, locomotion, posture, and texture) for camouflage and signaling. Benthic octopuses and cuttlefish possess the capability, unique in the animal kingdom, to dramatically and quickly change their skin from smooth and flat to rugose and three-dimensional. The organs responsible for this physical change are the skin papillae, whose biomechanics have not been investigated. In this study, small dorsal papillae from cuttlefish (Sepia officinalis) were preserved in their retracted or extended state, and examined with a variety of histological techniques including brightfield, confocal, and scanning electron microscopy. Analyses revealed that papillae are composed of an extensive network of dermal erector muscles, some of which are arranged in concentric rings while others extend across each papilla's diameter. Like cephalopod arms, tentacles, and suckers, skin papillae appear to function as muscular hydrostats. The collective action of dermal erector muscles provides both movement and structural support in the absence of rigid supporting elements. Specifically, concentric circular dermal erector muscles near the papilla's base contract and push the overlying tissue upward and away from the mantle surface, while horizontally arranged dermal erector muscles pull the papilla's perimeter toward its center and determine its shape. Each papilla has a white tip, which is produced by structural light reflectors (leucophores and iridophores) that lie between the papilla's muscular core and the skin layer that contains the pigmented chromatophores. In extended papillae, the connective tissue layer appeared thinner above the papilla's apex than in surrounding areas. This result suggests that papilla extension might create tension in the overlying connective tissue and chromatophore layers, storing energy for elastic retraction. Numerous, thin subepidermal muscles form a meshwork between the chromatophore layer

  16. Interdental papilla regeneration around implants: A novel window technique (2 years follow-up)

    PubMed Central

    Lambodharan, R.; Balaji, V. R.

    2015-01-01

    Reconstructing predictable and esthetic papilla is the most complex and challenging aspect of implant dentistry. To obtain an esthetic and predictable gingival architecture and implant restoration, interdental papilla plays an important role. The main objective of the surgeon during the second stage of implant treatment should be the creation of interdental papilla prior to prosthetic restoration. The aim of this case report was to demonstrate a novel window technique for developing predictable and esthetic papilla around dental implants, which was followed for 2 years with excellent esthetic results. PMID:26538979

  17. Comparative anatomical and ultrastructural features of the sensory papillae in the tongue of hibernating bats.

    PubMed

    Azzali, G; Gabbi, C; Grandi, D; Arcari, M L

    1992-01-01

    The papillae of the tongue dorsal surface of the insectivorous, hibernating bats (Vespertilionidae and Rhinolophidae), whose function is mainly sensorial, consist of two circumvallate papillae, two foliate papillae, located at the side edges at the glossopalatine arch, and numerous fungiform papillae. The circumvallate and foliate papillae are characterized not only by their position, but also by presence of several taste buds which open through the external orifice of the gustatory canal into the cavity of the vallum, or furrow, which divides the two folds of the lingual mucosa. The fungiform papillae (extremely numerous on the whole dorsal surface) are characterized by an unusual arrangement (along 3 oblique lines on the anterior two-thirds and predominantly on the middle line of the tongue body) and by the presence of only one to three taste buds which open on the heavily keratinized dorsal epithelial surface. The taste buds are made up of sensory cells with a light or dark matrix; their apical cytoplasmic expansions are not found beyond the middle part of the gustatory canal, in contrast with the circumvallate and foliate papillae which protrude from the orifice of the gustatory pore. Comparisons with the papillae of other types of bats and Insectivora and evaluations of the morphological characteristics and their functional values (unusual areas of distribution of the papillae, apical cytoplasmic expansions and behaviour of microfolds observed under SEM) have been made in different environmental conditions and nutritional habits, with attention to the mechanical events in the course of feeding. PMID:1285680

  18. Novel type of ornithine-glutathione double conjugate excreted as a major metabolite into the bile of rats administered clebopride

    SciTech Connect

    Ishizuka, T.; Komiya, I.; Hiratsuka, A.; Watabe, T. )

    1990-06-01

    Rats orally given radioactive Clebopride ((14C)CP; N-(1'-benzyl-4'-piperidyl)-2-(14C)methoxy-4-amino-5-chlorobenzamide++ +), an antiulcer agent, excreted a novel type of ornithine (Orn)-GSH double conjugate in the bile as a major metabolite ((14C)BMCP), corresponding to 18% of the dose. The present study provides the first evidence for Orn conjugation of a xenobiotic in mammals and demonstrates that the structure of the radioactive conjugate differs fundamentally from those known in birds and reptiles. The structure of the biliary metabolite, (14C)BMCP, purified to homogeneity by silica gel thin layer and reverse phase high pressure liquid chromatography, was elucidated as S-(2-ornithylamino-4-(14C)methoxy-5-(1'-methyl-4'-piperidylamin o) carboxyphenyl)glutathione, based mainly on the following facts: (1) BMCP showed a protonated molecular ion (M + H)+ peak at m/z 683 in the secondary ion mass spectrum and (2) (14C)BMCP afforded Orn, glutamic acid, glycine, S-(2-amino-4-(14C)methoxy-5-carboxyphenyl)cysteine (( 14C)AMCC), and 1-methyl-4-aminopiperidine (MAP) quantitatively, in an equal molar ratio, by complete hydrolysis with peptidase. Thus, BMCP was a metabolite with three enzymatically hydrolyzable amide bonds in addition to the one existing originally in the parent structure of the drug, which produces MAP by peptic digestion. Of the three additional amide bonds of BMCP, one was a novel type of bond formed by condensation of the alpha-carboxylic acid group of Orn with the primary aromatic amino group of the drug and the other two were in the S-glutathionyl residue, substituted for the chlorine atom vicinal to the Orn-conjugating primary amino group in the aromatic ring and affording glutamic acid, glycine, and the S-cysteine conjugate AMCC by hydrolysis of BMCP with the peptidase.

  19. A Double-Blind Randomized Controlled Trial of Ethyl-Eicosapentaenoate (EPA-E) for Major Depressive Disorder

    PubMed Central

    Mischoulon, David; Papakostas, George I.; Dording, Christina M.; Farabaugh, Amy H.; Sonawalla, Shamsah B.; Agoston, Monica; Smith, Juliana; Beaumont, Erin; Dahan, Liat; Alpert, Jonathan E.; Nierenberg, Andrew A.; Fava, Maurizio

    2010-01-01

    Objective We examined the efficacy and tolerability of ethyl-eicosapentaenoate (EPA-E) monotherapy for major depressive disorder (MDD) in a double-blind, randomized controlled pilot study. Methods 57 adults with DSM-IV MDD were randomized from 1/2003-6/2006 to receive 1 gram/day of EPA or placebo (PBO) for 8 weeks. Response criteria were based on the Hamilton-D-17 scale. Subjects' plasma lipid profiles were examined by gas chromatography. Results 35 subjects (63% female; mean age 45+/-13 yrs) were eligible for the intent to treat (ITT) analysis. In the ITT sample, mean HAM-D-17 scores decreased from 21.6+/-2.7 to 13.9+/-8.9 for the EPA group (n=16) and from 20.5+/-3.6 to 17.5+/-7.5 for the PBO group (n=19) (p=0.123); the effect size for EPA was 0.55. ITT response rates were 38% (6/16) for EPA, and 21% (4/19) for PBO (p=0.45). Among the 24 study completers, mean HAM-D-17 scores decreased from 21.3+/-3.0 to 11.1+/-8.1 for the EPA group and from 20.5+/-3.8 to 16.3+/-6.9 for the PBO group (p=0.087); the effect size for EPA was 0.73. Completer response rates were 45% (5/11) for EPA, and 23% (3/13) for PBO (p=0.39). Among EPA subjects, baseline n-6/n-3 ratio was associated with decrease in HAM-D-17 score (r= -0.686, p=0.030) and with treatment response (p=0.032); change in n-6/n-3 ratio was associated with change in HAM-D-17 score (r=0.784, p=0.032). Side effects, reported in 2 EPA subjects and 5 PBO subjects, were exclusively gastrointestinal, mild, and not associated with discontinuation. Conclusions EPA demonstrated an advantage over placebo that did not reach statistical significance, possibly due to the small sample and low completer rates, which were the major study limitations. PMID:19709502

  20. [Local resection of cancer of the Vater's papilla].

    PubMed

    Søndenaa, K; Andersen, E; Søreide, J A; Tysvaer, A

    1992-09-10

    Tumours of the papilla of Vater are almost always adenocarcinomas and are often less than 2.5 cm in diameter. Lymph node metastases occur in one fourth of the patients with tumours with a diameter of less than 2.5 cm. Whipple's procedure has been the most common operation when attempting radical excision. Local resection has not won acclaim, even though the five year survival rates are often reported to be about the same as for Whipple's procedure. We present a patient who was operated on by local resection, and describe the operative technique. PMID:1412308

  1. Development of Double Eastern Blotting for Major Licorice Components, Glycyrrhizin and Liquiritin for Chemical Quality Control of Licorice Using anti-Glycyrrhizin and anti-Liquiritin Monoclonal Antibodies.

    PubMed

    Fujii, Shunsuke; Morinaga, Osamu; Uto, Takuhiro; Nomura, Shuichi; Shoyama, Yukihiro

    2016-02-10

    Licorice is utilized in various food industries around the world for seasoning agents, confectioneries, drinks, and functional foods. Glycyrrhizin (GL) and liquiritin (Liq) are major quality control chemical markers of licorice that have multifunctional bioactivities. Chemical quality control of licorice is important because its component profiles change depending environmental factors (climate, soil condition, and water deficit) and differences between species. Double eastern blotting using anti-GL and anti-Liq monoclonal antibodies was developed for more convenient, rapid, and specific quality control analysis of GL and Liq, respectively. Moreover, double eastern blotting was applied to investigate the immunohistochemical distributions of GL and Liq in the root of fresh licorice; the localization of both components was then clarified visually. This double eastern blotting technique for GL and Liq may serve as a powerful approach for visually determining the chemical quality of licorice. PMID:26765784

  2. Changes in electrogustometry thresholds, tongue tip vascularization, density and form of the fungiform papillae in smokers.

    PubMed

    Pavlidis, Pavlos; Gouveris, Charalampos; Kekes, Georgios; Maurer, Jan

    2014-08-01

    The objective of this study was to evaluate differences in gustatory function in smokers of both sexes and identify any differences in the shape, density and vascularisation of the fungiform papillae (fPap) of smokers' tongue. Additional aim was to investigate any relation between the age, pack years and differences in shape, density, vascularization of fPap and sex. In 166 smokers (81 males, 85 females, age range 20-80 years), divided in age groups, electrogustometry (EGM) thresholds at the chorda tympani area, at the soft palate area and at the area of the vallate papillae were recorded bilaterally. Morphology and density of the fPap and blood vessels' density and morphology at the tip of the tongue were examined using contact endoscopy (CE). EGM thresholds of all smoking subjects tended to increase compared to the non-smoking participants. Morphology, vascularization and density of fPap were found to be worse in smokers than in non-smokers. Interestingly, some participants, despite having increased number of pack years, tended to have almost similar EGM thresholds with non-smoking subjects of the same age group. Smoking tends to affect density, morphology and vascularization of the fPap. There is a correlation between the duration of smoking (pack years) and the afore-mentioned parameters. The use of τ-Kendall criterion provided useful information about the different correlation between the EGM thresholds and vascularization, the EGM thresholds and morphology of fPap and EGM thresholds and density of fPap. The majority of smokers had elevated EGM thresholds compared to non-smokers. Smoking is an important factor which can lead to decreased taste acuity. The combination of methods, such as EGM and CE, can provide useful information about the morphology and function of taste buds. Of interest, women are less affected than men, irrespective of the age group. PMID:24633309

  3. Comparative transcriptome analysis of papilla and skin in the sea cucumber, Apostichopus japonicus

    PubMed Central

    Kong, Derong; Sun, He; Gu, Chenlei; Wang, Hongdi; Qiu, Xuemei; Chang, Yaqing; Liu, Zhanjiang

    2016-01-01

    Papilla and skin are two important organs of the sea cucumber. Both tissues have ectodermic origin, but they are morphologically and functionally very different. In the present study, we performed comparative transcriptome analysis of the papilla and skin from the sea cucumber (Apostichopus japonicus) in order to identify and characterize gene expression profiles by using RNA-Seq technology. We generated 30.6 and 36.4 million clean reads from the papilla and skin and de novo assembled in 156,501 transcripts. The Gene Ontology (GO) analysis indicated that cell part, metabolic process and catalytic activity were the most abundant GO category in cell component, biological process and molecular funcation, respectively. Comparative transcriptome analysis between the papilla and skin allowed the identification of 1,059 differentially expressed genes, of which 739 genes were expressed at higher levels in papilla, while 320 were expressed at higher levels in skin. In addition, 236 differentially expressed unigenes were not annotated with any database, 160 of which were apparently expressed at higher levels in papilla, 76 were expressed at higher levels in skin. We identified a total of 288 papilla-specific genes, 171 skin-specific genes and 600 co-expressed genes. Also, 40 genes in papilla-specific were not annotated with any database, 2 in skin-specific. Development-related genes were also enriched, such as fibroblast growth factor, transforming growth factor-β, collagen-α2 and Integrin-α2, which may be related to the formation of the papilla and skin in sea cucumber. Further pathway analysis identified ten KEGG pathways that were differently enriched between the papilla and skin. The findings on expression profiles between two key organs of the sea cucumber should be valuable to reveal molecular mechanisms involved in the development of organs that are related but with morphological differences in the sea cucumber. PMID:26989617

  4. Comparative transcriptome analysis of papilla and skin in the sea cucumber, Apostichopus japonicus.

    PubMed

    Zhou, Xiaoxu; Cui, Jun; Liu, Shikai; Kong, Derong; Sun, He; Gu, Chenlei; Wang, Hongdi; Qiu, Xuemei; Chang, Yaqing; Liu, Zhanjiang; Wang, Xiuli

    2016-01-01

    Papilla and skin are two important organs of the sea cucumber. Both tissues have ectodermic origin, but they are morphologically and functionally very different. In the present study, we performed comparative transcriptome analysis of the papilla and skin from the sea cucumber (Apostichopus japonicus) in order to identify and characterize gene expression profiles by using RNA-Seq technology. We generated 30.6 and 36.4 million clean reads from the papilla and skin and de novo assembled in 156,501 transcripts. The Gene Ontology (GO) analysis indicated that cell part, metabolic process and catalytic activity were the most abundant GO category in cell component, biological process and molecular funcation, respectively. Comparative transcriptome analysis between the papilla and skin allowed the identification of 1,059 differentially expressed genes, of which 739 genes were expressed at higher levels in papilla, while 320 were expressed at higher levels in skin. In addition, 236 differentially expressed unigenes were not annotated with any database, 160 of which were apparently expressed at higher levels in papilla, 76 were expressed at higher levels in skin. We identified a total of 288 papilla-specific genes, 171 skin-specific genes and 600 co-expressed genes. Also, 40 genes in papilla-specific were not annotated with any database, 2 in skin-specific. Development-related genes were also enriched, such as fibroblast growth factor, transforming growth factor-β, collagen-α2 and Integrin-α2, which may be related to the formation of the papilla and skin in sea cucumber. Further pathway analysis identified ten KEGG pathways that were differently enriched between the papilla and skin. The findings on expression profiles between two key organs of the sea cucumber should be valuable to reveal molecular mechanisms involved in the development of organs that are related but with morphological differences in the sea cucumber. PMID:26989617

  5. Papillae alterations around single-implant restorations in the anterior maxillae: thick versus thin mucosa.

    PubMed

    Si, Mi-Si; Zhuang, Long-Fei; Huang, Xin; Gu, Ying-Xin; Chou, Chung-Hao; Lai, Hong-Chang

    2012-06-01

    To evaluate the papilla alterations around single-implant restorations in the anterior maxillae after crown attachment and to study the influence of soft tissue thickness on the papilla fill alteration. According to the inclusion criteria, 32 patients subjected to implant-supported single-tooth restorations in anterior maxillae were included. The patients were assigned to two groups according to the mucosal thickness: (i) group 1, 1.5 mm s mucosal thickness 3 mm; and (ii) group 2, 3 mmpapillae at the time of crown placement (baseline) and at 6-month post loading (follow-up) were made by two prosthodontists using papilla fill index (PFI). The mean mucosal thickness was (2.49±_0.31) mm (group 1) and (3.81±_0.31) mm(group 2) for the two groups respectively. A significant difference in PFI between the groups was detected at the baseline (P<0.001).PFI improvements over time occurred after 6-month follow-up irrespective of the groups. When compared to group 1, the likelihood to obtain papilla fill was significantly higher for group 2 with an odds ratio of 6.05 (P<0.001). The interproximal papilla level around single-implant restorations could improve significantly over time after 6-month restoration according to PFI assessment. The thicker mucosa before implant placement implied a more favorable esthetic outcome in papilla alteration. PMID:22627613

  6. FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size

    PubMed Central

    Mostowfi, Pasha; Charles, Cyril; Ching, Saunders; Thirumangalathu, Shoba; Barlow, Linda A.; Klein, Ophir D.

    2011-01-01

    The sense of taste is fundamental to our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Sensory taste buds are housed in papillae that develop from epithelial placodes. Three distinct types of gustatory papillae reside on the rodent tongue: small fungiform papillae are found in the anterior tongue, whereas the posterior tongue contains the larger foliate papillae and a single midline circumvallate papilla (CVP). Despite the great variation in the number of CVPs in mammals, its importance in taste function, and its status as the largest of the taste papillae, very little is known about the development of this structure. Here, we report that a balance between Sprouty (Spry) genes and Fgf10, which respectively antagonize and activate receptor tyrosine kinase (RTK) signaling, regulates the number of CVPs. Deletion of Spry2 alone resulted in duplication of the CVP as a result of an increase in the size of the placode progenitor field, and Spry1−/−;Spry2−/− embryos had multiple CVPs, demonstrating the redundancy of Sprouty genes in regulating the progenitor field size. By contrast, deletion of Fgf10 led to absence of the CVP, identifying FGF10 as the first inductive, mesenchyme-derived factor for taste papillae. Our results provide the first demonstration of the role of epithelial-mesenchymal FGF signaling in taste papilla development, indicate that regulation of the progenitor field size by FGF signaling is a critical determinant of papilla number, and suggest that the great variation in CVP number among mammalian species may be linked to levels of signaling by the FGF pathway. PMID:21655085

  7. Morphofunctional structure of the lingual papillae in three species of South American Camelids: Alpaca, guanaco, and llama.

    PubMed

    Erdoğan, Serkan; Villar Arias, Silvia; Pérez, William

    2016-02-01

    The aim of this study was to compare the anatomical and functional characteristics of the lingual papilla among the Camelidae. For this purpose, tongues of alpaca, guanaco, and llama were used. Numerous long and thin filiform papillae were located in the median groove and none were detected on the rest of the dorsal surface of the lingual apex in alpaca. Secondary papillae originated from the base of some filiform papillae on the ventral surface of alpaca tongue. The bases of some filiform papillae of the lateral surface of the lingual apex were inserted into conspicuous grooves in guanaco and tips of filiform papillae on the dorsal surface of the lingual body were ended by bifurcated apex. On the dorsal surface of the lingual apex of llama, there were no filiform papillae but there were numerous filiform papillae on both the lateral margins of the ventral surface of the lingual apex. Fungiform papillae were distributed randomly on dorsal lingual surface and ventral margins of the tongues of all camelid species. Lenticular papillae were located on the lingual torus and varied in size and topographical distribution for each species. Circumvallate papillae had irregular surfaces in llama and alpaca, and smooth surface in guanaco. In conclusion, llama and alpaca tongues were more similar to each other, and tongues of all camelid species displayed more similarities to those of Bactrian and dromedary camels in comparison with other herbivores and ruminants. PMID:26572928

  8. Multiple Shh signaling centers participate in fungiform papilla and taste bud formation and maintenance

    PubMed Central

    Liu, H-X; Ermilov, A; Grachtchouk, M; Li, L; Gumucio, DL; Dlugosz, AA; Mistretta, CM

    2014-01-01

    The adult fungiform taste papilla is a complex of specialized cell types residing in the stratified squamous tongue epithelium. This unique sensory organ includes taste buds, papilla epithelium and lateral walls that extend into underlying connective tissue to surround a core of lamina propria cells. Fungiform papillae must contain long-lived, sustaining or stem cells and short-lived, maintaining or transit amplifying cells that support the papilla and specialized taste buds. Shh signaling has established roles in supporting fungiform induction, development and patterning. However, for a full understanding of how Shh transduced signals act in tongue, papilla and taste bud formation and maintenance, it is necessary to know where and when the Shh ligand and pathway components are positioned. We used immunostaining, in situ hybridization and mouse reporter strains for Shh, Ptch1, Gli1 and Gli2-expression and proliferation markers to identify cells that participate in hedgehog signaling. Whereas there is a progressive restriction in location of Shh ligand-expressing cells, from placode and apical papilla cells to taste bud cells only, a surrounding population of Ptch1 and Gli1 responding cells is maintained in signaling centers throughout papilla and taste bud development and differentiation. The Shh signaling targets are in regions of active cell proliferation. Using genetic-inducible lineage tracing for Gli1-expression, we found that Shh-responding cells contribute not only to maintenance of filiform and fungiform papillae, but also to taste buds. A requirement for normal Shh signaling in fungiform papilla, taste bud and filiform papilla maintenance was shown by Gli2 constitutive activation. We identified proliferation niches where Shh signaling is active and suggest that epithelial and mesenchymal compartments harbor potential stem and/or progenitor cell zones. In all, we report a set of hedgehog signaling centers that regulate development and maintenance of taste

  9. Frequency-Selective Response of the Tectorial Membrane in the Frog Basilar Papilla

    NASA Astrophysics Data System (ADS)

    Schoffelen, R. L. M.; Segenhout, J. M.; van Dijk, P.

    2009-02-01

    The frog's basilar papilla is a useful study object for cochlear mechanics, because of it's relatively simple anatomy and functionality. We investigated the displacement amplitudes of the basilar papilla's tectorial membrane in response to stimulation of the oval window at various frequencies within the auditory range of the Northern leopard frog. From our measurement data we find that the tectorial membrane exhibits a frequency selective response. The peak response was found to occur at 1500Hz in correspondence with known data for the response of auditory nerve fibers from the organ. From these data we conclude that mechanical tuning contributes significantly to the frequency selectivity of the frog's basilar papilla

  10. Paroxetine Treatment in Children and Adolescents with Major Depressive Disorder: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    ERIC Educational Resources Information Center

    Emslie, Graham J.; Wagner, Karen Dineen; Kutcher, Stan; Krulewicz, Stan; Fong, Regan; Carpenter, David J.; Lipschitz, Alan; Machin, Andrea; Wilkinson, Christel

    2006-01-01

    Objective: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. Method: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating…

  11. Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells.

    PubMed

    Chen, Tian; Liu, Zhi; Sun, Wenhua; Li, Jingyu; Liang, Yan; Yang, Xianrui; Xu, Yang; Yu, Mei; Tian, Weidong; Chen, Guoqing; Bai, Ding

    2015-01-01

    Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway. PMID:26639148

  12. Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells

    PubMed Central

    Chen, Tian; Liu, Zhi; Sun, Wenhua; Li, Jingyu; Liang, Yan; Yang, Xianrui; Xu, Yang; Yu, Mei; Tian, Weidong; Chen, Guoqing; Bai, Ding

    2015-01-01

    Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway. PMID:26639148

  13. The association between radiographic embrasure morphology and interdental papilla reconstruction using injectable hyaluronic acid gel

    PubMed Central

    2016-01-01

    Purpose The purpose of this study was to evaluate the clinical efficacy of enhancing deficient interdental papilla with hyaluronic acid gel injection by assessing the radiographic anatomical factors affecting the reconstruction of the interdental papilla. Methods Fifty-seven treated sites from 13 patients (6 males and 7 females) were included. Patients had papillary deficiency in the upper anterior area. Prior to treatment, photographic and periapical radiographic standardization devices were designed for each patient. A 30-gauge needle was used with an injection-assistance device to inject a hyaluronic acid gel to the involved papilla. This treatment was repeated up to 5 times every 3 weeks. Patients were followed up for 6 months after the initial gel application. Clinical photographic measurements of the black triangle area (BTA), height (BTH), and width (BTW) and periapical radiographic measurements of the contact point and the bone crest (CP-BC) and the interproximal distance between roots (IDR) were undertaken using computer software. The interdental papilla reconstruction rate (IPRR) was calculated to determine the percentage change of BTA between the initial and final examination and the association between radiographic factors and the reconstruction of the interdental papilla by means of injectable hyaluronic acid gel were evaluated. Results All sites showed improvement between treatment examinations. Thirty-six sites had complete interdental papilla reconstruction and 21 sites showed improvement ranging from 19% to 96%. The CP-BC correlated with the IPRR. More specifically, when the CP-BC reached 6 mm, virtually complete interdental papilla reconstruction via injectable hyaluronic acid gel was achieved. Conclusions These results suggest that the CP-BC is closely related to the efficacy of hyaluronic acid gel injection for interdental papilla reconstruction. PMID:27588217

  14. Esrrg functions in early branch generation of the ureteric bud and is essential for normal development of the renal papilla.

    PubMed

    Berry, Rachel; Harewood, Louise; Pei, Liming; Fisher, Malcolm; Brownstein, David; Ross, Allyson; Alaynick, William A; Moss, Julie; Hastie, Nicholas D; Hohenstein, Peter; Davies, Jamie A; Evans, Ronald M; FitzPatrick, David R

    2011-03-01

    Congenital anomalies of the kidney and urinary tract (CAKUTs) are common disorders of human development affecting the renal parechyma, renal pelvis, ureter, bladder and urethra; they show evidence of shared genetic aetiology, although the molecular basis of this remains unknown in the majority of cases. Breakpoint mapping of a de novo, apparently balanced, reciprocal translocation associated with bilateral renal agenesis has implicated the gene encoding the nuclear steroid hormone receptor ESRRG as a candidate gene for CAKUT. Here we show that the Esrrg protein is detected throughout early ureteric ducts as cytoplasmic/sub-membranous staining; with nuclear localization seen in developing nephrons. In 14.5-16.5 dpc (days post-conception) mouse embryos, Esrrg localizes to the subset of ductal tissue within the kidney, liver and lung. The renal ductal expression becomes localized to renal papilla by 18.5 dpc. Perturbation of function was performed in embryonic mouse kidney culture using pooled siRNA to induce knock-down and a specific small-molecule agonist to induce aberrant activation of Esrrg. Both resulted in severe abnormality of early branching events of the ureteric duct. Mouse embryos with a targeted inactivation of Esrrg on both alleles (Esrrg(-/-)) showed agenesis of the renal papilla but normal development of the cortex and remaining medulla. Taken together, these results suggest that Esrrg is required for early branching events of the ureteric duct that occur prior to the onset of nephrogenesis. These findings confirm ESRRG as a strong candidate gene for CAKUT. PMID:21138943

  15. Morphological study of the lingual papillae of the giant panda (Ailuropoda melanoleuca) by scanning electron microscopy

    PubMed Central

    Pastor, J F; Barbosa, M; De Paz, F J

    2008-01-01

    Due to the scarcity of giant pandas, there are few descriptions of their morphology and even fewer of their microscopic anatomy and the ultrastructure of their organs. In this study of the complete tongue of an adult male giant panda, we describe the morphology of its lingual surface, the different types of papillae, their characteristics and topographic distribution. It was seen that there are four main types of lingual papillae: filiform, conical, fungiform and vallate. There was no sign of foliate papillae, tuberculum intermolare or sublingua. Papilla distribution was not limited to the dorsum of the tongue, but was also seen on the anterior and ventral surfaces of the tongue. In the anterior third of the midline there is a smooth area with no papillae at all. Morphology of the microgrooves and pores is similar to that observed in other mammals. The papillae share characteristics encountered in Carnivora and herbivorous species of mammals. A narrow bamboo-based diet and specialized manner of eating have together resulted in modification of the tongue of a carnivoran, giving it some characteristics typical of an herbivore. PMID:18254792

  16. Double-strand break formation by the RAG complex at the bcl-2 major breakpoint region and at other non-B DNA structures in vitro.

    PubMed

    Raghavan, Sathees C; Swanson, Patrick C; Ma, Yunmei; Lieber, Michael R

    2005-07-01

    The most common chromosomal translocation in cancer, t(14;18) at the 150-bp bcl-2 major breakpoint region (Mbr), occurs in follicular lymphomas. The bcl-2 Mbr assumes a non-B DNA conformation, thus explaining its distinctive fragility. This non-B DNA structure is a target of the RAG complex in vivo, but not because of its primary sequence. Here we report that the RAG complex generates at least two independent nicks that lead to double-strand breaks in vitro, and this requires the non-B DNA structure at the bcl-2 Mbr. A 3-bp mutation is capable of abolishing the non-B structure formation and the double-strand breaks. The observations on the bcl-2 Mbr reflect more general properties of the RAG complex, which can bind and nick at duplex-single-strand transitions of other non-B DNA structures, resulting in double-strand breaks in vitro. Hence, the present study reveals novel insight into a third mechanism of action of RAGs on DNA, besides the standard heptamer/nonamer-mediated cleavage in V(D)J recombination and the in vitro transposase activity. PMID:15988007

  17. Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder.

    PubMed

    Hewett, K; Chrzanowski, W; Jokinen, R; Felgentreff, R; Shrivastava, R K; Gee, M D; Wightman, D S; O'Leary, M C; Millen, L S; Leon, M C; Briggs, M A; Krishen, A; Modell, J G

    2010-04-01

    Major depressive disorder in the elderly is associated with increased morbidity and reduced quality of life. This 10 week, placebo-controlled study investigated the efficacy and tolerability of extended-release bupropion (150-300 mg once daily) in depressed patients aged 65 years or older. The statistical assumptions necessary for the validity of the protocol-specified analysis of covariance were not met for the analysis of the primary outcome variable (Montgomery-Asberg Depression Rating Scale total score at Week 10, last observation carried forward). Alternative statistical methods used for the analysis of this variable demonstrated statistical significance. Statistically significant improvements were observed on the majority of secondary end points when compared with placebo, including the health outcome measures for motivation and energy, and life satisfaction and contentment. Adverse events were generally mild to moderate and similar between treatment groups. This study demonstrated that the extended-release bupropion is an effective, well-tolerated treatment for major depression in the elderly. PMID:19164492

  18. Dkk2/Frzb in the dermal papillae regulates feather regeneration.

    PubMed

    Chu, Qiqi; Cai, Linyan; Fu, Yu; Chen, Xi; Yan, Zhipeng; Lin, Xiang; Zhou, Guixuan; Han, Hao; Widelitz, Randall B; Chuong, Cheng-ming; Wu, Wei; Yue, Zhicao

    2014-03-15

    Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-β signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation. PMID:24463139

  19. A Pollen Coat–Inducible Autoinhibited Ca2+-ATPase Expressed in Stigmatic Papilla Cells Is Required for Compatible Pollination in the Brassicaceae[W

    PubMed Central

    Iwano, Megumi; Igarashi, Motoko; Tarutani, Yoshiaki; Kaothien-Nakayama, Pulla; Nakayama, Hideki; Moriyama, Hideki; Yakabe, Ryo; Entani, Tetsuyuki; Shimosato-Asano, Hiroko; Ueki, Masao; Tamiya, Gen; Takayama, Seiji

    2014-01-01

    In the Brassicaceae, intraspecific non-self pollen (compatible pollen) can germinate and grow into stigmatic papilla cells, while self-pollen or interspecific pollen is rejected at this stage. However, the mechanisms underlying this selective acceptance of compatible pollen remain unclear. Here, using a cell-impermeant calcium indicator, we showed that the compatible pollen coat contains signaling molecules that stimulate Ca2+ export from the papilla cells. Transcriptome analyses of stigmas suggested that autoinhibited Ca2+-ATPase13 (ACA13) was induced after both compatible pollination and compatible pollen coat treatment. A complementation test using a yeast Saccharomyces cerevisiae strain lacking major Ca2+ transport systems suggested that ACA13 indeed functions as an autoinhibited Ca2+ transporter. ACA13 transcription increased in papilla cells and in transmitting tracts after pollination. ACA13 protein localized to the plasma membrane and to vesicles near the Golgi body and accumulated at the pollen tube penetration site after pollination. The stigma of a T-DNA insertion line of ACA13 exhibited reduced Ca2+ export, as well as defects in compatible pollen germination and seed production. These findings suggest that stigmatic ACA13 functions in the export of Ca2+ to the compatible pollen tube, which promotes successful fertilization. PMID:24569769

  20. A pollen coat-inducible autoinhibited Ca2+-ATPase expressed in stigmatic papilla cells is required for compatible pollination in the Brassicaceae.

    PubMed

    Iwano, Megumi; Igarashi, Motoko; Tarutani, Yoshiaki; Kaothien-Nakayama, Pulla; Nakayama, Hideki; Moriyama, Hideki; Yakabe, Ryo; Entani, Tetsuyuki; Shimosato-Asano, Hiroko; Ueki, Masao; Tamiya, Gen; Takayama, Seiji

    2014-02-01

    In the Brassicaceae, intraspecific non-self pollen (compatible pollen) can germinate and grow into stigmatic papilla cells, while self-pollen or interspecific pollen is rejected at this stage. However, the mechanisms underlying this selective acceptance of compatible pollen remain unclear. Here, using a cell-impermeant calcium indicator, we showed that the compatible pollen coat contains signaling molecules that stimulate Ca(2+) export from the papilla cells. Transcriptome analyses of stigmas suggested that autoinhibited Ca(2+)-ATPase13 (ACA13) was induced after both compatible pollination and compatible pollen coat treatment. A complementation test using a yeast Saccharomyces cerevisiae strain lacking major Ca(2+) transport systems suggested that ACA13 indeed functions as an autoinhibited Ca(2+) transporter. ACA13 transcription increased in papilla cells and in transmitting tracts after pollination. ACA13 protein localized to the plasma membrane and to vesicles near the Golgi body and accumulated at the pollen tube penetration site after pollination. The stigma of a T-DNA insertion line of ACA13 exhibited reduced Ca(2+) export, as well as defects in compatible pollen germination and seed production. These findings suggest that stigmatic ACA13 functions in the export of Ca(2+) to the compatible pollen tube, which promotes successful fertilization. PMID:24569769

  1. Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized, double-blind, placebo-controlled trial.

    PubMed

    Salardini, Elaheh; Zeinoddini, Atefeh; Mohammadinejad, Payam; Khodaie-Ardakani, Mohammad-Reza; Zahraei, Nagmeh; Zeinoddini, Arefeh; Akhondzadeh, Shahin

    2016-04-01

    Recent evidences suggest that glutamatergic dysregulation implicated in neural plasticity and cellular resilience may contribute to the pathophysiology of Major Depressive Disorder (MDD). Riluzole, which exerts its effect by targeting glutamate neurotransmission, has shown antidepressant effect in recent preclinical, observational and open label studies. This study aimed to assess the efficacy and tolerability of riluzole in patients with MDD. Sixty-four inpatients with diagnosis of moderate to severe major depressive disorder participated in a parallel, randomized, controlled trial, and sixty patients underwent 6 weeks treatment with either riluzole (50 mg/bid) plus citalopram (40 mg/day) or placebo plus citalopram (40 mg/day). All participants were inpatients for the whole duration of the study. Patients were assessed using Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4 and 6. The primary outcome measure was to assess the efficacy of riluzole compared to placebo in improving the depressive symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on HDRS [F (1.86, 107.82) = 8.63, p < 0.001]. Significantly greater improvement was observed in HDRS scores in the riluzole group compared to the placebo group from baseline HDRS score at weeks 2, 4 and 6 (p < 0.001, p = 0.001, p = 0.002, respectively). Significantly greater response with greater speed to treatment was observed in the riluzole group than the placebo group. No serious adverse event occurred. This study showed a favorable safety and efficacy profile in patients with major depressive disorder. Larger controlled studies with longer treatment periods are needed to investigate long term safety, efficacy and optimal dosing. PMID:26800392

  2. Recombinant Human Plasminogen Activator Inhibitor-1 Accelerates Odontoblastic Differentiation of Human Stem Cells from Apical Papilla.

    PubMed

    Jin, Bin; Choung, Pill-Hoon

    2016-05-01

    Dental caries, the most prevalent oral disease in dental patients, involves the phases of demineralization and destruction of tooth hard tissues like enamel, dentin, and cementum. Dentin is a major component of the root and is also the innermost layer that protects the tooth nerve, exposure of which results in pain. In this study, we used human stem cells from apical papilla (hSCAP), which are early progenitor cells, to examine the effects of recombinant human plasminogen activator inhibitor-1 (rhPAI-1) on odontogenic differentiation in vitro and in vivo. We demonstrated that rhPAI-1 promoted the proliferation and odontogenic differentiation of hSCAP and increased the expression levels of odontoblast-associated markers. We also observed that rhPAI-1 upregulated the expression of Smad4, nuclear factor I-C (NFI-C), Runx2, and osterix (OSX) during odontogenic differentiation. Notably, transplantation of rhPAI-1-treated hSCAP effectively induced odontoblastic differentiation and dentinal formation. And the differentiated odontoblast-like cells showed numerous odontoblast processes inserted in dentin tubules and arranged collagen fibers. Furthermore, odontoblast-associated markers were more highly expressed in the rhPAI-1-induced differentiated odontoblast-like cells compared with the control group. These markers were also more highly expressed in the newly formed dentin-like tissue of the rhPAI-1-treated group compared with the control group. Consistent with our in vitro results, the expression levels of Smad4, NFI-C, and OSX were also increased in the rhPAI-1-treated group compared with the control group. Taken together, these results suggest that rhPAI-1 promotes odontoblast differentiation and dentin formation of hSCAP, and Smad4/NFI-C/OSX may play critical roles in the rhPAI-1-induced odontogenic differentiation. Thus, dental stem cells from apical papilla combined with rhPAI-1 could lead to dentin regeneration in clinical implications. PMID:27046084

  3. Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice.

    PubMed

    Patris, M; Bouchard, J M; Bougerol, T; Charbonnier, J F; Chevalier, J F; Clerc, G; Cyran, C; Van Amerongen, P; Lemming, O; Høpfner Petersen, H E

    1996-06-01

    Two selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, both at a daily dose of 20 mg, were compared in patients with unipolar major depression treated in general practice. This was a multicentre, double-blind, randomized trial carried out in France. The duration of treatment was 8 weeks. Patients were assessed by means of the Montgomery-Asberg Depression Rating Scale (MADRS), the 17 items Hamilton Depression Rating Scale (HAMD) and the investigator's Clinical Global Impressions (CGI), Observed and spontaneously reported adverse events were also recorded. A total of 357 patients of both sexes, aged between 21 and 73 years, entered the double-blind phase of the trial. A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments. Apart from back pain recorded more frequently in the citalopram group, no significant difference was found between the two treatment groups with regard to adverse events, and both citalopram and fluoxetine were considered to be well tolerated. It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression. Citalopram showed an earlier onset of recovery than fluoxetine. PMID:8803650

  4. Alterations of papilla dimensions after orthodontic closure of the maxillary midline diastema: a retrospective longitudinal study

    PubMed Central

    2016-01-01

    Purpose The aim of this study was to evaluate alterations of papilla dimensions after orthodontic closure of the diastema between maxillary central incisors. Methods Sixty patients who had a visible diastema between maxillary central incisors that had been closed by orthodontic approximation were selected for this study. Various papilla dimensions were assessed on clinical photographs and study models before the orthodontic treatment and at the follow-up examination after closure of the diastema. Influences of the variables assessed before orthodontic treatment on the alterations of papilla height (PH) and papilla base thickness (PBT) were evaluated by univariate regression analysis. To analyze potential influences of the 3-dimensional papilla dimensions before orthodontic treatment on the alterations of PH and PBT, a multiple regression model was formulated including the 3-dimensional papilla dimensions as predictor variables. Results On average, PH decreased by 0.80 mm and PBT increased after orthodontic closure of the diastema (P<0.01). Univariate regression analysis revealed that the PH (P=0.002) and PBT (P=0.047) before orthodontic treatment influenced the alteration of PH. With respect to the alteration of PBT, the diastema width (P=0.045) and PBT (P=0.000) were found to be influential factors. PBT before the orthodontic treatment significantly influenced the alteration of PBT in the multiple regression model. Conclusions PH decreased but PBT increased after orthodontic closure of the diastema. The papilla dimensions before orthodontic treatment influenced the alterations of PH and PBT after closure of the diastema. The PBT increased more when the diastema width before the orthodontic treatment was larger. PMID:27382507

  5. Expression of Prostatic Acid Phosphatase in Rat Circumvallate Papillae

    PubMed Central

    Nishida, Kentaro; Kubota, Teruyo; Matsumoto, Saki; Kato, Junki; Watanabe, Yu; Yamamoto, Atsuko; Furui, Mari; Ohishi, Akihiro; Nagasawa, Kazuki

    2016-01-01

    ATP and its metabolites are important for taste signaling in taste buds, and thus a clearance system for them would play critical roles in maintenance of gustatory function. A previous report revealed that mRNAs for ecto-5′-nucleotidase (NT5E) and prostatic acid phosphatase (PAP) were expressed by taste cells of taste buds, and NT5E-immunoreactivity was detected in taste cells. However, there was no information on PAP-immunoreactivity in taste buds. In this study, we examined the expression profile of PAP in rat taste buds. In the isolated rat taste buds, we detected expression of mRNA for PAP, but NT5E was not detected differing from the case of mouse ones (Dando et al., 2012, J Neuroscience). On immunohistochemical analysis, PAP-immunoreactivity was found predominantly in NTPDase2-positive type I and SNAP25-positive type III taste cells, while there were no apparent signals of it in PLC-β2-positive type II, α-gustducin-positive type II, AADC-positive type III and 5HT-positive type III ones. As for NT5E, we could not detect its immunoreactivity in rat taste buds, and co-localization of it with any taste cell markers, although mouse taste buds expressed NT5E as reported previously. These findings suggest that PAP expressed by type I and one of type III taste cells of rats may contribute to metabolic regulation of the extracellular levels of adenine nucleotides in the taste buds of circumvallate papillae, and the regulating mechanisms for adenine nucleotides in taste buds might be different between rats and mice. PMID:27348306

  6. Audiogram, body mass, and basilar papilla length: correlations in birds and predictions for extinct archosaurs

    NASA Astrophysics Data System (ADS)

    Gleich, Otto; Dooling, Robert J.; Manley, Geoffrey A.

    2005-12-01

    The inner ear in the group of archosaurs (birds, crocodilians, and extinct dinosaurs) shows a high degree of structural similarity, enabling predictions of their function in extinct species based on relationships among similar variables in living birds. Behavioral audiograms and morphological data on the length of the auditory sensory epithelium (the basilar papilla) are available for many avian species. By bringing different data sets together, we show that body mass and the size of the basilar papilla are significantly correlated, and the most sensitive frequency in a given species is inversely related to the body mass and the length of the basilar papilla. We also demonstrate that the frequency of best hearing is correlated with the high-frequency limit of hearing. Small species with a short basilar papilla hear higher frequencies compared with larger species with a longer basilar papilla. Based on the regression analysis of two significant correlations in living archosaurs (best audiogram frequency vs body mass and best audiogram frequency vs papillar length), we suggest that hearing in large dinosaurs was restricted to low frequencies with a high-frequency limit below 3 kHz.

  7. Comparison between two different methods for evaluating rumen papillae measures related to different diets.

    PubMed

    Scocco, Paola; Brusaferro, Andrea; Catorci, Andrea

    2012-07-01

    Although the Geographical Information System (GIS), which integrates computerized drawing computer assisted design (CAD) and relational databases (data base management system (DBMS)), is best known for applications in geographical and planning cartography, it can also use many kinds of information concerning the territory. A multidisciplinary project was initiated since 5 years a multidisciplinary study was initiated to use GIS to integrate environmental and ecological data with findings on animal health, ethology, and anatomy. This study is chiefly aimed at comparing two different methods for measuring the absorptive surface of rumen papillae. To this scope, 21 female sheep (Ovis aries) on different alimentary regimes (e.g., milk and forage mixed diet, early herbaceous diet, dry hay diet, and fresh hay diet at the maximum of pasture flowering and at the maximum of pasture dryness) were used; after slaughtering, 20 papillae were randomly removed from each sample collected from four indicator regions of rumen wall, placed near a metric reference and digitally photographed. The images were developed with the ArcGIS™ software to calculate the area of rumen papillae by means of GIS and to measure their mid-level width and length to calculate the papillae area as previously performed with a different method. Spatial measurements were analyzed using univariate and multivariate methods. This work demonstrates that the GIS methodology can be efficiently used for measuring the absorptive surface of rumen papillae. In addition, GIS demonstrated to be a rapid, precise, and objective tool when compared with previously used method. PMID:22223350

  8. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

    PubMed Central

    Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

    2014-01-01

    Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration. PMID:25383178

  9. Meta-analysis of randomized, double-blind, placebo-controlled, efficacy and safety studies of mirtazapine versus amitriptyline in major depression.

    PubMed

    Stahl, S; Zivkov, M; Reimitz, P E; Panagides, J; Hoff, W

    1997-01-01

    A meta-analysis was performed on efficacy and safety data from 4 randomized, double-blind, 6-week, single-center studies comparing mirtazapine (n = 194; 5-35 mg/day) with amitriptyline (n = 193, 40-280 mg/day) and placebo (n = 193) in outpatients with a DSM-III diagnosis of major depressive episode. On all the main efficacy variables both active drugs consistently produced significantly greater improvements and significantly greater percentages of responders or remitters than placebo. The meta-analysis of adverse events shows that mirtazapine was better tolerated than amitriptyline, particularly with respect to anticholinergic and cardiac adverse events. There were no differences between mirtazapine and placebo regarding the incidence of serotonergic adverse events. In conclusion, the results of this meta-analysis demonstrate that mirtazapine is as effective as amitriptyline but has a better tolerability profile. PMID:9265948

  10. Time Course of Morphological Alterations of Fungiform Papillae and Taste Buds Following Chorda Tympani Transection in Neonatal Rats

    PubMed Central

    Sollars, Suzanne I.; Smith, Peter C.; Hill, David L.

    2016-01-01

    The time course of structural changes in fungiform papillae was analyzed in rats that received unilateral chorda tympani nerve transection at 10 days of age. Morphological differences between intact and denervated sides of the tongue were first observed at 8 days postsection, with an increase in the number of fungiform papillae that did not have a pore. In addition, the first papilla with a filiform-like appearance was noted on the denervated side at 8 days postsectioning. By 11 days after surgery, the total number of papillae and the number of papillae with a pore were significantly lower on the transected side of the tongue as compared to the intact side. At 50 days postsection, there was an average of 70.5 fungiform papillae on the intact side and a mean of only 20.8 fungiform papillae the denervated side. Of those few remaining papillae on the cut side, an average of 13.5 papillae were categorized as filiform-like, while no filiform-like papillae occurred on the intact side. Significant reduction in taste bud volume was noted at 4 days posttransection and further decrements in taste bud volume were noted at 8 and 30 days postsection. Electron microscopy of the lingual branch of the trigeminal nerve from adult rats that received neonatal chorda tympani transection showed normal numbers of both myelinated and unmyelinated fibers. Thus, in addition to the well-characterized dependence of taste bud maintenance on the chorda tympani nerve, the present study shows an additional role of the chorda tympani nerve in papilla maintenance during early postnatal development. PMID:11984844

  11. A Phase III, Double-Blind, Placebo-Controlled, Flexible-Dose Study of Levomilnacipran Extended-Release in Patients With Major Depressive Disorder

    PubMed Central

    Bose, Anjana; Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Sheehan, David V.

    2014-01-01

    Abstract Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor; an extended-release (ER) formulation allows for once-daily dosing. This phase III study (NCT01034462) evaluated the efficacy, the safety, and the tolerability of 40 to 120 mg/d of levomilnacipran ER versus placebo in the treatment of patients (18-80 y) with major depressive disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comprised a 1-week single-blind, placebo run-in period; an 8-week double-blind treatment; and a 2-week double-blind down-taper period. The primary efficacy parameter was total score change from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS); the secondary efficacy was the Sheehan Disability Scale. Analysis was performed using the mixed-effects model for repeated measures on a modified intent-to-treat population. A total of 434 patients received at least 1 dose of double-blind treatment (safety population); 429 patients also had 1 or more postbaseline MADRS assessments (modified intent-to-treat population). The least squares mean differences and 95% confidence interval were statistically significant in favor of levomilnacipran ER versus placebo for the MADRS total score (−3.095 [−5.256, −0.935]; P = 0.0051) and the SDS total score (−2.632 [−4.193, −1.070]; P = 0.0010) change from baseline to week 8. Adverse events were reported in 61.8% of the placebo patients and in 81.6% of the levomilnacipran ER patients. Frequently reported adverse events (≥5% in levomilnacipran ER and twice the rate of placebo) were nausea, dizziness, constipation, tachycardia, urinary hesitation, hyperhidrosis, insomnia, vomiting, hypertension, and ejaculation disorder. In conclusion, there was a statistically significant difference in the score change from baseline to week 8 between levomilnacipran ER and placebo on several depression rating scales

  12. A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder.

    PubMed

    Sambunaris, Angelo; Bose, Anjana; Gommoll, Carl P; Chen, Changzheng; Greenberg, William M; Sheehan, David V

    2014-02-01

    Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor; an extended-release (ER) formulation allows for once-daily dosing. This phase III study (NCT01034462) evaluated the efficacy, the safety, and the tolerability of 40 to 120 mg/d of levomilnacipran ER versus placebo in the treatment of patients (18-80 y) with major depressive disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comprised a 1-week single-blind, placebo run-in period; an 8-week double-blind treatment; and a 2-week double-blind down-taper period. The primary efficacy parameter was total score change from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS); the secondary efficacy was the Sheehan Disability Scale. Analysis was performed using the mixed-effects model for repeated measures on a modified intent-to-treat population. A total of 434 patients received at least 1 dose of double-blind treatment (safety population); 429 patients also had 1 or more postbaseline MADRS assessments (modified intent-to-treat population). The least squares mean differences and 95% confidence interval were statistically significant in favor of levomilnacipran ER versus placebo for the MADRS total score (-3.095 [-5.256, -0.935]; P = 0.0051) and the SDS total score (-2.632 [-4.193, -1.070]; P = 0.0010) change from baseline to week 8. Adverse events were reported in 61.8% of the placebo patients and in 81.6% of the levomilnacipran ER patients. Frequently reported adverse events (≥ 5% in levomilnacipran ER and twice the rate of placebo) were nausea, dizziness, constipation, tachycardia, urinary hesitation, hyperhidrosis, insomnia, vomiting, hypertension, and ejaculation disorder. In conclusion, there was a statistically significant difference in the score change from baseline to week 8 between levomilnacipran ER and placebo on several depression rating scales, reflecting symptomatic

  13. Lingual nerve injury after third molar removal: Unilateral atrophy of fungiform papillae

    PubMed Central

    de-Pablo-Garcia-Cuenca, Alba; Bescós-Atín, Maria S.

    2014-01-01

    Background: Pain and sensory changes due to lingual nerve injury are one of the most common alterations that follow surgical removal of third molar. They are usually transient but other less common complications, such as the atrophy of fungiform papillae, have an uncertain prognosis. Case Description: We report a case of a 34-year-old woman who presented a unilateral lingual atrophy of fungiform papillae after third molar extraction accompanied by severe dysesthesia that altered her daily life significantly during the following months and how this complication evolved over time. We conducted a literature review on the different factors that can lead to a lingual nerve injury. Clinical Implications: The clinical evolution of temporary and permanent somatosensitve injuries is an important fact to take into consideration during the postoperative management because it will indicate the lesion prognosis. Key words:Lingual nerve, third molar removal, somatosensitive alteration, papillae atrophy, permanent injury, temporary injury. PMID:24790723

  14. Genetic Analysis of Tongue Size and Taste Papillae Number and Size in Recombinant Inbred Strains of Mice

    PubMed Central

    Reiner, David J.; Jan, Taha A.; Boughter, John D.; Li, Cheng-Xiang; Lu, Lu; Williams, Robert W.

    2008-01-01

    Quantitative trait loci (QTLs) analysis has been used to examine natural variation of phenotypes in the mouse somatosensory cortex, hippocampus, cerebellum, and amygdala. QTL analysis has also been utilized to map and identify genes underlying anatomical features such as muscle, organ, and body weights. However, this methodology has not been previously applied to identification of anatomical structures related to gustatory phenotypes. In this study, we used QTL analysis to map and characterize genes underlying tongue size, papillae number, and papillae area. In a set of 43 BXD recombinant inbred (RI) mice (n = 111) and 2 parental strains (C57BL/6J and DBA/2J; n = 7), we measured tongue length, width, and weight. In a subset of 23 BXD RI mice and the parental mice, we measured filiform and fungiform papillae number and fungiform papillae area. Using QTL linkage analysis (through WebQTL), we detected 2 significant and noninteracting QTLs influencing tongue length on chromosomes 5 and 7. We also found a significant QTL on chromosome 19 underlying fungiform papillae area and a suggestive QTL on chromosome 2 linked to fungiform papillae number. From these QTLs, we identified a number of candidate genes within the QTL intervals that include SRY-box containing gene, nebulin-related anchoring protein, and actin-binding LIM protein 1. This study is an important first step in identifying genetic factors underlying tongue size, papillae size, and papillae number using QTL analysis. PMID:18653645

  15. Comparison of Taste Threshold in Smokers and Non-Smokers Using Electrogustometry and Fungiform Papillae Count: A Case Control Study

    PubMed Central

    Narayanan, Veena Sathya; Puttabuddi, Jaishankar Homberhalli; Chengappa, Rachita; Ambaldhage, Vijaya Kumara; Naik, Purnachandrarao; Raheel, Syed Ahmed

    2016-01-01

    Introduction Smoking in long term is not only responsible for cancerous changes but is also one of the reasons of altered taste sensation in smokers. These taste changes are hypothesized to be due to reduction in density of fungiform papillae on the dorsum of the tongue. Aim The aim of this study was to assess the relationship between fungiform papillae count, blood Red Cell Distribution Width (RDW) and electrogustometric thresholds in smokers and non-smokers. Materials and Methods Fungiform papillae count was assessed using digital photography and imaging software while electrogustometric thresholds were assessed using modified Transcutaneous Electric Nerve Stimulation (TENS) machine in 30 smokers and 30 non-smokers. The subjects also underwent RDW evaluation. The data collected was analyzed using Pearson’s correlation coefficient. Results Fungiform papillae counts in smokers were less than those of non-smokers and an inverse relationship was detected between smoking and fungiform papillae count. Electrogustometric thresholds were more in smokers than non-smokers and showed direct relationship with smoking. RDW was significantly more in smokers compared to non-smokers. An inverse relationship was observed between fungiform papillae count and RDW. Conclusion Our results suggest that smokers have a high taste threshold because of decrease in the number of fungiform papillae on the tongue and RDW values do show an inverse relationship with fungiform papillae density which depicts subclinical nutritional deficiency bringing atrophic changes in tongue. PMID:27437340

  16. Method for Dissecting the Auditory Epithelium (Basilar Papilla) in Developing Chick Embryos.

    PubMed

    Levic, Snezana; Yamoah, Ebenezer N

    2016-01-01

    Chickens are an invaluable model for exploring auditory physiology. Similar to humans, the chicken inner ear is morphologically and functionally close to maturity at the time of hatching. In contrast, chicks can regenerate hearing, an ability lost in all mammals, including humans. The extensive morphological, physiological, behavioral, and pharmacological data available, regarding normal development in the chicken auditory system, has driven the progress of the field. The basilar papilla is an attractive model system to study the developmental mechanisms of hearing. Here, we describe the dissection technique for isolating the basilar papilla in developing chick inner ear. We also provide detailed examples of physiological (patch clamping) experiments using this preparation. PMID:27259942

  17. Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis.

    PubMed

    Reynolds, A J; Jahoda, C A

    1992-06-01

    Adult rat pelage follicle dermal papilla cells induced follicle neogenesis and external hair growth when associated with adult footpad skin epidermis. They thus demonstrated a capacity to completely change the structural arrangement and gene expression of adult epidermis--an ability previously undocumented for cultured adult cells. Isolation chambers ensured that de novo follicle formation must have occurred by eliminating the possibility of cellular contributions, and/or inductive influences, from local skin follicles. These findings argue against previous suggestions of vibrissa follicle specificity, and imply that the potential for hair follicle induction may be common to all adult papilla cells. PMID:1425341

  18. Efficacy and safety of vilazodone 20 and 40 mg in major depressive disorder: a randomized, double-blind, placebo-controlled trial

    PubMed Central

    Gommoll, Carl; Chen, Dalei; Nunez, Rene; Khan, Arif

    2015-01-01

    Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder (MDD) treatment in adults. This was a 10-week, multicenter, double-blind, placebo-controlled and active-controlled, fixed-dose trial (NCT01473381). Adult patients with MDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision criteria) were randomized 1 : 1 : 1 : 1 to vilazodone 20 or 40 mg/day, citalopram 40 mg/day, or placebo. Primary efficacy: Montgomery–Åsberg Depression Rating Scale (MADRS); secondary efficacy: Clinical Global Impressions-Severity and sustained response (MADRS total score≤12 for at least the last two consecutive double-blind visits). The intent-to-treat population comprised 1133 patients, (placebo=281; vilazodone 20 mg/day=288; vilazodone 40 mg/day=284; citalopram=280). MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20 mg/day, vilazodone 40 mg/day, and citalopram versus placebo. Sustained response rates were numerically higher, but not significantly different, in all active treatment groups versus placebo. The most common adverse events (≥5% of vilazodone patients, twice the rate of placebo) were diarrhea, nausea, vomiting (vilazodone 40 mg/day only), and insomnia. Improved sexual function (Changes in Sexual Functioning Questionnaire scores) was seen in all groups; between-group differences were not significant. Vilazodone 20 and 40 mg/day demonstrated efficacy and tolerability in the treatment of MDD. PMID:25500685

  19. A major role of the RecFOR pathway in DNA double-strand-break repair through ESDSA in Deinococcus radiodurans.

    PubMed

    Bentchikou, Esma; Servant, Pascale; Coste, Geneviève; Sommer, Suzanne

    2010-01-01

    In Deinococcus radiodurans, the extreme resistance to DNA-shattering treatments such as ionizing radiation or desiccation is correlated with its ability to reconstruct a functional genome from hundreds of chromosomal fragments. The rapid reconstitution of an intact genome is thought to occur through an extended synthesis-dependent strand annealing process (ESDSA) followed by DNA recombination. Here, we investigated the role of key components of the RecF pathway in ESDSA in this organism naturally devoid of RecB and RecC proteins. We demonstrate that inactivation of RecJ exonuclease results in cell lethality, indicating that this protein plays a key role in genome maintenance. Cells devoid of RecF, RecO, or RecR proteins also display greatly impaired growth and an important lethal sectoring as bacteria devoid of RecA protein. Other aspects of the phenotype of recFOR knock-out mutants paralleled that of a DeltarecA mutant: DeltarecFOR mutants are extremely radiosensitive and show a slow assembly of radiation-induced chromosomal fragments, not accompanied by DNA synthesis, and reduced DNA degradation. Cells devoid of RecQ, the major helicase implicated in repair through the RecF pathway in E. coli, are resistant to gamma-irradiation and have a wild-type DNA repair capacity as also shown for cells devoid of the RecD helicase; in contrast, DeltauvrD mutants show a markedly decreased radioresistance, an increased latent period in the kinetics of DNA double-strand-break repair, and a slow rate of fragment assembly correlated with a slow rate of DNA synthesis. Combining RecQ or RecD deficiency with UvrD deficiency did not significantly accentuate the phenotype of DeltauvrD mutants. In conclusion, RecFOR proteins are essential for DNA double-strand-break repair through ESDSA whereas RecJ protein is essential for cell viability and UvrD helicase might be involved in the processing of double stranded DNA ends and/or in the DNA synthesis step of ESDSA. PMID:20090937

  20. MHC class II restricted innate-like double negative T cells contribute to optimal primary and secondary immunity to Leishmania major.

    PubMed

    Mou, Zhirong; Liu, Dong; Okwor, Ifeoma; Jia, Ping; Orihara, Kanami; Uzonna, Jude Ezeh

    2014-09-01

    Although it is generally believed that CD4(+) T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3(+)CD4(-)CD8(-) (double negative, DN) T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17) and granzyme B (GrzB) in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95%) alpha-beta T cell receptor (αβ TCR), are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis. PMID:25233487

  1. Esrrg functions in early branch generation of the ureteric bud and is essential for normal development of the renal papilla

    PubMed Central

    Berry, Rachel; Harewood, Louise; Pei, Liming; Fisher, Malcolm; Brownstein, David; Ross, Allyson; Alaynick, William A.; Moss, Julie; Hastie, Nicholas D.; Hohenstein, Peter; Davies, Jamie A.; Evans, Ronald M.; FitzPatrick, David R.

    2011-01-01

    Congenital anomalies of the kidney and urinary tract (CAKUTs) are common disorders of human development affecting the renal parechyma, renal pelvis, ureter, bladder and urethra; they show evidence of shared genetic aetiology, although the molecular basis of this remains unknown in the majority of cases. Breakpoint mapping of a de novo, apparently balanced, reciprocal translocation associated with bilateral renal agenesis has implicated the gene encoding the nuclear steroid hormone receptor ESRRG as a candidate gene for CAKUT. Here we show that the Esrrg protein is detected throughout early ureteric ducts as cytoplasmic/sub-membranous staining; with nuclear localization seen in developing nephrons. In 14.5–16.5 dpc (days post-conception) mouse embryos, Esrrg localizes to the subset of ductal tissue within the kidney, liver and lung. The renal ductal expression becomes localized to renal papilla by 18.5 dpc. Perturbation of function was performed in embryonic mouse kidney culture using pooled siRNA to induce knock-down and a specific small-molecule agonist to induce aberrant activation of Esrrg. Both resulted in severe abnormality of early branching events of the ureteric duct. Mouse embryos with a targeted inactivation of Esrrg on both alleles (Esrrg−/−) showed agenesis of the renal papilla but normal development of the cortex and remaining medulla. Taken together, these results suggest that Esrrg is required for early branching events of the ureteric duct that occur prior to the onset of nephrogenesis. These findings confirm ESRRG as a strong candidate gene for CAKUT. PMID:21138943

  2. VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK

    SciTech Connect

    Li, Wei; Man, Xiao-Yong; Li, Chun-Ming; Chen, Jia-Qi; Zhou, Jiong; Cai, Sui-Qing; Lu, Zhong-Fa; Zheng, Min

    2012-08-15

    Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF{sub 165} stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF{sub 165}-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF{sub 165}. Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: Black-Right-Pointing-Pointer We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. Black-Right-Pointing-Pointer VEGF{sub 165} stimulated proliferation of human DP cells in a dose-dependent manner. Black-Right-Pointing-Pointer This stimulation was through VEGFR-2-mediated activation of ERK.

  3. Comparison of Calcium and Barium Microcapsules as Scaffolds in the Development of Artificial Dermal Papillae.

    PubMed

    Liu, Yang; Lin, Changmin; Zeng, Yang; Li, Haihong; Cai, Bozhi; Huang, Keng; Yuan, Yanping; Li, Yu

    2016-01-01

    This study aimed to develop and evaluate barium and calcium microcapsules as candidates for scaffolding in artificial dermal papilla. Dermal papilla cells (DPCs) were isolated and cultured by one-step collagenase treatment. The DPC-Ba and DPC-Ca microcapsules were prepared by using a specially designed, high-voltage, electric-field droplet generator. Selected microcapsules were assessed for long-term inductive properties with xenotransplantation into Sprague-Dawley rat ears. Both barium and calcium microcapsules maintained xenogenic dermal papilla cells in an immunoisolated environment and induced the formation of hair follicle structures. Calcium microcapsules showed better biocompatibility, permeability, and cell viability in comparison with barium microcapsules. Before 18 weeks, calcium microcapsules gathered together, with no substantial immune response. After 32 weeks, some microcapsules were near inflammatory cells and wrapped with fiber. A few large hair follicles were found. Control samples showed no marked changes at the implantation site. Barium microcapsules were superior to calcium microcapsules in structural and mechanical stability. The cells encapsulated in hydrogel barium microcapsules exhibited higher short-term viability. This study established a model to culture DPCs in 3D culture conditions. Barium microcapsules may be useful in short-term transplantation study. Calcium microcapsules may provide an effective scaffold for the development of artificial dermal papilla. PMID:27123456

  4. Callose-mediated resistance to pathogenic intruders in plant defense-related papillae

    PubMed Central

    Voigt, Christian A.

    2014-01-01

    Plants are exposed to a wide range of potential pathogens, which derive from diverse phyla. Therefore, plants have developed successful defense mechanisms during co-evolution with different pathogens. Besides many specialized defense mechanisms, the plant cell wall represents a first line of defense. It is actively reinforced through the deposition of cell wall appositions, so-called papillae, at sites of interaction with intruding microbial pathogens. The papilla is a complex structure that is formed between the plasma membrane and the inside of the plant cell wall. Even though the specific biochemical composition of papillae can vary between different plant species, some classes of compounds are commonly found which include phenolics, reactive oxygen species, cell wall proteins, and cell wall polymers. Among these polymers, the (1,3)-β-glucan callose is one of the most abundant and ubiquitous components. Whereas the function of most compounds could be directly linked with cell wall reinforcement or an anti-microbial effect, the role of callose has remained unclear. An evaluation of recent studies revealed that the timing of the different papilla-forming transport processes is a key factor for successful plant defense. PMID:24808903

  5. Comparison of Calcium and Barium Microcapsules as Scaffolds in the Development of Artificial Dermal Papillae

    PubMed Central

    Liu, Yang; Lin, Changmin; Zeng, Yang; Li, Haihong; Cai, Bozhi; Huang, Keng; Yuan, Yanping; Li, Yu

    2016-01-01

    This study aimed to develop and evaluate barium and calcium microcapsules as candidates for scaffolding in artificial dermal papilla. Dermal papilla cells (DPCs) were isolated and cultured by one-step collagenase treatment. The DPC-Ba and DPC-Ca microcapsules were prepared by using a specially designed, high-voltage, electric-field droplet generator. Selected microcapsules were assessed for long-term inductive properties with xenotransplantation into Sprague-Dawley rat ears. Both barium and calcium microcapsules maintained xenogenic dermal papilla cells in an immunoisolated environment and induced the formation of hair follicle structures. Calcium microcapsules showed better biocompatibility, permeability, and cell viability in comparison with barium microcapsules. Before 18 weeks, calcium microcapsules gathered together, with no substantial immune response. After 32 weeks, some microcapsules were near inflammatory cells and wrapped with fiber. A few large hair follicles were found. Control samples showed no marked changes at the implantation site. Barium microcapsules were superior to calcium microcapsules in structural and mechanical stability. The cells encapsulated in hydrogel barium microcapsules exhibited higher short-term viability. This study established a model to culture DPCs in 3D culture conditions. Barium microcapsules may be useful in short-term transplantation study. Calcium microcapsules may provide an effective scaffold for the development of artificial dermal papilla. PMID:27123456

  6. Feasibility and safety of endoscopic cryoablation at the duodenal papilla: Porcine model

    PubMed Central

    Yang, Dennis; Reinhard, Mary K; Wagh, Mihir S

    2015-01-01

    AIM: To assess the feasibility and safety of liquid nitrogen spray cryoablation at the duodenal papilla in a porcine model. METHODS: This prospective study protocol was approved by the University of Florida Institutional Animal Care and Use Committee. Six pigs underwent liquid nitrogen spray cryotherapy at the duodenal papilla. Freeze time of 20-s was applied per cycle (4 cycles/session). Survival animals (n = 4) were monitored for adverse events. Hemoglobin, white blood count, liver tests, and lipase were obtained at baseline and post-treatment. EGD was performed on day#7 to evaluate the papilla and for histology. All animals were euthanized and necropsy was performed at the end of the one-week survival period. Feasibility was defined as successful placement of the decompression tube in the duodenum, followed by delivery of spray cryotherapy to the duodenal papilla. Safety was determined by monitoring post-treatment blood tests and clinical course. Treatment effect was defined as endoscopic and histologic changes after cryotherapy. This was established by comparing endoscopic and histologic findings from mucosal biopsies prior to cryotherapy and on post-operative day (POD)#7. Full-thickness specimen was obtained post-mortem to assess depth of injury. RESULTS: Spray cryotherapy was feasible and successfully performed in all 6/6 (100%) animals. Cryospray with liquid nitrogen (four 20-s freeze-thaw cycles) at the duodenal papilla resulted in white frost formation at and around the target region. The mean procedural time was 54.5 min (range 50-58 min). All six animals studied had stable blood pressure, heart rate, and pulse oximetry measurements during the procedure. There were no significant intra-procedural adverse events. There were no significant differences in hemoglobin, white cell count, liver tests or lipase from baseline to post-cryotherapy. Survival animals were monitored daily post-operatively without any clinical ill effects from the cryotherapy. There was

  7. The microstructure of lingual papillae in the Egyptian fruit bat (Rousettus aegyptiacus) as observed by light microscopy and scanning electron microscopy.

    PubMed

    Jackowiak, Hanna; Trzcielińska-Lorych, Joanna; Godynicki, Szymon

    2009-03-01

    The microstructure of lingual papillae on the dorsal surface of the tongue of adult Egyptian fruit bats was examined by light microscopy (LM) and scanning electron microscopy (SEM). This elongated tongue with a rounded apex is approximately 3 cm long -- including the 1.7cm length of the anterior free part of the tongue -- which facilitates considerable freedom of movement. The surface of the tongue has four types of lingual papillae: two types of mechanical papillae -- filiform and conical papillae, and two types of gustatory papillae -- fungiform and vallate papillae. Most numerous are filiform papillae with well developed keratinized processes represented by four morphological subtypes -- small, giant, elongated, and bifid papillae. Our observations showed the small and giant filiform papillae to be present in the anterior part of the tongue and tilted to the back of the tongue. In the posterior part of the tongue, the filiform papillae with elongated processes were arranged on each side of the tongue and oriented perpendicularly to the median line of tongue. This arrangement of filiform papillae is considered to be useful for the efficient uptake of semiliquid food as it can be collected toward the median line of the tongue. Gustatory fungiform papillae were distributed among filiform papillae on the border of the apex and the anterior part of the body of the tongue and also on the posterior part of the tongue, while three vallate papillae surrounded by conical papillae were found on the root of the tongue. There were also taste buds along the ducts of the posterior lingual glands in the posterior-lateral part of the tongue. These morphological features are discussed in relation to adaptation to food uptake in the Egyptian fruit bat. PMID:19789409

  8. Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder.

    PubMed

    Benkert, Otto; Szegedi, Armin; Philipp, Michael; Kohnen, Ralf; Heinrich, Claus; Heukels, Anja; van der Vegte-Senden, Monique; Baker, Ross A; Simmons, John H; Schutte, Albert-Jan

    2006-02-01

    This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties. PMID:16415711

  9. Simultaneous initiation (coinitiation) of pharmacotherapy with triiodothyronine and a selective serotonin reuptake inhibitor for major depressive disorder: a quantitative synthesis of double-blind studies.

    PubMed

    Papakostas, George I; Cooper-Kazaz, Rena; Appelhof, Bente C; Posternak, Michael A; Johnson, Daniel P; Klibanski, Anne; Lerer, Bernard; Fava, Maurizio

    2009-01-01

    To examine the efficacy and overall tolerability of the simultaneous initiation of treatment (coinitiation) with triiodothyronine (T3) and a selective serotonin reuptake inhibitor (SSRI) for major depressive disorder (MDD). Sources of date were Medline/Pubmed, EMBASE, the Cochrane database, and program syllabi from major psychiatric meetings held since 1995. The study selection comprised double-blind, randomized clinical trials comparing T3-SSRI coinitiation therapy versus SSRI monotherapy for MDD. Data were extracted with the use of a precoded form. Data from four clinical trials involving a total of 444 patients with MDD were identified and combined using a random effects model. There was no statistically significant difference in terms of remission rates or response rates at week 1, week 2, or at endpoint between the two treatment groups (SSRI+T3 coinitiation therapy vs. SSRI monotherapy). Pooled response and remission rates at endpoint for the SSRI+T3 versus SSRI monotherapy groups were 64.6 versus 58.5% and 46.8 versus 44.8%, respectively. In addition, there was no statistically significant difference in overall rates of premature discontinuation of treatment, or in the rate of premature discontinuation of treatment owing to inefficacy or intolerance between the two treatment groups. Notwithstanding important methodological differences between the studies included in the meta-analysis in terms of patient characteristics and treatment protocols, these results do not support the notion that simultaneous initiation of treatment of MDD with an SSRI and T3 is more effective than SSRI monotherapy. However, given the etiologically diverse and clinically heterogeneous nature of MDD, it is at least plausible that T3-SSRIs coinitiation therapy may be effective for a particular subgroup of patients including patients with atypical depression or patients with a functional polymorphism of the D-1 deiodinase gene. Clearly, further work is needed to help determine whether

  10. The effect of desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder: a substudy of a randomized, double-blind, placebo-controlled trial.

    PubMed

    Reddy, Sujana; Fayyad, Rana; Edgar, Chris J; Guico-Pabia, Christine J; Wesnes, Keith

    2016-06-01

    The objective of this substudy was to examine the effect of desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with desvenlafaxine 50 mg/day (n=52) compared with placebo (n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for desvenlafaxine (-226.6 msec (-316.7, -136.4); P<0.0001) and for placebo (-133.3 msec (-257.2, -9.4); P=0.0354); however, the treatment effect was not significant. No significant differences between groups were observed on composite measures for attention. Treatment of depression with desvenlafaxine 50 mg/day may improve aspects of cognitive functioning, including working memory.Clinical Trial Registry No.: Clinicaltrials.gov identifier: NCT00824291. PMID:27009044

  11. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.

    PubMed

    Reimherr, F W; Chouinard, G; Cohn, C K; Cole, J O; Itil, T M; LaPierre, Y D; Masco, H L; Mendels, J

    1990-12-01

    A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo. PMID:2258378

  12. Redescription and biology of Diopatra neapolitana (Annelida: Onuphidae), a protandric hermaphrodite with external spermaducal papillae

    NASA Astrophysics Data System (ADS)

    Arias, Andrés; Paxton, Hannelore; Budaeva, Nataliya

    2016-06-01

    A one-year study of the reproductive biology of a population of Diopatra neapolitana at Villaviciosa estuary, northern Spain, was undertaken. Field observations together with a histological study of monthly collected individuals revealed that the population was iteroparous, had a discontinuous reproductive season with a resting period during August and September and a spawning season from March to July. The study showed that D. neapolitana was not dioecious as previously suggested but consisted of protandric sequential hermaphrodites, pure males and pure females with a male biased sex ratio of 3:1. During the peak reproductive period from May to August we observed simultaneous hermaphrodites with two dorsal papillae per segment in the branchial region. Histological studies demonstrated that the papillae were acting as seminal vesicles, storing own sperm, and also as sperm ducts, providing an exit route; hence we termed them 'spermaducal papillae'. The papillae are not the only sperm repositories as the coelom of males and simultaneous hermaphrodites in smaller size classes is also filled with sperm. The worms are broadcast spawners with a brief pelagic larval stage as previously reported but the finer points of this unusual fertilisation system need still to be elaborated. Diopatra cryptornata was recently described as a new species, supposedly differing from D. neapolitana in chaetal detail and the possession of the papillae. We have shown conclusively with morphological and genetical studies that the former species is a junior synonym of the latter. In the absence of type material we are here designating a neotype from recently collected material from Naples.

  13. Hair matrix germinative epidermal cells confer follicle-inducing capabilities on dermal sheath and high passage papilla cells.

    PubMed

    Reynolds, A J; Jahoda, C A

    1996-10-01

    Low passage cultured dermal papilla cells from adult rats stimulate complete hair follicle neogenesis when re-implanted into heterotypic skin. In contrast, cultured sheath cells are non-inductive despite sharing other behavioural characteristics (a common lineage and in situ proximity) with papilla cells. However, since sheath cells can behave inductively in amputated follicles after regenerating the papilla, this poses the question of what influences the sheath to papilla cell transition? During reciprocal tissue interactions specific epidermal cues are crucial to skin appendage development, and while in vivo assays to date have focussed on dermal interactive influence, our aim was to investigate epidermal potential. We have previously observed that hair follicle epidermal cells display exceptional interactive behaviour when combined with follicle dermal cells in vitro. Thus in the present study, hair follicle germinative, outer root sheath or skin basal epidermal cells were separately combined with each of three non-inductive dermal cell types (high passage papilla, low passage sheath or fibroblast) and then implanted into small ear skin wounds. The sheath/germinative and papilla/germinative cell implants repeatedly induced giant vibrissa-type follicles and fibres. In complete contrast, any single cell type and all other forms of recombination were consistently non-inductive. Hence, the adult germinative epidermal cells enable non-inductive adult dermal cells to stimulate hair follicle neogenesis, effectively, by altering their 'status', causing the sheath cells to 'specialise' and the 'aged' papilla cells to 'rejuvenate'. PMID:8898222

  14. A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40–120 mg/day) in patients with major depressive disorder

    PubMed Central

    Gommoll, Carl P.; Greenberg, William M.; Chen, Changzheng

    2014-01-01

    Objective Levomilnacipran ER is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD). Efficacy and safety have been evaluated in five Phase II/III studies, four of which met the pre-specified primary efficacy outcome. Results of the negative trial (ClinicalTrials.gov NCT00969150) are reported here. Methods A Phase III randomized, double-blind, placebo-controlled trial comparing flexible-dose levomilnacipran ER 40–120 mg/day with placebo was conducted in outpatients with MDD. Patients met the DSM-IV-TR criteria for MDD, had a current episode of depression of at least 4 weeks’ duration, and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥30. The study comprised a 1-week, single-blind, placebo lead-in, 8-week double-blind treatment, and a 2-week down-taper. The primary and secondary efficacy measures were change from baseline to Week 8 in MADRS and Sheehan Disability Scale (SDS) total scores, respectively, analyzed using a mixed-effects model for repeated measures approach. Safety outcomes included adverse events (AEs), laboratory and vital sign measures, the Columbia-Suicide Severity Rating Scale, and the Arizona Sexual Experiences Scale (ASEX). Results Three hundred and fifty-five patients received the study drug and had ≥1 post-baseline MADRS total score assessment (ITT Population); 81.9% of placebo and 77.1% of levomilnacipran ER patients completed the study. For levomilnacipran ER vs placebo, MADRS (−15.7 vs −14.2) and SDS (−8.8 vs −8.2) total score improvements, and rates of MADRS response (38.5% vs 34.8%) and remission (25.3% vs 23.8%) were numerically greater but differences were not statistically significant. Levomilnacipran ER was generally well tolerated. More levomilnacipran ER patients vs placebo reported AEs; the most common AEs for levomilnacipran ER were nausea (17%) and headache (16%). Mean changes in most safety measures were

  15. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder

    PubMed Central

    Wang, Gang; McIntyre, Alexander; Earley, Willie R; Raines, Shane R; Eriksson, Hans

    2014-01-01

    Objectives To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD). Patients and methods This was a 10-week (8-week active treatment/2-week post-treatment) randomized, double-blind, placebo- and active-controlled study (D1448C00004). Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score) at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement) and remission (score ≤8); Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI) global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout. Results A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward) with either active treatment (quetiapine XR, −17.21 [P=0.174]; escitalopram, −16.73 [P=0.346]) versus placebo (−15.61). There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, −4.96 [P<0.01] versus placebo, −3.37). Mixed-model repeated-measures analysis of observed-case data suggested that the primary analysis may not be robust. Most commonly reported adverse events included dry mouth, somnolence, and dizziness for quetiapine XR, and headache and nausea for escitalopram. Conclusion In this study, neither quetiapine XR (150/300 mg/day) nor escitalopram (10/20 mg/day) showed

  16. Cell type-specific transcriptome of Brassicaceae stigmatic papilla cells from a combination of laser microdissection and RNA sequencing.

    PubMed

    Osaka, Masaaki; Matsuda, Tomoki; Sakazono, Satomi; Masuko-Suzuki, Hiromi; Maeda, Shunsuke; Sewaki, Misato; Sone, Mikako; Takahashi, Hirokazu; Nakazono, Mikio; Iwano, Megumi; Takayama, Seiji; Shimizu, Kentaro K; Yano, Kentaro; Lim, Yong Pyo; Suzuki, Go; Suwabe, Keita; Watanabe, Masao

    2013-11-01

    Pollination is an early and critical step in plant reproduction, leading to successful fertilization. It consists of many sequential processes, including adhesion of pollen grains onto the surface of stigmatic papilla cells, foot formation to strengthen pollen-stigma interaction, pollen hydration and germination, and pollen tube elongation and penetration. We have focused on an examination of the expressed genes in papilla cells, to increase understanding of the molecular systems of pollination. From three representative species of Brassicaceae (Arabidopsis thaliana, A. halleri and Brassica rapa), stigmatic papilla cells were isolated precisely by laser microdissection, and cell type-specific gene expression in papilla cells was determined by RNA sequencing. As a result, 17,240, 19,260 and 21,026 unigenes were defined in papilla cells of A. thaliana, A. halleri and B. rapa, respectively, and, among these, 12,311 genes were common to all three species. Among the17,240 genes predicted in A. thaliana, one-third were papilla specific while approximately half of the genes were detected in all tissues examined. Bioinformatics analysis revealed that genes related to a wide range of reproduction and development functions are expressed in papilla cells, particularly metabolism, transcription and membrane-mediated information exchange. These results reflect the conserved features of general cellular function and also the specific reproductive role of papilla cells, highlighting a complex cellular system regulated by a diverse range of molecules in these cells. This study provides fundamental biological knowledge to dissect the molecular mechanisms of pollination in papilla cells and will shed light on our understanding of plant reproduction mechanisms. PMID:24058146

  17. Comparative Morphology of the Papillae Linguales and their Connective Tissue Cores in the Tongue of the Greater Japanese Shrew-mole, Urotrichus talpoides

    PubMed Central

    Yoshimura, K; Shindo, J; Kageyama, I

    2013-01-01

    The external morphology of the papillae linguales (papillae filiformes, papillae fungiformes and papillae vallatae) and their connective tissue cores (CTCs) of the greater Japanese shrew-mole (Urotrichus talpoides) were analysed by optical and scanning electron microscopy. Papillae filiformes were distributed over the dorsal surface of the apex linguae, and on the rostral and caudal regions of the corpus linguae but were less numerous in the mid-region. They were absent from the radix linguae. A pair of oval papillae vallatae was situated at the border between the corpus linguae and the radix linguae. Papillae foliatae were absent. The epithelial surface of each papilla filiformis consisted of a circular concavity, a ring-like wall and either a single thumb-like process or 2–3 slender pointed processes, depending on their location. The morphology of the CTCs of the papillae filiformes also varied regionally. The papillae linguales of the Japanese shrew-mole were morphologically similar to those of other Talpidae and Soricidae, including the common shrew, particularly with respect to the papillae filiformes in the mid- and caudal regions of the corpus linguae. PMID:22571539

  18. Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial

    PubMed Central

    Salehi, B.; Mohammadbeigi, A.; Kamali, A. R.; Taheri-Nejad, M. R.; Moshiri, I.

    2015-01-01

    Background: Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD). Materials and Methods: In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2nd, 4th, 6th, and 8th ECT. Depression was assessed by Hamilton depression scale. Results: The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05). Conclusion: Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD. PMID:26440233

  19. A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder.

    PubMed

    Mahableshwarkar, Atul R; Zajecka, John; Jacobson, William; Chen, Yinzhong; Keefe, Richard S E

    2015-07-01

    This multicenter, randomized, double-blind, placebo-controlled, active-referenced (duloxetine 60 mg), parallel-group study evaluated the short-term efficacy and safety of vortioxetine (10-20 mg) on cognitive function in adults (aged 18-65 years) diagnosed with major depressive disorder (MDD) who self-reported cognitive dysfunction. Efficacy was evaluated using ANCOVA for the change from baseline to week 8 in the digit symbol substitution test (DSST)-number of correct symbols as the prespecified primary end point. The patient-reported perceived deficits questionnaire (PDQ) and physician-assessed clinical global impression (CGI) were analyzed in a prespecified hierarchical testing sequence as key secondary end points. Additional predefined end points included the objective performance-based University of San Diego performance-based skills assessment (UPSA) (ANCOVA) to measure functionality, MADRS (MMRM) to assess efficacy in depression, and a prespecified multiple regression analysis (path analysis) to calculate direct vs indirect effects of vortioxetine on cognitive function. Safety and tolerability were assessed at all visits. Vortioxetine was statistically superior to placebo on the DSST (P < 0.05), PDQ (P < 0.01), CGI-I (P < 0.001), MADRS (P < 0.05), and UPSA (P < 0.001). Path analysis indicated that vortioxetine's cognitive benefit was primarily a direct treatment effect rather than due to alleviation of depressive symptoms. Duloxetine was not significantly different from placebo on the DSST or UPSA, but was superior to placebo on the PDQ, CGI-I, and MADRS. Common adverse events (incidence ⩾ 5%) for vortioxetine were nausea, headache, and diarrhea. In this study of MDD adults who self-reported cognitive dysfunction, vortioxetine significantly improved cognitive function, depression, and functionality and was generally well tolerated. PMID:25687662

  20. A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder

    PubMed Central

    Mahableshwarkar, Atul R; Zajecka, John; Jacobson, William; Chen, Yinzhong; Keefe, Richard SE

    2015-01-01

    This multicenter, randomized, double-blind, placebo-controlled, active-referenced (duloxetine 60 mg), parallel-group study evaluated the short-term efficacy and safety of vortioxetine (10–20 mg) on cognitive function in adults (aged 18–65 years) diagnosed with major depressive disorder (MDD) who self-reported cognitive dysfunction. Efficacy was evaluated using ANCOVA for the change from baseline to week 8 in the digit symbol substitution test (DSST)–number of correct symbols as the prespecified primary end point. The patient-reported perceived deficits questionnaire (PDQ) and physician-assessed clinical global impression (CGI) were analyzed in a prespecified hierarchical testing sequence as key secondary end points. Additional predefined end points included the objective performance-based University of San Diego performance-based skills assessment (UPSA) (ANCOVA) to measure functionality, MADRS (MMRM) to assess efficacy in depression, and a prespecified multiple regression analysis (path analysis) to calculate direct vs indirect effects of vortioxetine on cognitive function. Safety and tolerability were assessed at all visits. Vortioxetine was statistically superior to placebo on the DSST (P<0.05), PDQ (P<0.01), CGI-I (P<0.001), MADRS (P<0.05), and UPSA (P<0.001). Path analysis indicated that vortioxetine's cognitive benefit was primarily a direct treatment effect rather than due to alleviation of depressive symptoms. Duloxetine was not significantly different from placebo on the DSST or UPSA, but was superior to placebo on the PDQ, CGI-I, and MADRS. Common adverse events (incidence ⩾5%) for vortioxetine were nausea, headache, and diarrhea. In this study of MDD adults who self-reported cognitive dysfunction, vortioxetine significantly improved cognitive function, depression, and functionality and was generally well tolerated. PMID:25687662

  1. Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies.

    PubMed

    Weisler, Richard H; Montgomery, Stuart A; Earley, Willie R; Szamosi, Johan; Lazarus, Arthur

    2012-01-01

    Prospectively planned pooled analysis evaluating the efficacy of quetiapine extended release (XR) monotherapy in major depressive disorder (MDD). Data were pooled from two 6-week, randomized, double-blind, placebo-controlled studies of quetiapine XR in outpatients with MDD. The primary endpoint was Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from randomization at week 6. Other evaluations were MADRS response/remission, Hamilton Rating Scale for Anxiety, and subgroup analyses. A total of 968 patients were randomized to quetiapine XR, 150 mg/day (n=315), 300 mg/day (n=323), or placebo (n=330). The mean MADRS total score reductions from randomization were significant at week 6 with quetiapine XR, 150 mg/day (-14.7; P<0.001) and 300 mg/day (-14.7; P<0.001) versus placebo (-11.1), with significant reductions versus placebo from week 1 onward. Response rates (week 6): 52.7% (P<0.001) quetiapine XR 150 mg/day and 49.5% (P<0.001) quetiapine XR 300 mg/day versus placebo (33.0%). MADRS remission (score≤8; week 6): 23.5% (P=0.208) quetiapine XR 150 mg/day and 28.8% (P<0.01) quetiapine XR 300 mg/day versus placebo (19.4%). Quetiapine XR (both doses) significantly improved eight of 10 MADRS items versus placebo at week 6. The therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as sex, age, or severity of depression. In patients with MDD, quetiapine XR (150 and 300 mg/day) monotherapy reduced depressive symptoms, with significant improvements compared with placebo from week 1 onward. PMID:22027845

  2. Efficacy of Generic Granisetron vs Kytril® for PONV in Major Gynecological Operations: A Randomized, Double-blind Clinical Trial

    PubMed Central

    Aleyasin, Ashraf; Hanafi, Somayeh; Saffarieh, Elham; Torkamandi, Hassan; Allahyari, Sara; Sadeghi, Fariborz; Javadi, Mohammadreza

    2012-01-01

    Background Granisetron is a first-generation 5-HT3-receptor antagonist that has shown efficacy in preventing postoperative nausea and vomiting (PONV). In this randomized double-blind parallel-group clinical trial, we assessed the efficacy of generic granisetron versus Kytril®, in the prevention of PONV in patients undergoing general anesthesia for gynaecological surgeries. Method One hundred and twenty patients who were supposed to undergo major gynaecological surgeries (myomectomy and hysterectomy) in Dr. Shariati Teaching Hospital, Tehran, Iran were randomly assigned to either single dose generic granisetron (40 mcg/kg), or Kytril® (40 mcg/kg) at the end of the surgery. Two episodes of emetic symptoms (nausea and vomiting) were recorded by a gynaecologist who had no knowledge of which treatment each patient had received. This gynaecologist observed the patients at three different intervals: 6, 12 and 18 h post surgery. At the end of the observation period each patient evaluated the satisfaction with the study drug, and the gynaecologist evaluated sedation of the patients. Results In the generic granisetron group 47 and 13 patients, and in the Kytril® group 45 and 15 patients underwent hysterectomy and myomectomy respectively. No difference was observed between two treatment groups regarding postoperative nausea and vomiting control during 18 hours after the drugs administration. Also there were no differences in the satisfaction with the study drug between the generic granisetron and Kytril®. No difference in sedation scores was observed between two groups. Conclusion Generic granisetron exerts efficacy against PONV after gynaecological surgeries which is non-inferior to that of Kytril®. PMID:24250537

  3. Protocol and Rationale-The Efficacy of Minocycline as an Adjunctive Treatment for Major Depressive Disorder: A Double Blind, Randomised, Placebo Controlled Trial

    PubMed Central

    Maes, Michael; Ashton, Melanie; Berk, Lesley; Kanchanatawan, Buranee; Sughondhabirom, Atapol; Tangwongchai, Sookjareon; Ng, Chee; Dowling, Nathan; Malhi, Gin S.; Berk, MIchael

    2014-01-01

    While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression. PMID:25598820

  4. The periparturient period is associated with structural and transcriptomic adaptations of rumen papillae in dairy cattle.

    PubMed

    Steele, M A; Schiestel, C; AlZahal, O; Dionissopoulos, L; Laarman, A H; Matthews, J C; McBride, B W

    2015-04-01

    The structural and functional adaption of the rumen epithelium during the transition period is largely undescribed. To characterize the adaptation of the rumen epithelium during transition, multiparous dairy cattle (n=12) fitted with rumen fistulas and fed a low-energy dry cow diet (1.37 Mcal/kg, net energy for lactation) were transitioned abruptly to a high-energy lactating cow diet (1.68 Mcal/kg, net energy for lactation) immediately after parturition. Rumen papillae were biopsied at -3, +1, and +6 wk relative to calving. The histology of morphology of the rumen papillae was evaluated under the light microscope and electron microscope, and mRNA profiling was performed using an Affymetrix GeneChip Bovine Gene 1.0 ST Array (Affymetrix, Santa Clara, CA). Data preprocessing was conducted using the robust multi-array average method, and detection of significant genes was conducted using ANOVA. Also, the Benjamini-Hochberg false discovery rate of 0.1 was applied. Microscopic examination of rumen papillae revealed an increase in epithelial desquamation during early lactation as sloughing scores increased from 1.7 ± 0.2 at -3 wk to 4.1 ± 0.3 and 3.4 ± 0.2 at +1 and + 6 wk, respectively. A total of 1,011 (-3 vs. +1 wk) and 729 (-3 vs. +6 wk) differentially expressed genes were identified (false discovery rate of 0.10, P<10(-3), fold-change ± 1.2 cut-off). A group of differentially expressed genes involved in desmosome assembly (DSG1, CDSN), epidermal growth factor signaling (EGFR, EREG), transforming growth factor β signaling (TGFB1), and the insulin-like growth factor-axis (GHR, IGFBP2, IGFBP3, CTGF) was also validated using PCR. Gene network analysis found that EGFR, GHR, and TGFB1 were focal points of the top pathways, thereby supporting the importance of these regulatory genes to the adaptive response of rumen papillae in early lactation. The microscopic and transcriptomic changes in this study provide insight into the mechanisms responsible for the rapid rate of

  5. Bright light in elderly subjects with nonseasonal major depressive disorder: a double blind randomised clinical trial using early morning bright blue light comparing dim red light treatment

    PubMed Central

    Lieverse, Ritsaert; Nielen, Marjan MA; Veltman, Dick J; Uitdehaag, Bernard MJ; van Someren, Eus JW; Smit, Jan H; Hoogendijk, Witte JG

    2008-01-01

    Background Depression frequently occurs in the elderly. Its cause is largely unknown, but several studies point to disturbances of biological rhythmicity. In both normal aging, and depression, the functioning of the suprachiasmatic nucleus (SCN) is impaired, as evidenced by an increased prevalence of day-night rhythm perturbations, such as sleeping disorders. Moreover, the inhibitory SCN neurons on the hypothalamus-pituitary adrenocortical axis (HPA-axis) have decreased activity and HPA-activity is enhanced, when compared to non-depressed elderly. Using bright light therapy (BLT) the SCN can be stimulated. In addition, the beneficial effects of BLT on seasonal depression are well accepted. BLT is a potentially safe, nonexpensive and well accepted treatment option. But the current literature on BLT for depression is inconclusive. Methods/Design This study aims to show whether BLT can reduce non-seasonal major depression in elderly patients. Randomized double blind placebo controlled trial in 126 subjects of 60 years and older with a diagnosis of major depressive disorder (MDD, DSM-IV/SCID-I). Subjects are recruited through referrals of psychiatric outpatient clinics and from case finding from databases of general practitioners and old-people homes in the Amsterdam region. After inclusion subjects are randomly allocated to the active (bright blue light) vs. placebo (dim red light) condition using two Philips Bright Light Energy boxes type HF 3304 per subject, from which the light bulbs have been covered with bright blue- or dim red light- permitting filters. Patients will be stratified by use of antidepressants. Prior to treatment a one-week period without light treatment will be used. At three time points several endocrinological, psychophysiological, psychometrically, neuropsychological measures are performed: just before the start of light therapy, after completion of three weeks therapy period, and three weeks thereafter. Discussion If BLT reduces nonseasonal

  6. A case of upper gastrointestinal acute bleeding as a complication of renal carcinoma metastases to the papilla Vateri

    PubMed Central

    Piskorz, Łukasz; Wawrzycki, Marcin; Jabłoński, Sławomir; Brocki, Marian

    2013-01-01

    Acute bleeding from metastatic tumour of the papilla Vateri is an extremely rare case. In this report the case of a woman who suffered from complications after a metastatic tumour of the papilla is described. Seventeen years following resection of the kidney due to clear cell carcinoma the patient was admitted to the clinic because of massive bleeding (Forrest IB) to the upper digestive tract in the form of sanguineous vomiting. The conducted diagnostics revealed a bleeding tumour of the papilla Vateri. Endoscopic treatment could not effectively stop the bleeding. A surgical procedure was performed by Whipple's method. A histopathological examination showed a metastatic clear cell tumour of the kidney. The patient was discharged from hospital on the 8th day following her admission and was also referred for further oncological treatment. The discussion is based on other cases of rare bleeding from the digestive tract within tumours of the bile duct and papilla Vateri. PMID:24596540

  7. Morphological study by scanning electron microscopy of the lingual papillae in the common European bat (Pipistrellus pipistrellus).

    PubMed

    Pastor, J F; Moro, J A; Verona, J A; Gato, A; Represa, J J; Barbosa, E

    1993-07-01

    There are many accounts of the tongues of mammals observed with scanning electron microscopy (SEM), but apparently only one article about the tongue of the Chiroptera. In the present study the tongue surface (after removing extracellular material) of the European common bat (Pipistrellus pipstrellus) was examined. The tongue is covered with papillae and has an elevation between its medial and posterior half. There are three types of papillae: filiform, fungiform and circumvallate, and the filiform can be classified as strictly filiform, conical and crown-like. The shapes and disposition of these papillae are related to function, which is principally to retain captured food during flight. At higher magnification the surface of the filiform papillae has many pores and microridges, which may serve for the production and distribution of mucus over the papillary surface. PMID:7690226

  8. The role of emergence profile in papilla maintenance after diastema closure with direct composite resin restorations.

    PubMed

    Sobrinho, Kleyver Nascimento; Lima, Liliane Motta de; Cohen-Carneiro, Flávia; Silva, Luciana Mendonça da; Martins, Leandro Moura; Pontes, Danielson Guedes

    2016-01-01

    The dental morphology usually determines the shape and volume of the interdental space, which must be filled by a dense connective tissue covered by oral epithelium to achieve pleasant esthetics. When composite resin restorations are placed to solve esthetic problems, the restorative procedure must be designed to allow the formation of healthy interdental papilla. This case report discusses aspects that should be considered when composite resin restorations are proposed for diastema closure. A 23-year-old man sought treatment for variations of space in the anterior dentition after orthodontic treatment. Direct composite resin restorations were placed in a way that respected the emergence profile, even though "black triangles" were evident immediately after the procedure. At the 45-day follow-up, complete closure of the interdental spaces by healthy papillae was observed. The emergence profile should be identified and respected when restorations are placed to obtain diastema closure because healthy periodontal tissues and acceptable esthetics depend on it. PMID:27148664

  9. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells.

    PubMed

    Zhang, Hui-ming; Talbot, Mark J; McCurdy, David W; Patrick, John W; Offler, Christina E

    2015-09-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca(2+) levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane-microtubule inter-relationship is discussed. PMID:26136268

  10. Calcium-dependent depletion zones in the cortical microtubule array coincide with sites of, but do not regulate, wall ingrowth papillae deposition in epidermal transfer cells

    PubMed Central

    Zhang, Hui-ming; Talbot, Mark J.; McCurdy, David W.; Patrick, John W.; Offler, Christina E.

    2015-01-01

    Trans-differentiation to a transfer-cell morphology is characterized by the localized deposition of wall ingrowth papillae that protrude into the cytosol. Whether the cortical microtubule array directs wall ingrowth papillae formation was investigated using a Vicia faba cotyledon culture system in which their adaxial epidermal cells were spontaneously induced to trans-differentiate to transfer cells. During deposition of wall ingrowth papillae, the aligned cortical microtubule arrays in precursor epidermal cells were reorganized into a randomized array characterized by circular depletion zones. Concurrence of the temporal appearance, spatial pattern, and size of depletion zones and wall ingrowth papillae was consistent with each papilla occupying a depletion zone. Surprisingly, microtubules appeared not to regulate construction of wall ingrowth papillae, as neither depolymerization nor stabilization of cortical microtubules changed their deposition pattern or morphology. Moreover, the size and spatial pattern of depletion zones was unaltered when the formation of wall ingrowth papillae was blocked by inhibiting cellulose biosynthesis. In contrast, the depletion zones were absent when the cytosolic calcium plumes, responsible for directing wall ingrowth papillae formation, were blocked or dissipated. Thus, we conclude that the depletion zones within the cortical microtubule array result from localized depolymerization of microtubules initiated by elevated cytosolic Ca2+ levels at loci where wall ingrowth papillae are deposited. The physiological significance of the depletion zones as a mechanism to accommodate the construction of wall ingrowth papillae without compromising maintenance of the plasma membrane–microtubule inter-relationship is discussed. PMID:26136268

  11. Papilla preserving modified roll technique for stage 2 soft tissue augmentation

    PubMed Central

    Dhir, Sangeeta

    2014-01-01

    The aim of the article is to describe a modification of the roll flap, performed at the implant second surgical stage, allowing the correction of small horizontal defects by enhancing the soft-tissue thickness and improving the buccal soft-tissue profile. The advantages for this modification lies in the fact to preserve the papilla morphology and enhancement of the soft-tissue esthetic results. PMID:25210270

  12. Electrical tuning and transduction in short hair cells of the chicken auditory papilla

    PubMed Central

    Tan, Xiaodong; Beurg, Maryline; Hackney, Carole; Mahendrasingam, Shanthini

    2013-01-01

    The avian auditory papilla contains two classes of sensory receptor, tall hair cells (THCs) and short hair cells (SHCs), the latter analogous to mammalian outer hair cells with large efferent but sparse afferent innervation. Little is known about the tuning, transduction, or electrical properties of SHCs. To address this problem, we made patch-clamp recordings from hair cells in an isolated chicken basilar papilla preparation at 33°C. We found that SHCs are electrically tuned by a Ca2+-activated K+ current, their resonant frequency varying along the papilla in tandem with that of the THCs, which also exhibit electrical tuning. The tonotopic map for THCs was similar to maps previously described from auditory nerve fiber measurements. SHCs also possess an A-type K+ current, but electrical tuning was observed only at resting potentials positive to −45 mV, where the A current is inactivated. We predict that the resting potential in vivo is approximately −40 mV, depolarized by a standing inward current through mechanotransducer (MT) channels having a resting open probability of ∼0.26. The resting open probability stems from a low endolymphatic Ca2+ concentration (0.24 mM) and a high intracellular mobile Ca2+ buffer concentration, estimated from perforated-patch recordings as equivalent to 0.5 mM BAPTA. The high buffer concentration was confirmed by quantifying parvalbumin-3 and calbindin D-28K with calibrated postembedding immunogold labeling, demonstrating >1 mM calcium-binding sites. Both proteins displayed an apex-to-base gradient matching that in the MT current amplitude, which increased exponentially along the papilla. Stereociliary bundles also labeled heavily with antibodies against the Ca2+ pump isoform PMCA2a. PMID:23365177

  13. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth.

    PubMed

    Higgins, Claire A; Chen, James C; Cerise, Jane E; Jahoda, Colin A B; Christiano, Angela M

    2013-12-01

    De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

  14. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

    PubMed Central

    Higgins, Claire A.; Chen, James C.; Cerise, Jane E.; Jahoda, Colin A. B.; Christiano, Angela M.

    2013-01-01

    De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

  15. Hedgehog signaling regulates dental papilla formation and tooth size during zebrafish odontogenesis

    PubMed Central

    Yu, Jeffrey C.; Fox, Zachary D.B.; Crimp, James L.; Littleford, Hana E.; Jowdry, Andrea L.; Jackman, William R.

    2015-01-01

    Background Intercellular communication by the hedgehog cell signaling pathway is necessary for tooth development throughout the vertebrates, but it remains unclear which specific developmental signals control cell behavior at different stages of odontogenesis. To address this issue, we have manipulated hedgehog activity during zebrafish tooth development and visualized the results using confocal microscopy. Results We first established that reporter lines for dlx2b, fli1, NF-κB, and prdm1a are markers for specific subsets of tooth germ tissues. We then blocked hedgehog signaling with cyclopamine and observed a reduction or elimination of the cranial neural crest derived dental papilla, which normally contains the cells that later give rise to dentin-producing odontoblasts. Upon further investigation we observed that the dental papilla begins to form and then regresses in the absence of hedgehog signaling, through a mechanism unrelated to cell proliferation or apoptosis. We also found evidence of an isometric reduction in tooth size that correlates with the time of earliest hedgehog inhibition. Conclusions We hypothesize that these results reveal a previously uncharacterized function of hedgehog signaling during tooth morphogenesis, regulating the number of cells in the dental papilla and thereby controlling tooth size. PMID:25645398

  16. Activation of fibroblast and papilla cells by glycolipid biosurfactants, mannosylerythritol lipids.

    PubMed

    Morita, Tomotake; Kitagawa, Masaru; Yamamoto, Shuhei; Suzuki, Michiko; Sogabe, Atsushi; Imura, Tomohiro; Fukuoka, Tokuma; Kitamoto, Dai

    2010-01-01

    Mannosylerythritol lipids (MELs), the extracellular glycolipids produced from feedstock by yeasts belonging to the genus Pseudozyma, are the most promising biosurfactants known due to its versatile interfacial and biochemical actions. In order to broaden the application in cosmetics, the cell activating property of MELs was investigated using cultured fibroblast and papilla cells, and a three-dimensional cultured human skin model. The di-acetylated MEL (MEL-A) produced from soybean oil significantly increased the viability of the fibroblast cells over 150% compared with that of control cells. On the other hand, no cell activation was observed by the treatment with MEL-A produced from olive oil. The mono-acetylated MEL (MEL-B) hardly increased the cell viability. The viability of the fibroblast cells decreased with the addition of more than 1 microg/L of MELs, whereas the cultured human skin cells showed high viability with 5 microg/L of MELs. Interestingly, the papilla cells were dramatically activated with 0.001 microg/L of MEL-A produced from soybean oil: the cell viability reached at 150% compared with that of control cells. Consequently, the present MEL-A produced from soybean oil should have a potential as a new hair growth agent stimulating the papilla cells. PMID:20625237

  17. Diversity of form in the amphibian papilla of Puerto Rican frogs

    NASA Technical Reports Server (NTRS)

    Lewis, E. R.; Hecht, E. I.; Narins, P. M.

    1992-01-01

    In modern frogs, the amphibian papilla exhibits a caudal extension whose shape, relative length, and proportion of hair cells vary markedly from species to species. Tuning in the caudal extension is organized tonotopically and evidently involves the tectorium. In terms of the proportion of amphibian-papillar hair cells in the caudal extension, we report more diversity among 8 species of a single genus (Eleutherodactylus) on a single island (Puerto Rico) than has been found so far among all of the (more than 50) other modern anurans examined for this feature from around the world. These 8 Puerto Rican species have overlapping habitat and conspicuous diversity in the male advertisement call. For 7 of the 8 species, we report that the call has transient spectral components in the frequency range of the amphibian papilla, and that the proportion of caudal extension hair cells and the frequency distribution of those components are correlated. Thus one might conclude that the selective pressures that led to diversity of calls among the 8 species also led to diversity in form of the amphibian papilla.

  18. Neonatal vascularization and oxygen tension regulate appropriate perinatal renal medulla/papilla maturation.

    PubMed

    Phua, Yu Leng; Gilbert, Thierry; Combes, Alexander; Wilkinson, Lorine; Little, Melissa H

    2016-04-01

    Congenital medullary dysplasia with obstructive nephropathy is a common congenital disorder observed in paediatric patients and represents the foremost cause of renal failure. However, the molecular processes regulating normal papillary outgrowth during the postnatal period are unclear. In this study, transcriptional profiling of the renal medulla across postnatal development revealed enrichment of non-canonical Wnt signalling, vascular development, and planar cell polarity genes, all of which may contribute to perinatal medulla/papilla maturation. These pathways were investigated in a model of papillary hypoplasia with functional obstruction, the Crim1(KST264/KST264) transgenic mouse. Postnatal elongation of the renal papilla via convergent extension was unaffected in the Crim1(KST264/KST264) hypoplastic renal papilla. In contrast, these mice displayed a disorganized papillary vascular network, tissue hypoxia, and elevated Vegfa expression. In addition, we demonstrate the involvement of accompanying systemic hypoxia arising from placental insufficiency, in appropriate papillary maturation. In conclusion, this study highlights the requirement for normal vascular development in collecting duct patterning, development of appropriate nephron architecture, and perinatal papillary maturation, such that disturbances contribute to obstructive nephropathy. PMID:26800422

  19. Light and scanning electron microscopic study on the lingual papillae and their connective tissue cores of the Cape hyrax Procavia capensis

    PubMed Central

    Yoshimura, Ken; Hama, Natsuki; Shindo, Junji; Kobayashi, Kan; Kageyama, Ikuo

    2008-01-01

    We examined the epithelial surface and connective tissue cores (CTCs) of each lingual papilla on the Paenungulata, Cape hyrax (Procavia capensis), by scanning electron microscopy and light microscopy. The tongue consisted of a lingual apex, lingual body and lingual root. Filiform, fungiform and foliate papillae were observed on the dorsal surface of the tongue; however, fungiform papillae were quite diminished on the lingual prominence. Moreover, no clearly distinguishable vallate papillae were found on the tongue. Instead of vallate papillae, numerous dome-like large fungiform papillae were arranged in a row just in front of the rather large foliate papillae. Foliate papillae were situated in the one-third postero-lateral margin of the lingual body. The epithelium of filiform papillae was covered by a keratinized layer with kerato-hyaline granules, whereas weak keratinization was observed on the interpapillary epithelium. The external surface of the filiform papillae was conical in shape. CTCs of the filiform papillae were seen as a hood-like core with a semicircular concavity in the anterior portion of each core. Large filiform papillae were distributed on the lingual prominence. The CTCs of large filiform papillae after exfoliation of their epithelium consisted of a concave primary core and were associated with several small protrusions. The surface of fungiform papillae was smooth and dome-like. After removal of the epithelium, CTCs appeared as a flower bud-like primary core and were associated with several protrusions that were arranged on the rim of the primary core. Several taste buds were found on the top of the dorsal part of the epithelium of both fungiform and large fungiform papillae. Well-developed foliate papillae were seen and numerous taste buds could be observed in the lateral wall of the epithelium in a slit-like groove. The morphological characteristics of the tongue of the Cape hyrax had similarities with other Paenungulata such as Sirenia

  20. Localization of type III collagen in the lingual mucosa of rats during the morphogenesis of circumvallate papillae.

    PubMed

    Iwasaki, Shin-ichi; Yoshizawa, Hideki; Aoyagi, Hidekazu

    2012-01-01

    In an effort to identify a possible role for type III collagen in the morphogenesis of circumvallate papillae on the surface of the rat tongue, we examined its appearance by fluorescent immunostaining, in conjunction with differential interference contrast images and images obtained, after staining with toluidine blue, in the transmission mode by laser-scanning microscopy. We analyzed semi-ultrathin sections of epoxy resin-embedded samples of the lingual mucosa of embryonic and juvenile rats, 13 days after conception (E13) to day 21 after birth (P21). Immunoreactivity specific for type III collagen was recognized first in the mesenchymal connective tissue just beneath the circumvallate papilla placode in fetuses on E13. At this stage, most of the lingual epithelium with the exception of the circumvallate papilla placode was pseudostratified epithelium composed of one or two layers of cuboidal cells. However, the epithelium of the circumvallate papilla placode was composed of several layers of cuboidal cells. Immunoreactivity specific for type III collagen was detected mainly on the lamina propria just beneath the lingual epithelium of the rudiment of the circumvallate papilla and the developing circumvallate papilla in fetuses on E15 and E17, and slight immunostaining was detected on the lamina propria around the rudiment. In fetuses on E19, immunoreactivity specific for type III collagen was widely and densely distributed on the connective tissue around the developing circumvallate papillae and, also, on the connective tissue that surrounded the lingual muscle. However, the immunoreactivity specific for type III collagen was sparsely distributed on the lamina propria of each central papillar structure. After birth, from P0 to P14, morphogenesis of the circumvallate papillae advanced gradually with the increase in the total volume of the tongue. At these postnatal stages, the intensity of the fluorescence due to immunoreactivity specific for type III collagen was

  1. Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth.

    PubMed

    Zhou, Linli; Xu, Mingang; Yang, Yongguang; Yang, Kun; Wickett, Randall R; Andl, Thomas; Millar, Sarah E; Zhang, Yuhang

    2016-01-01

    The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth. PMID:27472062

  2. Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth

    PubMed Central

    Zhou, Linli; Xu, Mingang; Yang, Yongguang; Yang, Kun; Wickett, Randall R.; Andl, Thomas; Millar, Sarah E.

    2016-01-01

    The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth. PMID:27472062

  3. An animal homolog of plant Mep/Amt transporters promotes ammonia excretion by the anal papillae of the disease vector mosquito Aedes aegypti.

    PubMed

    Chasiotis, Helen; Ionescu, Adrian; Misyura, Lidiya; Bui, Phuong; Fazio, Kimberly; Wang, Jason; Patrick, Marjorie; Weihrauch, Dirk; Donini, Andrew

    2016-05-01

    The transcripts of three putative ammonia (NH3/NH4 (+)) transporters, Rhesus-like glycoproteins AeRh50-1, AeRh50-2 and Amt/Mep-like AeAmt1 were detected in the anal papillae of larval Aedes aegypti Quantitative PCR studies revealed 12-fold higher transcript levels of AeAmt1 in anal papillae relative to AeRh50-1, and levels of AeRh50-2 were even lower. Immunoblotting revealed AeAmt1 in anal papillae as a pre-protein with putative monomeric and trimeric forms. AeAmt1 was immunolocalized to the basal side of the anal papillae epithelium where it co-localized with Na(+)/K(+)-ATPase. Ammonium concentration gradients were measured adjacent to anal papillae using the scanning ion-selective electrode technique (SIET) and used to calculate ammonia efflux by the anal papillae. dsRNA-mediated reductions in AeAmt1 decreased ammonia efflux at larval anal papillae and significantly increased ammonia levels in hemolymph, indicating a principal role for AeAmt1 in ammonia excretion. Pharmacological characterization of ammonia transport mechanisms in the anal papillae suggests that, in addition to AeAmt1, the ionomotive pumps V-type H(+)-ATPase and Na(+)/K(+)-ATPase as well as NHE3 are involved in ammonia excretion at the anal papillae. PMID:26944496

  4. TongueSim: Development of an Automated Method for Rapid Assessment of Fungiform Papillae Density for Taste Research.

    PubMed

    Sanyal, Shourjya; O'Brien, Shauna M; Hayes, John E; Feeney, Emma L

    2016-05-01

    Taste buds are found on the tongue in 3 types of structures: the fungiform papillae, the foliate papillae, and the circumvallate papillae. Of these, the fungiform papillae (FP) are present in the greatest numbers on the tongue, and are thought to be correlated to the overall number of taste buds. For this reason, FP density on the tongue is often used to infer taste function, although this has been controversial. Historically, videomicroscopy techniques were used to assess FP. More recently, advances in digital still photography and in software have allowed the development of rapid methods for obtaining high quality images in situ. However, these can be subject to inter-researcher variation in FP identification, and are somewhat limited in the parameters that can be measured. Here, we describe the development of a novel, automated method to count the FP, using the TongueSim suite of software. Advantages include the reduction in time required for image analysis, elimination of researcher bias, and the added potential to measure characteristics such as the degree of roundness of each papilla. We envisage that such software has a wide variety of novel research applications. PMID:26892308

  5. Firing properties of auditory primary afferents from the basilar papilla in the chick.

    PubMed

    Galicia, Salvador; Cortes, Celso; Cebada, Jorge; Méndez-Balbuena, Ignacio; Flores, Amira

    2015-08-01

    We performed intracellular and single-unit extracellular recordings of neurons from different regions of the basilar papilla in the isolated chicken inner ear. We compared the spontaneous activity and the response properties of these neurons in embryos at E15 versus posthatching animals at P1. The recordings were carried out from the apical (position 0) to the basal extension at three positions of the basilar papilla, at 5%, 10% and 40% of the entire length of the cochlea. We found that the neurons at E15 recorded from these three regions exhibited a significant higher coefficient of variation compared with those neurons at P1 recorded in the same positions. This shows that in the posthatching age P1 the neurons from the whole basilar papilla become less irregular. We found that the intracellular action potential waveforms generated at E15 had small amplitudes and small depolarization slopes in comparison to those recorded at P1, respectively (53 ± 1 mV vs. 62 ± 2 mV; 66 ± 12 mV/msec vs. 166 ± 23 mV/msec). Furthermore, we also found that the response patterns to injection of current steps were phasic, tonic, or in the form of a not yet reported "burst" pattern. Our study shows that the low irregular discharge, the immature action potential waveforms, and the differences in the response patterns to current injection, highlights the important differences between neurons at E15 and P1, consistent with the incapacity of auditory neurons at embryonic age E16, to respond at sound levels <100 decibels. PMID:26070862

  6. Ovine rumen papillae biopsy via oral endoscopy; a rapid and repeatable method for serial sampling

    PubMed Central

    McRae, KM; Schultz, M; Mackintosh, CG; Shackell, GH; Martinez, MF; Knowler, KJ; Williams, M; Ho, C; Elmes, SN; McEwan, JC

    2016-01-01

    Abstract AIMS: To explore and validate the utility of rumen endoscopy for collection of rumen papillae for gene expression measurement. METHODS: Four adult Coopworth ewes were fasted for either 4 or 24 hours. Animals were sedated, placed in a dorsally recumbent position at 45 degrees with the head upright, and an endoscope inserted via a tube inserted into the mouth. Biopsies of rumen papillae were taken from the ventral surface of the rumen atrium under visual guidance. Two biopsies were collected from one of the animals that had been fasted for 4 hours, and three from one of the animals that had been fasted for 24 hours. Video of the rumen atrium and reticulum was also collected. The animals recovered uneventfully. Biopsies were subsequently used for extraction and sequencing of mRNA. RESULTS: The ventral surface of the rumen atrium was accessible after 4 hours off pasture, but a larger region was accessible after 24 hours of fasting. Sedation allowed access for endoscope use for around 5 to 10 minutes after which increased saliva flow was noted. Rumen papillae biopsies were easily collected, with samples from a variety of sites collected in the ∼10 minute time window. High quality RNA was obtained for stranded mRNA sequencing. Of the resulting reads, 69–70% mapped uniquely to version 3.1 of the ovine genome, and 48–49% to a known gene. The rumen mRNA profiles were consistent with a previously reported study. CONCLUSIONS: This method for obtaining rumenal tissue was found to be rapid and resulted in no apparent short or long term effects on the animal. High quality RNA was successfully extracted and amplified from the rumen papillae biopsies, indicating that this technique could be used for future gene expression studies. The use of rumen endoscopy could be extended to collection of a variety of rumen and reticulum anatomical measurements and deposition and retrieval of small sensors from the rumen. Rumen endoscopy offers an attractive and cost effective

  7. Three-Dimensional Aspects of the Lingual Papillae and Their Connective Tissue Cores in the Tongue of Rats: A Scanning Electron Microscope Study

    PubMed Central

    Reginato, Gabriela de Souza; Watanabe, Ii-sei; Ciena, Adriano Polican

    2014-01-01

    The aim of the present study was to describe the tridimensional morphological characteristics of the lingual papillae and their connective tissue cores (CTCs) in Sprague Dawley rats. Four types of papillae were reported on the dorsal surface. Filiform papillae were distributed on the tongue surface and after epithelial maceration a conic and multifilamentary shape of the CTCs was revealed. Fungiform papillae were reported on the rostral and middle regions covered by a squamous epithelium. After the removal of the epithelium, the shape of a volcano with the taste orifice at its top was noted. Foliate papillae were composed of five pairs of epithelial folds situated on the lateral-caudal margin of the tongue. After the removal of the epithelium, they were shown to be limited by thin laminar projections. The vallate papilla with an oval shape was present in the caudal region and delimited by an incomplete groove. The morphological characteristics of the lingual papillae of Sprague Dowley rats, three-dimensional SEM images, and the types of papillae on the dorsal surface were similar to those reported previously in other rodent mammals. The maceration technique revealed the details of extracellular matrix with varied shapes form of connective tissue cores. PMID:25436229

  8. Ultrastructural study of the relationship between the morphogenesis of filiform papillae and the keratinization of the lingual epithelium in the mouse.

    PubMed

    Iwasaki, S; Okumura, Y; Kumakura, M

    1999-01-01

    Tongues were removed from fetuses of mice on the 15th day of gestation (E15), from newborns (P0), and from juveniles on the 7th day (p7) and on the 21st day (P21) after birth for examination by light microscopy and transmission electron microscopy. In the fetuses at E15, no rudiments of filiform papillae were visible on the dorsal surface of the tongue. No evidence of keratinization was recognized throughout the entire dorsal lingual epithelium. At P0, rudiments of filiform papillae were compactly distributed over the dorsal surface, as are the filiform papillae in the adult, but their tips were rounder than those of the filiform papillae in the adult. Cell columns in the epithelium, with different degrees of keratinization of the type observed in the matured adult were indistinct. However, a keratinized layer was clearly visible on the tip of each filiform papilla. In juveniles at P7, the filiform papillae on the anterior part of the tongue were long and slender, and the anterior and posterior cell columns of the filiform papillae were identical to those in the adult. These results indicate that, in mice, the morphogenesis of filiform papillae advances in parallel with keratinization of the lingual epithelium from the stage just before birth to a stage a few weeks after birth. PMID:10516422

  9. Perforation of the Papilla of Vater in Wire-Guided Cannulation

    PubMed Central

    Maruoka, Naotaka

    2016-01-01

    Background. WGC in ERCP is considered a safe technique, although rare complications can occur. One unique complication of WGC is the perforation of the papilla of Vater by the guidewire. Subjects and Methods. Of 2032 patients who underwent ERCP at our department between January 2010 and December 2014, we selected 208 patients who underwent WGC for naïve papilla as subjects. A detailed examination of patients in whom a perforation occurred was conducted, and risk factors for perforations were investigated. Results. The perforation was observed in 7 of 208 patients (3.4%). All patients recovered with conservative treatment without the need for surgery. The perforation rate was significantly higher in the patients with juxtapapillary duodenal diverticula than those without diverticula (12.5% versus 0.6%, p < 0.001). Cannulation of the bile duct was ultimately achieved in 5 of 7 patients; PSP was performed for 4 of these patients. Conclusion. Caution must be exercised when dealing with patients who have a juxtapapillary duodenal diverticula because they are at higher risk of perforations. Because these are small perforations made by a wire, most of them heal with conservative treatment. However, perforations can make cannulation difficult, and PSP may be useful for deep cannulation. PMID:27446851

  10. Quantitative analysis of intrinsic skin aging in dermal papillae by in vivo harmonic generation microscopy

    PubMed Central

    Liao, Yi-Hua; Kuo, Wei-Cheng; Chou, Sin-Yo; Tsai, Cheng-Shiun; Lin, Guan-Liang; Tsai, Ming-Rung; Shih, Yuan-Ta; Lee, Gwo-Giun; Sun, Chi-Kuang

    2014-01-01

    Chronological skin aging is associated with flattening of the dermal-epidermal junction (DEJ), but to date no quantitative analysis focusing on the aging changes in the dermal papillae (DP) has been performed. The aim of the study is to determine the architectural changes and the collagen density related to chronological aging in the dermal papilla zone (DPZ) by in vivo harmonic generation microscopy (HGM) with a sub-femtoliter spatial resolution. We recruited 48 Asian subjects and obtained in vivo images on the sun-protected volar forearm. Six parameters were defined to quantify 3D morphological changes of the DPZ, which we analyzed both manually and computationally to study their correlation with age. The depth of DPZ, the average height of isolated DP, and the 3D interdigitation index decreased with age, while DP number density, DP volume, and the collagen density in DP remained constant over time. In vivo high-resolution HGM technology has uncovered chronological aging-related variations in DP, and sheds light on real-time quantitative skin fragility assessment and disease diagnostics based on collagen density and morphology. PMID:25401037

  11. Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid

    PubMed Central

    Aihara, Eitaro; Mahe, Maxime M.; Schumacher, Michael A.; Matthis, Andrea L.; Feng, Rui; Ren, Wenwen; Noah, Taeko K.; Matsu-ura, Toru; Moore, Sean R.; Hong, Christian I.; Zavros, Yana; Herness, Scott; Shroyer, Noah F.; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A.; Montrose, Marshall H.

    2015-01-01

    Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5+) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5+ cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration. PMID:26597788

  12. WNT5A inhibits human dental papilla cell proliferation and migration

    SciTech Connect

    Peng, L.; Ye, L.; Dong, G.; Ren, L.B.; Wang, C.L.; Xu, P.; Zhou, X.D.

    2009-12-18

    WNT proteins are a large family of cysteine-rich secreted molecules that are linked to both canonical and non-canonical signal pathways, and have been implicated in oncogenesis and tissue development. Canonical WNT proteins have been proven to play critical roles in tooth development, while little is known about the role of non-canonical WNT proteins such as WNT5A. In this study, WNT5A was localized to human dental papilla tissue and human dental papilla cells (HDPCs) cultured in vitro, using immunochemistry and RT-PCR. Recombinant adenovirus encoding full-length Wnt5a cDNA was constructed to investigate the biological role of WNT5A on HDPCs. The BrdU incorporation assay, the MTT assay and flow cytometric analysis showed that over-expression of Wnt5a strongly inhibited the proliferation of HDPCs in vitro. Wound healing and transwell migration assays indicated that over-expression of WNT5A reduced migration of HDPCs. In conclusion, our results showed that WNT5A negatively regulates both proliferation and migration of HDPCs, suggesting its important role in odontogenesis via controlling the HDPCs.

  13. Single transcription factor reprogramming of hair follicle dermal papilla cells to induced pluripotent stem cells.

    PubMed

    Tsai, Su-Yi; Bouwman, Britta Am; Ang, Yen-Sin; Kim, Soo Jeong; Lee, Dung-Fang; Lemischka, Ihor R; Rendl, Michael

    2011-06-01

    Reprogramming patient-specific somatic cells into induced pluripotent stem (iPS) cells has great potential to develop feasible regenerative therapies. However, several issues need to be resolved such as ease, efficiency, and safety of generation of iPS cells. Many different cell types have been reprogrammed, most conveniently even peripheral blood mononuclear cells. However, they typically require the enforced expression of several transcription factors, posing mutagenesis risks as exogenous genetic material. To reduce this risk, iPS cells were previously generated with Oct4 alone from rather inaccessible neural stem cells that endogenously express the remaining reprogramming factors and very recently from fibroblasts with Oct4 alone in combination with additional small molecules. Here, we exploit that dermal papilla (DP) cells from hair follicles in the skin express all but one reprogramming factors to show that these accessible cells can be reprogrammed into iPS cells with the single transcription factor Oct4 and without further manipulation. Reprogramming was already achieved after 3 weeks and with efficiencies similar to other cell types reprogrammed with four factors. Dermal papilla-derived iPS cells are comparable to embryonic stem cells with respect to morphology, gene expression, and pluripotency. We conclude that DP cells may represent a preferred cell type for reprogramming accessible cells with less manipulation and for ultimately establishing safe conditions in the future by replacing Oct4 with small molecules. PMID:21563278

  14. Endoscopic treatment for pancreatic diseases: Needle-knife-guided cannulation via the minor papilla

    PubMed Central

    Wang, Wei; Gong, Biao; Jiang, Wei-Song; Liu, Lei; Bielike, Kouken; Xv, Bin; Wu, Yun-Lin

    2015-01-01

    AIM: To determine the efficacy and safety of meticulous cannulation by needle-knife. METHODS: Three needle-knife procedures were used to facilitate cannulation in cases when standard cannulation techniques failed. A total of 104 cannulations via the minor papilla attempted in 74 patients at our center between January 2008 and June 2014 were retrospectively reviewed. RESULTS: Standard methods were successful in 79 cannulations. Of the 25 cannulations that could not be performed by standard methods, 19 were performed by needle-knife, while 17 (89.5%) were successful. Needle-knife use improved the success rate of cannulation [76.0%, 79/104 vs 92.3%, (79 + 17)/104; P = 0.001]. When the 6 cases not appropriate for needle-knife cannulation were excluded, the success rate was improved further (80.6%, 79/98 vs 98.0%, 96/98; P = 0.000). There were no significant differences in the rates of post-endoscopic retrograde cholangiopancreatography adverse events between the group using standard methods alone and the group using needle-knife after failure of standard methods (4.7% vs 10.5%, P = 0.301). CONCLUSION: The needle-knife procedure may be an alternative method for improving the success rate of cannulation via the minor papilla, particularly when standard cannulation has failed. PMID:26019460

  15. Implication of microRNA regulation in para-phenylenediamine-induced cell death and senescence in normal human hair dermal papilla cells.

    PubMed

    Lee, Ok-Kyu; Cha, Hwa Jun; Lee, Myung Joo; Lim, Kyung Mi; Jung, Jae Wook; Ahn, Kyu Joong; An, In-Sook; An, Sungkwan; Bae, Seunghee

    2015-07-01

    Para-phenylenediamine (PPD) is a major component of hair coloring and black henna products. Although it has been largely demonstrated that PPD induces allergic reactions and increases the risk of tumors in the kidney, liver, thyroid gland and urinary bladder, the effect on dermal papilla cells remains to be elucidated. Therefore, the current study evaluated the effects of PPD on growth, cell death and senescence using cell-based assays and microRNA (miRNA) microarray in normal human hair dermal papilla cells (nHHDPCs). Cell viability and cell cycle analyses demonstrated that PPD exhibited a significant cytotoxic effect on nHHDPCs through inducing cell death and G2 phase cell cycle arrest in a dose-dependent manner. It was additionally observed that treatment of nHHDPCs with PPD induced cellular senescence by promoting cellular oxidative stress. In addition, the results of the current study indicated that these PPD-mediated effects were involved in the alteration of miRNA expression profiles. Treatment of nHHDPCs with PPD altered the expression levels of 74 miRNAs by ≥ 2-fold (16 upregulated and 58 downregulated miRNAs). Further bioinformatics analysis determined that these identified miRNA target genes were likely to be involved in cell growth, cell cycle arrest, cell death, senescence and the induction of oxidative stress. In conclusion, the observations of the current study suggested that PPD was able to induce several cytotoxic effects through alteration of miRNA expression levels in nHHDPCs. PMID:25776079

  16. Efficacy of agomelatine and escitalopram on depression, subjective sleep and emotional experiences in patients with major depressive disorder: a 24-wk randomized, controlled, double-blind trial.

    PubMed

    Corruble, Emmanuelle; de Bodinat, Christian; Belaïdi, Carole; Goodwin, Guy M

    2013-11-01

    In the present randomized, controlled, double-blind trial (12 wk treatment plus double-blind extension for 12 wk), 25-50 mg/d agomelatine (n = 164) and 10-20 mg/d escitalopram (n = 160) were compared for short- and long-term efficacy, subjective sleep and tolerability. The effects of these drugs on emotional experiences were also compared in patients having completed the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (agomelatine: n = 25; escitalopram: n = 20). Agomelatine and escitalopram similarly improved depressive symptoms, with clinically relevant score changes over 12 and 24 wk and notable percentage of remitters (week 12: 60.9 and 54.4%; week 24: 69.6 and 63.1% respectively). Over the 12 and 24-wk treatment periods, the 'global satisfaction on sleep' scores increased in both treatment groups and did not differ between groups. Satisfaction with sleep-wake quality was high in both groups; the 'wellness feeling on waking' was more improved with agomelatine than with escitalopram (p = 0.02). In patients with pronounced sleep complaints, quality of sleep and feeling on waking were significantly more improved with agomelatine than with escitalopram (p = 0.016 and p = 0.009, respectively). Emotional blunting was less frequent on agomelatine than on escitalopram. Indeed, 28% of patients on agomelatine vs. 60% on escitalopram felt that their emotions lacked intensity and 16% of patients on agomelatine vs. 53% on escitalopram felt that things that they cared about before illness did not seem important any more (p = 0.024). The tolerability profile of agomelatine was found to be superior to that of escitalopram and the incidence of patients with at least one emergent adverse event leading to treatment discontinuation was lower in the agomelatine group than in the escitalopram group (5.5 vs. 10.6%). The findings suggest that agomelatine displays additional long-term clinical benefits on sleep-wake quality and emotional experiences over

  17. Different patterns of 5{alpha}-reductase expression, cellular distribution, and testosterone metabolism in human follicular dermal papilla cells

    SciTech Connect

    Liu, Shicheng Yamauchi, Hitoshi

    2008-04-18

    Androgens regulate hair growth, and 5{alpha}-reductase (5{alpha}R) plays a pivotal role in the action of androgens on target organs. To clarify the molecular mechanisms responsible for controlling hair growth, the present study presents evidence that the human follicular dermal papilla cells (DPCs) from either beard (bDPCs) or scalp hair (sDPCs) possess endogenous 5{alpha}R activity. Real-time RT-PCR revealed that the highest level of 5{alpha}R1 mRNA was found in bDPCs, followed by sDPCs, and a low but detectable level of 5{alpha}R1 mRNA was observed in fibroblasts. Minimally detectable levels of 5{alpha}R2 mRNA were found in all three cell types. A weak band at 26 kDa corresponding to the human 5{alpha}R1 protein was detected by Western blot in both DPCs, but not in fibroblasts. Immuonofluorescence analysis confirmed that 5{alpha}R1 was localized to the cytoplasm rather than in the nuclei in both DPCs Furthermore, a 5{alpha}R assay using [{sup 14}C]testosterone labeling in intact cells revealed that testosterone was transformed primarily into androstenedione, and in small amounts, into DHT. Our results demonstrate that the 5{alpha}R activities of either bDPCs or sDPCs are stronger than that of dermal fibroblasts, despite the fact that the major steroidogenic activity is attributed to 17{beta}-HSD rather than 5{alpha}R among the three cell types. The 5{alpha}R1 inhibitor MK386 exhibited a more potent inhibitory effect on 5{alpha}R activity than finasteride (5{alpha}R2 inhibitor) in bDPCs.

  18. Intracellular papillae of Actinocephalus (Eriocaulaceae-Poales) roots and their interaction with fungi: a light and transmission electron microscopy study.

    PubMed

    Oriani, Aline; Scatena, Vera L

    2007-01-01

    The genus Actinocephalus comprises 25 species and is restricted to Brazil, occurring mainly in the Espinhaço Mountains of Minas Gerais and Bahia States. Previous anatomical studies have reported the occurrence of intracellular papillae in the Actinocephalus roots, without dealing with their ultrastructure and function. The purpose of this paper is to investigate the structure, the composition and the probable function of the intracellular papillae of Actinocephalus roots, based on light microscopy, transmission electron microscopy and histochemical tests. The intracellular papillae occurred in all root tissues, from the rhizodermis to the vascular cylinder; they presented different forms and sizes and, ultrastructurally, they corresponded to material deposited between the cell wall and the plasma membrane. The histochemical tests carried out were positive for cellulose, pectin and callose. The intracellular papillae are responses of the plant cells to the interaction with fungi. They work as a physical barrier restricting fungal penetration, and they may also favor the supply of water and nutrients to the plant, since they increase root absorption surface. This might explain why the species of Actinocephalus are among the tallest Eriocaulaceae despite their reduced radicular system and the nutritional deficiency of the soil in which they grow. PMID:17067802

  19. Shh, Bmp-2, Bmp-4 and Fgf-8 are associated with initiation and patterning of mouse tongue papillae.

    PubMed

    Jung, H S; Oropeza, V; Thesleff, I

    1999-03-01

    Spacing patterns are of fundamental importance in various repeated structures which develop at regular intervals such as feathers, teeth and insect ommatidia. The mouse tongue develops a regular papilla pattern and provides a good model to study pattern formation. We examined the expression patterns of the signalling molecules, sonic hedgehog (Shh), bone morphogenetic proteins -2 and -4 (Bmp-2 and Bmp-4), and fibroblast growth factor-8 (Fgf-8) in mouse embryos between E 10.5 and 15. We show that all four genes are expressed uniformly in the tongue epithelium between E 10.5 and 11. At E 13, before morphologically detectable gustatory papillae initiation, Shh, Bmp-2 and Bmp-4 expression segregates into discrete spots, whereas, Fgf-8 is downregulated. At E 14, small eminences in the anterior part of the tongue are the first morphological indications of fungiform papillae, and they express Shh and Bmp-2, whereas, Bmp-4 is almost absent in the tongue. We conclude that these conserved signalling molecules are associated with the initiation and early morphogenesis of the tongue papillae. PMID:10330496

  20. Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial

    PubMed Central

    Zeba, Augustin N; Sorgho, Hermann; Rouamba, Noël; Zongo, Issiaka; Rouamba, Jeremie; Guiguemdé, Robert T; Hamer, Davidson H; Mokhtar, Najat; Ouedraogo, Jean-Bosco

    2008-01-01

    Background Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum. Methods A randomized, double-blind, placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village, Burkina Faso. Children aged from 6 to 72 months were randomized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc, six days a week (n = 74) or placebo (n = 74) for a period of six months. Cross-sectional surveys were conducted at the beginning and the end of the study, and children were evaluated daily for fever. Microscopic examination of blood smear was done in the case of fever (temperature ≥37.5°C) for malaria parasite detection. Results At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group (34%) compared to the placebo group (3.5%) (p < 0.001). Malaria episodes were lower in the supplemented group (p = 0.029), with a 30.2% reduction of malaria cases (p = 0.025). Time to first malaria episode was longer in the supplemented group (p = 0.015). The supplemented group also had 22% fewer fever episodes than the placebo group (p = 0.030). Conclusion These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children, and thus may play a key role in malaria control strategies for children in Africa. PMID:18237394

  1. Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

    PubMed

    Yu, Jing-Jie; Pei, Liu-Bao; Zhang, Yong; Wen, Zi-Yu; Yang, Jian-Li

    2015-08-01

    Major depressive disorder is a devastating mental illness leading to a lifetime prevalence of higher than 16% on individuals. The treatment delay and inevitable adverse effects are major limitations of current depression interventions. Emerging evidence indicates that curcumin produced significant antidepressant properties in depression in both rodents and humans without adverse effects. Therefore, it is necessary to further clarify the antidepressant actions of curcumin and the underlying mechanism in depressed patients. A total of 108 male adults aged between 31 and 59 years were systematically recruited in Tianjin Anding Hospital. Subjects were administered the Chinese version of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale that measures different scores of depressive symptoms. The subjects were asked to take 2 capsules containing either 1000 mg of curcumin or placebo soybean powder daily for 6 weeks on the basis of their current antidepressant medications. The plasma levels of interleukin 1β, tumor necrosis factor α, brain-derived neurotrophic factor, and salivary cortisol were measured by enzyme-linked immunosorbent assay before and after curcumin or placebo treatment during the 6-week procedure. Chronic supplementation with curcumin produced significant antidepressant behavioral response in depressed patients by reduction of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores. Furthermore, curcumin decreases inflammatory cytokines interleukin 1β and tumor necrosis factor α level, increases plasma brain-derived neurotrophic factor levels, and decreases salivary cortisol concentrations compared with placebo group. These findings indicate the potential benefits of further implications of supplementary administration of curcumin to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder. PMID:26066335

  2. Polarized and persistent Ca²⁺ plumes define loci for formation of wall ingrowth papillae in transfer cells.

    PubMed

    Zhang, Hui-Ming; Imtiaz, Mohammad S; Laver, Derek R; McCurdy, David W; Offler, Christina E; van Helden, Dirk F; Patrick, John W

    2015-03-01

    Transfer cell morphology is characterized by a polarized ingrowth wall comprising a uniform wall upon which wall ingrowth papillae develop at right angles into the cytoplasm. The hypothesis that positional information directing construction of wall ingrowth papillae is mediated by Ca(2+) signals generated by spatiotemporal alterations in cytosolic Ca(2+) ([Ca(2+)]cyt) of cells trans-differentiating to a transfer cell morphology was tested. This hypothesis was examined using Vicia faba cotyledons. On transferring cotyledons to culture, their adaxial epidermal cells synchronously trans-differentiate to epidermal transfer cells. A polarized and persistent Ca(2+) signal, generated during epidermal cell trans-differentiation, was found to co-localize with the site of ingrowth wall formation. Dampening Ca(2+) signal intensity, by withdrawing extracellular Ca(2+) or blocking Ca(2+) channel activity, inhibited formation of wall ingrowth papillae. Maintenance of Ca(2+) signal polarity and persistence depended upon a rapid turnover (minutes) of cytosolic Ca(2+) by co-operative functioning of plasma membrane Ca(2+)-permeable channels and Ca(2+)-ATPases. Viewed paradermally, and proximal to the cytosol-plasma membrane interface, the Ca(2+) signal was organized into discrete patches that aligned spatially with clusters of Ca(2+)-permeable channels. Mathematical modelling demonstrated that these patches of cytosolic Ca(2+) were consistent with inward-directed plumes of elevated [Ca(2+)]cyt. Plume formation depended upon an alternating distribution of Ca(2+)-permeable channels and Ca(2+)-ATPase clusters. On further inward diffusion, the Ca(2+) plumes coalesced into a uniform Ca(2+) signal. Blocking or dispersing the Ca(2+) plumes inhibited deposition of wall ingrowth papillae, while uniform wall formation remained unaltered. A working model envisages that cytosolic Ca(2+) plumes define the loci at which wall ingrowth papillae are deposited. PMID:25504137

  3. Standardized Scalp Massage Results in Increased Hair Thickness by Inducing Stretching Forces to Dermal Papilla Cells in the Subcutaneous Tissue

    PubMed Central

    Kobayashi, Kazuhiro; Hama, Takanori; Murakami, Kasumi; Ogawa, Rei

    2016-01-01

    Objective: In this study, we evaluated the effect of scalp massage on hair in Japanese males and the effect of stretching forces on human dermal papilla cells in vitro. Methods: Nine healthy men received 4 minutes of standardized scalp massage per day for 24 weeks using a scalp massage device. Total hair number, hair thickness, and hair growth rate were evaluated. The mechanical effect of scalp massage on subcutaneous tissue was analyzed using a finite element method. To evaluate the effect of mechanical forces, human dermal papilla cells were cultured using a 72-hour stretching cycle. Gene expression change was analyzed using DNA microarray analyses. In addition, expression of hair cycle-related genes including IL6, NOGGIN, BMP4, and SMAD4 were evaluated using real-time reverse transcription-polymerase chain reaction. Results: Standardized scalp massage resulted in increased hair thickness 24 weeks after initiation of massage (0.085 ± 0.003 mm vs 0.092 ± 0.001 mm). Finite element method showed that scalp massage caused z-direction displacement and von Mises stress on subcutaneous tissue. In vitro, DNA microarray showed gene expression change significantly compared with nonstretching human dermal papilla cells. A total of 2655 genes were upregulated and 2823 genes were downregulated. Real-time reverse transcription-polymerase chain reaction demonstrated increased expression of hair cycle–related genes such as NOGGIN, BMP4, SMAD4, and IL6ST and decrease in hair loss–related genes such as IL6. Conclusions: Stretching forces result in changes in gene expression in human dermal papilla cells. Standardized scalp massage is a way to transmit mechanical stress to human dermal papilla cells in subcutaneous tissue. Hair thickness was shown to increase with standardized scalp massage. PMID:26904154

  4. Comparison of nestin-expressing multipotent stem cells in the tongue fungiform papilla and vibrissa hair follicle.

    PubMed

    Mii, Sumiyuki; Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2014-06-01

    We have previously reported that hair follicles contain multipotent stem cells, which express nestin and participate in follicle growth at anagen as well as in the extension of the follicle sensory nerve. The nestin-driven green fluorescent protein (ND-GFP) transgenic mouse labels all nestin-expressing cells with GFP. The hair follicle nestin-GFP cells can differentiate into neurons, Schwann cells, and other cell types. In this study, we describe nestin-expressing multipotent stem cells in the fungiform papilla in the tongue. The nestin-expressing multipotent stem cells in the fungiform papilla are located around a peripheral sensory nerve immediately below the taste bud and co-express the neural crest cell marker p75(NTR) . The fungiform papilla cells formed spheres in suspension culture in DMEM-F12 medium supplemented with basic fibroblast growth factor (bFGF). The spheres consisted of nestin-expressing cells that co-expressed the neural crest marker p75(NTR) and which developed expression of the stem cell marker CD34. P75(NTR), CD34 and nestin co-expression suggested that nestin-expressing cells comprising the fungiform papilla spheres were in a relatively undifferentiated state. The nestin-expressing cells of these spheres acquired the following markers: β III tubulin typical of nerve cells; GFAP typical of glial cells; K15 typical of keratinocytes; and smooth-muscle antigen (SMA), after transfer to RPMI 1640 medium with 10% fetal bovine serum (FBS), suggesting they differentiated into multiple cell types. The results of the current study indicate nestin-expressing fungiform papilla cells and the nestin-expressing hair follicle stem cells have common features of cell morphology and ability to differentiate into multiple cell types, suggesting their remarkable similarity. PMID:24142339

  5. Polarized and persistent Ca2+ plumes define loci for formation of wall ingrowth papillae in transfer cells

    PubMed Central

    Zhang, Hui-Ming; Imtiaz, Mohammad S.; Laver, Derek R.; McCurdy, David W.; Offler, Christina E.; van Helden, Dirk F.; Patrick, John W.

    2015-01-01

    Transfer cell morphology is characterized by a polarized ingrowth wall comprising a uniform wall upon which wall ingrowth papillae develop at right angles into the cytoplasm. The hypothesis that positional information directing construction of wall ingrowth papillae is mediated by Ca2+ signals generated by spatiotemporal alterations in cytosolic Ca2+ ([Ca2+]cyt) of cells trans-differentiating to a transfer cell morphology was tested. This hypothesis was examined using Vicia faba cotyledons. On transferring cotyledons to culture, their adaxial epidermal cells synchronously trans-differentiate to epidermal transfer cells. A polarized and persistent Ca2+ signal, generated during epidermal cell trans-differentiation, was found to co-localize with the site of ingrowth wall formation. Dampening Ca2+ signal intensity, by withdrawing extracellular Ca2+ or blocking Ca2+ channel activity, inhibited formation of wall ingrowth papillae. Maintenance of Ca2+ signal polarity and persistence depended upon a rapid turnover (minutes) of cytosolic Ca2+ by co-operative functioning of plasma membrane Ca2+-permeable channels and Ca2+-ATPases. Viewed paradermally, and proximal to the cytosol–plasma membrane interface, the Ca2+ signal was organized into discrete patches that aligned spatially with clusters of Ca2+-permeable channels. Mathematical modelling demonstrated that these patches of cytosolic Ca2+ were consistent with inward-directed plumes of elevated [Ca2+]cyt. Plume formation depended upon an alternating distribution of Ca2+-permeable channels and Ca2+-ATPase clusters. On further inward diffusion, the Ca2+ plumes coalesced into a uniform Ca2+ signal. Blocking or dispersing the Ca2+ plumes inhibited deposition of wall ingrowth papillae, while uniform wall formation remained unaltered. A working model envisages that cytosolic Ca2+ plumes define the loci at which wall ingrowth papillae are deposited. PMID:25504137

  6. Automatic counting of fungiform papillae by shape using cross-correlation.

    PubMed

    Valencia, Eréndira; Ríos, Homero V; Verdalet, Iñigo; Hernández, Jesús; Juárez, Sergio; Herrera, Rosa; Silva, Erik R

    2016-09-01

    The determination of the number of fungiform papillae (FP) on the human tongue is important for taste sensitivity studies. Most of the time, the counting of the FP is done manually. In this paper we propose a novel algorithm to count the FP using shape characteristics measured by cross-correlation. The accuracy of the algorithm is evaluated by counting the FP manually on the same images and then doing a statistical analysis. A Poisson regression model is fitted using maximum likelihood. The result is that the algorithm counts are very similar to the human experts. Another advantage of the algorithm is its facility of use, velocity and that it can work on a plain tongue image, without the need to stain the tongue as is usual in manual counting. PMID:27468169

  7. Ultrastructural study of the relationship between the morphogenesis of filiform papillae and the keratinisation of the lingual epithelium in the rat.

    PubMed

    Iwasaki, S; Yoshizawa, H; Kawahara, I

    1999-07-01

    Tongues were removed from rat fetuses on d 16 of gestation (E16) and from newborn (P0) and juvenile rats on d 7 (P7) and d 21 (P21) postnatally for examination by light and transmission electron microscopy. In the fetuses at E16, no rudiments of filiform papillae were visible on the dorsal surface of the tongue. No evidence of keratinisation could be recognised over the entire dorsal lingual epithelium. At P0, rudiments of filiform papillae showed a similar distribution to that seen in the adult, but had a more rounded appearance. The columnar structure of cells in the epithelium, with the different degrees of keratinisation as observed in the mature adult, was indistinct, but a keratinised layer was clearly located at the tip of each filiform papilla. In juveniles at P7, the filiform papillae on the anterior part of the tongue were long and slender, and the anterior and posterior cell columns of the filiform papillae and the interpapillary cell columns were clearly distinguishable. In juveniles at P21, the structure of filiform papillae was identical to that in the adult. These results indicate that, in rats, the morphogenesis of filiform papillae advances in parallel with keratinisation of the lingual epithelium from just before birth to a few weeks after birth. PMID:10473290

  8. White Mineral Trioxide Aggregate Induces Migration and Proliferation of Stem Cells from the Apical Papilla

    PubMed Central

    Schneider, Robert; Holland, G. Rex; Chiego, Daniel; Hu, Jan C. C.; Nör, Jacques E.; Botero, Tatiana M.

    2014-01-01

    Introduction Regenerative endodontic protocols recommend White Mineral Trioxide Aggregate (WMTA) as a capping material due to its osteoinductive properties. Stem Cells from the Apical Papilla (SCAP) are presumed to be involved in this regenerative process, but the effects of WMTA on SCAP are largely unknown. Our hypothesis is that WMTA induces proliferation and migration of SCAP. Methods Here, we used an unsorted population of SCAP (passages 3 to 5) characterized by high CD24, CD146 and Stro-1 expression. The effect of WMTA on SCAP migration was assessed using transwells and its effect on proliferation was determined by the WST-1 assay. Fetal bovine serum (FBS) and calcium-chloride enriched media were used as positive controls. Results The SCAP analyzed here showed a low percentage of STRO-1+ and CD24+ cells. Both set and unset WMTA significantly increased the short-term migration of SCAP after 6 hours (P<0.05), whereas calcium-chloride enriched medium did after 24 hours of exposure. Set WMTA significantly increased proliferation on days 1 to 5 while calcium-enriched media showed a significant increase on day 7 with a significant reduction on proliferation afterwards. SCAP migration and proliferation were significantly and steadily induced by the presence of 2% and 10% FBS Conclusions Collectively, these data demonstrate that WMTA induced an early short-term migration and proliferation of a mixed population of stem cells from apical papilla as compared to a later and longer-term induction by calcium-chloride or FBS. PMID:24935538

  9. Specific DNA binding to a major histocompatibility complex enhancer sequence by a synthetic 57-residue double zinc finger peptide from a human enhancer binding protein.

    PubMed

    Sakaguchi, K; Appella, E; Omichinski, J G; Clore, G M; Gronenborn, A M

    1991-04-15

    Two 57-residue peptides containing one pair of "zinc fingers" from a human enhancer binding protein were prepared by solid-phase peptide synthesis. One peptide (MBP-DF) contained the native sequence, while the second peptide ([Abu11]MBP-DF) has an alpha-aminobutyric acid residue substituted for a nonconserved cysteine residue at position 11. The peptides were characterized by several chemical and physical methods, and their DNA binding properties were evaluated using gel retardation experiments. Spectroscopic studies demonstrated that addition of metal ions such as zinc and cobalt resulted in specific conformational changes in both peptides, indicating that cysteine-11 does not appear to be involved in metal chelation. One-dimensional 1H NMR studies indicate that a stable folded structure is formed upon addition of zinc, and the chemical shift pattern is consistent with that previously observed for one constituent single finger (Omichinski, J., Clore, G. M., Appella, E., Sakaguchi, K., and Gronenborn, A. M. (1990) Biochemistry 29, 9324-9334). Gel retardation experiments demonstrate that the peptides are capable of interacting with a 15-mer oligonucleotide comprising a portion of the major histocompatibility complex enhancer sequence and that the interaction is zinc-dependent. The dissociation constant for the [Abu11]MBP-DF peptide is 1.4 x 10(-7) M with maximal binding occurring at a zinc-to-peptide ratio of 2 to 1. The binding specificity observed with respect to related enhancer sequences exhibits the same relative order as noted previously for the whole protein. Studies with point mutants of the major histocompatibility complex enhancer binding sequence indicate that the last GC base pair in a four-guanine stretch plays a pivotal role in the interaction between the peptide and DNA. PMID:2016331

  10. Efficacy of levomilnacipran extended-release in improving functional impairment associated with major depressive disorder: pooled analyses of five double-blind, placebo-controlled trials.

    PubMed

    Sambunaris, Angelo; Gommoll, Carl; Chen, Changzheng; Greenberg, William M

    2014-07-01

    Major depressive disorder (MDD) is characterized by increased rates of impaired function and disability. During antidepressant treatment, functional improvement often lags behind symptomatic resolution, and residual impairment is associated with an increased risk for relapse. When evaluating MDD treatments, it is important to assess not only depressive symptoms but also functional outcomes. In this post-hoc analysis, data from five studies were pooled to examine the effect of levomilnacipran extended-release (ER) versus placebo on functional impairment as measured using the Sheehan Disability Scale. The mean change in the Sheehan Disability Scale total score was significantly greater for levomilnacipran ER versus placebo in the overall pooled population, for both sexes, and across all ages. Statistically significantly higher rates of functional response, functional remission, combined (functional and symptomatic) response, and combined remission were achieved with levomilnacipran ER compared with placebo in the pooled population, as well as in the male, female, younger, and middle-aged population subgroups. The levomilnacipran ER group also showed significantly improved functional outcomes versus placebo regardless of baseline depression severity. Similarly, functional impairment was significantly improved and higher functional and combined response and remission rates were achieved with levomilnacipran ER compared with placebo regardless of the baseline level of functional impairment. PMID:24667487

  11. A Randomized Double-Blind Placebo-Controlled Study to Compare Preemptive Analgesic Efficacy of Novel Antiepileptic Agent Lamotrigine in Patients Undergoing Major Surgeries

    PubMed Central

    Shah, Priyank; Bhosale, Uma A; Gupta, Ankush; Yegnanarayan, Radha; Sardesai, Shalini

    2016-01-01

    Background: If postoperative acute pain remains unrelieved, it may result in significant morbidity and mortality. Preemptive analgesic initiated before surgery offers premature analgesia even before exposure to an initial noxious stimulus bestowing effective postoperative analgesia. In developed countries, it is regularly practiced as a part of well-defined protocol. In our country however, only a few centers practice it and that too irregularly and with undefined protocol. Few studies support preemptive analgesic efficacy of novel antiepileptic agent gabapentin. Though lamotrigine is a proven analgesic in animal models of chronic pain and clinical studies of gabapentin-resistant neuropathic pain, a literature search revealed scarce data on its preemptive analgesic efficacy. Aims: The present study is designed to study the preemptive analgesic efficacy of lamotrigine in comparison with diclofenac sodium in postoperative pain control. Materials and Methods: This randomized clinical trial included 90 patients of both sexes, between 18 years and 70 years undergoing major surgeries. Patients were randomly allocated into placebo, control, and test groups and received the respective treatment 30 min before the induction of anesthesia. Aldrete score and pain score were recorded using visual analog scale (VAS), facial rating scale (FRS), and behavioral rating scale (BRS) at awakening and at 1 h, 2 h, 4 h, 6 h, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Results: Significantly higher pain scores were observed in the placebo group postoperatively for 2 h on all pain scales (P < 0.05), whereas in the control group it was significantly higher at 1 h (P < 0.05). The test group patients were more comfortable throughout the study and postoperative analgesic requirement was significantly less (P < 0.05). Conclusions: The study recommends the use of single oral dose lamotrigine as preemptive analgesic for effective postoperative pain control. PMID

  12. Osteo-/odontogenic differentiation of BMP2 and VEGF gene-co-transfected human stem cells from apical papilla

    PubMed Central

    ZHANG, WEN; ZHANG, XIAOLEI; LING, JUNQI; WEI, XI; JIAN, YUTAO

    2016-01-01

    Stem cells from apical papilla (SCAP) possess clear osteo-/odontogenic differentiation capabilities, and are regarded as the major cellular source for root dentin development. Bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) serve pivotal roles in the modulation of tooth development and dentin formation. However, the synergistic effects of BMP2 and VEGF on osteo-/odontogenic differentiation of SCAP remain unclear. The current study aimed to investigate the proliferative and osteo-/odontogenic differentiating capabilities of BMP2 and VEGF gene-co-transfected SCAP (SCAP-BMP2-VEGF) in vitro. The basic characteristics of the isolated SCAP were identified by the induction of multipotent differentiation and by flow cytometry. Lentiviral vector-mediated gene transfection was conducted with SCAP in order to construct blank vector-transfected SCAP (SCAP-green fluorescent protein), BMP2 gene-transfected SCAP (SCAP-BMP2), VEGF gene-transfected SCAP (SCAP-VEGF) and SCAP-BMP2-VEGF. The Cell Counting Kit 8 assay was used to analyze the proliferative capacities of the four groups of cells. The expression of osteo-/odontogenic genes and proteins in the cells were evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting. The mineralized nodules formed by the four group cells were visualized by alkaline phosphatase (ALP) staining. Among the four groups of cells, SCAP-VEGF was demonstrated to exhibit increased proliferation, and SCAP-BMP2-VEGF exhibited reduced proliferation during eight days observation. SCAP-BMP2-VEGF exhibited significantly increased expression levels of ALP, osteocalcin, dentin sialophosphoprotein, dentin matrix acidic phosphoprotein gene 1 and dentin sialoprotein than the other three groups at the majority of the time points. Furthermore, the SCAP-BMP2-VEGF group exhibited a significantly greater number of ALP-positive mineralized nodules than the other groups following 16 days culture in

  13. Osteo-/odontogenic differentiation of BMP2 and VEGF gene-co-transfected human stem cells from apical papilla.

    PubMed

    Zhang, Wen; Zhang, Xiaolei; Ling, Junqi; Wei, Xi; Jian, Yutao

    2016-05-01

    Stem cells from apical papilla (SCAP) possess clear osteo‑/odontogenic differentiation capabilities, and are regarded as the major cellular source for root dentin development. Bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) serve pivotal roles in the modulation of tooth development and dentin formation. However, the synergistic effects of BMP2 and VEGF on osteo‑/odontogenic differentiation of SCAP remain unclear. The current study aimed to investigate the proliferative and osteo‑/odontogenic differentiating capabilities of BMP2 and VEGF gene-co-transfected SCAP (SCAP-BMP2-VEGF) in vitro. The basic characteristics of the isolated SCAP were identified by the induction of multipotent differentiation and by flow cytometry. Lentiviral vector‑mediated gene transfection was conducted with SCAP in order to construct blank vector‑transfected SCAP (SCAP-green fluorescent protein), BMP2 gene-transfected SCAP (SCAP-BMP2), VEGF gene‑transfected SCAP (SCAP‑VEGF) and SCAP-BMP2-VEGF. The Cell Counting Kit 8 assay was used to analyze the proliferative capacities of the four groups of cells. The expression of osteo-/odontogenic genes and proteins in the cells were evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting. The mineralized nodules formed by the four group cells were visualized by alkaline phosphatase (ALP) staining. Among the four groups of cells, SCAP‑VEGF was demonstrated to exhibit increased proliferation, and SCAP‑BMP2‑VEGF exhibited reduced proliferation during eight days observation. SCAP‑BMP2‑VEGF exhibited significantly increased expression levels of ALP, osteocalcin, dentin sialophosphoprotein, dentin matrix acidic phosphoprotein gene 1 and dentin sialoprotein than the other three groups at the majority of the time points. Furthermore, the SCAP‑BMP2‑VEGF group exhibited a significantly greater number of ALP‑positive mineralized nodules than the other

  14. Rosa damascena oil improves SSRI-induced sexual dysfunction in male patients suffering from major depressive disorders: results from a double-blind, randomized, and placebo-controlled clinical trial

    PubMed Central

    Farnia, Vahid; Shirzadifar, Mehdi; Shakeri, Jalal; Rezaei, Mansour; Bajoghli, Hafez; Holsboer-Trachsler, Edith; Brand, Serge

    2015-01-01

    Background A substantial disadvantage of psychopharmacological treatment of major depressive disorder (MDD) with selective serotonin-reuptake inhibitors (SSRIs) is the impact on sexual dysfunction. The aim of the present study was to investigate whether the oil of Rosa damascena can have a positive influence on SSRI-induced sexual dysfunction (SSRI-I SD) of male patients who are suffering from MDD and are being treated with SSRIs. Method In a double-blind, randomized, and placebo-controlled clinical trial, a total of 60 male patients treated with an SSRI and suffering from MDD (mean age =32 years) and SSRI-I SD were randomly assigned to take either verum (R. damascena oil) or a placebo. Patients completed self-ratings of depression and sexual function at baseline, at 4 weeks later, and at the end of the study, 8 weeks after it started. Results Over time, sexual dysfunction improved more in the verum group than in the control group. Improvements were observed in the verum group from week 4 to week 8. Self-rated symptoms of depression reduced over time in both groups, but did so more so in the verum group than in the control group. Conclusion This double-blind, randomized, and placebo-controlled clinical trial showed that the administration of R. damascena oil ameliorates sexual dysfunction in male patients suffering from both MDD and SSRI-I SD. Further, the symptoms of depression reduced as sexual dysfunction improved. PMID:25834441

  15. Myosins XI-K, XI-1, and XI-2 are required for development of pavement cells, trichomes, and stigmatic papillae in Arabidopsis

    PubMed Central

    2012-01-01

    Background The positioning and dynamics of vesicles and organelles, and thus the growth of plant cells, is mediated by the acto-myosin system. In Arabidopsis there are 13 class XI myosins which mediate vesicle and organelle transport in different cell types. So far the involvement of five class XI myosins in cell expansion during the shoot and root development has been shown, three of which, XI-1, XI-2, and XI-K, are essential for organelle transport. Results Simultaneous depletion of Arabidopsis class XI myosins XI-K, XI-1, and XI-2 in double and triple mutant plants affected the growth of several types of epidermal cells. The size and shape of trichomes, leaf pavement cells and the elongation of the stigmatic papillae of double and triple mutant plants were affected to different extent. Reduced cell size led to significant size reduction of shoot organs in the case of triple mutant, affecting bolt formation, flowering time and fertility. Phenotype analysis revealed that the reduced fertility of triple mutant plants was caused by delayed or insufficient development of pistils. Conclusions We conclude that the class XI myosins XI-K, XI-1 and XI-2 have partially redundant roles in the growth of shoot epidermis. Myosin XI-K plays more important role whereas myosins XI-1 and XI-2 have minor roles in the determination of size and shape of epidermal cells, because the absence of these two myosins is compensated by XI-K. Co-operation between myosins XI-K and XI-2 appears to play an important role in these processes. PMID:22672737

  16. Identification of Wnt/β-catenin signaling pathway in dermal papilla cells of human scalp hair follicles: TCF4 regulates the proliferation and secretory activity of dermal papilla cell.

    PubMed

    Xiong, Ya; Liu, Yi; Song, Zhiqiang; Hao, Fei; Yang, Xichuan

    2014-01-01

    It is clear that the dermal papilla cell (DPC), which is located at the bottom of the hair follicle, is a special mesenchymal component, and it plays a leading role in regulating hair follicle development and periodic regeneration. Recent studies showed that the Wnt signaling pathway through β-catenin (canonical Wnt signaling pathway) is an essential component in maintaining the hair-inducing activity of the dermal papilla and growth of hair papilla cells. However, the intrinsic pathways and regulating mechanism are largely unknown. In the previous work, we constructed a cDNA subtractive library of DPC and first found that the TCF4 gene, as a key factor of Wnt signaling pathway, was expressed as the upregulated gene of the hair follicle in low-passage DPC. This study was to explore the role of TCF4 in regulating the proliferation and secretory activity of DPC. We constructed a pcDNA3.0-TCF4 expression vector and transfected it into DPC to achieve stable expression by bangosome 2000. Furthermore, we used the method of chemosynthesis to synthesize three pairs of TCF4 siRNA and transfected them into DPC. Meanwhile, we compared the transfection group and non-transfection group. We first proposed that there was expression difference in TCF4 in DPC under different biological condition. This study may have a high impact on the molecular mechanism of follicular lesions and provide a new vision for the treatment of clinic diseases. PMID:24354472

  17. Antioxidant activity in plasma and rumen papillae development in lambs fed fermented apple pomace.

    PubMed

    Rodríguez-Muela, C; Rodríguez, H E; Arzola, C; Díaz-Plascencia, D; Ramírez-Godínez, J A; Flores-Mariñelarena, A; Mancillas-Flores, P F; Corral, G

    2015-05-01

    The effect of fermented apple pomace (FAP) on animal health, antioxidant activity (AA), hematic biometry (HBm) and the development of ruminal epithelium were investigated in a study with 24 finishing lambs (BW = 25.4 ± 3.3 Kg). Lambs were grouped by sex (12 male and 12 female) and fed (n = 6 per group of treatment) a basal fattening diet (Control diet, T1) or the basal diet supplemented to include 10.91% of fermented apple pomace (FAP diet, T2). The animals were kept 56 d in individual metabolic cages, with ad libitum access to water and feed. Two blood samples were collected from each animal on d 0, 28, and 56 to determine AA in plasma and hematic biometry (HBm). Four samples of ruminal tissue were taken postmortem to evaluate the development of ruminal epithelium based on the length (LP) and width (WP) of papillae. AA and HBm data were analyzed with a mixed model (fixed effects: diet, sampling, sex, and their interaction; using the experimental unit nested in the effect of the diet as the random effect). LP and WP were analyzed with a hierarchical model, as simple and nested effects in the sampling site, where the fixed effects were the diet and the sex of the animal and their interaction. There was an effect of diet on AA, which was higher (P < 0.06) in T2 vs. T1 at 56 d (24.34 vs. 21.79 mM Fe2). Leukocytes increased (P < 0.05) from 7.52*10(3) ± 1.29*10/(3)μL to 9.14*10(3) ± 1.24*10(3)/μL in all the animals in the experiment, with a marked increased (P < 0.05) at 28 d after beginning of the feeding period, with values within the normal range for this species and without effect of the diet (P > 0.05) for the other indicators of HBm. Males' LP was higher in T2 than in T1 (P < 0.05). It was concluded that the use of FAP in the diets of finishing sheep reaped benefits on animal health and the development of rumen epithelium by improving antioxidant activity in plasma and stimulating the growth of papillae. PMID:26020331

  18. Morphogenesis of chimeric hair follicles in engineered skin substitutes with human keratinocytes and murine dermal papilla cells.

    PubMed

    Sriwiriyanont, Penkanok; Lynch, Kaari A; Maier, Elizabeth A; Hahn, Jennifer M; Supp, Dorothy M; Boyce, Steven T

    2012-10-01

    Engineered skin substitutes (ESS) have been used successfully to treat life-threatening burns, but lack cutaneous appendages. To address this deficiency, dermal constructs were prepared using collagen-glycosaminoglycan scaffolds populated with murine dermal papilla cells expressing green fluorescent protein (mDPC-GFP), human dermal papilla cells (hDPC) and/or human fibroblasts (hF). Subsequently, human epidermal keratinocytes (hK) or hK genetically modified to overexpress stabilized β-catenin (hK') were used to prepare ESS epithelium. After 10 days incubation at air-liquid interface, ESS were grafted to athymic mice and were evaluated for 6 weeks. Neofollicles were observed in ESS containing mDPC-GFP, but not hDPC or hF, independent of whether or not the hK were genetically modified. Based on detection of GFP fluorescence, mDPC were localized to the dermal papillae of the well-defined follicular structures of grafted ESS. In addition, statistically significant increases in LEF1, WNT10A and WNT10B were found in ESS with neofollicles. These results demonstrate a model for generation of chimeric hair in ESS. PMID:23078401

  19. [The fine structure of the gustatory cells of the circumvallate, foliate and fungiform papillae in hibernating bats].

    PubMed

    Arcari, M L; Galanti, G; Azzali, G

    1996-01-01

    The cells of vallate, foliate and fungiform papillae were studied in insectivore hibernating bats (Pipistrellus pipistrellus and Rhinolophus ferrumequinum) in the various epochs of the year in order to show cell types the seasonal changes. On the basis of the ultrastructural aspects and the relationships with nerve endings, besides the few basal cells, three types of sensorial cells can be identified: dark type I cells, light type II cells and light type III cells. All gustatory cells, long and narrow shaped, extend from the epithelial basal lamina to the gustatory canal, where they send long microvillous expansions of the apical cytoplasm. These expansions, except those of the fungiform papillae which never extend beyond the lower two thirds, usually reach the external opening of the taste pore, always completely void of dense substance. Dark type I cells are characterized by a developed RER and large granules. Light type III cells show peculiar dense core light vesicles, labelled protein A-gold particles immunoreactive to 5-HT. These cells only in the foliate and fungiform papillae also have bundles of microtubules whose function is still unknown. After comparative evaluation and discussion of topographical and ultrastructural aspects with those of other mammals and humans, the Authors states that bats are provided with a valid gustatory system and that all cell types are involved in taste transduction. PMID:10021731

  20. Functional and comparative study of lingual papillae in four species of bear (Ursidae) by scanning electron microscopy.

    PubMed

    Pastor, J F; Barbosa, M; de Paz, F J; García, M; Ferrero, E

    2011-10-01

    The eight current species of bear (Ursidae) are widely distributed throughout Europe, Asia, and America. They are mainly encountered in the northern hemisphere, except for the spectacled bear and the sun bear, which are also found in the south of the equator. Adaptations of the masticatory apparatus (teeth, tongue, and musculature) to diet are one of the factors that imply the greatest structural changes in the cranium. This diet may be carnivorous, herbivorous, melliferous, or insectivorous, with one type of food predominating according to the time of year. The way in which food is eaten determines the morphology of the lingual surface; generally speaking, all bears put their mouth to the food, which, initially, they lick or they let the food stick to their tongue, as occurs when insects are eaten. As in all mammals, a distinction can be made between mechanical and gustatory papillae and the development and distribution of which depend on the species and their eating habits. In this study of the complete tongues of four species of adult bears, we describe the morphology of the lingual surfaces, the different types of papillae, their characteristics, and topographic distribution. It was seen that there were five main types of lingual papillae: filiform, conical, fungiform, foliate, and vallate. Morphology of the microgrooves and pores was similar to that observed in other mammals. In general, there were no great differences among the four species of bears studied, perhaps due to the similarity in the kind of food they consume in captivity. PMID:21936024

  1. Comparison of odontogenic differentiation of human dental follicle cells and human dental papilla cells.

    PubMed

    Guo, Lijuan; Li, Jie; Qiao, Xiangchen; Yu, Mei; Tang, Wei; Wang, Hang; Guo, Weihua; Tian, Weidong

    2013-01-01

    Classical tooth development theory suggests that dental papilla cells (DPCs) are the precursor cells of odontoblasts, which are responsible for dentin development. However, our previous studies have indicated that dental follicle cells (DFCs) can differentiate into odontoblasts. To further our understanding of tooth development, and the differences in dentinogenesis between DFCs and DPCs, the odontogenic differentiation of DFCs and DPCs was characterized in vitro and in vivo. DFCs and DPCs were individually combined with treated dentin matrix (TDM) before they were subcutaneously implanted into the dorsum of mice for 8 weeks. Results showed that 12 proteins were significantly differential, and phosphoserine aminotransferase 1 (PSAT1), Isoform 2 of hypoxia-inducible factor 1-alpha (HIF1A) and Isoform 1 of annexin A2 (ANXA2), were the most significantly differential proteins. These proteins are related to regulation of bone balance, angiogenesis and cell survival in an anoxic environment. Both DFCs and DPCs express odontogenic, neurogenic and peridontogenic markers. Histological examination of the harvested grafts showed that both DFCs and DPCs form pulp-dentin/cementum-periodentium-like tissues in vivo. Hence, DFCs and DPCs have similar odontogenic differentiation potential in the presence of TDM. However, differences in glucose and amino acid metabolism signal transduction and protein synthesis were observed for the two cell types. This study expands our understanding on tooth development, and provides direct evidence for the use of alternative cell sources in tooth regeneration. PMID:23620822

  2. Polyclonal origin and hair induction ability of dermal papillae in neonatal and adult mouse back skin

    PubMed Central

    Collins, Charlotte A.; Jensen, Kim B.; MacRae, Elizabeth J.; Mansfield, William; Watt, Fiona M.

    2012-01-01

    Hair follicle development and growth are regulated by Wnt signalling and depend on interactions between epidermal cells and a population of fibroblasts at the base of the follicle, known as the dermal papilla (DP). DP cells have a distinct gene expression signature from non-DP dermal fibroblasts. However, their origins are largely unknown. By generating chimeric mice and performing skin reconstitution assays we show that, irrespective of whether DP form during development, are induced by epidermal Wnt activation in adult skin or assemble from disaggregated cells, they are polyclonal in origin. While fibroblast proliferation is necessary for hair follicle formation in skin reconstitution assays, mitotically inhibited cells readily contribute to DP. Although new hair follicles do not usually develop in adult skin, adult dermal fibroblasts are competent to contribute to DP during hair follicle neogenesis, irrespective of whether they originate from skin in the resting or growth phase of the hair cycle or skin with β-catenin-induced ectopic follicles. We propose that during skin reconstitution fibroblasts may be induced to become DP cells by interactions with hair follicle epidermal cells, rather than being derived from a distinct subpopulation of cells. PMID:22537489

  3. Erythrocyte flow and dynamic hematocrit in the renal papilla of the rat.

    PubMed

    Zimmerhackl, B; Dussel, R; Steinhausen, M

    1985-12-01

    The microcirculation of the renal papilla was investigated in 32 vasa recta of Wistar rats. Using fluorescence microscopy in combination with a high-sensitivity television system we measured the velocity and flux of fluorescent-tagged erythrocytes in descending (DVR) and ascending vasa recta (AVR). After staining the plasma with fluorescent high molecular weight dextran we determined the diameters of DVR and AVR. Red cell flux (Qrbc) was determined from the ratio of the frequency of fluorescent-tagged red cells detected per unit time (fFITC) to the number of fluorescent-tagged red cells per nanoliter packed red cells (NFITC). From red cell velocity (Vrbc) and vessel diameter (D) we calculated the volume flow (Vapp). The dynamic hematocrit was directly derived as the ratio of Qrbc to Vapp. During antidiuresis Vrbc was 1.35 +/- 0.15 mm X s-1 (mean +/- SE) in DVR and 0.47 +/- 0.07 mm X s-1 in AVR. Qrbc in the same vessels averaged 3.26 +/- 0.9 and 1.72 +/- 0.35 nl X min-1, respectively. The diameter in DVR was 14.3 +/- 0.9 and in AVR 17.9 +/- 0.9 micron. From these values we calculated a dynamic hematocrit of 26 +/- 4 in DVR and 25 +/- 4% in AVR. The systemic hematocrit was 44 +/- 1%. The dynamic hematocrit in vasa recta represented 59 +/- 9 and 57 +/- 8% of the value in the systemic circulation, respectively. PMID:4073272

  4. Follicular dermal papilla structures by organization of epithelial and mesenchymal cells in interfacial polyelectrolyte complex fibers.

    PubMed

    Lim, Tze Chiun; Leong, Meng Fatt; Lu, Hongfang; Du, Chan; Gao, Shujun; Wan, Andrew C A; Ying, Jackie Y

    2013-09-01

    The hair follicle is a regenerating organ that produces a new hair shaft during each growth cycle. Development and cycling of the hair follicle is governed by interactions between the epithelial and mesenchymal components. Therefore, development of an engineered 3D hair follicle would be useful for studying these interactions to identify strategies for treatment of hair loss. We have developed a technique suitable for assembly of different cell types in close proximity in fibrous hydrogel scaffolds with resolutions of ∼50 μm. By assembly of dermal papilla (DP) and keratinocytes, structures similar to the native hair bulb arrangement are formed. Gene expression of these constructs showed up-regulation of molecules involved in epithelial-mesenchymal interactions of the hair follicle. Implantation of the follicular structures in SCID mice led to the formation of hair follicle-like structures, thus demonstrating their hair inductive ability. The transparency of the fiber matrix and the small dimensions of the follicular structures allowed the direct quantitation of DP cell proliferation by confocal microscopy, clearly illustrating the promoting or inhibitory effects of hair growth regulating agents. Collectively, our results suggested a promising application of these 3D engineered follicular structures for in vitro screening and testing of drugs for hair growth therapy. PMID:23796577

  5. Slow motility in hair cells of the frog amphibian papilla: Ca2+-dependent shape changes.

    PubMed

    Farahbakhsh, Nasser A; Narins, Peter M

    2006-02-01

    We investigated the process of slow motility in non-mammalian auditory hair cells by recording the time course of shape change in hair cells of the frog amphibian papilla. The tall hair cells in the rostral segment of this organ, reported to be the sole recipients of efferent innervation, were found to shorten in response to an increase in the concentration of the intracellular free calcium. These shortenings are composed of two partially-overlapping phases: an initial rapid iso-volumetric contraction, followed by a slower length decrease accompanied with swelling. It is possible to unmask the iso-volumetric contraction by delaying the cell swelling with the help of K+ or Cl- channel inhibitors, quinine or furosemide. Furthermore, it appears that the longitudinal contraction in these cells is Ca2+-calmodulin-dependent: in the presence of W-7, a calmodulin inhibitor, only a slow, swelling phase could be observed. These findings suggest that amphibian rostral AP hair cells resemble their mammalian counterparts in expressing both a Ca2+-calmodulin-dependent contractile structure and an "osmotic" mechanism capable of mediating length change in response to extracellular stimuli. Such a mechanism might be utilized by the efferent neurotransmitters for adaptive modulation of mechano-electrical transduction, sensitivity enhancement, frequency selectivity, and protection against over-stimulation. PMID:16426781

  6. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties.

    PubMed

    Rendl, Michael; Polak, Lisa; Fuchs, Elaine

    2008-02-15

    Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial-mesenchymal cross-talk necessary to make hair. PMID:18281466

  7. Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction

    PubMed Central

    Huang, Chin-Fu; Chang, Ya-Ju; Hsueh, Yuan-Yu; Huang, Chia-Wei; Wang, Duo-Hsiang; Huang, Tzu-Chieh; Wu, Yi-Ting; Su, Fong-Chin; Hughes, Michael; Chuong, Cheng-Ming; Wu, Chia-Ching

    2016-01-01

    Intradermal adipose tissue plays an essential role for hair follicles (HFs) regeneration by regulating hair cycles. However, the effect of reconstruction of HFs and the involvement of adipose-related cells are poorly understood. We investigated assembly strategies for the interactions of dermal papilla (DP) cells with adipose-derived stem cells (ASCs) in promoting hair formation. DP cells lose DP traits during adherent culture, but preserved DP markers with a unified sphere diameter by seeding on chitosan-coated microenvironments. Next, ASCs isolated from rats were co-cultured with DP spheres by different assembling approaches to determine their interactions; a mixed sphere of ASCs with DP cells (MA-DPS), or a core-shell structure, outer ASCs shell and an inner DP core (CSA-DPS). CSA-DPS exhibited superior DP characteristics compared to MA-DPS. Conditional medium from ASCs, but not differentiated adipocytes, promoted DP markers and functional alkaline phosphatase activity from the DP cells. In vivo patch assay showed the core-shell assembling of CSA-DPS can reconstruct cellular arrangements and microenvironmental niches as dominated by PPARα signal in ASCs to induce the greater hair induction than MA-DPS or DP spheres alone. Therefore, the assembling of a core-shell sphere for DP with ASCs could reconstruct the HF cellular arrangement for hair formation. This paper set the groundwork for further evaluation of the input of other cell types. PMID:27210831

  8. Epidermal growth factor promotes proliferation of dermal papilla cells via Notch signaling pathway.

    PubMed

    Zhang, Haihua; Nan, Weixiao; Wang, Shiyong; Zhang, Tietao; Si, Huazhe; Wang, Datao; Yang, Fuhe; Li, Guangyu

    2016-08-01

    The effect of epidermal growth factor (EGF) on the development and growth of hair follicle is controversial. In the present study, 2-20 ng/ml EGF promoted the growth of mink hair follicles in vitro, whereas 200 ng/ml EGF inhibited follicle growth. Further, dermal papilla (DP) cells, a group of mesenchymal cells that govern hair follicle development and growth, were isolated and cultured in vitro. Treatment with or forced expression of EGF accelerated proliferation and induced G1/S transition in DP cells. Moreover, EGF upregulated the expression of DP mesenchymal genes, such as alkaline phosphatase (ALP) and insulin-like growth factor (IGF-1), as well as the Notch pathway molecules including Notch1, Jagged1, Hes1 and Hes5. In addition, inhibition of Notch signaling pathway by DAPT significantly reduced the basal and EGF-enhanced proliferation rate, and also suppressed cell cycle progression. We also show that the expression of several follicle-regulatory genes, such as Survivin and Msx2, were upregulated by EGF, and was inhibited by DAPT. In summary, our study demonstrates that the concentration of EGF is critical for the switch between hair follicle growth and inhibition, and EGF promotes DP cell proliferation via Notch signaling pathway. PMID:27109378

  9. Canonical Wnts, specifically Wnt-10b, show ability to maintain dermal papilla cells

    SciTech Connect

    Ouji, Yukiteru Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide

    2013-08-30

    Highlights: •First report on effects of various Wnts on DP cells. •Wnt-10b promoted trichogenesis, while Wnt-3a showed to a limited extent. •Canonical Wnts, specifically Wnt-10b, is important for DP cells maintenance. -- Abstract: Although Wnts are expressed in hair follicles (HFs) and considered to be crucial for maintaining dermal papilla (DP) cells, the functional differences among them remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, 5a, 10b, 11) on the proliferation of mouse-derived primary DP cells in vitro as well as their trichogenesis-promoting ability using an in vivo skin reconstitution protocol. Wnt-10b promoted cell proliferation and trichogenesis, while Wnt-3a showed those abilities to a limited extent, and Wnt-5a and 11 had no effects. Furthermore, we investigated the effects of these Wnts on cultured DP cells obtained from versican-GFP transgenic mice and found that Wnt-10b had a potent ability to sustain their GFP-positivity. These results suggest that canonical Wnts, specifically Wnt-10b, play important roles in the maintenance of DP cells and trichogenesis.

  10. Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction.

    PubMed

    Huang, Chin-Fu; Chang, Ya-Ju; Hsueh, Yuan-Yu; Huang, Chia-Wei; Wang, Duo-Hsiang; Huang, Tzu-Chieh; Wu, Yi-Ting; Su, Fong-Chin; Hughes, Michael; Chuong, Cheng-Ming; Wu, Chia-Ching

    2016-01-01

    Intradermal adipose tissue plays an essential role for hair follicles (HFs) regeneration by regulating hair cycles. However, the effect of reconstruction of HFs and the involvement of adipose-related cells are poorly understood. We investigated assembly strategies for the interactions of dermal papilla (DP) cells with adipose-derived stem cells (ASCs) in promoting hair formation. DP cells lose DP traits during adherent culture, but preserved DP markers with a unified sphere diameter by seeding on chitosan-coated microenvironments. Next, ASCs isolated from rats were co-cultured with DP spheres by different assembling approaches to determine their interactions; a mixed sphere of ASCs with DP cells (MA-DPS), or a core-shell structure, outer ASCs shell and an inner DP core (CSA-DPS). CSA-DPS exhibited superior DP characteristics compared to MA-DPS. Conditional medium from ASCs, but not differentiated adipocytes, promoted DP markers and functional alkaline phosphatase activity from the DP cells. In vivo patch assay showed the core-shell assembling of CSA-DPS can reconstruct cellular arrangements and microenvironmental niches as dominated by PPARα signal in ASCs to induce the greater hair induction than MA-DPS or DP spheres alone. Therefore, the assembling of a core-shell sphere for DP with ASCs could reconstruct the HF cellular arrangement for hair formation. This paper set the groundwork for further evaluation of the input of other cell types. PMID:27210831

  11. Fate of Prominin-1 Expressing Dermal Papilla Cells during Homeostasis, Wound Healing and Wnt Activation

    PubMed Central

    Kaushal, Grace S; Rognoni, Emanuel; Lichtenberger, Beate M; Driskell, Ryan R; Kretzschmar, Kai; Hoste, Esther; Watt, Fiona M

    2015-01-01

    Prominin-1/CD133 (Prom1) is expressed by fibroblasts in the dermal papilla (DP) of the hair follicle (HF). By examining endogenous Prom1 expression and expression of LacZ in the skin of Prom1CreERLacZ (Prom1C-L) mice, in which a CreERT2-IRES-nuclear LacZ cassette is knocked into the first ATG codon of Prom1, we confirmed that Prom1 is expressed in the DP of all developing HFs and also by postnatal anagen follicles. To analyze the fate of Prom1+ DP cells, we crossed Prom1C-L mice with Rosa26-CAG flox/stop/flox tdTomato reporter mice and applied 4-hydroxytamoxifen (4OHT) to back skin at postnatal day (P) 1 and P2. We detected tdTomato+ cells in ~50% of DPs. The proportion of labeled cells per DP increased between P5 and P63, while the total number of cells per DP declined. Following full thickness wounding, there was no migration of tdTomato-labeled cells out of the DP. When β-catenin was activated in Prom1+ DP cells there was an increase in the size of anagen and telogen DP, but the proportion of tdTomato-labeled cells did not increase. We conclude that Prom1+ DP cells do not contribute to dermal repair but are nevertheless capable of regulating DP size via β-catenin-mediated intercellular communication. PMID:26288357

  12. Fate of Prominin-1 Expressing Dermal Papilla Cells during Homeostasis, Wound Healing and Wnt Activation.

    PubMed

    Kaushal, Grace S; Rognoni, Emanuel; Lichtenberger, Beate M; Driskell, Ryan R; Kretzschmar, Kai; Hoste, Esther; Watt, Fiona M

    2015-12-01

    Prominin-1/CD133 (Prom1) is expressed by fibroblasts in the dermal papilla (DP) of the hair follicle (HF). By examining endogenous Prom1 expression and expression of LacZ in the skin of Prom1CreERLacZ (Prom1C-L) mice, in which a CreERT2-IRES-nuclear LacZ cassette is knocked into the first ATG codon of Prom1, we confirmed that Prom1 is expressed in the DP of all developing HFs and also by postnatal anagen follicles. To analyze the fate of Prom1+ DP cells, we crossed Prom1C-L mice with Rosa26-CAG flox/stop/flox tdTomato reporter mice and applied 4-hydroxytamoxifen (4OHT) to back skin at postnatal day (P) 1 and P2. We detected tdTomato+ cells in ~50% of DPs. The proportion of labeled cells per DP increased between P5 and P63, while the total number of cells per DP declined. Following full thickness wounding, there was no migration of tdTomato-labeled cells out of the DP. When β-catenin was activated in Prom1+ DP cells there was an increase in the size of anagen and telogen DP, but the proportion of tdTomato-labeled cells did not increase. We conclude that Prom1+ DP cells do not contribute to dermal repair but are nevertheless capable of regulating DP size via β-catenin-mediated intercellular communication. PMID:26288357

  13. Effect of 5alpha-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells.

    PubMed

    Winiarska, A; Mandt, N; Kamp, H; Hossini, A; Seltmann, H; Zouboulis, C C; Blume-Peytavi, U

    2006-01-01

    Pathogenetic mechanisms in androgenetic alopecia are not yet fully understood; however, it is commonly accepted that androgens like testosterone (T) and 5alpha-dihydrotestosterone (5alpha-DHT) inhibit hair follicle activity with early induction of the catagen. Thus, we investigated the influence of T and 5alpha-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers. T and 5alpha-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10(-5) M was found. Interestingly, bcl-2 protein expression was decreased in T- and 5alpha-DHT-treated cells, leading to an increase in the bax/bcl-2 ratio. In addition, T and 5alpha-DHT induced proteolytic cleavage of caspase 8 and inhibited proliferation of DPC at 10(-5) M. High concentrations of T and 5alpha-DHT were needed to induce apoptotic effects in DPC. These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia. PMID:16931898

  14. Endoscopic Papillectomy into the Treatment of Neoplastic Lesions of Vater Papilla

    PubMed Central

    Ghidirim, G.; Mişin, I.; Istrate, V.; Cazacu, S.

    2009-01-01

    Adenomas of the duodenal papilla are rare. The frequency of malignant adenomas is 15-30%. Villous adenoma is a premalignant lesion with the highest rate of transformation. Options for surgical treatment include endoscopic and ablation resection, transduodenal ampullectomy, duodeno-pancreatectomy. Aim: Evaluation of the efficacy and safety of endoscopic papillectomy for ampullary adenomas. Material and method: 12 patients were selected (F:M, 5:7, age range 37 - 68 years) with ampullary adenoma, treated by endoscopic papillectomy. Biliary sphincterotomy was performed in 6 cases; and pancreatic sphincterotomy was performed in 3 cases. Biliary stenting was performed in 2 cases; pancreatic stent was placed in 11 cases. Results: En bloc resection was performed in 8 cases, and piecemeal resection in 4 cases. Complete resection R0 was noted in 10 cases. Pathology examination has show: tubulo-villous adenoma (5 patients); villous adenoma (4 patients), tubular adenoma (2 cases), adenocarcinoma (one case). Complications were immediate: bleeding (2 cases) and pancreatitis (1 case). Follow-up endoscopy reveals no ductal stenosis or recurrence. Conclusion: Endoscopic papillectomy is a safe and well-tolerated alternative to surgical treatment of ampullary adenoma. PMID:24778815

  15. Polyclonal origin and hair induction ability of dermal papillae in neonatal and adult mouse back skin.

    PubMed

    Collins, Charlotte A; Jensen, Kim B; MacRae, Elizabeth J; Mansfield, William; Watt, Fiona M

    2012-06-15

    Hair follicle development and growth are regulated by Wnt signalling and depend on interactions between epidermal cells and a population of fibroblasts at the base of the follicle, known as the dermal papilla (DP). DP cells have a distinct gene expression signature from non-DP dermal fibroblasts. However, their origins are largely unknown. By generating chimeric mice and performing skin reconstitution assays we show that, irrespective of whether DP form during development, are induced by epidermal Wnt activation in adult skin or assemble from disaggregated cells, they are polyclonal in origin. While fibroblast proliferation is necessary for hair follicle formation in skin reconstitution assays, mitotically inhibited cells readily contribute to DP. Although new hair follicles do not usually develop in adult skin, adult dermal fibroblasts are competent to contribute to DP during hair follicle neogenesis, irrespective of whether they originate from skin in the resting or growth phase of the hair cycle or skin with β-catenin-induced ectopic follicles. We propose that during skin reconstitution fibroblasts may be induced to become DP cells by interactions with hair follicle epidermal cells, rather than being derived from a distinct subpopulation of cells. PMID:22537489

  16. Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity.

    PubMed

    Zhou, Linli; Yang, Kun; Xu, Mingang; Andl, Thomas; Millar, Sarah E; Boyce, Steven; Zhang, Yuhang

    2016-08-01

    Bioengineering hair follicles using cells isolated from human tissue remains a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of growth factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and integrin α8. After a 2-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin compared to control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was up-regulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells. PMID:27312243

  17. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan

    PubMed Central

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202

  18. The efficacy of extended-release levomilnacipran in moderate to severe major depressive disorder: secondary and post-hoc analyses from a randomized, double-blind, placebo-controlled study.

    PubMed

    Montgomery, Stuart A; Mansuy, Lucilla; Ruth, Adam C; Li, Dayong; Gommoll, Carl

    2014-01-01

    Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor that is Food and Drug Administration approved for once-daily treatment of major depressive disorder in adults. Secondary and post-hoc analyses were carried out on data from a positive 10-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, proof-of-concept trial (EudraCT Number: 2006-002404-34) on 75 or 100 mg/day levomilnacipran extended release (ER). Included outpatients (18-70 years) met the criteria for a major depressive episode. There was a statistically significant difference in favor of levomilnacipran ER versus placebo in change from baseline to week 10 on every Montgomery Åsberg Depression Rating Scale (MADRS) single item (mixed-effects model for repeated measures; P<0.05) and most Hamilton Depression Rating Scale (HAMD17) single items. Significantly more levomilnacipran ER versus placebo patients (P < 0.05) achieved 'complete' (MADRS ≤ 5; 24 vs. 10%) and 'sustained' (MADRS ≤ 10 in Weeks 4-10; 16 vs. 10%) remission, Sheehan Disability Scale (SDS) response (total score ≤ 12 and each item score ≤ 4; 52 vs. 35%) and remission (total score ≤ 6 and each item score ≤ 2; 26 vs. 17%), and combined symptomatic (MADRS) and functional (SDS) remission (19 vs. 8%). Treatment effects of similar magnitude were observed in the severe depression subgroup (MADRS ≥ 30). These results demonstrate the benefit of levomilnacipran ER over placebo for patients with symptomatic and functional impairment associated with major depressive disorder. PMID:24172160

  19. Epigallocatechin Gallate-Mediated Alteration of the MicroRNA Expression Profile in 5α-Dihydrotestosterone-Treated Human Dermal Papilla Cells

    PubMed Central

    Shin, Shanghun; Kim, Karam; Lee, Myung Joo; Lee, Jeongju; Choi, Sungjin; Kim, Kyung-Suk; Ko, Jung-Min; Han, Hyunjoo; Kim, Su Young; Youn, Hae Jeong; Ahn, Kyu Joong; An, In-Sook; An, Sungkwan

    2016-01-01

    Background Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level. Objective We showed that epigallocatechin gallate (EGCG), a major component of green tea, protects DHT-induced cell death by regulating the cellular miRNA expression profile. Methods We used a miRNA microarray to identify miRNA expression levels in human dermal papilla cells (DPCs). We investigated whether the miRNA expression influenced the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular ROS levels, and senescence. Results EGCG protected against the effects of DHT by altering the miRNA expression profile in human DPCs. In addition, EGCG attenuated DHT-mediated cell death and growth arrest and decreased intracellular ROS levels and senescence. A bioinformatics analysis elucidated the relationship between the altered miRNA expression and EGCG-mediated protective effects against DHT. Conclusion Overall, our results suggest that EGCG ameliorates the negative effects of DHT by altering the miRNA expression profile in human DPCs. PMID:27274631

  20. Angiogenic Potential and Secretome of Human Apical Papilla Mesenchymal Stem Cells in Various Stress Microenvironments.

    PubMed

    Bakopoulou, Athina; Kritis, Aristeidis; Andreadis, Dimitrios; Papachristou, Eleni; Leyhausen, Gabriele; Koidis, Petros; Geurtsen, Werner; Tsiftsoglou, Asterios

    2015-11-01

    Stem cells from the apical papilla (SCAP) of human adult teeth are considered an accessible source of cells with angiogenic properties. The aims of this study were to investigate the endothelial transdifferentiation of SCAP, the secretion of pro- and antiangiogenic factors from SCAP, and the paracrine effects of SCAP when exposed to environmental stress to stimulate tissue damage. SCAP were exposed to serum deprivation (SD), glucose deprivation (GD), and oxygen deprivation/hypoxia (OD) conditions, individually or in combination. Endothelial transdifferentiation was evaluated by in vitro capillary-like formation assays, real-time polymerase chain reaction, western blot, and flow cytometric analyses of angiogenesis-related markers; secretome by antibody arrays and enzyme-linked immunosorbent assays (ELISA); and paracrine impact on human umbilical vein endothelial cells (HUVECs) by in vitro transwell migration and capillary-like formation assays. The short-term exposure of SCAP to glucose/oxygen deprivation (GOD) in the presence, but mainly in deprivation, of serum (SGOD) elicited a proangiogenesis effect indicated by expression of angiogenesis-related genes involved in vascular endothelial growth factor (VEGF)/VEGFR and angiopoietins/Tie pathways. This effect was unachievable under SD in normoxia, suggesting that the critical microenvironmental condition inducing rapid endothelial shift of SCAP is the combination of SGOD. Interestingly, SCAP showed high adaptability to these adverse conditions, retaining cell viability and acquiring a capillary-forming phenotype. SCAP secreted higher numbers and amounts of pro- (angiogenin, IGFBP-3, VEGF) and lower amounts of antiangiogenic factors (serpin-E1, TIMP-1, TSP-1) under SGOD compared with SOD or SD alone. Finally, secretome obtained under SGOD was most effective in inducing migration and capillary-like formation by HUVECs. These data provide new evidence on the microenvironmental factors favoring endothelial

  1. Histone demethylase KDM2B inhibits the chondrogenic differentiation potentials of stem cells from apical papilla.

    PubMed

    Wang, Jing-Jing; Dong, Rui; Wang, Li-Ping; Wang, Jin-Song; Du, Juan; Wang, Song-Lin; Shan, Zhao-Chen; Fan, Zhi-Peng

    2015-01-01

    Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSCs differentiation. Previous studies determined that KDM2B can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2B is involved in the other cell lineages differentiation of MSCs. Here we used the stem cells from apical papilla (SCAPs) to study the role of KDM2B on the chondrogenic differentiation potentials in MSCs. In this study, Gain- and loss-of-function assays were applied to investigate the role of KDM2B on the chondrogenic differentiation. Alcian Blue Staining and Quantitative Analysis were used to investigate the synthesis of proteoglycans by chondrocytes. Real-time RT-PCR was used to detect the expressions of chondrogenesis related genes. The Alcian Blue staining and Quantitative Analysis results revealed that overexpression of KDM2B decreased the proteoglycans production, and real-time RT-PCR results showed that the expressions of the chondrogenic differentiation markers, COL1, COL2 and SOX9 were inhibited by overexpression of KDM2B in SCAPs. On the contrary, depletion of KDM2B increased the proteoglycans production, and inhibited the expressions of COL1, COL2 and SOX9. In conclusion, our results indicated that KDM2B is a negative regulator of chondrogenic differentiation in SCAPs and suggest that inhibition of KDM2B might improve MSC mediated cartilage regeneration. PMID:25932147

  2. Synaptic Calcium Regulation in Hair Cells of the Chicken Basilar Papilla

    PubMed Central

    Im, Gi Jung; Moskowitz, Howard S.; Lehar, Mohammed; Hiel, Hakim

    2014-01-01

    Cholinergic inhibition of hair cells occurs by activation of calcium-dependent potassium channels. A near-membrane postsynaptic cistern has been proposed to serve as a store from which calcium is released to supplement influx through the ionotropic ACh receptor. However, the time and voltage dependence of acetylcholine (ACh)-evoked potassium currents reveal a more complex relationship between calcium entry and release from stores. The present work uses voltage steps to regulate calcium influx during the application of ACh to hair cells in the chicken basilar papilla. When calcium influx was terminated at positive membrane potential, the ACh-evoked potassium current decayed exponentially over ∼100 ms. However, at negative membrane potentials, this current exhibited a secondary rise in amplitude that could be eliminated by dihydropyridine block of the voltage-gated calcium channels of the hair cell. Calcium entering through voltage-gated channels may transit through the postsynaptic cistern, since ryanodine and sarcoendoplasmic reticulum calcium-ATPase blockers altered the time course and magnitude of this secondary, voltage-dependent contribution to ACh-evoked potassium current. Serial section electron microscopy showed that efferent and afferent synaptic structures are juxtaposed, supporting the possibility that voltage-gated influx at afferent ribbon synapses influences calcium homeostasis during long-lasting cholinergic inhibition. In contrast, spontaneous postsynaptic currents (“minis”) resulting from stochastic efferent release of ACh were made briefer by ryanodine, supporting the hypothesis that the synaptic cistern serves primarily as a calcium barrier and sink during low-level synaptic activity. Hypolemmal cisterns such as that at the efferent synapse of the hair cell can play a dynamic role in segregating near-membrane calcium for short-term and long-term signaling. PMID:25505321

  3. Cytotoxicity of Various Endodontic Materials on Stem Cells of Human Apical Papilla

    PubMed Central

    Saberi, Eshagh Ali; Karkehabadi, Hamed; Mollashahi, Narges Farhad

    2016-01-01

    Introduction: This in vitro study assessed and compared the cytotoxicity of mineral trioxide aggregate (MTA), calcium-enriched mixture (CEM) cement, Biodentine (BD) and octacalcium phosphate (OCP) on stem cells of the human apical papilla (SCAP). Methods and Materials: SCAPs were isolated from two semi-impacted third molars. The cells were cultured in wells of an insert 24-well plate and were then incubated. The plates were then removed from the incubator and randomly divided into four experimental groups that were exposed to 1-mm discs of set MTA, CEM, BD or OCP, and one untreated control group. After 24, 48 and 168 h, the plates were removed from the incubator and 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) solution was added to each well. Data were analyzed at different time points using the repeated measures ANOVA followed by Bonferroni test and the level of significance was set at 0.05. Results: Cytotoxicity of the four materials was not significantly different from that of the control group at 24, 48 and 168 h (P>0.05). Two-by-two comparison revealed that cytotoxicity of MTA and CEM cement was significantly different from each other at 168 h (P<0.05) although the cytotoxicity of CEM was less than MTA. Cytotoxicity of OCP and MTA was also significantly different from each other at 48 h and OCP had more favorable biocompatibility than MTA (P<0.05). Conclusion: CEM, OCP, BD and MTA showed acceptable biocompatibility when exposed to SCAP. Over time, CEM showed the least cytotoxicity among the materials under study. PMID:26843872

  4. Profiling the Secretome of Human Stem Cells from Dental Apical Papilla.

    PubMed

    Yu, Shi; Zhao, Yuming; Ma, Yushi; Ge, Lihong

    2016-03-15

    Recent studies have shown that secretion of bioactive factors from mesenchymal stem cells (MSCs) plays a primary role in MSC-mediated therapy; especially for bone marrow-derived MSCs (BMSCs). MSCs from dental apical papilla (SCAPs) are involved in root development and may play a critical role in the formation of dentin and pulp. Bioactive factors secreted from SCAPs actively contribute to their environment; however, the SCAPs secretome remains unclear. To address this and gain a deeper understanding of the relevance of SCAPs secretions in a clinical setting, we used isobaric chemical tags and high-performance liquid chromatography with tandem mass spectrometry to profile the secretome of human SCAPs and then compared it to that of BMSCs. A total of 2,046 proteins were detected from the conditioned medium of SCAPs, with a false discovery rate of less than 1.0%. Included were chemokines along with angiogenic, immunomodulatory, antiapoptotic, and neuroprotective factors and extracellular matrix (ECM) proteins. The secreted levels of 151 proteins were found to differ by at least twofold when BMSCs and SCAPs were compared. Relative to BMSCs, SCAPs exhibited increased secretion of proteins that are involved in metabolic processes and transcription and lower levels of those associated with biological adhesion, developmental processes, and immune function. In addition, SCAPs secreted significantly larger amounts of chemokines and neurotrophins than BMSCs, whereas BMSCs secreted more ECM proteins and proangiogenic factors. These results may provide important clues regarding the molecular mechanisms associated with tissue regeneration and how they differ between cell sources. PMID:26742889

  5. Herbal Extracts Induce Dermal Papilla Cell Proliferation of Human Hair Follicles

    PubMed Central

    Rastegar, Hosein; Aghaei, Mahmoud; Barikbin, Behrooz; Ehsani, Amirohushang

    2015-01-01

    Background The number of people suffering from balding or hair thinning is increasing, despite the advances in various medical therapies. Therefore, it is highly important to develop new therapies to inhibit balding and increase hair proliferation. Objective We investigated the effects of herbal extracts commonly used for improving balding in traditional medicine to identify potential agents for hair proliferation. Methods The expression levels of 5α-reductase isoforms (type I and II) were analyzed using quantitative real-time reverse transcription polymerase chain reaction in the human follicular dermal papilla cells (DPCs). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylteterazolium bromide and bromodeoxyuridine tests were used to evaluate the cell proliferation effect of herbal extracts in DPCs. The expression levels of extracellular signal-regulated kinase (ERK), Akt, cyclin D1, cyclin-dependent kinase 4 (Cdk4), B-cell lymphoma (Bcl-2) and Bcl-2-associated X protein (Bax) were measured using western blot analysis. Results The 5α-reductase isoform mRNAs and proteins were detected in the cultured DPCs, and the expression level of 5α-R2 in DPCs in the presence of the herbal extracts was gradually decreased. Herbal extracts were found to significantly increase the proliferation of human DPCs at concentrations ranging from 1.5% to 4.5%. These results show that the herbal extracts tested affected the protein expressions of ERK, Akt, cyclin D1, Cdk4, Bcl-2, and Bax in DPCs. Conclusion These results suggest that herbal extracts exert positive effects on hair proliferation via ERK, Akt, cyclin D1, and Cdk4 signaling in DPCs; they also suggest that herbal extracts could be a great alternative therapy for increasing hair proliferation. PMID:26719634

  6. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin–noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine†

    PubMed Central

    Montgomery, Stuart A; Nielsen, Rebecca Z; Poulsen, Lis H; Häggström, Lars

    2014-01-01

    Objective This randomised, double-blind, 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine (10–20 mg/day) versus agomelatine (25–50 mg/day) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin–noradrenaline reuptake inhibitor (SNRI) monotherapy. Methods Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine. Primary endpoint was change from baseline to week 8 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score analysed by mixed model for repeated measurements, using a noninferiority test followed by a superiority test. Secondary endpoints included response and remission rates, anxiety symptoms (Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life (EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale). Results Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p < 0.01). Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12; MADRS, Hamilton Anxiety Rating Scale, Clinical Global Impression, Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards; work limitation questionnaire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12. Fewer patients withdrew because of adverse events with vortioxetine (5.9% vs 9.5%). Adverse events (incidence ≥5%) were nausea, headache, dizziness and somnolence. Conclusions Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy. Vortioxetine was safe and well tolerated. PMID:25087600

  7. Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial.

    PubMed

    Russell, I Jon; Mease, Philip J; Smith, Timothy R; Kajdasz, Daniel K; Wohlreich, Madelaine M; Detke, Michael J; Walker, Daniel J; Chappell, Amy S; Arnold, Lesley M

    2008-06-01

    The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia. PMID:18395345

  8. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder

    PubMed Central

    Loft, Henrik; Olsen, Christina Kurre

    2014-01-01

    This study assessed the efficacy, tolerability and safety of vortioxetine versus placebo in adults with recurrent major depressive disorder. This double-blind, randomized, placebo-controlled study included 608 patients [Montgomery–Åsberg Depression Rating Scale (MADRS) total score≥26 and Clinical Global Impression – Severity score≥4]. Patients were randomly assigned (1 : 1 : 1 : 1) to vortioxetine 15 mg/day, vortioxetine 20 mg/day, duloxetine 60 mg/day or placebo. The primary efficacy endpoint was change from baseline in MADRS total score at week 8 (mixed model for repeated measurements). Key secondary endpoints were: MADRS responders; Clinical Global Impression – Improvement scale score; MADRS total score in patients with baseline Hamilton Anxiety Rating Scale ≥20; remission (MADRS≤10); and Sheehan Disability Scale total score at week 8. On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n=158) of −5.5 (vortioxetine 15 mg, P<0.0001, n=149) and −7.1 MADRS points (vortioxetine 20 mg, P<0.0001, n=151). Duloxetine (n=146) separated from placebo, thus validating the study. In all key secondary analyses, both vortioxetine doses were statistically significantly superior to placebo. Vortioxetine treatment was well tolerated; common adverse events (incidence≥5%) were nausea, headache, diarrhea, dry mouth and dizziness. No clinically relevant changes were seen in clinical safety laboratory values, weight, ECG or vital signs parameters. Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder. PMID:24257717

  9. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder.

    PubMed

    Boulenger, Jean-Philippe; Loft, Henrik; Olsen, Christina Kurre

    2014-05-01

    This study assessed the efficacy, tolerability and safety of vortioxetine versus placebo in adults with recurrent major depressive disorder. This double-blind, randomized, placebo-controlled study included 608 patients [Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 26 and Clinical Global Impression - Severity score ≥ 4]. Patients were randomly assigned (1 : 1 : 1 : 1) to vortioxetine 15 mg/day, vortioxetine 20 mg/day, duloxetine 60 mg/day or placebo. The primary efficacy endpoint was change from baseline in MADRS total score at week 8 (mixed model for repeated measurements). Key secondary endpoints were: MADRS responders; Clinical Global Impression - Improvement scale score; MADRS total score in patients with baseline Hamilton Anxiety Rating Scale ≥ 20; remission (MADRS ≤ 10); and Sheehan Disability Scale total score at week 8. On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n = 158) of -5.5 (vortioxetine 15 mg, P < 0.0001, n = 149) and -7.1 MADRS points (vortioxetine 20 mg, P < 0.0001, n = 151). Duloxetine (n = 146) separated from placebo, thus validating the study. In all key secondary analyses, both vortioxetine doses were statistically significantly superior to placebo. Vortioxetine treatment was well tolerated; common adverse events (incidence ≥ 5%) were nausea, headache, diarrhea, dry mouth and dizziness. No clinically relevant changes were seen in clinical safety laboratory values, weight, ECG or vital signs parameters. Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder. PMID:24257717

  10. Adhesive papillae on the brachiolar arms of brachiolaria larvae in two starfishes, Asterina pectinifera and Asterias amurensis, are sensors for metamorphic inducing factor(s).

    PubMed

    Murabe, Naoyuki; Hatoyama, Hideo; Komatsu, Miéko; Kaneko, Hiroyuki; Nakajima, Yoko

    2007-10-01

    It has been hypothesized by Barker that starfish brachiolaria larvae initiate metamorphosis by sensing of metamorphic inducing factor(s) with neural cells within the adhesive papillae on their brachiolar arms. We present evidence supporting Barker's hypothesis using brachiolaria larvae of the two species, Asterina pectinifera and Asterias amurensis. Brachiolaria larvae of these two species underwent metamorphosis in response to pebbles from aquaria in which adults were kept. Time-lapse analysis of A. pectinifera indicated that the pebbles were explored with adhesive papillae prior to establishment of a stable attachment for metamorphosis. Microsurgical dissections, which removed adhesive papillae, resulted in failure of the brachiolaria larvae to respond to the pebbles, but other organs such as the lateral ganglia, the oral ganglion, the adhesive disk or the adult rudiment were not required. Immunohistochemical analysis with a neuron-specific monoclonal antibody and transmission electron microscopy revealed that the adhesive papillae contained neural cells that project their processes towards the external surface of the adhesive papillae and they therefore qualify as sensory neural cells. PMID:17711475

  11. Chorda Tympani Nerve Transection at Different Developmental Ages Produces Differential Effects on Taste Bud Volume and Papillae Morphology in the Rat

    PubMed Central

    Sollars, Suzanne I.

    2016-01-01

    Chorda tympani nerve transection (CTX) results in morphological changes to fungiform papillae and associated taste buds. When transection occurs during neonatal development in the rat, the effects on fungiform taste bud and papillae structure are markedly more severe than observed following a comparable surgery in the adult rat. The present study examined the potential “sensitive period” for morphological modifications to tongue epithelium following CTX. Rats received unilateral transection at 65, 30, 25, 20, 15, 10, or 5 days of age. With each descending age at the time of transection, the effects on the structural integrity of fungiform papillae were more severe. Significant losses in total number of taste buds and filiform-like papillae were observed when transection occurred 5–30 days of age. Significant reduction in the number of taste pores was indicated at every age of transection. Another group of rats received chorda tympani transection at 10, 25, or 65 days of age to determine if the time course of taste bud degeneration differed depending on the age of the rat at the time of transection. Taste bud volumes differed significantly from intact sides of the tongue at 2, 8, and 50 days posttransection after CTX at 65 days of age. Volume measurements did not differ 2 days posttransection after CTX at 10 or 25 days of age, but were significantly reduced at the other time points. Findings demonstrate a transitional period throughout development wherein fungiform papillae are highly dependent upon the chorda tympani for maintenance of morphological integrity. PMID:15898061

  12. Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells.

    PubMed

    Aljuffali, Ibrahim A; Sung, Calvin T; Shen, Feng-Ming; Huang, Chi-Ting; Fang, Jia-You

    2014-01-01

    Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related cells is important in the treatment of alopecia. Here we report the development of "squarticles," nanoparticles formed from sebum-derived lipids such as squalene and fatty esters, for use in achieving targeted drug delivery to the follicles. Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions (NE), were prepared. The physicochemical properties of squarticles, including size, zeta potential, drug encapsulation efficiency, and drug release, were examined. Squarticles were compared to a free control solution with respect to skin absorption, follicular accumulation, and dermal papilla cell targeting. The particle size of the NLC type was 177 nm; that of the NE type was 194 nm. Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles. An improved drug deposition in the skin was observed in the in vitro absorption test. Compared to the free control, the squarticles reduced minoxidil penetration through the skin. This may indicate a minimized absorption into systemic circulation. Follicular uptake by squarticles was 2- and 7-fold higher for DPCP and minoxidil respectively compared to the free control. Fluorescence and confocal images of the skin confirmed a great accumulation of squarticles in the follicles and the deeper skin strata. Vascular endothelial growth factor expression in dermal papilla cells was significantly upregulated after the loading of minoxidil into the squarticles. In vitro papilla cell viability and in vivo skin irritancy tests in nude mice suggested a good tolerability of squarticles to skin. Squarticles provide a promising nanocarrier for topical delivery of DPCP and minoxidil. PMID:24307611

  13. Analysis of Relative Parallelism Between Hamular-Incisive-Papilla Plane and Campers Plane in Edentulous Subjects: A Comparative Study.

    PubMed

    Tambake, Deepti; Shetty, Shilpa; Satish Babu, C L; Fulari, Sangamesh G

    2014-12-01

    The study was undertaken to evaluate the parallelism between hamular-incisive-papilla plane (HIP) and the Campers plane. And to determine which part of the posterior reference of the tragus i.e., the superior, middle or the inferior of the Camper's plane is parallel to HIP using digital lateral cephalograms. Fifty edentulous subjects with well formed ridges were selected for the study. The master casts were obtained using the standard selective pressure impression procedure. On the deepest point of the hamular notches and the centre of the incisive papilla stainless steel spherical bearings were glued to the cast at the marked points. The study templates were fabricated with autopolymerizing acrylic resin. The subjects were prepared for the lateral cephalograms. Stainless steel spherical bearings were adhered to the superior, middle, inferior points of the tragus of the ear and inferior border of the ala of the nose using surgical adhesive tape. The subjects with study templates were subjected to lateral cephalograms. Cephalometric tracings were done using Autocad 2010 software. Lines were drawn connecting the incisive papilla and hamular notch and the stainless steel spherical bearings placed on the superior, middle and inferior points on the tragus and the ala of the nose i.e., the Campers line S, Campers line M, Campers line I. The angles between the three Camper's line and the HIP were measured and recorded. Higher mean angulation was recorded in Campers line S -HIP (8.03) followed by Campers line M-HIP (4.60). Campers line I-HIP recorded the least angulation (3.80). The HIP is parallel to the Camper's plane. The Camper's plane formed with the posterior reference point as inferior point of the tragus is relatively parallel to the HIP. PMID:26199503

  14. Sprouty/FGF signaling regulates the proximal-distal feather morphology and the size of dermal papillae.

    PubMed

    Yue, Zhicao; Jiang, Ting Xin; Wu, Ping; Widelitz, Randall B; Chuong, Cheng Ming

    2012-12-01

    In a feather, there are distinct morphologies along the proximal-distal axis. The proximal part is a cylindrical stalk (calamus), whereas the distal part has barb and barbule branches. Here we focus on what molecular signaling activity can modulate feather stem cells to generate these distinct morphologies. We demonstrate the drastic tissue remodeling during feather cycling which includes initiation, growth and resting phases. In the growth phase, epithelial components undergo progressive changes from the collar growth zone to the ramogenic zone, to maturing barb branches along the proximal-distal axis. Mesenchymal components also undergo progressive changes from the dermal papilla, to the collar mesenchyme, to the pulp along the proximal-distal axis. Over-expression of Spry4, a negative regulator of receptor tyrosine kinases, promotes barb branch formation at the expense of the epidermal collar. It even induces barb branches from the follicle sheath (equivalent to the outer root sheath in hair follicles). The results are feathers with expanded feather vane regions and small or missing proximal feather shafts (the calamus). Spry4 also expands the pulp region while reducing the size of dermal papillae, leading to a failure to regenerate. In contrast, over-expressing Fgf10 increases the size of the dermal papillae, expands collar epithelia and mesenchyme, but also prevents feather branch formation and feather keratin differentiation. These results suggest that coordinated Sprouty/FGF pathway activity at different stages is important to modulate feather epidermal stem cells to form distinct feather morphologies along the proximal-distal feather axis. PMID:23000358

  15. Endoscopic ultrasound-guided pancreaticobiliary intervention in patients with surgically altered anatomy and inaccessible papillae: A review of current literature

    PubMed Central

    Martin, Aaron; Kistler, Charles Andrew; Wrobel, Piotr; Yang, Juliana F.; Siddiqui, Ali A.

    2016-01-01

    The management of pancreaticobiliary disease in patients with surgically altered anatomy is a growing problem for gastroenterologists today. Over the years, endoscopic ultrasound (EUS) has emerged as an important diagnostic and therapeutic modality in the treatment of pancreaticobiliary disease. Patient anatomy has become increasingly complex due to advances in surgical resection of pancreaticobiliary disease and EUS has emerged as the therapy of choice when endoscopic retrograde cholangiopancreatography failed cannulation or when the papilla is inaccessible such as in gastric obstruction or duodenal obstruction. The current article gives a comprehensive review of the current literature for EUS-guided intervention of the pancreaticobiliary tract in patients with altered surgical anatomy. PMID:27386471

  16. Major depression

    MedlinePlus

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... Doctors do not know the exact causes of depression. It is believed that chemical changes in the ...

  17. New species of Trimma (Actinopterygii, Gobiidae) from Indonesia, with comments on head papillae nomenclature.

    PubMed

    Winterbottom, Richard; Erdmann, Mark V

    2015-01-01

    Three new species of the gobiid Trimma are described from Indonesian waters, and a partially reformulated nomenclature for the cephalic sensory papillae of members of this genus is provided. Trimma aturirii possesses two dark oblique stripes on either side of the pupil (blue, edged with red in life, dark brown in preservative), the lower of which continues posteriorly across the dorsal margin of the opercle, with the dorsal half of the body red and the ventral half abruptly white in life. The species has a narrow bony interorbital (≤50% pupil width), a moderate interorbital trench with a slight groove posterodorsal to the eye, no scales on the cheek, opercle or in the predorsal midline, no elongate spines in the first dorsal fin, 9-10 dorsal and 9 anal fin rays, 17-18 (7-11 branched) pectoral fin rays and an unbranched fifth pelvic fin ray. Trimma kardium has a pair of tapering oval red spots which join anteriorly over the anterior region of the hyoid arches, forming an approximate heart-shaped marking on the ventral surface of the head. It has a narrow bony interorbital (≤40% pupil width), a moderate interorbital trench with a slight groove posterodorsal to the eye, 17-18 unbranched pectoral fin rays, 1-5 cycloid scales in the predorsal midline confined to about the middle third of the nape, and a single row of 1-3 cycloid scales along the upper border of the opercle. Trimma trioculatum has a large (slightly greater than pupil diameter in width) round, black, ocellated spot in the first dorsal fin between spines 1 and 5, a second, much smaller black or dark red spot just posterior to the spine of the second dorsal fin and above the basal stripe, a yellow body with a dark purplish or gray head with two distinct red bars across the cheek, no round spots of any colour on the nape, opercle or cheek, a small dark (preserved) or white (alive) spot on the upper pectoral fin base, a narrow bony interorbital (<70% pupil diameter), no elongate spines in the first dorsal

  18. Effects of two different strategies of fluid administration on inflammatory mediators, plasma electrolytes and acid/base disorders in patients undergoing major abdominal surgery: a randomized double blind study

    PubMed Central

    2013-01-01

    Background Administration of normal saline might increase circulating levels of pro-inflammatory cytokines and may cause variation of plasmatic electrolytic and hyperchloremic acidosis, which in turn can impair renal function. Hence the use of balanced solutions could influence the inflammatory cascade triggered by the surgical procedures, the plasmatic electrolyte concentration, the acid–base equilibrium, and the renal function. Methods This is a double blind randomized trial. Forty patients undergoing major abdominal surgery (bowel cancer) were allocated in two groups, the balanced solution (BS) group in which the fluids administered were balanced solutions (colloids and crystalloids); and the unbalanced solution (UBS) group in which the fluids administered were unbalanced solutions (colloids and crystalloids). Measurements were performed after anaesthesia induction (T0), at the end of surgery (T1), within 2 h after surgery (T2) and 24 h after the beginning of surgery (T3). The following data were collected: 1) active matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1), IL-6, IL-8, IL-10; 2) blood gases variables; 3) electrolytes, albumin, total serum protein and the strong ion difference; 4) neutrophil gelatinase-associated lipocalin (NGAL) from urinary sample. Results The BS group exhibited higher circulating level of IL-10 and TIMP-1 and lower level of active MMP-9. The UBS group experienced hypercloremia, hypocalcemia, hypomagnesemia, worse acid–base equilibrium and higher level of NGAL. Conclusions The use of balanced solutions was responsible of less alteration of plasmatic electrolytes, acid–base equilibrium, kidney function and it might be associated with an early anti-inflammatory mechanisms triggering. Trial registration ClinicalTrials.gov (Ref: NCT01320891). PMID:24059479

  19. Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of anxiety symptoms in major depressive disorder: a meta-analysis of individual patient data from 10 double-blind, randomized clinical trials.

    PubMed

    Papakostas, George I; Trivedi, Madhukar H; Alpert, Jonathan E; Seifert, Cheryl A; Krishen, Alok; Goodale, Elizabeth P; Tucker, Vivian L

    2008-01-01

    The goal of this work was to compare the efficacy of the norepinephrine-dopamine reuptake inhibitor bupropion with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of anxiety symptoms in major depressive disorder (MDD). Ten double-blind, randomized studies, involving a total of 2890 bupropion-, SSRI- or placebo- treated patients were pooled. Anxiety symptoms of depression were defined using the Hamilton depression rating scale (HDRS) Anxiety-Somatization factor (HDRS-AS) score, as well as the Hamilton anxiety scale (HAM-A) score. Both bupropion and the SSRIs led to a comparable degree of improvement in anxiety symptoms, defined using the HDRS-AS score (-3.8+/-2.8 vs. -3.9+/-2.8, p=0.130) or HAM-A score (-8.8+/-7.2 vs. -9.1+/-7.0, p=0.177). There was no consistent difference in the time to anxiolysis between the two treatment groups. In addition, there was no difference in the proportion of bupropion- and SSRI- remitters who continued to experience residual anxiety, defined as a HDRS-AS score >0 at endpoint (69.2% vs. 74.7%, p=0.081) or a HAM-A score >7 at endpoint (9.5% vs. 8.4%, p=0.284). Finally, there was no statistically significant difference in the severity of residual anxiety symptoms between bupropion- or SSRI- treated patients with remitted depression, defined using the HDRS-AS (1.15+/-1.14 vs. 1.25+/-1.09, p=0.569), or HAM-A scores at endpoint (3.30+/-2.89 vs. 3.31+/-2.89, p=0.552). Contrary to clinician impression, there does not appear to be any difference in the anxiolytic efficacy of bupropion and the SSRIs when used to treat MDD. PMID:17631898

  20. Evaluation of Proportion between Incisal Edge to Gingival Zenith Distance and Interdental Papilla in Maxillary Anterior Dentition of Indian Population

    PubMed Central

    Damodaran, Anand; Balasubramanium, Muthukumar

    2016-01-01

    Introduction Not many investigations have evaluated the relationship between the height of the interdental papillae, gingival zenith and maxillary anterior teeth. The assessment of these parameters can aid in fabricating definitive aesthetic restoration. Aim The aim of this study was to evaluate the existence of proportional ratio between the incisal edge to gingival zenith (HGZ) and the tip of the interdental papilla (HIP) in maxillary anterior teeth for Indian population. Materials and Methods One hundred healthy volunteers with an average age of 25-30 years comprised the evaluation group. Impression was made using irreversible hydrocolloid impression material and type IV Dental stone cast was made. A calibrated digital caliper measured the distance between HGZ and HIP. The values for all six maxillary teeth were recorded and the proportional ratio was evaluated and statistically analysed. Results The mean ratio between HGZ and HIP of all maxillary anteriors in 1st and 2nd quadrant was 1.80, 1.71, and 2.03 in central incisor, lateral incisor and canine respectively with p-value > 0.9. Conclusion The mean proportional measurements for maxillary anterior teeth were determined and no definitive proportion existed between HGZ and HIP of maxillary anterior teeth. PMID:27134999

  1. Immortalized Mouse Floxed Bmp2 Dental Papilla Mesenchymal Cell Lines Preserve Odontoblastic Phenotype and Respond to BMP2

    PubMed Central

    WU, LI-AN; FENG, JUNSHENG; WANG, LYNN; MU, YAN-DONG; BAKER, ANDREW; DONLY, KEVIN J; GLUHAK-HEINRICH, JELICA; HARRIS, STEPHEN E; MACDOUGALL, MARY; CHEN, SHUO

    2010-01-01

    Bone morphogenetic protein 2 (Bmp2) is essential for odontogensis and dentin mineralization. Generation of floxed Bmp2 dental mesenchymal cell lines is a valuable application for studying the effects of Bmp2 on dental mesenchymal cell differentiation and its signaling pathways during dentinogenesis. Limitation of the primary culture of dental mesenchymal cells has led to the development of cell lines that serve as good surrogate models for the study of dental mesenchymal cell differentiation into odontoblasts and mineralization. In this study, we established and characterized immortalized mouse floxed Bmp2 dental papilla mesenchymal cell lines, which were isolated from 1st mouse mandibular molars at postnatal day 1 and immortalized with pSV40 and clonally selected. These transfected cell lines were characterized by RT-PCR, immunohistochemistry, and analyzed for alkaline phosphatase activity and mineralization nodule formation. One of these immortalized cell lines, iBmp2-dp, displayed a higher proliferation rate, but retained the genotypic and phenotypic characteristics similar to primary cells as determined by expression of tooth-specific markers as well as demonstrated the ability to differentiate and form mineralized nodules. In addition, iBmp2-dp cells were inducible and responded to BMP2 stimulation. Thus, we for the first time described the establishment of an immortalized mouse floxed Bmp2 dental papilla mesenchyma cell line that might be used for studying the mechanisms of dental cell differentiation and dentin mineralization mediated by Bmp2 and other growth factor signaling pathways. PMID:20458728

  2. Short-Term Biliary Stent Placement Contributing Common Bile Duct Stone Disappearance with Preservation of Duodenal Papilla Function

    PubMed Central

    Kodama, Yuzo; Kurokami, Takafumi

    2016-01-01

    Aims. To investigate the effect of biliary stent placement without endoscopic sphincterotomy (EST) on common bile duct stones (CBDS) disappearance and the contribution of preserving the duodenal papilla function to reduce recurrence of CBDS. Methods. Sixty-six patients admitted for acute obstructive cholangitis due to CBDS who underwent biliary stent placement without EST for 2 years from March 2011 were evaluated retrospectively. The second endoscopic retrograde cholangiopancreatography (ERCP) was performed for treatment of CBDS 3 to 4 months after the first ERCP. We estimated the rate of stone disappearance at the time of second ERCP. Results. CBDS disappearance was observed in 32 (48.5%) of 66 patients. The diameter of the bile ducts and the diameter of CBDS in patients with CBDS disappearance were significantly smaller than in those with CBDS requiring extraction (p = 0.007 and p < 0.001, resp.). Stone disappearance was evident when the diameter of bile ducts and that of CBDS were <10 and 7 mm, respectively (p = 0.002). Conclusions. Short-term stent placement without EST eliminates CBDS while preserving duodenal papilla function and may be suitable for treating CBDS in patients with nondilated bile ducts and small CBDS. PMID:27247568

  3. Late-onset hereditary ataxia with global thermoanalgesia and absence of fungiform papillae on the tongue in a Japanese family.

    PubMed

    Fukutake, T; Kita, K; Sakakibara, R; Takagi, K; Tokumaru, Y; Kojima, S; Hattori, T; Hirayama, K

    1996-06-01

    Two Japanese male siblings, aged 68 and 59 years, affected by late-onset progressive ataxia distinguished by extensive sensory and mild autonomic disturbances are described. They had global thermoanalgesia, positive Romberg signs, sensorineural deafness, canal paresis and ageusia. Their autonomic disturbances consisted of absence of overflow tears with usual stimuli, dysphagia, blood pressure and vasomotor instability, diarrhoea/constipation, and urinary frequency. Sensory nerve action potentials were completely absent, whereas motor conduction velocity was slightly reduced only in the lower extremities. Sural nerve biopsy on the younger brother demonstrated a marked loss of myelinated fibres and a reduction in the number of unmyelinated axons. Tongue histology revealed absence of fungiform papillae and taste buds. Autonomic function tests showed widespread but mild sympathetic and parasympathetic failures. Neuro-imaging studies revealed atrophy of the spinal cord, cerebellum, brainstem and corpus callosum, and enlargement of the lateral, third and fourth ventricles. These siblings represent a previously unrecognized variant of late-onset hereditary spinocerebellar degeneration with global thermoanalgesia and absence of fungiform papillae on the tongue. PMID:8673478

  4. Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia.

    PubMed

    Chew, Elaine G Y; Tan, Joanna H J; Bahta, Adiam W; Ho, Bryan S-Y; Liu, Xingliang; Lim, Tze Chiun; Sia, Yee Yen; Bigliardi, Paul L; Heilmann, Stefanie; Wan, Andrew C A; Nöthen, Markus M; Philpott, Michael P; Hillmer, Axel M

    2016-08-01

    Androgenetic alopecia (AGA) is a common heritable and androgen-dependent hair loss condition in men. Twelve genetic risk loci are known to date, but it is unclear which genes at these loci are relevant for AGA. Dermal papilla cells (DPCs) located in the hair bulb are the main site of androgen activity in the hair follicle. Widely used monolayer-cultured primary DPCs in hair-related studies often lack dermal papilla characteristics. In contrast, immortalized DPCs have high resemblance to intact dermal papilla. We derived immortalized human DPC lines from balding (BAB) and non-balding (BAN) scalp. Both BAB and BAN retained high proportions of dermal papilla signature gene and versican protein expression. We performed expression analysis of BAB and BAN and annotated AGA risk loci with differentially expressed genes. We found evidence for AR but not EDA2R as the candidate gene at the AGA risk locus on chromosome X. Further, our data suggest TWIST1 (twist family basic helix-loop-helix transcription factor 1) and SSPN (sarcospan) to be the functionally relevant AGA genes at the 7p21.1 and 12p12.1 risk loci, respectively. Down-regulated genes in BAB compared to BAN were highly enriched for vasculature-related genes, suggesting that deficiency of DPC from balding scalps in fostering vascularization around the hair follicle may contribute to the development of AGA. PMID:27060448

  5. Papillaes-enhanced hydrophobicity of large-sized polytetrafluoroethylene-polyphenylene sulfite soft film prepared by layer-by-layer construction

    NASA Astrophysics Data System (ADS)

    Hou, Cheng Cheng; Wang, Wen Jun; Zhang, Yu; Guan, Zi Sheng

    2012-07-01

    Large-sized superhydrophobic soft film with hierarchical structures were prepared by combining papillaes on the polytetrafluoroethylene-polyphenylene sulfite (PTFE-PPS) surface via layer-by-layer construction on the glass substrate and heat treatment processes, therein, the papillaes were formed by 0.1 μm PTFE coated on the pollen grains. The water contact angles (CAs) and sliding angles (SAs) of the films are strongly dependent on the number density of the papillaes on the PTFE-PPS surface. A superhydrophobic surface with a water CA = 151.5° and SA = 4° was obtained when the number density was about 649 mm-2. The papillaes with micro/submicroscale structures play an important role in the formation of the superhydrophobic surface and can change Wenzel-type surface into Cassie-Baxter-type surface. The condensation of water vapor on the Cassie-Baxter-type PTFE-PPS film is much more difficult than that of on the Wenzel-type film. Our method may develop into a facile method to prepare large-sized soft film with low cost, which limited only by the size of the loading substrates.

  6. Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles.

    PubMed

    Inui, Shigeki; Fukuzato, Yoko; Nakajima, Takeshi; Kurata, Sotaro; Itami, Satoshi

    2007-10-01

    Androgen site-specifically affects human hair growth after puberty through androgen receptors in the dermal papilla, which transactivate target genes acting in conjunction with co-activators. To examine the regulation of androgen sensitivity in hair follicles, we focused on androgen receptor co-activator Hic-5/ARA55. Its interaction with transfected androgen receptor in beard dermal papilla cells was confirmed with mammalian two-hybrid assays. The semiquantitative reverse transcriptase-polymerase chain reaction showed that Hic-5/ARA55 mRNA expression was high in dermal papilla cells from the beard and bald frontal scalp but low in cells from the occipital scalp. To determine whether Hic-5/ARA55 mRNA level correlates with its endogenous activity, we studied the effect of dominant negative Hic-5/ARA55 on transfected androgen receptor transactivation induced by R1881 using mouse mammary tumor virus-luciferase assays. We found that it suppressed the transactivation by 64.5 and 71.4% in dermal papilla cells from the beard and bald frontal scalp, respectively, whereas it showed no significant effect in cells from the occipital scalp. Our findings suggest that Hic-5/ARA55 is a molecular regulator for androgen sensitivity in human hair follicles. PMID:17508020

  7. Secretory activity is rapidly induced in stigmatic papillae by compatible pollen, but inhibited for self-incompatible pollen in the Brassicaceae.

    PubMed

    Safavian, Darya; Goring, Daphne R

    2013-01-01

    [In the Brassicaceae, targeted exocytosis to the stigmatic papillar plasma membrane under the compatible pollen grain is hypothesized to be essential for pollen hydration and pollen tube penetration. In contrast, polarized secretion is proposed to be inhibited in the stigmatic papillae during the rejection of self-incompatible pollen. Using transmission electron microscopy (TEM), we performed a detailed time-course of post-pollination events to view the cytological responses of the stigmatic papillae to compatible and self-incompatible pollinations. For compatible pollinations in Arabidopsis thaliana and Arabidopsis lyrata, vesicle secretion was observed at the stigmatic papillar plasma membrane under the pollen grain while Brassica napus stigmatic papillae appeared to use multivesicular bodies (MVBs) for secretion. Exo70A1, a component of the exocyst complex, has been previously implicated in the compatible pollen responses, and disruption of Exo70A1 in both A. thaliana and B. napus resulted in a loss of secretory vesicles/MVBs at the stigmatic papillar plasma membrane. Similarly, for self-incompatible pollinations, secretory vesicles/MVBs were absent from the stigmatic papillar plasma membrane in A. lyrata and B. napus; and furthermore, autophagy appeared to be induced to direct vesicles/MVBs to the vacuole for degradation. Thus, these findings support a model where the basal pollen recognition pathway in the stigmatic papilla promotes exocytosis to accept compatible pollen, and the basal pollen recognition pathway is overridden by the self-incompatibility pathway to prevent exocytosis and reject self-pollen. PMID:24386363

  8. Secretory Activity Is Rapidly Induced in Stigmatic Papillae by Compatible Pollen, but Inhibited for Self-Incompatible Pollen in the Brassicaceae

    PubMed Central

    Safavian, Darya; Goring, Daphne R.

    2013-01-01

    [In the Brassicaceae, targeted exocytosis to the stigmatic papillar plasma membrane under the compatible pollen grain is hypothesized to be essential for pollen hydration and pollen tube penetration. In contrast, polarized secretion is proposed to be inhibited in the stigmatic papillae during the rejection of self-incompatible pollen. Using transmission electron microscopy (TEM), we performed a detailed time-course of post-pollination events to view the cytological responses of the stigmatic papillae to compatible and self-incompatible pollinations. For compatible pollinations in Arabidopsis thaliana and Arabidopsis lyrata, vesicle secretion was observed at the stigmatic papillar plasma membrane under the pollen grain while Brassica napus stigmatic papillae appeared to use multivesicular bodies (MVBs) for secretion. Exo70A1, a component of the exocyst complex, has been previously implicated in the compatible pollen responses, and disruption of Exo70A1 in both A. thaliana and B. napus resulted in a loss of secretory vesicles/MVBs at the stigmatic papillar plasma membrane. Similarly, for self-incompatible pollinations, secretory vesicles/MVBs were absent from the stigmatic papillar plasma membrane in A. lyrata and B. napus; and furthermore, autophagy appeared to be induced to direct vesicles/MVBs to the vacuole for degradation. Thus, these findings support a model where the basal pollen recognition pathway in the stigmatic papilla promotes exocytosis to accept compatible pollen, and the basal pollen recognition pathway is overridden by the self-incompatibility pathway to prevent exocytosis and reject self-pollen. PMID:24386363

  9. Genetic tracing of the gustatory neural pathway originating from Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae

    PubMed Central

    Yamamoto, Kurumi; Ishimaru, Yoshiro; Ohmoto, Makoto; Matsumoto, Ichiro; Asakura, Tomiko; Abe, Keiko

    2011-01-01

    Polycystic kidney disease 1-like 3 (Pkd1l3) is expressed specifically in sour-sensing type III taste cells that have synaptic contacts with afferent nerve fibers in circumvallate and foliate papillae located in the posterior region of the tongue, though not in fungiform papillae or the palate. To visualize the gustatory neural pathways that originate from type III taste cells in circumvallate and foliate papillae, we established transgenic mouse lines that express the transneuronal tracer wheat germ agglutinin (WGA) under the control of the mouse Pkd1l3 gene promoter/enhancer. The WGA transgene was accurately expressed in Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae. Punctate WGA protein signals appeared to be detected specifically in type III taste cells but not in other types of taste cells. WGA protein was transferred primarily to a subset of neurons located in close proximity to the glossopharyngeal nerve bundles in the nodose/petrosal ganglion. WGA signals were also observed in a small population of neurons in the geniculate ganglion. This result demonstrates the anatomical connection between taste receptor cells in the foliate papillae and the chorda tympani nerves. WGA protein was further conveyed to neurons in a rostro-central subdivision of the nucleus of the solitary tract. These findings demonstrate that the approximately 10 kb 5’-flanking region of the mouse Pkd1l3 gene functions as a type III taste cell-specific promoter/enhancer. In addition, experiments using the pkd1l3-WGA transgenic mice reveal a sour gustatory pathway that originates from taste receptor cells in the posterior region of the tongue. PMID:21883212

  10. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis

    PubMed Central

    Wu, Lian; Wang, Feng; Donly, Kevin J.; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E.; Macdougall, Mary; Chen, Shuo

    2016-01-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2ko/ko dp) cell line by introducing Cre fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2fx/fx dp) cells. iBmp2ko/ko dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2ko/ko dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmpko/ko cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  11. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.

    PubMed

    Wu, Lian; Wang, Feng; Donly, Kevin J; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-11-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  12. Hair follicle dermal stem cells regenerate the dermal sheath, repopulate the dermal papilla, and modulate hair type.

    PubMed

    Rahmani, Waleed; Abbasi, Sepideh; Hagner, Andrew; Raharjo, Eko; Kumar, Ranjan; Hotta, Akitsu; Magness, Scott; Metzger, Daniel; Biernaskie, Jeff

    2014-12-01

    The dermal papilla (DP) provide instructive signals required to activate epithelial progenitors and initiate hair follicle regeneration. DP cell numbers fluctuate over the hair cycle, and hair loss is associated with gradual depletion/atrophy of DP cells. How DP cell numbers are maintained in healthy follicles remains unclear. We performed in vivo fate mapping of adult hair follicle dermal sheath (DS) cells to determine their lineage relationship with DP and found that a subset of DS cells are retained following each hair cycle, exhibit self-renewal, and repopulate the DS and the DP with new cells. Ablating these hair follicle dermal stem cells and their progeny retarded hair regrowth and altered hair type specification, suggesting that they function to modulate normal DP function. This work identifies a bipotent stem cell within the adult hair follicle mesenchyme and has important implications toward restoration of hair growth after injury, disease, and aging. PMID:25465495

  13. The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle.

    PubMed

    Morgan, Bruce A

    2014-07-01

    The dermal papilla (DP) of the hair follicle is both a chemical and physical niche for epithelial progenitor cells that regenerate the cycling portion of the hair follicle and generate the hair shaft. Here, we review experiments that revealed the importance of the DP in regulating the characteristics of the hair shaft and frequency of hair follicle regeneration. More recent work showed that the size of this niche is dynamic and actively regulated and reduction in DP cell number per follicle is sufficient to cause hair thinning and loss. The formation of the DP during follicle neogenesis provides a context to contemplate the mechanisms that maintain DP size and the potential to exploit these processes for hair preservation or restoration. PMID:24985131

  14. The Dermal Papilla: An Instructive Niche for Epithelial Stem and Progenitor Cells in Development and Regeneration of the Hair Follicle

    PubMed Central

    Morgan, Bruce A.

    2014-01-01

    The dermal papilla (DP) of the hair follicle is both a chemical and physical niche for epithelial progenitor cells that regenerate the cycling portion of the hair follicle and generate the hair shaft. Here, we review experiments that revealed the importance of the DP in regulating the characteristics of the hair shaft and frequency of hair follicle regeneration. More recent work showed that the size of this niche is dynamic and actively regulated and reduction in DP cell number per follicle is sufficient to cause hair thinning and loss. The formation of the DP during follicle neogenesis provides a context to contemplate the mechanisms that maintain DP size and the potential to exploit these processes for hair preservation or restoration. PMID:24985131

  15. An 8-Week Randomized, Double-Blind Trial Comparing Efficacy, Safety, and Tolerability of 3 Vilazodone Dose-Initiation Strategies Following Switch From SSRIs and SNRIs in Major Depressive Disorder

    PubMed Central

    Rele, Shilpa; Millet, Robert; Kim, Sungman; Paik, Jong-Woo; Kim, Seonghwan; Masand, Prakash S.

    2015-01-01

    Introduction: Vilazodone, a selective and potent 5-HT1A partial agonist and 5-HT reuptake inhibitor, has been approved for treatment of major depressive disorder (MDD) in adults. The primary objective of the study was to compare the efficacy and tolerability of switching to 3 different doses of vilazodone from an equivalent dose range of generic selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in adult subjects with MDD. Method: This was an 8-week, randomized, double-blind, parallel-group, 3-arm trial to compare vilazodone 10 mg/d, 20 mg/d, and 40 mg/d as starting doses. Data were collected from December 2012 to December 2013. There was no washout phase, prior medications were stopped at the baseline visit, and vilazodone was started the next day in adults with MDD (DSM-IV criteria). The 10-mg/d and 20-mg/d dose was increased to 40 mg/d by week 3 and week 1, respectively, and the 40-mg/d initiation dose continued unchanged. The primary efficacy measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score between the 3 dose groups. The secondary efficacy measures were changes in Clinical Global Impressions–Severity (CGI-S), CGI-Improvement (CGI-I), and Hamilton Anxiety Rating Scale (HARS) scores. Safety measures were obtained by spontaneously reported adverse events, vital signs recording, and laboratory tests. Multivariate tests were used for statistical analysis. Results: Seventy subjects were randomized, and 60 subjects completed the study (n = 20 in each group). Overall, there was a significant reduction in MADRS score from baseline (26.08 ± 1.1) to week 8 (9.86 ± 1.2) in the entire sample (P < .001). Similarly, there was a significant improvement in CGI-S (P < .001), CGI-I (P < .001) and HDRS (P < .001) scores from baseline to the end of the trial. There were no significant differences between the 3 vilazodone dose-initiation groups in changes in MADRS scores (P = .95) or changes in CGI

  16. Major Links.

    ERIC Educational Resources Information Center

    Henderson, Tona

    1995-01-01

    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  17. Major depression.

    PubMed

    Bentley, Susan M; Pagalilauan, Genevieve L; Simpson, Scott A

    2014-09-01

    Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co-morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered. PMID:25134869

  18. The Gustin (CA6) Gene Polymorphism, rs2274333 (A/G), as a Mechanistic Link between PROP Tasting and Fungiform Taste Papilla Density and Maintenance

    PubMed Central

    Melis, Melania; Atzori, Elena; Cabras, Stefano; Zonza, Andrea; Calò, Carla; Muroni, Patrizia; Nieddu, Mariella; Padiglia, Alessandra; Sogos, Valeria; Tepper, Beverly J.; Tomassini Barbarossa, Iole

    2013-01-01

    Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli. PMID:24040192

  19. Major Andre

    ERIC Educational Resources Information Center

    Henisch, B. A.; Henisch, H. K.

    1976-01-01

    If most Revolutionary era people seem two-dimensional their lives simpler to understand than ours, it may be only that history, with the benefit of hindsight, clarifies. Examines a profile of Major John Andre, the British liaison officer in Benedict Arnold's plan to surrender West Point, as both hero and villain to show the complexity of early…

  20. Morphological adaptation of rumen papillae during the dry period and early lactation as affected by rate of increase of concentrate allowance.

    PubMed

    Dieho, K; Bannink, A; Geurts, I A L; Schonewille, J T; Gort, G; Dijkstra, J

    2016-03-01

    Knowledge of the morphological adaptation of rumen papilla, which plays an important role in volatile fatty acid absorption, in dry and early lactation dairy cattle is limited. Therefore, macro- and microscopic changes in papilla morphology during the dry period and lactation and the effect of rate of increase of concentrate allowance were studied. Samples were collected from 12 rumen-cannulated Holstein Friesian dairy cows during a pretreatment period, 50, 30, and 10 d antepartum (the dry period) and 3 d postpartum (pp), and a treatment period, 9, 16, 30, 44, 60, and 80 d pp. Cows had free access to either a dry period ration [27% grass silage, 27% corn silage, 35% wheat straw, and 11% soybean meal on a dry matter (DM) basis] or a basal lactation ration (42% grass silage, 41% corn silage, and 17% soybean meal on a DM basis, and 0.9 kg of DM/d concentrate). Treatment consisted of either a rapid (1.0 kg of DM/d; RAP; n=6) or gradual (0.25 kg of DM/d; GRAD; n=6) increase of concentrate allowance (up to 10.9 kg of DM/d), starting at d 4 pp, aimed at creating a contrast in rumen-fermentable organic matter (FOM) intake. Papillae were collected from the ventral, ventral blind, and dorsal blind rumen sacs and measured digitally. Intake of DM (11.9 kg/d) and FOM (5.7 kg/d) did not change during the pretreatment period, but increased during the treatment period to 24.5 and 15.0 kg/d at 80 d pp, respectively. Concentrate treatment and sampling day interacted for FOM intake, which was 22% greater in RAP at 16 d pp compared with GRAD. Papilla surface area decreased during the pretreatment period by 19% to 28.0mm(2) at 3 d pp, thereafter increasing to 63.0mm(2) at 80 d pp. Concentrate treatment and sampling day interacted for surface area, which was greater in RAP compared with GRAD at 16 (46.0 vs. 33.2mm(2)), 30 (55.4 vs. 41.2mm(2)), and 44 (60.5 vs. 49.7 mm(2)) days pp, showing that papillae can respond to a rapid rate of increase of FOM intake by increasing growth rate

  1. Parameters of hormonal regulation of fluid-electrolyte exchange and camp reception in the rat renal papilla during adaptation to cold

    SciTech Connect

    Selyatitskaya, V.G.; Ivanova, L.N.; Shorin, Y.P.; Solenov, E.I.

    1986-03-01

    The authors study the intracellular reaction of cAMP, which is an important functional component of the action of antidiuretic hormone (ADH) in target tissues, in the renal papilla. The aldosterone concentration of the rats' urine was determined by radioimmunoassay. The experiments showed that specific binding of /sup 3/H-cAMP in the cytosol of the renal papilla in animals adapted to cold was 3.2 +/- 0.6 femtomoles/kg protein. A decrease in the concentration of hormones participating in the regulation of fluid-electrolyte exchange was discovered in these experiments. A significant fall in the ADH concentration was observed in the blood plasma of the experimental animals.

  2. Coculture of Stem Cells from Apical Papilla and Human Umbilical Vein Endothelial Cell Under Hypoxia Increases the Formation of Three-Dimensional Vessel-Like Structures in Vitro

    PubMed Central

    Yuan, Changyong; Wang, Penglai; Zhu, Lifang; Dissanayaka, Waruna Lakmal; Green, David William; Tong, Edith H.Y.; Jin, Lijian

    2015-01-01

    The success of bioengineered dental pulp depends on two principles, (1) whether the transplanted tissue can develop its own vascular endothelial tubule network and (2) whether the host vasculature can be induced to penetrate the bioengineered pulp replacement and conjoin. Major inductive molecules that participate in laying down blood vessels include vascular endothelial growth factor (VEGF), ephrinB2, and hypoxia-inducible factor 1α (HIF-1α). Being able to modulate the genes encoding these angiogenic molecules is a therapeutic target in pulp regeneration for endogenous blood vessel formation, prevention of graft rejection, and exclusion of infection. Once implanted inside the root canal, bioengineered pulp is subjected to severe hypoxia that causes tissue degeneration. However, short-term hypoxia is known to stimulate angiogenesis. Thus, it may be feasible to prime dental cells for angiogenic activity before implantation. Stem cells from apical papilla (SCAP) are arguably one of the most potent and versatile dental stem cell populations for bioengineering pulp in vitro. Our study aimed to investigate whether coculture of SCAP and human umbilical vein endothelial cells (HUVECs) under hypoxia promotes the formation of endothelial tubules and a blood vessel network. In addition, we clarified the interplay between the genes that orchestrate these important angiogenic molecules in SCAP under hypoxic conditions. We found that SCAP cocultured with HUVEC at a 1:5 ratio increased the number of endothelial tubules, tubule lengths, and branching points. Fluorescence staining showed that HUVEC formed the trunk of tubular structures, whereas SCAP located adjacent to the endothelial cell line, resembling the pericyte location. When we used CoCl2 (0.5 mM) to induce hypoxic environment, the expression of proteins, HIF-1α and VEGF, and transcript of ephrinB2 in SCAP was upregulated. However, minimal VEGF levels in supernatants of HUVEC and coculture Petri dishes were detected

  3. Proteomics demonstration that histone H4 is a colchicine-induced retro-modulator of growth and alkaline phosphatase activity in hair follicle dermal papilla culture.

    PubMed

    Hsia, Ching-Wu; Shui, Hao-Ai; Wang, Chih-Yuan; Yu, Hui-Ming; Ho, Ming-Yi; Cheng, Kur-Ta; Tseng, Min-Jen

    2011-05-16

    Dermal papilla cells (DPCs) control the development of hair follicles via cell-cell interactions and extracellular molecules. Colchicine affected active anagen DPCs to result in hair loss in the clinical setting. The purpose of this study was to identify the retro-modulator released by DPCs exposed to sub-toxic dose of colchicine and elucidate its effect on dermal papilla culture. The molecular-weight cutoff ultrafiltration and HPLC were used to purify the components of colchicine-treated DPC secretomes and examined their ability to down-regulate the growth and alkaline phosphatase (ALP) activity of DPCs. The active product was identified by in-gel trypsin digestion, nano-LC-ESI-MS/MS and validated by Western blot to be histone H4 (P62804), which inhibited the proliferation and diminished the ALP activity of cultured DPCs. Treating DPCs with recombinant histone H4 reproduced the growth inhibition effect whereas adding antibody to immunoneutralize histone H4 abolished this growth inhibitory consequence. DPCs with high ALP activity can induce the neogenesis of hair follicles and support the hair fiber growth in vivo. Our results indicated that sub-lethal colchicine can inactivate DPCs through releasing histone H4. Through the investigation of the retro-modulation of histone H4 on dermal papillae may give implications for understanding the mechanism of colchicine-induced hair disorder. PMID:21362507

  4. Double Layers in Astrophysics

    NASA Technical Reports Server (NTRS)

    Williams, Alton C. (Editor); Moorehead, Tauna W. (Editor)

    1987-01-01

    Topics addressed include: laboratory double layers; ion-acoustic double layers; pumping potential wells; ion phase-space vortices; weak double layers; electric fields and double layers in plasmas; auroral double layers; double layer formation in a plasma; beamed emission from gamma-ray burst source; double layers and extragalactic jets; and electric potential between plasma sheet clouds.

  5. STAT5 Activation in the Dermal Papilla Is Important for Hair Follicle Growth Phase Induction.

    PubMed

    Legrand, Julien M D; Roy, Edwige; Ellis, Jonathan J; Francois, Mathias; Brooks, Andrew J; Khosrotehrani, Kiarash

    2016-09-01

    Hair follicles are skin appendages that undergo periods of growth (anagen), regression (catagen), and rest (telogen) regulated by their mesenchymal component, the dermal papilla (DP). On the basis of the reports of its specific expression in the DP, we investigated signal transducer and activator of transcription (STAT5) activation during hair development and cycling. STAT5 activation in the DP began in late catagen, reaching a peak in early anagen before disappearing for the rest of the cycle. This was confirmed by the expression profile of suppressor of cytokine signaling 2, a STAT5 target in the DP. This pattern of expression starts after the first postnatal hair cycle. Quantification of hair cycling using the Flash canonical Wnt signaling in vivo bioluminescence reporter found that conditional knockout of STAT5A/B in the DP targeted through Cre-recombinase under the control of the Sox18 promoter resulted in delayed anagen entry compared with control. Microarray analysis of STAT5 deletion versus control revealed key changes in tumor necrosis factor-α, Wnt, and fibroblast growth factor ligands, known for their role in inducing anagen entry. We conclude that STAT5 activation acts as a mesenchymal switch to trigger natural anagen entry in postdevelopmental hair follicle cycling. PMID:27131881

  6. Nuclear Factor I-C promotes proliferation and differentiation of apical papilla-derived human stem cells in vitro

    SciTech Connect

    Zhang, Jing; Wang, Zhihua; Jiang, Yong; Niu, Zhongying; Fu, Lei; Luo, Zhirong; Cooper, Paul R.; Smith, Anthony J.; He, Wenxi

    2015-03-15

    The transcription factor Nuclear Factor I-C (NFIC) has been implicated in the regulation of tooth root development, where it may be anticipated to impact on the behavior of stem cells from the apical papilla (SCAPs) and root odontoblast activity. We hypothesized that NFIC may provide an important target for promoting dentin/root regeneration. In the present study, the effects of NFIC on the proliferation and differentiation of SCAPs were investigated. Over-expression of NFIC increased cell proliferation, mineralization nodule formation and alkaline phosphatase (ALP) activity in SCAPs. Furthermore, NFIC up-regulated the mRNA levels of odontogenic-related markers, ALP, osteocalcin and collagen type I as well as dentin sialoprotein protein levels. In contrast, knockdown of NFIC by si-RNA inhibited the mineralization capacity of SCAPs and down-regulated the expression of odontogenic-related markers. In conclusion, the results indicated that upregulation of NFIC activity in SCAPs may promote osteo/odontoblastic differentiation of SCAPs. - Highlights: • NFIC promotes the proliferation of SCAPs in vitro. • NFIC promotes osteo/odontogenic differentiation of SCAPs in vitro. • Knockdown of NFIC inhibits odontogenic differentiation in SCAPs.

  7. Bone Morphogenetic Protein-9 Effectively Induces Osteo/Odontoblastic Differentiation of the Reversibly Immortalized Stem Cells of Dental Apical Papilla

    PubMed Central

    Wang, Jinhua; Zhang, Hongmei; Zhang, Wenwen; Huang, Enyi; Wang, Ning; Wu, Ningning; Wen, Sheng; Chen, Xian; Liao, Zhan; Deng, Fang; Yin, Liangjun; Zhang, Junhui; Zhang, Qian; Yan, Zhengjian; Liu, Wei; Zhang, Zhonglin; Ye, Jixing; Deng, Youlin; Luu, Hue H.; Haydon, Rex C.

    2014-01-01

    Dental pulp/dentin regeneration using dental stem cells combined with odontogenic factors may offer great promise to treat and/or prevent premature tooth loss. We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing bone formation. Here, we investigate whether BMP9 can effectively induce odontogenic differentiation of the stem cells from mouse apical papilla (SCAPs). Using a reversible immortalization system expressing SV40 T flanked with Cre/loxP sites, we demonstrate that the SCAPs can be immortalized, resulting in immortalized SCAPs (iSCAPs) that express mesenchymal stem cell markers. BMP9 upregulates Runx2, Sox9, and PPARγ2 and odontoblastic markers, and induces alkaline phosphatase activity and matrix mineralization in the iSCAPs. Cre-mediated removal of SV40 T antigen decreases iSCAP proliferation. The in vivo stem cell implantation studies indicate that iSCAPs can differentiate into bone, cartilage, and, to lesser extent, adipocytes upon BMP9 stimulation. Our results demonstrate that the conditionally iSCAPs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages, including osteo/odontoblastic differentiation. Thus, the reversibly iSCAPs may serve as an important tool to study SCAP biology and SCAP translational use in tooth engineering. Further, BMP9 may be explored as a novel and efficacious factor for odontogenic regeneration. PMID:24517722

  8. NOTCH3 is expressed in human apical papilla and in subpopulations of stem cells isolated from the tissue

    PubMed Central

    Jamal, Mohamed; Chogle, Sami M.; Karam, Sherif M.; Huang, George T.-J.

    2015-01-01

    NOTCH plays a role in regulating stem cell function and fate decision. It is involved in tooth development and injury repair. Information regarding NOTCH expression in human dental root apical papilla (AP) and its residing stem cells (SCAP) is limited. Here we investigated the expression of NOTCH3, its ligand JAG1, and mesenchymal stem cell markers CD146 and STRO-1 in the AP or in the primary cultures of SCAP isolated from AP. Our in situ immunostaining showed that in the AP NOTCH3 and CD146 were co-expressed and associated with blood vessels having NOTCH3 located more peripherally. In cultured SCAP, NOTCH3 and JAG1 were co-expressed. Flow cytometry analysis showed that 7%, 16% and 98% of the isolated SCAP were positive for NOTCH3, STRO-1 and CD146, respectively with a rare 1.5% subpopulation of SCAP co-expressing all three markers. The expression level of NOTCH3 reduced when SCAP underwent osteogenic differentiation. Our findings are the first step towards defining the regulatory role of NOTCH3 in SCAP fate decision. PMID:26989760

  9. Baicalin, a flavonoid, affects the activity of human dermal papilla cells and promotes anagen induction in mice.

    PubMed

    Shin, Seung Hyun; Bak, Soon-Sun; Kim, Moon Kyu; Sung, Young Kwan; Kim, Jung Chul

    2015-05-01

    Baicalin, a flavonoid isolated from Scutellaria baicalensis, is known to have multiple biological functions. Recent studies have demonstrated that baicalin treatment increases alkaline phosphatase activity (ALP) and osteoprotegerin secretion by osteoblasts. Furthermore, baicalin induces the differentiation of cultured osteoblasts via the activation of the Wnt/β-catenin signaling pathway. In this study, we evaluated the hair growth-promoting effects of baicalin in human follicular dermal papilla (DP) cells. A reporter assay and Western blotting were used to assess the effect of baicalin on β-catenin signaling in DP cells. ALP activity and messenger RNA (mRNA) expression were examined by ALP staining and real-time polymerase chain reaction (PCR), respectively. Growth factor expression levels were also evaluated using real-time PCR. Finally, the effect of baicalin on hair growth in vivo was examined by topical application of baicalin on the shaved dorsal skin of C57BL/6 mice. Our results indicate that baicalin activates Wnt/β-catenin signaling in a dose-dependent manner in human DP cells. ALP mRNA expression and activity were significantly induced in the presence of baicalin. In addition, treatment with baicalin induced the mRNA expression of growth factors, such as insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). Moreover, compared to vehicle treatment, baicalin treatment induced an earlier conversion from telogen to anagen. Our results strongly suggest that baicalin promotes hair growth by regulating the activity of DP cells. PMID:25434532

  10. Scalable production of controllable dermal papilla spheroids on PVA surfaces and the effects of spheroid size on hair follicle regeneration.

    PubMed

    Huang, Yi-Ching; Chan, Chih-Chieh; Lin, Wei-Ting; Chiu, Hsien-Yi; Tsai, Ren-Yeu; Tsai, Tsung-Hua; Chan, Jung-Yi; Lin, Sung-Jan

    2013-01-01

    Organ size and numbers are vital issues in bioengineering for hair follicle (HF) regeneration. Murine HF dermal papilla (DP) cells are able to induce HF neogenesis when transplanted as aggregates. However, how the preparation of murine and human DP aggregates affects HF inductivity and the size of regenerated HF is yet to be determined. Here we report a scalable method for production of controllable human and rat DP spheroids in general labs for reproducible experiments. Compared with more hydrophobic polyethylene and poly(ethylene-co-vinyl alcohol), DP cells are poorly adhesive to hydrophilic polyvinyl alcohol (PVA). Seeded in PVA-coated 96-welled commercial PCR tube arrays, DP cells quickly aggregate into single spheroids with progressive compaction. Varying seeded cell numbers and culture periods enables us to control the size and cell number of the spheroids. The spheroids obtained have high viability and preserve DP characters. A proof of principle experiment was conducted to examine the size effect on the efficiency and efficacy of HF regeneration. We found that both human and rat DP spheroids are able to induce HF neogenesis and larger DP spheroids exhibit higher HF inductivity. However, the average diameter of regenerated hair fiber did not significantly change with the increasing size of transplanted DP spheroids. The result suggests that an appropriate size of DP spheroid is essential for HF inductivity, but its size cannot be directly translated to a thicker regenerated hair. Our results also have implications on the efficiency and efficacy in the regeneration of other epithelial organs. PMID:23092862