Pharmacologic inhibition of lactate production prevents myofibroblast differentiation.

PubMed

Kottmann, Robert Matthew; Trawick, Emma; Judge, Jennifer L; Wahl, Lindsay A; Epa, Amali P; Owens, Kristina M; Thatcher, Thomas H; Phipps, Richard P; Sime, Patricia J

2015-12-01

Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-β (TGF-β) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-β. Here we explore whether pharmacologic inhibition of LDH activity can prevent TGF-β-induced myofibroblast differentiation. Primary human lung fibroblasts from healthy patients and those with pulmonary fibrosis were treated with TGF-β and or gossypol, an LDH inhibitor. Protein and RNA were analyzed for markers of myofibroblast differentiation and extracellular matrix generation. Gossypol inhibited TGF-β-induced expression of the myofibroblast marker α-smooth muscle actin (α-SMA) in a dose-dependent manner in both healthy and fibrotic human lung fibroblasts. Gossypol also inhibited expression of collagen 1, collagen 3, and fibronectin. Gossypol inhibited LDH activity, the generation of extracellular lactic acid, and the rate of extracellular acidification in a dose-dependent manner. Furthermore, gossypol inhibited TGF-β bioactivity in a dose-dependent manner. Concurrent treatment with an LDH siRNA increased the ability of gossypol to inhibit TGF-β-induced myofibroblast differentiation. Gossypol inhibits TGF-β-induced myofibroblast differentiation through inhibition of LDH, inhibition of extracellular accumulation of lactic acid, and inhibition of TGF-β bioactivity. These data support the hypothesis that pharmacologic inhibition of LDH may play an important role in the treatment of pulmonary fibrosis. Copyright © 2015 the American Physiological Society.

Poly(ethylene glycol)/chitosan/sodium glycerophosphate gel replaced the joint capsule with slow-release lubricant after joint surgery.

PubMed

Lu, Hailin; Ren, Shanshan; Li, Xing; Guo, Junde; Dong, Guangneng; Li, Jianhui; Gao, Li

2018-08-01

Body fluid is normally the only lubricant after joint replacement surgery, but wear problems have occurred because body fluid has poor lubrication ability. However, traditional lubricant would be diluted by body fluids and then absorbed by the human body. Therefore, an injectable gel with the ability to slow-release lubricant was designed to replace the joint capsule. The proposed gel, poly(ethylene glycol)/chitosan/sodium glycerophosphate (PEG/CS/GP) composite gel was then tested. The tribology results showed that the PEG/CS/GP gel had excellent slow-release properties, especially under pressure, and the PEG played an important role in improving the gel's rheological and mechanical properties. Moreover, this study revealed that the release solution had a good lubrication effect because the PEG and GP could crosslink via the hydrogen bond effect.

Efficacy of lateral- versus medial-approach hip joint capsule denervation as surgical treatments of the hip joint pain; a neuronal tract tracing study in the sheep

PubMed Central

Sienkiewicz, Waldemar; Dudek, Agnieszka; Czaja, Krzysztof; Janeczek, Maciej; Chrószcz, Aleksander; Kaleczyc, Jerzy

2018-01-01

Objective To evaluate efficacy of denervation of the of the hip joint capsule (HJC), as a treatment of hip joint pain. Specifically, we tested the hypothesis that HJC denervation will significantly reduce the number of sensory neurons innervating the capsule. Study design Denervation of the HJC from a medial or lateral approach was followed by retrograde tracing of sensory neurons innervating the capsule. Animals Twenty adult male sheep (30–40 kg of body weight; Polish merino breed) were used in the study. Methods The hip joint was denervated from medial (n = 5) or lateral (n = 5) surgical approaches. Immediately after denervation, the retrograde neural tract tracer Fast Blue (FB) was injected into the HJC. An additional ten animals (n = 5 for medial and n = 5 for lateral approach) received the same treatment without HJC denervation to provide the appropriate controls. Results Results of the study revealed that the vast majority of retrogradely labelled sensory neurons innervating the HJC originate from fifth lumbar to second sacral dorsal root ganglia. Both the medial and the lateral denervations significantly reduced the number of sensory neurons innervating the HJC (39.2% and 69.0% reduction respectively). Conclusions These results show that denervation of the HJC is an effective surgical procedure for reduction of the sensory neuronal input to the HJC. Moreover, the lateral approach was found to be significantly more effective for reducing sensory innervation as compared to the medial one. PMID:29329303

Low-grade myofibroblastic proliferations of the urinary bladder.

PubMed

Alquati, Sara; Gira, Federica Alessandra; Bartoli, Veronica; Contini, Sandro; Corradi, Domenico

2013-08-01

Myofibroblastic proliferations of the urinary bladder, which share some similarities with nodular fasciitis, were first reported in 1980. Since then, they have had several designations, the most frequently used being inflammatory myofibroblastic tumor. Based on both histopathologic and prognostic grounds, some authors prefer the term pseudosarcomatous myofibroblastic proliferation, at least for some of the proliferations. These same scientists also assimilate the so-called postoperative spindle cell nodules with the pseudosarcomatous myofibroblastic proliferations. Little is known about these low-grade myofibroblastic proliferations. To review the literature about low-grade myofibroblastic proliferations occurring in the urinary bladder. Textbooks and literature review. We obtained most of the clinicopathologic peculiarities from a patient population composed of the most-relevant, previously reported cases. The low-grade myofibroblastic proliferations of the urinary bladder are rare lesions affecting males more often than they do females. The most-common signs and symptoms are hematuria and dysuria. Histopathologically, they are spindle cell proliferations in a loose myxoid stroma, even though compact proliferations or hypocellular fibrous patterns can be found. Immunohistochemistry is quite nonspecific, except for ALK-1 positivity (20%-89%). Fluorescence in situ hybridization has demonstrated clonal genetic aberrations involving the ALK gene in 50% to 60% of cases. After surgery, only 6% of patients experience local recurrence, without metastases or deaths from the disease. Malignant transformation has been reported exceptionally. These myofibroblastic proliferations are probably part of a continuum with, at one end, benign pseudosarcomatous proliferations and, at the opposite end, more-aggressive lesions. Because of the frequently indolent clinical course, aggressive treatment would be unjustified.

Glucagon-like petide-2 acts on colon cancer myofibroblasts to stimulate proliferation, migration and invasion of both myofibroblasts and cancer cells via the IGF pathway.

PubMed

Shawe-Taylor, Marianne; Kumar, J Dinesh; Holden, Whitney; Dodd, Steven; Varga, Akos; Giger, Olivier; Varro, Andrea; Dockray, Graham J

2017-05-01

Glucagon-like peptide (GLP)-2 stimulates intestinal epithelial proliferation by acting, in part, via IGF release from sub-epithelial myofibroblasts. The response of myofibroblasts to GLP-2 remains incompletely understood. We studied the action of GLP-2 on myofibroblasts from colon cancer and adjacent tissue, and the effects of conditioned medium from these cells on epithelial cell proliferation, migration and invasion. GLP-2 stimulated proliferation, migration and invasion of myofibroblasts and the proliferative and invasive responses of cancer-associated myofibroblasts were greater than those of myofibroblasts from adjacent tissue. The responses were inhibited by an IGF receptor inhibitor, AG1024. Conditioned medium from GLP-2 treated myofibroblasts increased proliferation, migration and invasion of SW480, HT29, LoVo epithelial cells and these responses were inhibited by AG1024; GLP-2 alone had no effect on these cells. In addition, when myofibroblasts and epithelial cells were co-cultured in Ibidi chambers there was mutual stimulation of migration in response to GLP-2. The latter increased both IGF-1 and IGF-2 transcript abundance in myofibroblasts. Moreover, a number of IGF binding proteins (IGFBP-4, -5, -7) were identified in myofibroblast medium; in the presence of GLP-2 there was increased abundance of the cleavage products of IGBBP-4 and IGFBP-5 suggesting activation of a degradation mechanism that might increase IGF bioavailability. The data suggest that GLP-2 stimulates cancer myofibroblast proliferation, migration and invasion; GLP-2 acts indirectly on epithelial cells partly via increased IGF expression in myofibroblasts and partly, perhaps, by increased bioavailability through degradation of IGFBPs. Copyright © 2017 Elsevier Inc. All rights reserved.

Translational Profiles of Medullary Myofibroblasts during Kidney Fibrosis

PubMed Central

Grgic, Ivica; Krautzberger, A. Michaela; Hofmeister, Andreas; Lalli, Matthew; DiRocco, Derek P.; Fleig, Susanne V.; Liu, Jing; Duffield, Jeremy S.; McMahon, Andrew P.; Aronow, Bruce

2014-01-01

Myofibroblasts secrete matrix during chronic injury, and their ablation ameliorates fibrosis. Development of new biomarkers and therapies for CKD will be aided by a detailed analysis of myofibroblast gene expression during the early stages of fibrosis. However, dissociating myofibroblasts from fibrotic kidney is challenging. We therefore adapted translational ribosome affinity purification (TRAP) to isolate and profile mRNA from myofibroblasts and their precursors during kidney fibrosis. We generated and characterized a transgenic mouse expressing an enhanced green fluorescent protein (eGFP)–tagged L10a ribosomal subunit protein under control of the collagen1α1 promoter. We developed a one-step procedure for isolation of polysomal RNA from collagen1α1-eGFPL10a mice subject to unilateral ureteral obstruction and analyzed and validated the resulting transcriptional profiles. Pathway analysis revealed strong gene signatures for cell proliferation, migration, and shape change. Numerous novel genes and candidate biomarkers were upregulated during fibrosis, specifically in myofibroblasts, and we validated these results by quantitative PCR, in situ, and Western blot analysis. This study provides a comprehensive analysis of early myofibroblast gene expression during kidney fibrosis and introduces a new technique for cell-specific polysomal mRNA isolation in kidney injury models that is suited for RNA-sequencing technologies. PMID:24652793

Joint capsule attachment to the extensor carpi radialis brevis origin: an anatomical study with possible implications regarding the etiology of lateral epicondylitis.

PubMed

Nimura, Akimoto; Fujishiro, Hitomi; Wakabayashi, Yoshiaki; Imatani, Junya; Sugaya, Hiroyuki; Akita, Keiichi

2014-02-01

To identify the unique anatomical characteristic of the extensor carpi radialis brevis (ECRB) origin and points of differentiation from other extensors and to clarify the specific relationship of the ECRB to the underlying structures. We studied the origin of each extensor macroscopically for its muscular and tendinous parts; to identify the relationship between the ECRB origin and the deeper structures, we also examined the attachment of the joint capsule under the ECRB origin. The ECRB simply originated as a tendon without any muscle, whereas other extensors originated as a mixture of tendon and muscle. At the anterior part of the ECRB origin, the thin attachment of the joint capsule (average width, 3.3 mm) lay deep to the ECRB and was distinct. However, at the posterodistal portion, the joint capsule, annular ligament, and supinator were intermingled and originated as a single wide sheet from the humerus (average width, 10.7 mm). The anterior part of the ECRB origin was delicate, because the ECRB origin was purely tendinous, and the attachment of the articular capsule was thin compared with that of the posterodistal attachment. This thin attachment could be an initial factor leading to the development of lateral epicondylitis. The results of the current study may enhance magnetic resonance imaging understanding and may help clarify the etiology of the lateral epicondylitis. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro.

PubMed

Palethorpe, Helen M; Leach, Damien A; Need, Eleanor F; Drew, Paul A; Smith, Eric

2018-04-10

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo , providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome.

Myofibroblast androgen receptor expression determines cell survival in co-cultures of myofibroblasts and prostate cancer cells in vitro

PubMed Central

Palethorpe, Helen M.; Leach, Damien A.; Need, Eleanor F.; Drew, Paul A.; Smith, Eric

2018-01-01

Fibroblasts express androgen receptor (AR) in the normal prostate and during prostate cancer development. We have reported that loss of AR expression in prostate cancer-associated fibroblasts is a poor prognostic indicator. Here we report outcomes of direct and indirect co-cultures of immortalised AR-positive (PShTert-AR) or AR-negative (PShTert) myofibroblasts with prostate cancer cells. In the initial co-cultures the AR-negative PC3 cell line was used so AR expression and signalling were restricted to the myofibroblasts. In both direct and indirect co-culture with PShTert-AR myofibroblasts, paracrine signalling to the PC3 cells slowed proliferation and induced apoptosis. In contrast, PC3 cells proliferated with PShTert myofibroblasts irrespective of the co-culture method. In direct co-culture PC3 cells induced apoptosis in and destroyed PShTerts by direct signalling. Similar results were seen in direct co-cultures with AR-negative DU145 and AR-positive LNCaP and C4-2B prostate cancer cell lines. The AR ligand 5α-dihydrotestosterone (DHT) inhibited the proliferation of the PShTert-AR myofibroblasts, thereby reducing the extent of their inhibitory effect on cancer cell growth. These results suggest loss of stromal AR would favour prostate cancer cell growth in vivo, providing an explanation for the clinical observation that reduced stromal AR is associated with a poorer outcome. PMID:29721186

Stromal haze, myofibroblasts, and surface irregularity after PRK.

PubMed

Netto, Marcelo V; Mohan, Rajiv R; Sinha, Sunilima; Sharma, Ajay; Dupps, William; Wilson, Steven E

2006-05-01

The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze. Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups: [see table in text]. Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr or 4 weeks after surgery and histochemical analysis was performed on corneas for apoptosis (TUNEL assay), myofibroblast marker alpha-smooth muscle actin (SMA), and integrin alpha4 to delineate the epithelial basement membrane. Slit-lamp grading revealed severe haze formation in corneas in groups IV and VI, with significantly less haze in groups II, III, and VII and insignificant haze compared with the unwounded control in groups I and V. Analysis of SMA staining at 4 weeks after surgery, the approximate peak of haze formation in rabbits, revealed low myofibroblast formation in group I (1.2+/-0.2 cells/400x field) and group V (1.8+/-0.4), with significantly more in groups II (3.5+/-1.8), III (6.8+/-1.6), VII (7.9+/-3.8), IV (12.4+/-4.2) and VI (14.6+/-5.1). The screened groups were significantly different from each other (p < 0.05), with myofibroblast generation increasing with higher surface irregularity in the -4.5 diopter PRK groups. The -9.0 diopter PRK group VI had significantly more myofibroblast generation than the -9.0 diopter PRK with PTK-smoothing group VII (p < 0.01). Areas of basement membrane disruption were demonstrated by staining corneas for integrin alpha4 and were prominent in corneas with grade I or higher haze. SMA-positive myofibroblasts tended to be present sub-adjacent to

The mechanism of joint capsule thermal modification in an in-vitro sheep model.

PubMed

Hayashi, K; Peters, D M; Thabit, G; Hecht, P; Vanderby, R; Fanton, G S; Markel, M D

2000-01-01

The purpose of this study was to understand the mechanism responsible for joint capsule shrinkage after nonablative laser application in an in-vitro sheep model. Femoropatellar joint capsular tissue specimens harvested from 20 adult sheep were treated with one of three power settings of a holmium:yttrium-aluminum-garnet laser or served as a control. Laser treatment significantly shortened the tissue and decreased tissue stiffness in all three laser groups, whereas failure strength was not altered significantly by laser treatment. Transmission electron microscopic examination showed swollen collagen fibrils and loss of membrane integrity of fibroblasts. A thermometric study revealed nonablative laser energy caused tissue temperature to rise in the range of 64 degrees C to 100 degrees C. Electrophoresis after trypsin digestion of the tissue revealed significant loss of distinct alpha bands of Type I collagen in laser treated samples, whereas alpha bands were present in laser treated tissue without trypsin digestion. The results of this study support the concept that the primary mechanism responsible for the effect of nonablative laser energy is thermal denaturation of collagen in joint capsular tissue associated with unwinding of the triple helical structure of the collagen molecule.

Inhibition of hyaluronan synthesis by vesnarinone in cultured human myofibroblasts.

PubMed

Ueki, N; Taguchi, T; Takahashi, M; Adachi, M; Ohkawa, T; Amuro, Y; Hada, T; Higashino, K

2000-02-02

Hyaluronan (HA), which is a major component of the extracellular matrix (ECM), is regulated during myofibroproliferative responses to numerous forms of inflammatory stimuli. It is a key factor involved in cellular migration and adherence. The development of a potent and non-toxic inhibitor of HA synthesis would open up a new avenue for the treatment of fibrocontractive diseases such as pulmonary fibrosis and liver cirrhosis. In this study, the effects of vesnarinone (OPC-8212: 3,4-dihydro-6-[4-(3, 4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone) on the secretion of HA in human myofibroblast cell lines (MRC-5 and LI90 cells, referred to as pulmonary and hepatic myofibroblasts, respectively) were examined. Vesnarinone specifically and dose-dependently inhibited HA secretion by myofibroblasts up-regulated by fetal calf serum (FCS). The treatment of vesnarinone did not modify the phenotype of myofibroblast cells in culture. Vesnarinone also potently inhibited the HA secretion by the two myofibroblast cell lines up-regulated by transforming growth factor-beta1 (TGF-beta1) or tumor necrosis factor-alpha (TNF-alpha). The addition of vesnarinone to myofibroblasts resulted in a significant decrease of HA synthase (HAS) activity, with or without the addition of FCS or either cytokine. These findings suggest that vesnarinone inhibits the secretion of HA in myofibroblasts by specifically suppressing HAS activity, and may therefore prove useful for the treatment of chronic inflammation and tissue fibrosis.

Regeneration of fat cells from myofibroblasts during wound healing.

PubMed

Plikus, Maksim V; Guerrero-Juarez, Christian F; Ito, Mayumi; Li, Yun Rose; Dedhia, Priya H; Zheng, Ying; Shao, Mengle; Gay, Denise L; Ramos, Raul; Hsi, Tsai-Ching; Oh, Ji Won; Wang, Xiaojie; Ramirez, Amanda; Konopelski, Sara E; Elzein, Arijh; Wang, Anne; Supapannachart, Rarinthip June; Lee, Hye-Lim; Lim, Chae Ho; Nace, Arben; Guo, Amy; Treffeisen, Elsa; Andl, Thomas; Ramirez, Ricardo N; Murad, Rabi; Offermanns, Stefan; Metzger, Daniel; Chambon, Pierre; Widgerow, Alan D; Tuan, Tai-Lan; Mortazavi, Ali; Gupta, Rana K; Hamilton, Bruce A; Millar, Sarah E; Seale, Patrick; Pear, Warren S; Lazar, Mitchell A; Cotsarelis, George

2017-02-17

Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro . Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans. Copyright © 2017, American Association for the Advancement of Science.

The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

PubMed Central

2012-01-01

Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases. PMID:23259712

Inflammatory myofibroblastic tumors in two dogs.

PubMed

Knight, C; Fan, E; Riis, R; McDonough, S

2009-03-01

Two soft tissue masses from different locations in 2 dogs were submitted for histopathologic examination. Each was well demarcated and consisted of interweaving streams of bland spindle cells among which numerous plasma cells and lymphocytes were scattered. All the spindle cells reacted strongly to antibodies against vimentin and calponin, whereas a subset of the spindle cells expressed smooth muscle actin and desmin. Immunohistochemistry results were consistent with a myofibroblastic derivation for the spindle-cell population and the diagnosis of inflammatory myofibroblastic tumor (IMT) was made. This is the second report of IMT in the veterinary literature.

Pulmonary inflammatory myofibroblastic tumor harboring EML4-ALK fusion gene.

PubMed

Sokai, Akihiko; Enaka, Makiko; Sokai, Risa; Mori, Shoichi; Mori, Shunsuke; Gunji, Masaharu; Fujino, Masahiko; Ito, Masafumi

2014-01-01

Inflammatory myofibroblastic tumor is a rare tumor deriving from mesenchymal tissue. Approximately 50% of inflammatory myofibroblastic tumors harbor an anaplastic lymphoma kinase fusion gene. Pulmonary inflammatory myofibroblastic tumors harboring tropomyosin3-anaplastic lymphoma kinase or protein tyrosine phosphatase receptor-type F polypeptide-interacting protein-binding protein 1-anaplastic lymphoma kinase have been reported previously. However, it has not been reported that inflammatory myofibroblastic tumors harbor echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene which is considered to be very specific to lung cancers. A few tumors harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene other than lung cancers have been reported and the tumors were all carcinomas. A 67-year-old man had been followed up for a benign tumor for approximately 3 years before the tumor demonstrated malignant transformation. Lobectomy and autopsy revealed that an inflammatory myofibroblastic tumor harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene had transformed into an undifferentiated sarcoma. This case suggests that echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion is an oncogenic event in not only carcinomas but also sarcomas originating from stromal cells.

YAP1 Is a Driver of Myofibroblast Differentiation in Normal and Diseased Fibroblasts.

PubMed

Piersma, Bram; de Rond, Saskia; Werker, Paul M N; Boo, Stellar; Hinz, Boris; van Beuge, Marike M; Bank, Ruud A

2015-12-01

Dupuytren disease is a fibrotic disorder characterized by contraction of myofibroblast-rich cords and nodules in the hands. The Hippo member Yes-associated protein 1 (YAP1) is activated by tissue stiffness and the profibrotic transforming growth factor-β1, but its role in cell fibrogenesis is yet unclear. We hypothesized that YAP1 regulates the differentiation of dermal fibroblasts into highly contractile myofibroblasts and that YAP1 governs the maintenance of a myofibroblast phenotype in primary Dupuytren cells. Knockdown of YAP1 in transforming growth factor-β1-stimulated dermal fibroblasts decreased the formation of contractile smooth muscle α-actin stress fibers and the deposition of collagen type I, which are hallmark features of myofibroblasts. Translating our findings to a clinically relevant model, we found that YAP1 deficiency in Dupuytren disease myofibroblasts resulted in decreased expression of ACTA2, COL1A1, and CCN2 mRNA, but this did not result in decreased protein levels. YAP1-deficient Dupuytren myofibroblasts showed decreased contraction of a collagen hydrogel. Finally, we showed that YAP1 levels and nuclear localization were elevated in affected Dupuytren disease tissue compared with matched control tissue and partly co-localized with smooth muscle α-actin-positive cells. In conclusion, our data show that YAP1 is a regulator of myofibroblast differentiation and contributes to the maintenance of a synthetic and contractile phenotype, in both transforming growth factor-β1-induced myofibroblast differentiation and primary Dupuytren myofibroblasts. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Myofibroblasts and colonic anastomosis healing in Wistar rats.

PubMed

Kosmidis, Christophoros; Efthimiadis, Christoforos; Anthimidis, Georgios; Basdanis, George; Apostolidis, Stylianos; Hytiroglou, Prodromos; Vasiliadou, Kalliopi; Prousalidis, John; Fahantidis, Epameinondas

2011-03-02

The myofibroblasts play a central role in wound healing throughout the body. The process of wound healing in the colon was evaluated with emphasis on the role of myofibroblasts. One hundred male Wistar rats weighing 274 ± 9.1 g (mean age: 3.5 months) were used. A left colonic segment was transected and the colon was re-anastomosed. Animals were randomly divided into two groups. The first group experimental animals (n = 50) were sacrificed on postoperative day 3, while the second group rats (n = 50) were sacrificed on postoperative day 7. Healing of colonic anastomosis was studied in terms of anastomotic bursting pressure, as well as myofibroblastic reaction and expression of α-smooth muscle actin (α-SMA), adhesion formation, inflammatory reaction and neovascularization. The mean anastomotic bursting pressure increased from 20.6 ± 3.5 mmHg on the 3rd postoperative day to 148.8 ± 9.6 Hg on the 7th postoperative day. Adhesion formation was increased on the 7th day, as compared to the 3rd day. In addition, the myofibroblastic reaction was more profound on the 7th postoperative day in comparison with the 3rd postoperative day. The staining intensity for α-SMA was progressive from the 3rd to the 7th postoperative day. On the 7th day the α-SMA staining in the myofibroblats reached the level of muscular layer cells. Our study emphasizes the pivotal role of myofibroblasts in the process of colonic anastomosis healing. The findings provide an explanation for the reduction in the incidence of wound dehiscence after the 7th postoperative day.

Evaluation of Role of Myofibroblasts in Oral Cancer: A Systematic Review.

PubMed

Sekhon, Harjeet K; Sircar, Keya; Kaur, Gurbani; Marwah, Muneet

2016-01-01

To conduct a systematic review on the role of myofibroblasts in progression of oral cancer. The myofibroblast is essential for the integrity of the mammalian body by virtue of its role in wound healing, but it also plays a negative role due to their role in promoting tumor development. Systematic review. Bibliographic searches were conducted in several electronic databases using all publications in PubMed, PubMed central, EMBASE, CancerLit, Google scholar, and Cochrane CCTR between 1990 and June 2015. The search of all publications from various electronic databases revealed 1,371 citations. The total number of studies considered for systematic review was 43. The total number of patients included in the studies was 990. Myofibroblasts are a significant component in stroma of oral cancer cases, though not identified in all cases. This systematic review shows that clinical, pathological, and immunohistochemistry tests have correlated the presence of high myofibroblast count in oral cancer cell stroma. Myofibroblasts play a significant role in oral cancer invasion and progression. Various studies have demonstrated their association with oral cancer. This review tends to highlight their role in the pathogenesis of oral cancer over the decade. Sekhon HK, Sircar K, Kaur G, Marwah M. Evaluation of Role of Myofibroblasts in Oral Cancer: A Systematic Review. Int J Clin Pediatr Dent 2016;9(3):233-239.

Immunohistochemical evaluation of myofibroblasts in odontogenic cysts and tumors: A comparative study

PubMed Central

Syamala, Deepa; Suresh, Rakesh; Janardhanan, Mahija; Savithri, Vindhya; Anand, Prem P; Jose, Amrutha

2016-01-01

Context: Myofibroblasts are fibroblasts with smooth muscle-like features characterized by the presence of a contractile apparatus and found in the connective tissue stroma of normal tissues such as blood vessels and lymph nodes. They are now thought to play a role in the synthesis and reorganization of extracellular matrix, which could contribute to the aggressive biologic behavior of the lesions. Aims: To compare the mean number of stromal myofibroblasts in dentigerous cysts (DCs), keratocystic odontogenic tumor (KCOT) and ameloblastoma; and to derive a correlation between the stromal myofibroblasts and the known biologic behavior of the lesions. Settings and Design: A cross-sectional immunohistochemical analysis of cases of DC, KCOT and ameloblastoma. Materials and Methods: Twenty paraffin-embedded tissue blocks each of DC, KCOT and multicystic ameloblastoma were selected for the study and diagnosis confirmed through hematoxylin and eosin staining. Tissue sections were analyzed for the number of myofibroblasts using alpha smooth muscle actin (α-SMA) immunostaining. Statistical Analysis: Differences in the mean number of α-SMA positive cells in each group were analyzed using one-way ANOVA test. Intergroup comparisons of mean values of α-SMA positive cells were performed using Mann-Whitney U-test. Results: Ameloblastoma showed the highest number of myofibroblasts, whereas DC showed the lowest. Among the groups, there were significant differences between the myofibroblast counts among DC and KCOT and between DC and ameloblastoma, whereas the difference in counts was not statistically significant between KCOT and ameloblastoma. A positive correlation was observed between the myofibroblast count and the known biologic behavior of the lesions. Conclusion: Myofibroblasts may act in close association with the epithelial cells to bring about changes in stromal microenvironment, favorable to the growth and progression of the lesion. They may be of great value in

Immunohistochemical evaluation of myofibroblasts in odontogenic cysts and tumors: A comparative study.

PubMed

Syamala, Deepa; Suresh, Rakesh; Janardhanan, Mahija; Savithri, Vindhya; Anand, Prem P; Jose, Amrutha

2016-01-01

Myofibroblasts are fibroblasts with smooth muscle-like features characterized by the presence of a contractile apparatus and found in the connective tissue stroma of normal tissues such as blood vessels and lymph nodes. They are now thought to play a role in the synthesis and reorganization of extracellular matrix, which could contribute to the aggressive biologic behavior of the lesions. To compare the mean number of stromal myofibroblasts in dentigerous cysts (DCs), keratocystic odontogenic tumor (KCOT) and ameloblastoma; and to derive a correlation between the stromal myofibroblasts and the known biologic behavior of the lesions. A cross-sectional immunohistochemical analysis of cases of DC, KCOT and ameloblastoma. Twenty paraffin-embedded tissue blocks each of DC, KCOT and multicystic ameloblastoma were selected for the study and diagnosis confirmed through hematoxylin and eosin staining. Tissue sections were analyzed for the number of myofibroblasts using alpha smooth muscle actin (α-SMA) immunostaining. Differences in the mean number of α-SMA positive cells in each group were analyzed using one-way ANOVA test. Intergroup comparisons of mean values of α-SMA positive cells were performed using Mann-Whitney U-test. Ameloblastoma showed the highest number of myofibroblasts, whereas DC showed the lowest. Among the groups, there were significant differences between the myofibroblast counts among DC and KCOT and between DC and ameloblastoma, whereas the difference in counts was not statistically significant between KCOT and ameloblastoma. A positive correlation was observed between the myofibroblast count and the known biologic behavior of the lesions. Myofibroblasts may act in close association with the epithelial cells to bring about changes in stromal microenvironment, favorable to the growth and progression of the lesion. They may be of great value in predicting the biologic behavior and growth potential of such lesions.

Bipolar Radiofrequency Facet Ablation of the Lumbar Facet Capsule: An Adjunct to Conventional Radiofrequency Ablation for Pain Management.

PubMed

Jacobson, Robert E; Palea, Ovidiu; Granville, Michelle

2017-09-01

Radiofrequency facet ablation (RFA) has been performed using the same technique for over 50 years. Except for variations in electrode size, tip shape, and change in radiofrequency (RF) stimulation parameters, using standard, pulsed, and cooled RF wavelengths, the target points have remained absolutely unchanged from the original work describing RFA for lumbar pain control. Degenerative changes in the facet joint and capsule are the primary location for the majority of lumbar segmental pathology and pain. Multiple studies show that the degenerated facet joint is richly innervated as a result of the inflammatory overgrowth of the synovium. The primary provocative clinical test to justify an RFA is to perform an injection with local anesthetic into the facet joint and the posterior capsule and confirm pain relief. However, after a positive response, the radiofrequency lesion is made not to the facet joint but to the more proximal fine nerve branches that innervate the joint. The accepted target points for the recurrent sensory branch ignore the characteristic rich innervation of the pathologic lumbar facet capsule and assume that lesioning of these recurrent branches is sufficient to denervate the painful pathologic facet joint. This report describes the additional targets and technical steps for further coagulation points along the posterior capsule of the lumbar facet joint and the physiologic studies of the advantage of the bipolar radiofrequency current in this location. Bipolar RF to the facet capsule is a simple, extra step that easily creates a large thermo-coagulated lesion in this capsule region of the pathologic facet joint. Early studies demonstrate bipolar RF to the facet capsule can provide long-term pain relief when used alone for specific localized facet joint pain, to coagulate lumbar facet cysts to prevent recurrence, and to get more extensive pain control by combining it with traditional lumbar RFA, especially when RFA is repeated.

Neuroanatomical distribution of mechanoreceptors in the human cadaveric shoulder capsule and labrum

PubMed Central

Witherspoon, Jessica W; Smirnova, Irina V; McIff, Terence E

2014-01-01

The distribution, location, and spatial arrangement of mechanoreceptors are important for neural signal conciseness and accuracy in proprioceptive information required to maintain functional joint stability. The glenohumeral joint capsule and labrum are mechanoreceptor-containing tissues for which the distribution of mechanoreceptors has not been determined despite the importance of these tissues in stabilizing the shoulder. More recently, it has been shown that damage to articular mechanoreceptors can result in proprioceptive deficits that may lead to recurrent instability. Awareness of mechanoreceptor distribution in the glenohumeral joint capsule and labrum may allow preservation of the mechanoreceptors during surgical treatment for shoulder instability, and in turn retain the joint's proprioceptive integrity. For this reason, we sought to develop a neuroanatomical map of the mechanoreceptors within the capsule and labrum. We postulated that the mechanoreceptors in these tissues are distributed in a unique pattern, with mechanoreceptor-scarce regions that may be more appropriate for surgical dissection. We determined the neuroanatomical distribution of mechanoreceptors and their associated fascicles in the capsule and labrum from eight human cadaver shoulder pairs using our improved gold chloride staining technique and light microscopy. A distribution pattern was consistently observed in the capsule and labrum from which we derived a neuroanatomical map. Both tissues demonstrated mechanoreceptor-dense and -scarce regions that may be considered during surgical treatment for instability. Capsular fascicles were located in the subsynovial layer, whereas labral fascicles were concentrated in the peri-core zone. The capsular fascicles presented as a lattice network and with a plexiform appearance. Fascicles within the labrum resembled a cable structure with the fascicles running in parallel. Our findings contribute to the neuroanatomical knowledge of the two

Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis

PubMed Central

Xie, Ting; Liang, Jiurong; Liu, Ningshan; Huan, Caijuan; Zhang, Yanli; Liu, Weijia; Kumar, Maya; Xiao, Rui; D’Armiento, Jeanine; Metzger, Daniel; Chambon, Pierre; Papaioannou, Virginia E.; Stripp, Barry R.; Jiang, Dianhua

2016-01-01

Progressive tissue fibrosis is a major cause of the morbidity and mortality associated with repeated epithelial injuries and accumulation of myofibroblasts. Successful treatment options are limited by an incomplete understanding of the molecular mechanisms that regulate myofibroblast accumulation. Here, we employed in vivo lineage tracing and real-time gene expression transgenic reporting methods to analyze the early embryonic transcription factor T-box gene 4 (TBX4), and determined that TBX4-lineage mesenchymal progenitors are the predominant source of myofibroblasts in injured adult lung. In a murine model, ablation of TBX4-expressing cells or disruption of TBX4 signaling attenuated lung fibrosis after bleomycin-induced injury. Furthermore, TBX4 regulated hyaluronan synthase 2 production to enable fibroblast invasion of matrix both in murine models and in fibroblasts from patients with severe pulmonary fibrosis. These data identify TBX4 as a mesenchymal transcription factor that drives accumulation of myofibroblasts and the development of lung fibrosis. Targeting TBX4 and downstream factors that regulate fibroblast invasiveness could lead to therapeutic approaches in lung fibrosis. PMID:27400124

TGF-β1 (Transforming Growth Factor-β1) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity.

PubMed

Salvarani, Nicolò; Maguy, Ange; De Simone, Stefano A; Miragoli, Michele; Jousset, Florian; Rohr, Stephan

2017-05-01

TGF-β 1 (transforming growth factor-β 1 ) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β 1 alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro. Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β 1 , applied for 24 to 48 hours at clinically relevant concentrations (≤2.5 ng/mL), causes substantial membrane depolarization concomitant with a several-fold increase of transmembrane currents. Transcriptome analysis revealed TGF-β 1 -dependent changes in 29 of 63 ion channel/pump/connexin transcripts, indicating a pleiotropic effect on the electrical phenotype of myofibroblasts. Whereas not affecting cardiomyocyte membrane potentials and cardiomyocyte-cardiomyocyte gap junctional coupling, TGF-β 1 depolarized cardiomyocytes coupled to myofibroblasts by ≈20 mV and increased gap junctional coupling between myofibroblasts and cardiomyocytes >5-fold as reflected by elevated connexin 43 and consortin transcripts. TGF-β 1 -dependent cardiomyocyte depolarization resulted from electrotonic crosstalk with myofibroblasts as demonstrated by immediate normalization of cardiomyocyte electrophysiology after targeted disruption of coupled myofibroblasts and by cessation of ectopic activity of cardiomyocytes coupled to myofibroblasts during pharmacological gap junctional uncoupling. In cardiac fibrosis models exhibiting slow conduction and ectopic activity, block of TGF-β 1 signaling completely abolished both arrhythmogenic conditions. TGF-β 1 profoundly alters the electrophysiological phenotype of cardiac myofibroblasts. Apart from possibly contributing to the control of cell function in general, the changes proved to be pivotal for proarrhythmic myofibroblast

Percutaneous radiofrequency facet capsule denervation as an alternative target in lumbar facet syndrome.

PubMed

Moussa, Wael Mohamed Mohamed; Khedr, Wael

2016-11-01

Percutaneous radiofrequency denervation of the medial dorsal branch is often used in chronic low back pain of intervertebral facet etiology, which is sometimes difficult to perform and recurrence of pain often ensues. We theorized that shifting the target of RF coagulation to the facet joint capsule would provide an easier target and a longer-lived pain relieving response. A prospective randomized controlled trial where 120 patients diagnosed with CLBP of a confirmed facet origin were randomly divided into three equal groups, the first was submitted to percutaneous radiofrequency coagulation of the facet joint capsule, the second underwent percuataneous denervation of the medial dorsal branch and the third did not receive radiofrequency lesioning. All the three groups received local injection of a mixture of local anesthetic and steroid. Cases were followed for up to 3 years. 87(72.5%) patients were females. By 3 months' post procedure, improvement in VAS was significantly better than pretreatment levels in all groups (p<0.05). The control group lost improvement by 1-year follow-up (p=0.017). At 2 years' follow-up, the joint capsule denervation group maintained significant improvement (p=0.033) whereas the medial branch denervation group lost its significant effect (p=0.479). By the end of follow-up period, only joint capsule denervation group kept significant improvement (p=0.026). In CLBP of facet origin, shifting the target of percutaneous radiofrequency to the facet joint capsule provides an easier technique with an extended period of pain relief compared to the medial dorsal branch of the facet joint. Copyright © 2016 Elsevier B.V. All rights reserved.

Pericellular Versican Regulates the Fibroblast-Myofibroblast Transition

PubMed Central

Hattori, Noriko; Carrino, David A.; Lauer, Mark E.; Vasanji, Amit; Wylie, James D.; Nelson, Courtney M.; Apte, Suneel S.

2011-01-01

The cell and its glycosaminoglycan-rich pericellular matrix (PCM) comprise a functional unit. Because modification of PCM influences cell behavior, we investigated molecular mechanisms that regulate PCM volume and composition. In fibroblasts and other cells, aggregates of hyaluronan and versican are found in the PCM. Dermal fibroblasts from Adamts5−/− mice, which lack a versican-degrading protease, ADAMTS5, had reduced versican proteolysis, increased PCM, altered cell shape, enhanced α-smooth muscle actin (SMA) expression and increased contractility within three-dimensional collagen gels. The myofibroblast-like phenotype was associated with activation of TGFβ signaling. We tested the hypothesis that fibroblast-myofibroblast transition in Adamts5−/− cells resulted from versican accumulation in PCM. First, we noted that versican overexpression in human dermal fibroblasts led to increased SMA expression, enhanced contractility, and increased Smad2 phosphorylation. In contrast, dermal fibroblasts from Vcan haploinsufficient (Vcanhdf/+) mice had reduced contractility relative to wild type fibroblasts. Using a genetic approach to directly test if myofibroblast transition in Adamts5−/− cells resulted from increased PCM versican content, we generated Adamts5−/−;Vcanhdf/+ mice and isolated their dermal fibroblasts for comparison with dermal fibroblasts from Adamts5−/− mice. In Adamts5−/− fibroblasts, Vcan haploinsufficiency or exogenous ADAMTS5 restored normal fibroblast contractility. These findings demonstrate that altering PCM versican content through proteolytic activity of ADAMTS5 profoundly influenced the dermal fibroblast phenotype and may regulate a phenotypic continuum between the fibroblast and its alter ego, the myofibroblast. We propose that a physiological function of ADAMTS5 in dermal fibroblasts is to maintain optimal versican content and PCM volume by continually trimming versican in hyaluronan-versican aggregates. PMID:21828051

Bipolar Radiofrequency Facet Ablation of the Lumbar Facet Capsule: An Adjunct to Conventional Radiofrequency Ablation for Pain Management

PubMed Central

Palea, Ovidiu; Granville, Michelle

2017-01-01

Radiofrequency facet ablation (RFA) has been performed using the same technique for over 50 years. Except for variations in electrode size, tip shape, and change in radiofrequency (RF) stimulation parameters, using standard, pulsed, and cooled RF wavelengths, the target points have remained absolutely unchanged from the original work describing RFA for lumbar pain control. Degenerative changes in the facet joint and capsule are the primary location for the majority of lumbar segmental pathology and pain. Multiple studies show that the degenerated facet joint is richly innervated as a result of the inflammatory overgrowth of the synovium. The primary provocative clinical test to justify an RFA is to perform an injection with local anesthetic into the facet joint and the posterior capsule and confirm pain relief. However, after a positive response, the radiofrequency lesion is made not to the facet joint but to the more proximal fine nerve branches that innervate the joint. The accepted target points for the recurrent sensory branch ignore the characteristic rich innervation of the pathologic lumbar facet capsule and assume that lesioning of these recurrent branches is sufficient to denervate the painful pathologic facet joint. This report describes the additional targets and technical steps for further coagulation points along the posterior capsule of the lumbar facet joint and the physiologic studies of the advantage of the bipolar radiofrequency current in this location. Bipolar RF to the facet capsule is a simple, extra step that easily creates a large thermo-coagulated lesion in this capsule region of the pathologic facet joint. Early studies demonstrate bipolar RF to the facet capsule can provide long-term pain relief when used alone for specific localized facet joint pain, to coagulate lumbar facet cysts to prevent recurrence, and to get more extensive pain control by combining it with traditional lumbar RFA, especially when RFA is repeated. PMID

An assessment of mast cells and myofibroblasts in denture-induced fibrous hyperplasia.

PubMed

Kiuchi, Misa; Yamamura, Takashi; Okudera, Michisato; Souksavanh, Vongsa; Ishigami, Tomohiko; Iwase, Takashi; Warnakulasuriya, Saman; Komiyama, Kazuo

2014-01-01

The pathogenesis of denture-induced fibrous hyperplasias has not been examined in detail to explain how tissue injury results in fibrous hyperplasia of the oral mucosa. We examined the presence of mast cells and myofibroblasts in 33 denture-induced fibrous hyperplasias (DIFH) compared with 10 healthy gingival tissues. The parameters examined included mast cell numbers, tissue distribution, degranulation, and cell subtypes using immunohistochemistry. The presence of myofibroblasts and their likely origin was also examined by double immunofluorescense staining. Furthermore, we investigated the synthesis of osteopontin and TGF-β, considered to be involved in the transformation of a fibroblast to a myofibroblast. The results demonstrated that the mast cell numbers are significantly increased in the DIFH compared with non-disease controls. The mast cell localization in lesions was higher in the superficial areas with inflammatory cell infiltration compared with the deep fibrotic area (P < 0.01). The number of tryptase-positive mast cells was significantly higher compared with chymase-positive ones. The TGF-β- or osteopontin-positive cell infiltration into the lesion was found in high numbers. The presence of myofibroblasts was identified in 14 of 33 cases (42%), and some of these cells showed apoptosis when assessed by the TUNEL assay. On the survey of the origin of myofibroblasts, results showed αSMA and vimentin positivity indicating these transformed from fibroblasts. These results are the first to show that mast cells and myofibroblasts can be detected in DIFH, indicating important roles of these cells in the pathogenesis of this lesion. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Myofibroblasts in interstitial lung diseases show diverse electron microscopic and invasive features.

PubMed

Karvonen, Henna M; Lehtonen, Siri T; Sormunen, Raija T; Harju, Terttu H; Lappi-Blanco, Elisa; Bloigu, Risto S; Kaarteenaho, Riitta L

2012-09-01

The characteristic features of myofibroblasts in various lung disorders are poorly understood. We have evaluated the ultrastructure and invasive capacities of myofibroblasts cultured from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples from patients with different types of lung diseases. Cells were cultured from samples of BAL fluid collected from 51 patients that had undergone bronchoscopy and BAL for diagnostic purposes. The cells were visualized by transmission electron microscopy and immunoelectron microscopy to achieve ultrastructural localization of alpha-smooth muscle actin (α-SMA) and fibronectin. The levels of α-SMA protein and mRNA and fibronectin mRNA were measured by western blot and quantitative real-time reverse transcriptase polymerase chain reaction. The invasive capacities of the cells were evaluated. The cultured cells were either fibroblasts or myofibroblasts. The structure of the fibronexus, and the amounts of intracellular actin, extracellular fibronectin and cell junctions of myofibroblasts varied in different diseases. In electron and immunoelectron microscopy, cells cultured from interstitial lung diseases (ILDs) expressed more actin filaments and α-SMA than normal lung. The invasive capacity of the cells obtained from patients with idiopathic pulmonary fibrosis was higher than that from patients with other type of ILDs. Cells expressing more actin filaments had a higher invasion capacity. It is concluded that electron and immunoelectron microscopic studies of myofibroblasts can reveal differential features in various diseases. An analysis of myofibroblasts cultured from diagnostic BAL fluid samples may represent a new kind of tool for diagnostics and research into lung diseases.

Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation.

PubMed

Kim, Sena; Ahn, Moonsang; Piao, Yibo; Ha, Yooseok; Choi, Dae-Kyoung; Yi, Min-Hee; Shin, Nara; Kim, Dong Woon; Oh, Sang-Ha

2016-11-01

One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-β1 signaling, in human fibroblasts. In vitro, cultured human fibroblasts were treated with TGF-β1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry. In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules. This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-β/Smad signaling pathway. Therapeutic, V.

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

PubMed

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Astaxanthin prevents pulmonary fibrosis by promoting myofibroblast apoptosis dependent on Drp1-mediated mitochondrial fission

PubMed Central

Zhang, Jinjin; Xu, Pan; Wang, Youlei; Wang, Meirong; Li, Hongbo; Lin, Shengcui; Mao, Cuiping; Wang, Bingsi; Song, Xiaodong; Lv, Changjun

2015-01-01

Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin-related protein-1 (Drp1)-mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro-apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin-induced mitochondrial fission and apoptosis in myofibroblasts. Drp1-associated genes, such as Bcl-2-associated X protein, cytochrome c, tumour suppressor gene p53 and p53-up-regulated modulator of apoptosis, were highly up-regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1-dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment. PMID:26119034

Sinonasal inflammatory myofibroblastic pseudotumor (plasma cell granuloma).

PubMed

Arpacı, Rabia Bozdoğan; Kara, Tuba; Özyedek, Esen; Serinsöz, Ebru; Vayısoğlu, Yusuf; Özgür, Anıl; Arpacı, Taner; Özcan, Cengiz

2015-01-01

Inflammatory myofibroblastic pseudotumor (plasma cell granuloma) is a soft tissue lesion consisting of myofibroblasts, mature lymphocytes, histiocytes, plasma cells, eosinophils, and extracellular collagen. Various sites in the body may harbor these lesions. Lungs, omentum, intestines, mesentery, and urinary system are the most susceptible areas. It is usually seen in children and young adults. The lesion is rarely detected in the head and neck region. The orbit and the upper respiratory system are the most common localizations in the head and neck region. Sinonasal tract is a rare site of involvement. The differential diagnosis includes squamous cell carcinoma (spindle cell variant), inflammatory fibrosarcoma, leiomyosarcoma, schwannoma, and nonspecific inflammation. Our patient who had a sinonasal mass showed a benign tumor consisting of spindle tumor cells and inflammatory cells histopathologically. This case was presented due to its rare existence to this site.

Epithelioid inflammatory myofibroblastic sarcoma: a case report

PubMed Central

Clevenger, Jessica A.; Masters, Gregory A.; Bauer, Thomas L.; Nam, Brian T.

2015-01-01

Inflammatory myofibroblastic tumor (IMT) of the lung is a rare malignancy with few cases reported in the literature. Histologically, it is composed by spindle cells and an infiltrate of inflammatory cells. Children and young, non-smoking adults constitute the majority of cases, the clinical behavior ranges from a benign entity to a malignant process with rapid recurrence and metastatic progression. We present a case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) of the pleura, a malignant variant of IMT, which was initially treated with debulking surgical resection followed by systemic chemotherapy. The tumor was found to have an anaplastic lymphoma kinase (ALK) gene rearrangement. An ALK directed tyrosine kinase inhibitor was used with an impressive response, the patient remains in remission nearly 1 year after presentation. The pathogenesis, pathologic findings, clinical behavior and imaging of pulmonary EIMS are discussed. PMID:26623133

Acute myelogenous leukemia cells with the MLL-ELL translocation convert morphologically and functionally into adherent myofibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tashiro, Haruko; Mizutani-Noguchi, Mitsuho; Shirasaki, Ryosuke

2010-01-01

Bone marrow-myofibroblasts, a major component of bone marrow-stroma, are reported to originate from hematopoietic stem cells. We show in this paper that non-adherent leukemia blasts can change into myofibroblasts. When myeloblasts from two cases of acute myelogenous leukemia with a fusion product comprising mixed lineage leukemia and RNA polymerase II elongation factor, were cultured long term, their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental myeloblasts. The original leukemia blasts, when cultured on the leukemia blast-derived myofibroblasts, grew extensively. Leukemia blasts can create their own microenvironment for proliferation.

Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis.

PubMed

Kramann, Rafael; Machado, Flavia; Wu, Haojia; Kusaba, Tetsuro; Hoeft, Konrad; Schneider, Rebekka K; Humphreys, Benjamin D

2018-05-03

Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney fibrosis, we demonstrate that a small fraction of genetically labeled renal myofibroblasts derive from the circulation. Single-cell RNA sequencing confirms this finding but indicates that these cells are circulating monocytes, express few extracellular matrix or other myofibroblast genes, and express many proinflammatory cytokines. We conclude that this small circulating myofibroblast progenitor population contributes to renal fibrosis by paracrine rather than direct mechanisms.

Astaxanthin prevents pulmonary fibrosis by promoting myofibroblast apoptosis dependent on Drp1-mediated mitochondrial fission.

PubMed

Zhang, Jinjin; Xu, Pan; Wang, Youlei; Wang, Meirong; Li, Hongbo; Lin, Shengcui; Mao, Cuiping; Wang, Bingsi; Song, Xiaodong; Lv, Changjun

2015-09-01

Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin-related protein-1 (Drp1)-mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro-apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin-induced mitochondrial fission and apoptosis in myofibroblasts. Drp1-associated genes, such as Bcl-2-associated X protein, cytochrome c, tumour suppressor gene p53 and p53-up-regulated modulator of apoptosis, were highly up-regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1-dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts

PubMed Central

Kollmannsberger, Philip; Bidan, Cécile M.; Dunlop, John W. C.; Fratzl, Peter; Vogel, Viola

2018-01-01

Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor–β (TGF-β) and tensile forces work synergistically in up-regulating the transition of fibroblasts into myofibroblasts and whether myofibroblasts undergo apoptosis or become deactivated by other means once tissue homeostasis is reached. We used three-dimensional microtissues grown in vitro from fibroblasts in macroscopically engineered clefts for several weeks and found that fibroblasts transitioned into myofibroblasts at the highly tensed growth front as the microtissue progressively closed the cleft, in analogy to closing a wound site. Proliferation was up-regulated at the growth front, and new highly stretched fibronectin fibers were deposited, as revealed by fibronectin fluorescence resonance energy transfer probes. As the tissue was growing, the ECM underneath matured into a collagen-rich tissue containing mostly fibroblasts instead of myofibroblasts, and the fibronectin fibers were under reduced tension. This correlated with a progressive rounding of cells from the growth front inward, with decreased α–smooth muscle actin expression, YAP nuclear translocation, and cell proliferation. Together, this suggests that the myofibroblast phenotype is stabilized at the growth front by tensile forces, even in the absence of endogenously supplemented TGF-β, and reverts into a quiescent fibroblast phenotype already 10 μm behind the growth front, thus giving rise to a myofibroblast-to-fibroblast transition. This is the hallmark of reaching prohealing homeostasis. PMID:29349300

CERA Attenuates Kidney Fibrogenesis in the db/db Mouse by Influencing the Renal Myofibroblast Generation

PubMed Central

Fischer, Christin; Deininger, Natalie; Wolf, Gunter; Loeffler, Ivonne

2018-01-01

Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing myofibroblasts can originate from different sources and different mechanisms are involved in the activation process of the myofibroblasts in the fibrotic kidney. In this study, 16-week-old db/db mice, a model for type 2 DN, were treated for two weeks with continuous erythropoietin receptor activator (CERA), a synthetic erythropoietin variant with possible non-hematopoietic, tissue-protective effects. Non-diabetic and diabetic mice treated with placebo were used as controls. The effects of CERA on tubulointerstitial fibrosis (TIF) as well as on the generation of the matrix-producing myofibroblasts were evaluated by morphological, immunohistochemical, and molecular biological methods. The placebo-treated diabetic mice showed significant signs of beginning renal TIF (shown by picrosirius red staining; increased connective tissue growth factor (CTGF), fibronectin and collagen I deposition; upregulated KIM1 expression) together with an increased number of interstitial myofibroblasts (shown by different mesenchymal markers), while kidneys from diabetic mice treated with CERA revealed less TIF and fewer myofibroblasts. The mechanisms, in which CERA acts as an anti-fibrotic agent/drug, seem to be multifaceted: first, CERA inhibits the generation of matrix-producing myofibroblasts and second, CERA increases the ability for tissue repair. Many of these CERA effects can be explained by the finding that CERA inhibits the renal expression of the cytokine TGF-β1. PMID:29385703

CERA Attenuates Kidney Fibrogenesis in the db/db Mouse by Influencing the Renal Myofibroblast Generation.

PubMed

Fischer, Christin; Deininger, Natalie; Wolf, Gunter; Loeffler, Ivonne

2018-01-30

Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing myofibroblasts can originate from different sources and different mechanisms are involved in the activation process of the myofibroblasts in the fibrotic kidney. In this study, 16-week-old db / db mice, a model for type 2 DN, were treated for two weeks with continuous erythropoietin receptor activator (CERA), a synthetic erythropoietin variant with possible non-hematopoietic, tissue-protective effects. Non-diabetic and diabetic mice treated with placebo were used as controls. The effects of CERA on tubulointerstitial fibrosis (TIF) as well as on the generation of the matrix-producing myofibroblasts were evaluated by morphological, immunohistochemical, and molecular biological methods. The placebo-treated diabetic mice showed significant signs of beginning renal TIF (shown by picrosirius red staining; increased connective tissue growth factor (CTGF), fibronectin and collagen I deposition; upregulated KIM1 expression) together with an increased number of interstitial myofibroblasts (shown by different mesenchymal markers), while kidneys from diabetic mice treated with CERA revealed less TIF and fewer myofibroblasts. The mechanisms, in which CERA acts as an anti-fibrotic agent/drug, seem to be multifaceted: first, CERA inhibits the generation of matrix-producing myofibroblasts and second, CERA increases the ability for tissue repair. Many of these CERA effects can be explained by the finding that CERA inhibits the renal expression of the cytokine TGF-β1.

Integrin-linked kinase is required for TGF-β1 induction of dermal myofibroblast differentiation.

PubMed

Vi, Linda; de Lasa, Cristina; DiGuglielmo, Gianni M; Dagnino, Lina

2011-03-01

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-β (TGF-β) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-β1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-β1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as α-smooth muscle actin. These alterations were not limited to Smad-associated TGF-β1 responses, as stimulation of noncanonical mitogen-activated protein kinase pathways by this growth factor was also diminished in the absence of ILK. ILK-deficient fibroblasts exhibited abnormalities in the actin cytoskeleton, and did not form supermature focal adhesions or contractile F-actin stress fibers, indicating a severe impairment in their capacity to differentiate into myofibroblasts. These defects extended to the inability of cells to contract extracellular matrices when embedded in collagen lattices. We conclude that ILK is necessary to transduce signals implicated in the transition of dermal fibroblasts to myofibroblasts originating from matrix substrates and TGF-β1.

Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation

PubMed Central

Shen, Chong; Jiang, Lifang; Shao, Huawei; You, Chuangang; Zhang, Guoliang; Ding, Sitong; Bian, Tingwei; Han, Chunmao; Meng, Qin

2016-01-01

Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by Pseudomonas aeruginosa, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including α-SMA expression and collagen secretion/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and α-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring. PMID:27901027

Effect of near infrared lasers and glycated chitosan on myofibroblast differentiation and contraction

NASA Astrophysics Data System (ADS)

Obioma, Christiana C.; Layton, Elivia; Doan, Khue Tu; Xu, Gang; Zhou, Feifan; Chen, Wei R.; Vaughan, Melville B.

2018-02-01

The ability to modulate myofibroblast phenotype will have an impact in wound healing, aging, cancer, and Dupuytren's contracture development. Our project focused on investigating the effect of 808 nm laser wavelength on the presence of myofibroblast and contraction using anchored delayed release collagen lattice models. Fibroblast cells were cultured and suspended in collagen lattices in the presence or absence of glycated chitosan (GC) to mimic a wound healing environment in-vitro. The cells were allowed to generate maximum tension for 6 days followed by laser light stimulation. The total number of cells and presence of fibroblast proliferation and differentiation into myofibroblasts was determined using immunostaining followed by fluorescent microscope photography. Lattice tension generation was assessed by releasing the lattices from their anchorage and measuring their diameters. Control lattices contracted more than GC lattices. Myofibroblast differentiation was slightly higher in the control group. Repeats of the experiment are needed to confirm our results to determine if near infra-red laser radiation can be applied to treat open wounds and study tumor stromas.

Active multilayered capsules for in vivo bone formation

PubMed Central

Facca, S.; Cortez, C.; Mendoza-Palomares, C.; Messadeq, N.; Dierich, A.; Johnston, A. P. R.; Mainard, D.; Voegel, J.-C.; Caruso, F.; Benkirane-Jessel, N.

2010-01-01

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled. PMID:20160118

Human Lumbar Spine Creep during Cyclic and Static Flexion: Creep Rate, Biomechanics, and Facet Joint Capsule Strain

PubMed Central

Little, Jesse S.; Khalsa, Partap S.

2005-01-01

There is a high incidence of low back pain (LBP) associated with occupations requiring sustained and/or repetitive lumbar flexion (SLF and RLF, respectively), which cause creep of the viscoelastic tissues. The purpose of this study was to determine the effect of creep on lumbar biomechanics and facet joint capsule (FJC) strain. Specimens were flexed for 10 cycles, to a maximum 10 Nm moment at L5-S1, before, immediately after, and 20 min after a 20-min sustained flexion at the same moment magnitude. The creep rates of SLF and RLF were also measured during each phase and compared to the creep rate predicted by the moment relaxation rate function of the lumbar spine. Both SLF and RLF resulted in significantly increased intervertebral motion, as well as significantly increased FJC strains at the L3-4 to L5-S1 joint levels. These parameters remained increased after the 20-min recovery. Creep during SLF occurred significantly faster than creep during RLF. The moment relaxation rate function was able to accurately predict the creep rate of the lumbar spine at the single moment tested. The data suggest that SLF and RLF result in immediate and residual laxity of the joint and stretch of the FJC, which could increase the potential for LBP. PMID:15868730

Pro-angiogenic capacities of microvesicles produced by skin wound myofibroblasts.

PubMed

Merjaneh, Mays; Langlois, Amélie; Larochelle, Sébastien; Cloutier, Chanel Beaudoin; Ricard-Blum, Sylvie; Moulin, Véronique J

2017-08-01

Wound healing is a very highly organized process where numerous cell types are tightly regulated to restore injured tissue. Myofibroblasts are cells that produce new extracellular matrix and contract wound edges. We previously reported that the human myofibroblasts isolated from normal wound (WMyos) produced microvesicles (MVs) in the presence of the serum. In this study, MVs were further characterized using a proteomic strategy and potential functions of the MVs were determined. MV proteins isolated from six WMyo populations were separated using two-dimensional differential gel electrophoresis. Highly conserved spots were selected and analyzed using mass spectrometry resulting in the identification of 381 different human proteins. Using the DAVID database, clusters of proteins involved in cell motion, apoptosis and adhesion, but also in extracellular matrix production (21 proteins, enrichment score: 3.32) and in blood vessel development/angiogenesis (19 proteins, enrichment score: 2.66) were identified. Another analysis using the functional enrichment analysis tool FunRich was consistent with these results. While the action of the myofibroblasts on extracellular matrix formation is well known, their angiogenic potential is less studied. To further characterize the angiogenic activity of the MVs, they were added to cultured microvascular endothelial cells to evaluate their influence on cell growth and migration using scratch test and capillary-like structure formation in Matrigel ® . The addition of a MV-enriched preparation significantly increased endothelial cell growth, migration and capillary formation compared with controls. The release of microvesicles by the wound myofibroblasts brings new perspectives to the field of communication between cells during the normal healing process.

The aryl hydrocarbon receptor ligand ITE inhibits TGFβ1-induced human myofibroblast differentiation.

PubMed

Lehmann, Geniece M; Xi, Xia; Kulkarni, Ajit A; Olsen, Keith C; Pollock, Stephen J; Baglole, Carolyn J; Gupta, Shikha; Casey, Ann E; Huxlin, Krystel R; Sime, Patricia J; Feldon, Steven E; Phipps, Richard P

2011-04-01

Fibrosis can occur in any human tissue when the normal wound healing response is amplified. Such amplification results in fibroblast proliferation, myofibroblast differentiation, and excessive extracellular matrix deposition. Occurrence of these sequelae in organs such as the eye or lung can result in severe consequences to health. Unfortunately, medical treatment of fibrosis is limited by a lack of safe and effective therapies. These therapies may be developed by identifying agents that inhibit critical steps in fibrotic progression; one such step is myofibroblast differentiation triggered by transforming growth factor-β1 (TGFβ1). In this study, we demonstrate that TGFβ1-induced myofibroblast differentiation is blocked in human fibroblasts by a candidate endogenous aryl hydrocarbon receptor (AhR) ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Our data show that ITE disrupts TGFβ1 signaling by inhibiting the nuclear translocation of Smad2/3/4. Although ITE functions as an AhR agonist, and biologically persistent AhR agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, cause severe toxic effects, ITE exhibits no toxicity. Interestingly, ITE effectively inhibits TGFβ1-driven myofibroblast differentiation in AhR(-/-) fibroblasts: Its ability to inhibit TGFβ1 signaling is AhR independent. As supported by the results of this study, the small molecule ITE inhibits myofibroblast differentiation and may be useful clinically as an antiscarring agent. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The Aryl Hydrocarbon Receptor Ligand ITE Inhibits TGFβ1-Induced Human Myofibroblast Differentiation

PubMed Central

Lehmann, Geniece M.; Xi, Xia; Kulkarni, Ajit A.; Olsen, Keith C.; Pollock, Stephen J.; Baglole, Carolyn J.; Gupta, Shikha; Casey, Ann E.; Huxlin, Krystel R.; Sime, Patricia J.; Feldon, Steven E.; Phipps, Richard P.

2011-01-01

Fibrosis can occur in any human tissue when the normal wound healing response is amplified. Such amplification results in fibroblast proliferation, myofibroblast differentiation, and excessive extracellular matrix deposition. Occurrence of these sequelae in organs such as the eye or lung can result in severe consequences to health. Unfortunately, medical treatment of fibrosis is limited by a lack of safe and effective therapies. These therapies may be developed by identifying agents that inhibit critical steps in fibrotic progression; one such step is myofibroblast differentiation triggered by transforming growth factor-β1 (TGFβ1). In this study, we demonstrate that TGFβ1-induced myofibroblast differentiation is blocked in human fibroblasts by a candidate endogenous aryl hydrocarbon receptor (AhR) ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Our data show that ITE disrupts TGFβ1 signaling by inhibiting the nuclear translocation of Smad2/3/4. Although ITE functions as an AhR agonist, and biologically persistent AhR agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, cause severe toxic effects, ITE exhibits no toxicity. Interestingly, ITE effectively inhibits TGFβ1-driven myofibroblast differentiation in AhR−/− fibroblasts: Its ability to inhibit TGFβ1 signaling is AhR independent. As supported by the results of this study, the small molecule ITE inhibits myofibroblast differentiation and may be useful clinically as an antiscarring agent. PMID:21406171

Liver myofibroblasts of murine origins express mesothelin: Identification of novel rat mesothelin splice variants*

PubMed Central

G. Lavoie, Elise; Dranoff, Jonathan A.

2017-01-01

Liver myofibroblasts are specialized effector cells that drive hepatic fibrosis, a hallmark process of chronic liver diseases, leading to progressive scar formation and organ failure. Liver myofibroblasts are increasingly recognized as heterogeneous with regards to their origin, phenotype, and functions. For instance, liver myofibroblasts express cell markers that are universally represented such as, ItgαV and Pdgfrβ, or restricted to a given subpopulation such as, Lrat exclusively expressed in hepatic stellate cells, and Gpm6a in mesothelial cells. To study liver myofibroblasts in vitro, we have previously generated and characterized a SV40-immortalized polyclonal rat activated portal fibroblast cell line called RGF-N2 expressing multiple mesothelin mRNA transcripts. Mesothelin, a cell-surface molecule expressed in normal mesothelial cells and overexpressed in several cancers such as, mesothelioma and cholangiocarcinoma, was recently identified as a key regulator of portal myofibroblast proliferation, and fibrosis progression in the setting of chronic cholestatic liver disease. Here, we identify novel mesothelin splice variants expressed in rat activated portal fibroblasts. RGF-N2 portal fibroblast cDNA was used as template for insertion of hemagglutinin tag consensus sequence into the complete open reading frame of rat mesothelin variant coding sequences by extension PCR. Purified amplicons were subsequently cloned into an expression vector for in vitro translation and transfection in monkey COS7 fibroblasts, before characterization of fusion proteins by immunoblot and immunofluorescence. We show that rat activated portal fibroblasts, hepatic stellate cells, and cholangiocarcinoma cells express wild-type mesothelin and additional splice variants, while mouse activated hepatic stellate cells appear to only express wild-type mesothelin. Notably, rat mesothelin splice variants differ from the wild-type isoform by their protein properties and cellular distribution

Closed Loop Control of a Tethered Magnetic Capsule Endoscope

PubMed Central

Taddese, Addisu Z.; Slawinski, Piotr R.; Obstein, Keith L.; Valdastri, Pietro

2017-01-01

Magnetic field gradients have repeatedly been shown to be the most feasible mechanism for gastrointestinal capsule endoscope actuation. An inverse quartic magnetic force variation with distance results in large force gradients induced by small movements of a driving magnet; this necessitates robotic actuation of magnets to implement stable control of the device. A typical system consists of a serial robot with a permanent magnet at its end effector that actuates a capsule with an embedded permanent magnet. We present a tethered capsule system where a capsule with an embedded magnet is closed loop controlled in 2 degree-of-freedom in position and 2 degree-of-freedom in orientation. Capitalizing on the magnetic field of the external driving permanent magnet, the capsule is localized in 6-D allowing for both position and orientation feedback to be used in a control scheme. We developed a relationship between the serial robot's joint parameters and the magnetic force and torque that is exerted onto the capsule. Our methodology was validated both in a dynamic simulation environment where a custom plug-in for magnetic interaction was written, as well as on an experimental platform. The tethered capsule was demonstrated to follow desired trajectories in both position and orientation with accuracy that is acceptable for colonoscopy. PMID:28286886

Closed Loop Control of a Tethered Magnetic Capsule Endoscope.

PubMed

Taddese, Addisu Z; Slawinski, Piotr R; Obstein, Keith L; Valdastri, Pietro

2016-06-01

Magnetic field gradients have repeatedly been shown to be the most feasible mechanism for gastrointestinal capsule endoscope actuation. An inverse quartic magnetic force variation with distance results in large force gradients induced by small movements of a driving magnet; this necessitates robotic actuation of magnets to implement stable control of the device. A typical system consists of a serial robot with a permanent magnet at its end effector that actuates a capsule with an embedded permanent magnet. We present a tethered capsule system where a capsule with an embedded magnet is closed loop controlled in 2 degree-of-freedom in position and 2 degree-of-freedom in orientation. Capitalizing on the magnetic field of the external driving permanent magnet, the capsule is localized in 6-D allowing for both position and orientation feedback to be used in a control scheme. We developed a relationship between the serial robot's joint parameters and the magnetic force and torque that is exerted onto the capsule. Our methodology was validated both in a dynamic simulation environment where a custom plug-in for magnetic interaction was written, as well as on an experimental platform. The tethered capsule was demonstrated to follow desired trajectories in both position and orientation with accuracy that is acceptable for colonoscopy.

Metabolic Reprogramming Is Required for Myofibroblast Contractility and Differentiation*

PubMed Central

Bernard, Karen; Logsdon, Naomi J.; Ravi, Saranya; Xie, Na; Persons, Benjamin P.; Rangarajan, Sunad; Zmijewski, Jaroslaw W.; Mitra, Kasturi; Liu, Gang; Darley-Usmar, Victor M.; Thannickal, Victor J.

2015-01-01

Contraction is crucial in maintaining the differentiated phenotype of myofibroblasts. Contraction is an energy-dependent mechanism that relies on the production of ATP by mitochondria and/or glycolysis. Although the role of mitochondrial biogenesis in the adaptive responses of skeletal muscle to exercise is well appreciated, mechanisms governing energetic adaptation of myofibroblasts are not well understood. Our study demonstrates induction of mitochondrial biogenesis and aerobic glycolysis in response to the differentiation-inducing factor transforming growth factor β1 (TGF-β1). This metabolic reprogramming is linked to the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Inhibition of p38 MAPK decreased accumulation of active peroxisome proliferator-activated receptor γ coactivator 1α in the nucleus and altered the translocation of mitochondrial transcription factor A to the mitochondria. Genetic or pharmacologic approaches that block mitochondrial biogenesis or glycolysis resulted in decreased contraction and reduced expression of TGF-β1-induced α-smooth muscle actin and collagen α-2(I) but not of fibronectin or collagen α-1(I). These data indicate a critical role for TGF-β1-induced metabolic reprogramming in regulating myofibroblast-specific contractile signaling and support the concept of integrating bioenergetics with cellular differentiation. PMID:26318453

Effect of Stretching Combined With Ultrashort Wave Diathermy on Joint Function and Its Possible Mechanism in a Rabbit Knee Contracture Model.

PubMed

Zhang, Quan Bing; Zhou, Yun; Zhong, Hua Zhang; Liu, Yi

2018-05-01

The aim of this study was to investigate the therapeutic effect of stretching combined with ultrashort wave on joint contracture and explore its possible mechanism. Thirty-two rabbits underwent unilateral immobilization of a knee joint at full extension to cause joint contracture. At 6 wks after immobilization, the rabbits were randomly divided into the following four groups: natural recovery group, stretching treatment group, ultrashort wave treatment group, and combined treatment group. For comparison, eight control group animals of corresponding age were also examined. The effect of stretching and ultrashort wave treatment on joint contracture was assessed by measuring the joint range of motion, evaluating the collagen deposition of joint capsule and assessing the mRNA and protein levels for transforming growth factor β1 in the joint capsule. The combined treatment group led to the best recovery of joint function. The combined treatment with stretching and ultrashort wave was more effective than stretching or ultrashort wave treatment alone against the synovial thickening of suprapatellar joint capsule, the collagen deposition of anterior joint capsule, and the elevated expression of transforming growth factor β1 in the joint capsule. Stretching combined with ultrashort wave treatment was effective in improving joint range of motion, reducing the biomechanical, histological, and molecular manifestations of joint capsule fibrosis in a rabbit model of extending joint contracture.

Human esophageal myofibroblasts secrete proinflammatory cytokines in response to acid and Toll-like receptor 4 ligands

PubMed Central

Gargus, Matthew; Niu, Chao; Vallone, John G.; Binkley, Jana; Rubin, Deborah C.

2015-01-01

The pathophysiology of esophageal injury, repair, and inflammation in gastroesophageal reflux-disease (GERD) is complex. Whereas most studies have focused on the epithelial response to GERD injury, we are interested in the stromal response. We hypothesized that subepithelial esophageal myofibroblasts in GERD secrete proinflammatory cytokines in response to injurious agents encountered via epithelial barrier breaches or through dilated epithelial intercellular spaces. We determined the percentage of myofibroblasts [α-smooth muscle actin (α-SMA)+vimentin+CD31−] in the subepithelial GERD and normal esophageal stroma by immunomorphologic analysis. We performed α-SMA coimmunostaining with IL-6 and p65. We established and characterized primary cultures of α-SMA+vimentin+CD31−CD45− human esophageal myofibroblasts (HuEso MFs). We modeled GERD by treatment with pH 4.5-acidified media and Toll-like receptor 4 (TLR4) ligands, LPS and high-mobility group box 1 protein (HMGB1), and determined myofibroblast cytokine secretion in response to GERD injury. We demonstrate that spindle-shaped cell myofibroblasts are located near the basement membrane of stratified squamous epithelium in normal esophagus. We identify an increase in subepithelial myofibroblasts and activation of proinflammatory pathways in patients with GERD. Primary cultures of stromal cells obtained from normal esophagus retain myofibroblast morphology and express the acid receptor transient receptor potential channel vanilloid subfamily 1 (TRPV1) and TLR4. HuEso MFs stimulated with acid and TLR4 agonists LPS and HMGB1 increase IL-6 and IL-8 secretion via TRPV1 and NF-κB activation. Our work implicates a role for human subepithelial stromal cells in the pathogenesis of GERD-related esophageal injury. Findings of this study can be extended to the investigation of epithelial-stromal interactions in inflammatory esophageal mucosal disorders. PMID:25882613

Systematic review and meta-analysis of the efficacy and safety of Biqi capsule in rheumatoid arthritis patients.

PubMed

Chen, Xiu-Min; Wu, Jia-Qi; Huang, Qing-Chun; Zhang, Jian-Yong; Pen, Jian-Hong; Huang, Zhi-Sheng; Chu, Yong-Liang; He, Xiao-Hong; Wang, Mao-Jie; Huang, Run-Yue

2018-06-01

Biqi capsule is a Traditional Chinese Medicine preparation for treating rheumatoid arthritis (RA), and clinical studies have indicatedthat its effect may be more beneficial than that of Western medicine. The present study aimed to estimate the efficacy and safety of Biqi capsule alone or combined with methotrexate (MTX) compared with MTX alone for treating RA by performing a meta-analysis of randomized controlled trials and controlled clinical trials. A systematic literature search of studies published until March 2017 was performed. References from relevant studies were screened to obtain additional articles. The results were independently evaluated for relevance, and full-text studies were assessed for eligibility. The risk of bias was assessed using the Cochrane collaboration tool for assessing risk of bias. Out of 558 citations that were initially retrieved, a total of 5 studies comprising 522 patients met the inclusion criteria. The risk of bias of these trials was generally unclear or high. Meta-analysis indicated that Biqi capsule had better effects on C-reactive protein [standardized mean difference (SMD), -7.05; 95% CI -(10.77-3.33)] and tender joint count [SMD, -3.02; 95% CI, -(3.81-2.22)] and fewer adverse effects (AEs) than MTX [relative risk (RR), 0.19; 95% CI, 0.08-0.43]. Biqi capsule plus MTX was superior to MTX in terms of the total effect (RR, 1.17; 95% CI, 1.06-1.28), rheumatoid factor [SMD, -12.54; 95% CI, -(16.87-8.20)], swollen joint count [SMD, -1.50; 95% CI, -(1.99-1.01)], score of joint swelling [SMD -2.07; 95% CI, -(2.76-1.38)], tender joint count [SMD, -2.16; 95% CI, -(2.86-1.47)] and score of joint tenderness [SMD, -4.69; 95% CI, -(5.92-3.47)]. There was no difference in AEs between Biqi capsule plus MTX and MTX (RR, 0.71; 95% CI, 0.34-1.50). In conclusion, the present study indicated that compared with MTX, Biqi capsule plus MTX appeared to have more benefits but that Biqi capsule alone was not better for RA patients than MTX. In the

Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Luca; Bellini, Alberto; Stacey, Martin A.

2005-03-10

Myofibroblasts play a key role in wound closure but their origin is poorly understood. To investigate whether fibrocytes contribute to myofibroblast population, we examined the phenotype of fibrocytes and myofibroblasts present in the wounded skin of BALB/c mice. During wound healing, there was a marked increase in the number of cells expressing the myofibroblast marker {alpha}-smooth muscle actin in the granulation tissue. Between 4 and 7 days post-wounding, more than 50% of these cells also expressed the CD13 antigen. CD13{sup +}/collagen I{sup +} fibrocytes could be isolated at an early stage of the healing process from digested fragments of woundedmore » tissue by fluorescence-activated cell sorting. Like authentic fibrocytes, these cells were also CD45{sup +}/CD34{sup +}/CD14{sup -}. Between 4 and 7 days post-injury, 61.4% of the isolated fibrocytes were found to express {alpha}-smooth muscle actin gene and protein. We repeated similar experiments in female mice that had received a male whole bone marrow transplant after total body irradiation. By in situ hybridization, we identified the Y chromosome in the nuclei of the majority of fibrocytes isolated from the wounded tissue of these animals. Our data indicate that circulating fibrocytes contribute to the myofibroblast population in the wounded skin and that they originate from the bone marrow.« less

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

PubMed Central

Thirdborough, Steve; Mellows, Toby; Garcia, Edwin; Woo, Jeongmin; Tod, Joanne; Frampton, Steve; Jenei, Veronika; Moutasim, Karwan A.; Kabir, Tasnuva D.; Brennan, Peter A; Venturi, Giulia; Ford, Kirsty; Herranz, Nicolas; Lim, Kue Peng; Clarke, James; Lambert, Daniel W.; Prime, Stephen S.; Underwood, Timothy J.; Vijayanand, Pandurangan; Eliceiri, Kevin W.; Woelk, Christopher; King, Emma V.; Gil, Jesus; Ottensmeier, Christian H.; Thomas, Gareth J.

2017-01-01

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes. PMID:27992856

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis.

PubMed

Mellone, Massimiliano; Hanley, Christopher J; Thirdborough, Steve; Mellows, Toby; Garcia, Edwin; Woo, Jeongmin; Tod, Joanne; Frampton, Steve; Jenei, Veronika; Moutasim, Karwan A; Kabir, Tasnuva D; Brennan, Peter A; Venturi, Giulia; Ford, Kirsty; Herranz, Nicolas; Lim, Kue Peng; Clarke, James; Lambert, Daniel W; Prime, Stephen S; Underwood, Timothy J; Vijayanand, Pandurangan; Eliceiri, Kevin W; Woelk, Christopher; King, Emma V; Gil, Jesus; Ottensmeier, Christian H; Thomas, Gareth J

2016-12-15

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo , showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro , we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes.

Cadaveric Study of the Articular Branches of the Shoulder Joint.

PubMed

Eckmann, Maxim S; Bickelhaupt, Brittany; Fehl, Jacob; Benfield, Jonathan A; Curley, Jonathan; Rahimi, Ohmid; Nagpal, Ameet S

This cadaveric study investigated the anatomic relationships of the articular branches of the suprascapular (SN), axillary (AN), and lateral pectoral nerves (LPN), which are potential targets for shoulder analgesia. Sixteen embalmed cadavers and 1 unembalmed cadaver, including 33 shoulders total, were dissected. Following dissections, fluoroscopic images were taken to propose an anatomical landmark to be used in shoulder articular branch blockade. Thirty-three shoulders from 17 total cadavers were studied. In a series of 16 shoulders, 16 (100%) of 16 had an intact SN branch innervating the posterior head of the humerus and shoulder capsule. Suprascapular sensory branches coursed laterally from the spinoglenoid notch then toward the glenohumeral joint capsule posteriorly. Axillary nerve articular branches innervated the posterolateral head of the humerus and shoulder capsule in the same 16 (100%) of 16 shoulders. The AN gave branches ascending circumferentially from the quadrangular space to the posterolateral humerus, deep to the deltoid, and inserting at the inferior portion of the posterior joint capsule. In 4 previously dissected and 17 distinct shoulders, intact LPNs could be identified in 14 (67%) of 21 specimens. Of these, 12 (86%) of 14 had articular branches innervating the anterior shoulder joint, and 14 (100%) of 14 LPN articular branches were adjacent to acromial branches of the thoracoacromial blood vessels over the superior aspect of the coracoid process. Articular branches from the SN, AN, and LPN were identified. Articular branches of the SN and AN insert into the capsule overlying the glenohumeral joint posteriorly. Articular branches of the LPN exist and innervate a portion of the anterior shoulder joint.

Capsule endoscopy

MedlinePlus

Capsule enteroscopy; Wireless capsule endoscopy; Video capsule endoscopy (VCE); Small bowel capsule endoscopy (SBCE) ... a computer and software turns them into a video. Your provider watches the video to look for ...

Very late antigen-5 facilitates stromal progenitor cell differentiation into myofibroblast.

PubMed

Sen, Namita; Weingarten, Mark; Peter, Yakov

2014-11-01

Fibrotic disease is associated with abrogated stromal cell proliferation and activity. The precise identity of the cells that drive fibrosis remains obscure, in part because of a lack of information on their lineage development. To investigate the role of an early stromal progenitor cell (SPC) on the fibrotic process, we selected for, and monitored the stages of, fibroblast development from a previously reported free-floating anchorage-independent cell (AIC) progenitor population. Our findings demonstrate that organotypic pulmonary, cardiac, and renal fibroblast commitment follows a two-step process of attachment and remodeling in culture. Cell differentiation was confirmed by the inability of SPCs to revert to the free-floating state and functional mesenchymal stem/stromal cell (MSC) differentiation into osteoblast, adipocyte, chondrocyte, and fibroblastic lineages. The myofibroblastic phenotype was reflected by actin stress-fiber formation, α-smooth muscle production, and a greater than threefold increase in proliferative activity compared with that of the progenitors. SPC-derived pulmonary myofibroblasts demonstrated a more than 300-fold increase in fibronectin-1 (Fn1), collagen, type 1, α1, integrin α-5 (Itga5), and integrin β-1 (Itgb1) transcript levels. Very late antigen-5 (ITGA5/ITGB1) protein cluster formations were also prevalent on the differentiated cells. Normalized SPC-derived myofibroblast expression patterns reflected those of primary cultured lung myofibroblasts. Intratracheal implantation of pulmonary AICs into recipient mouse lungs resulted in donor cell FN1 production and evidence of epithelial derivation. SPC derivation into stromal tissue in vitro and in vivo and the observation that MSC and fibroblast lineages share a common ancestor could potentially lead to personalized antifibrotic therapies. ©AlphaMed Press.

Influence of capsule shell composition on the performance indicators of hypromellose capsule in comparison to hard gelatin capsules.

PubMed

Al-Tabakha, Moawia M; Arida, Adi Issam; Fahelelbom, Khairi M S; Sadek, Bassem; Saeed, Dima Ahmed; Abu Jarad, Rami A; Jawadi, Jeevani

2015-01-01

The purpose of this study was to assess the in vitro performances of "vegetable" capsules in comparison to hard gelatin capsules in terms of shell weight variation, reaction to different humidity conditions, resistance to stress in the absence of moisture, powder leakage, disintegration and dissolution. Two types of capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight variability was relatively low for all tested capsules shells. Although Capsule 1 had the highest moisture content under different humidity conditions, all capsule types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone (PVP) powder from surrounding humidity. The initial disintegration for all Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n = 18). Dissolution of acetaminophen was better when the deionized water (DIW) temperature increased from 32 to 42 °C in case of Capsule 1, but the effect of temperature was not significant for the other types of capsules. Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and independent of the media pH or contents unlike Capsule 2 which was influenced by the pH and dissolution medium contents. It is feasible to use hypromellose capsules shells with or without gelling agent for new lines of pharmaceutical products, however, there is a window for capsule shells manufacturing companies to improve the dissolution of their hypromellose capsules to match the conventional gelatin capsule shells and eventually replace them.

Tanshinon IIA injection accelerates tissue expansion by reducing the formation of the fibrous capsule.

PubMed

Yu, Qingxiong; Sheng, Lingling; Yang, Mei; Zhu, Ming; Huang, Xiaolu; Li, Qingfeng

2014-01-01

The tissue expansion technique has been applied to obtain new skin tissue to repair large defects in clinical practice. The implantation of tissue expander could initiate a host response to foreign body (FBR), which leads to fibrotic encapsulation around the expander and prolongs the period of tissue expansion. Tanshinon IIA (Tan IIA) has been shown to have anti-inflammation and immunoregulation effect. The rat tissue expansion model was used in this study to observe whether Tan IIA injection systematically could inhibit the FBR to reduce fibrous capsule formation and accelerate the process of tissue expansion. Forty-eight rats were randomly divided into the Tan IIA group and control group with 24 rats in each group. The expansion was conducted twice a week to maintain a capsule pressure of 60 mmHg. The expansion volume and expanded area were measured. The expanded tissue in the two groups was harvested, and histological staining was performed; proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) were examined. The expansion volume and the expanded area in the Tan IIA group were greater than that of the control group. The thickness of the fibrous capsule in the Tan IIA group was reduced with no influence on the normal skin regeneration. Decreased infiltration of macrophages, lower level of TNF-α, IL-6, IL-1β and TGF-β, less proliferating myofibroblasts and enhanced neovascularization were observed in the Tan IIA group. Our findings indicated that the Tan IIA injection reduced the formation of the fibrous capsule and accelerated the process of tissue expansion by inhibiting the FBR.

Activation of MRTF-A–dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing

PubMed Central

Velasquez, Lissette S.; Sutherland, Lillian B.; Liu, Zhenan; Grinnell, Frederick; Kamm, Kristine E.; Schneider, Jay W.; Olson, Eric N.; Small, Eric M.

2013-01-01

Myocardin-related transcription factors (MRTFs) regulate cellular contractility and motility by associating with serum response factor (SRF) and activating genes involved in cytoskeletal dynamics. We reported previously that MRTF-A contributes to pathological cardiac remodeling by promoting differentiation of fibroblasts to myofibroblasts following myocardial infarction. Here, we show that forced expression of MRTF-A in dermal fibroblasts stimulates contraction of a collagen matrix, whereas contractility of MRTF-A null fibroblasts is impaired under basal conditions and in response to TGF–β1 stimulation. We also identify an isoxazole ring-containing small molecule, previously shown to induce smooth muscle α-actin gene expression in cardiac progenitor cells, as an agonist of myofibroblast differentiation. Isoxazole stimulates myofibroblast differentiation via induction of MRTF-A–dependent gene expression. The MRTF-SRF signaling axis is activated in response to skin injury, and treatment of dermal wounds with isoxazole accelerates wound closure and suppresses the inflammatory response. These results reveal an important role for MRTF-SRF signaling in dermal myofibroblast differentiation and wound healing and suggest that targeting MRTFs pharmacologically may prove useful in treating diseases associated with inappropriate myofibroblast activity. PMID:24082095

Multiple intraosseous inflammatory myofibroblastic tumors presenting with an aggressive clinical course: case report.

PubMed

Sasagawa, Yasuo; Akai, Takuya; Itou, Shoutarou; Iizuka, Hideaki

2011-10-01

The authors report a rare case of multiple intraosseous inflammatory myofibroblastic tumors presenting with an aggressive clinical course. A 60-year-old man presented with a 3-month history of headache and 2 weeks of jaw pain. Magnetic resonance imaging showed a homogeneously enhancing mass in the right parietal bone with subcutaneous and intracranial invasion. Bone scintigraphy revealed 4 intraosseous lesions involving the cranium, mandible, ischium, and calcaneum. After admission, the patient showed left hemiparesis and seizures caused by rapid intracranial tumor extension. The cranial and mandible tumors were resected. Histopathological examinations of both specimens revealed myofibroblastic spindle cell proliferation with inflammatory cell infiltration, and a diagnosis of inflammatory myofibroblastic tumor was made. Two days postoperatively, the patient presented with a high fever and disturbance of consciousness with swelling of the subcutaneous tissues of the head and mandibular lesions. Magnetic resonance imaging revealed a massive intracranial extension of the tumor. Corticosteroid therapy induced remarkable shrinkage of all lesions, and relief from symptoms was obtained. Radiotherapy was then performed for residual tumors. Multiple intraosseous inflammatory myofibroblastic tumors of the bone are very uncommon and may mimic malignant tumors. It is important to recognize that this entity can occur in the cranium and as multiple bony lesions. The recommended treatment is complete surgical resection with adjuvant steroid treatment. Considering the aggressive nature of this entity, additional chemo- and/or radiotherapy may be warranted.

Anti-inflammatory and antinociceptive effects of Chinese medicine SQ gout capsules and its modulation of pro-inflammatory cytokines focusing on gout arthritis.

PubMed

Kodithuwakku, Nandani Darshika; Pan, Min; Zhu, Yi-lin; Zhang, Yan-yan; Feng, Yi-dong; Fang, Wei-rong; Li, Yun-man

2013-12-12

Shuang-Qi gout capsule is a traditional Chinese medicine prescription, which has been used in the treatment of joint pain, inflammation and gout arthritis. This study evaluates anti-inflammatory and antinociceptive effects of Shuang-Qi gout capsule and its modulation of pro-inflammatory cytokines with special reference to gout arthritis. Anti-inflammatory effect of Shuang-Qi gout capsule was investigated bymice tail-flick response, acetic acid induced writhing response, Xylene-induced auricle inflammation and the hind paw volume of the monosodium urate (MSU) crystal induced rats with different time durations. To investigate the effects on gout arthritis, ankle joint of rats induced by MSU crystals and assessed for edema and histopathological changes. In vitro, prepared serum was incubated with urate crystal induced HUVE cells and the release of TNF-α and IL-1β determined by ELISA. Shuang-Qi gout capsule showed significant and dose dependent anti-inflammatory effect via reducing edema and pain, throughout all the models. The high dose of Shuang-Qi gout capsule and Indomethacin significantly attenuated the edema. Histopathological results showed that high and medium dose of Shuang-Qi gout capsule and Indomethacin reduced gouty joint inflammatory features, while the high dose of Shuang-Qi gout capsule showed a better therapeutic effect. High and medium dose of Shuang-Qi gout capsule significantly reduced the release of TNF-α and IL-1β (p<0.05). Shuang-Qi gout capsule can effectively inhibit the inflammation, analgesia, through the modulation of emission of pro-inflammatory cytokines and the curative effect is dose dependent. Conversely, these MSU induced in vivo and in vitro studies of Shuang-Qi gout capsule suggest that, Shuang-Qi gout capsule may be a potential agent for treatment in gouty arthritis. © 2013 Published by Elsevier Ireland Ltd.

Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4.

PubMed

Tsubouchi, Kazuya; Araya, Jun; Minagawa, Shunsuke; Hara, Hiromichi; Ichikawa, Akihiro; Saito, Nayuta; Kadota, Tsukasa; Sato, Nahoko; Yoshida, Masahiro; Kurita, Yusuke; Kobayashi, Kenji; Ito, Saburo; Fujita, Yu; Utsumi, Hirofumi; Yanagisawa, Haruhiko; Hashimoto, Mitsuo; Wakui, Hiroshi; Yoshii, Yutaka; Ishikawa, Takeo; Numata, Takanori; Kaneko, Yumi; Asano, Hisatoshi; Yamashita, Makoto; Odaka, Makoto; Morikawa, Toshiaki; Nakayama, Katsutoshi; Nakanishi, Yoichi; Kuwano, Kazuyoshi

2017-08-03

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.

EPAC expression and function in cardiac fibroblasts and myofibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy

In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF weremore » treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in

Transforming Growth Factor β-1 Stimulates Profibrotic Epithelial Signaling to Activate Pericyte-Myofibroblast Transition in Obstructive Kidney Fibrosis

PubMed Central

Wu, Ching-Fang; Chiang, Wen-Chih; Lai, Chun-Fu; Chang, Fan-Chi; Chen, Yi-Ting; Chou, Yu-Hsiang; Wu, Ting-Hui; Linn, Geoffrey R.; Ling, Hong; Wu, Kwan-Dun; Tsai, Tun-Jun; Chen, Yung-Ming; Duffield, Jeremy S.; Lin, Shuei-Liong

2014-01-01

Pericytes have been identified as the major source of precursors of scar-producing myofibroblasts during kidney fibrosis. The underlying mechanisms triggering pericyte-myofibroblast transition are poorly understood. Transforming growth factor β-1 (TGF-β1) is well recognized as a pluripotent cytokine that drives organ fibrosis. We investigated the role of TGF-β1 in inducing profibrotic signaling from epithelial cells to activate pericyte-myofibroblast transition. Increased expression of TGF-β1 was detected predominantly in injured epithelium after unilateral ureteral obstruction, whereas downstream signaling from the TGF-β1 receptor increased in both injured epithelium and pericytes. In mice with ureteral obstruction that were treated with the pan anti–TGF-β antibody (1D11) or TGF-β receptor type I inhibitor (SB431542), kidney pericyte-myofibroblast transition was blunted. The consequence was marked attenuation of fibrosis. In addition, epithelial cell cycle G2/M arrest and production of profibrotic cytokines were both attenuated. Although TGF-β1 alone did not trigger pericyte proliferation in vitro, it robustly induced α smooth muscle actin (α-SMA). In cultured kidney epithelial cells, TGF-β1 stimulated G2/M arrest and production of profibrotic cytokines that had the capacity to stimulate proliferation and transition of pericytes to myofibroblasts. In conclusion, this study identified a novel link between injured epithelium and pericyte-myofibroblast transition through TGF-β1 during kidney fibrosis. PMID:23142380

Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

NASA Astrophysics Data System (ADS)

Yu, Cheng-Chia; Yu, Chuan-Hang; Chang, Yu-Chao

2016-11-01

Oral submucous fibrosis (OSF), regarded as a precancerous condition, is characterized by juxta-epithelial inflammatory reaction followed by fibro-elastic change in the lamina properia and epithelial atrophy. The pathologic mechanisms of OSF still need to be further clarified. In the study, we investigated the functional expression of SSEA-4, which is a well-known stemness marker, in myofibroblast activity and the clinical significance in OSF tissues. The expression of SSEA-4 in OSF was evaluated by immunohistochemical staining. Functional analysis of SSEA-4 on myofibroblast activity of OSF was achieved by lentiviral silencing ST3GAL2. Immunohisitochemistry demonstrated that SSEA-4 expression was significantly higher expression in areca quid chewing-associated OSF tissues than those of normal oral mucosa tissues. From flow cytometry analysis, arecoline dose-dependently activated SSEA-4 expression in primary human normal buccal mucosal fibroblasts (BMFs). Sorted SSEA-4-positive cells from fibrotic BMFs (fBMFs) have higher colony-forming unit, collagen gel contraction, and α-smooth muscle actin (α-SMA) expression than SSEA-4-negative subset. Knockdown of ST3GAL2 in fBMFs suppressed SSEA-4 expression, collagen contraction, migration, invasiveness, and wound healing capability. Consistently, silencing ST3GAL2 was found to repress arecoline-induced myofibroblast activity in BMFs. The study highlights SSEA-4 as a critical marker for therapeutic intervention to mediate myofibroblast transdifferentiation in areca quid chewing-associated OSF.

Capsule Endoscope Aspiration after Repeated Attempts for Ingesting a Patency Capsule

PubMed Central

Mannami, Tomohiko; Ikeda, Genyo; Seno, Satoru; Sonobe, Hiroshi; Fujiwara, Nobukiyo; Komoda, Minori; Edahiro, Satoru; Ohtawa, Yasuyuki; Fujimoto, Yoshimi; Sato, Naohiro; Kambara, Takeshi; Waku, Toshihiko

2015-01-01

Capsule endoscope aspiration into the respiratory tract is a rare complication of capsule endoscopy. Despite the potential seriousness of this complication, no accepted methods exist to accurately predict and therefore prevent it. We describe the case of an 85-year-old male who presented for evaluation of iron deficiency anemia. He complained of dysphagia while ingesting a patency capsule, with several attempts over a period of 5 min before he was successful. Five days later, he underwent capsule endoscopy, where he experienced similar symptoms in swallowing the capsule. The rest of the examination proceeded uneventfully. On reviewing the captured images, the capsule endoscope was revealed to be aspirated, remaining in the respiratory tract for approximately 220 s before images of the esophagus and stomach appeared. To our knowledge, this is the first documented case of a patient who experienced capsule endoscope aspiration after ingestion of a patency capsule. This case suggests that repeated attempts required for ingesting the patency capsule can predict capsule endoscope aspiration. We presume that paying sufficient attention to the symptoms of a patient who ingests a patency capsule could help us prevent serious complications such as aspiration of the capsule endoscope. In addition, this experience implies the potential risk for ingesting the patency capsule. We must be aware that the patency capsule could also be aspirated and there may be more unrecognized aspiration cases. PMID:26600772

Capsule Endoscope Aspiration after Repeated Attempts for Ingesting a Patency Capsule.

PubMed

Mannami, Tomohiko; Ikeda, Genyo; Seno, Satoru; Sonobe, Hiroshi; Fujiwara, Nobukiyo; Komoda, Minori; Edahiro, Satoru; Ohtawa, Yasuyuki; Fujimoto, Yoshimi; Sato, Naohiro; Kambara, Takeshi; Waku, Toshihiko

2015-01-01

Capsule endoscope aspiration into the respiratory tract is a rare complication of capsule endoscopy. Despite the potential seriousness of this complication, no accepted methods exist to accurately predict and therefore prevent it. We describe the case of an 85-year-old male who presented for evaluation of iron deficiency anemia. He complained of dysphagia while ingesting a patency capsule, with several attempts over a period of 5 min before he was successful. Five days later, he underwent capsule endoscopy, where he experienced similar symptoms in swallowing the capsule. The rest of the examination proceeded uneventfully. On reviewing the captured images, the capsule endoscope was revealed to be aspirated, remaining in the respiratory tract for approximately 220 s before images of the esophagus and stomach appeared. To our knowledge, this is the first documented case of a patient who experienced capsule endoscope aspiration after ingestion of a patency capsule. This case suggests that repeated attempts required for ingesting the patency capsule can predict capsule endoscope aspiration. We presume that paying sufficient attention to the symptoms of a patient who ingests a patency capsule could help us prevent serious complications such as aspiration of the capsule endoscope. In addition, this experience implies the potential risk for ingesting the patency capsule. We must be aware that the patency capsule could also be aspirated and there may be more unrecognized aspiration cases.

Direct Posterior Bipolar Cervical Facet Radiofrequency Rhizotomy: A Simpler and Safer Approach to Denervate the Facet Capsule.

PubMed

Palea, Ovidiu; Andar, Haroon M; Lugo, Ramon; Granville, Michelle; Jacobson, Robert E

2018-03-14

Radiofrequency cervical rhizotomy has been shown to be effective for the relief of chronic neck pain, whether it be due to soft tissue injury, cervical spondylosis, or post-cervical spine surgery. The target and technique have traditionally been taught using an oblique approach to the anterior lateral capsule of the cervical facet joint. The goal is to position the electrode at the proximal location of the recurrent branch after it leaves the exiting nerve root and loops back to the cervical facet joint. The standard oblique approach to the recurrent nerve requires the testing of both motor and sensory components to verify the correct position and ensure safety so as to not damage the slightly more anterior nerve root. Bilateral lesions require the repositioning of the patient's neck. Poorly positioned electrodes can also pass anteriorly and contact the nerve root or vertebral artery. The direct posterior approach presented allows electrode positioning over a broader expanse of the facet joint without risk to the nerve root or vertebral artery. Over a four-year period, direct posterior radiofrequency ablation was performed under fluoroscopic guidance at multiple levels without neuro-stimulation testing with zero procedural neurologic events even as high as the C2 spinal segment. The direct posterior approach allows either unipolar or bipolar lesioning at multiple levels. Making a radiofrequency lesion along the larger posterior area of the facet capsule is as effective as the traditional target point closer to the nerve root but technically easier, allowing bilateral access and safety. The article will review the anatomy and innervation of the cervical facet joint and capsule, showing the diffuse nerve supply extending into the capsule of the facet joint that is more extensive than the recurrent medial sensory branches that have been the focus of radiofrequency lesioning.

Direct Posterior Bipolar Cervical Facet Radiofrequency Rhizotomy: A Simpler and Safer Approach to Denervate the Facet Capsule

PubMed Central

Palea, Ovidiu; Andar, Haroon M; Lugo, Ramon; Jacobson, Robert E

2018-01-01

Radiofrequency cervical rhizotomy has been shown to be effective for the relief of chronic neck pain, whether it be due to soft tissue injury, cervical spondylosis, or post-cervical spine surgery. The target and technique have traditionally been taught using an oblique approach to the anterior lateral capsule of the cervical facet joint. The goal is to position the electrode at the proximal location of the recurrent branch after it leaves the exiting nerve root and loops back to the cervical facet joint. The standard oblique approach to the recurrent nerve requires the testing of both motor and sensory components to verify the correct position and ensure safety so as to not damage the slightly more anterior nerve root. Bilateral lesions require the repositioning of the patient's neck. Poorly positioned electrodes can also pass anteriorly and contact the nerve root or vertebral artery. The direct posterior approach presented allows electrode positioning over a broader expanse of the facet joint without risk to the nerve root or vertebral artery. Over a four-year period, direct posterior radiofrequency ablation was performed under fluoroscopic guidance at multiple levels without neuro-stimulation testing with zero procedural neurologic events even as high as the C2 spinal segment. The direct posterior approach allows either unipolar or bipolar lesioning at multiple levels. Making a radiofrequency lesion along the larger posterior area of the facet capsule is as effective as the traditional target point closer to the nerve root but technically easier, allowing bilateral access and safety. The article will review the anatomy and innervation of the cervical facet joint and capsule, showing the diffuse nerve supply extending into the capsule of the facet joint that is more extensive than the recurrent medial sensory branches that have been the focus of radiofrequency lesioning. PMID:29765790

Experimental measurement and modeling analysis on mechanical properties of incudostapedial joint

PubMed Central

Zhang, Xiangming

2011-01-01

The incudostapedial (IS) joint between the incus and stapes is a synovial joint consisting of joint capsule, cartilage, and synovial fluid. The mechanical properties of the IS joint directly affect the middle ear transfer function for sound transmission. However, due to the complexity and small size of the joint, the mechanical properties of the IS joint have not been reported in the literature. In this paper, we report our current study on mechanical properties of human IS joint using both experimental measurement and finite element (FE) modeling analysis. Eight IS joint samples with the incus and stapes attached were harvested from human cadaver temporal bones. Tension, compression, stress relaxation and failure tests were performed on those samples in a micro-material testing system. An analytical approach with the hyperelastic Ogden model and a 3D FE model of the IS joint including the cartilage, joint capsule, and synovial fluid were employed to derive mechanical parameters of the IS joint. The comparison of measurements and modeling results reveals the relationship between the mechanical properties and structure of the IS joint. PMID:21061141

Experimental measurement and modeling analysis on mechanical properties of incudostapedial joint.

PubMed

Zhang, Xiangming; Gan, Rong Z

2011-10-01

The incudostapedial (IS) joint between the incus and stapes is a synovial joint consisting of joint capsule, cartilage, and synovial fluid. The mechanical properties of the IS joint directly affect the middle ear transfer function for sound transmission. However, due to the complexity and small size of the joint, the mechanical properties of the IS joint have not been reported in the literature. In this paper, we report our current study on mechanical properties of human IS joint using both experimental measurement and finite element (FE) modeling analysis. Eight IS joint samples with the incus and stapes attached were harvested from human cadaver temporal bones. Tension, compression, stress relaxation and failure tests were performed on those samples in a micro-material testing system. An analytical approach with the hyperelastic Ogden model and a 3D FE model of the IS joint including the cartilage, joint capsule, and synovial fluid were employed to derive mechanical parameters of the IS joint. The comparison of measurements and modeling results reveals the relationship between the mechanical properties and structure of the IS joint.

Inhibitory effects of hepatocyte growth factor and interleukin-6 on transforming growth factor-beta1 mediated vocal fold fibroblast-myofibroblast differentiation.

PubMed

Vyas, Bimal; Ishikawa, Keiko; Duflo, Suzy; Chen, Xia; Thibeault, Susan L

2010-05-01

The role of myofibroblasts in vocal fold scarring has not been extensively studied, partly because of the lack of a robust in vitro model. The objective of this investigation was to develop and characterize a myofibroblast in vitro model that could be utilized to investigate the molecular mechanism of myofibroblast differentiation and function in injured vocal fold tissue. Differentiation of human primary vocal fold fibroblasts (hVFFs) to myofibroblasts was stimulated with 5, 10, or 20 ng/mL of recombinant transforming growth factor-beta1 (TGF-beta1). Cultures were analyzed by immunofluorescence and Western blotting, with an alpha-smooth muscle actin (alpha-SMA) antibody used as a myofibroblast marker. Normal rabbit vocal folds were treated with 10 ng/mL of TGF-beta1 for 7 days for in vivo corroboration. The effects of interleukin-6 (IL-6) and hepatocyte growth factor (HGF) on myofibroblast differentiation were studied with Western blots. The hVFFs demonstrated positive alpha-SMA labeling in cells stimulated by 10 and 20 ng/mL TGF-beta1, indicating that hVFFs were capable of differentiation to myofibroblasts. Transforming growth factor-beta1 induced the largest increase in alpha-SMA at 10 ng/mL on day 5 of treatment. Both HGF and IL-6 suppressed the expression of TGF-beta1-induced alpha-SMA. Our work characterizes a useful in vitro model of TGF-beta1-mediated vocal fold fibroblast-myofibroblast differentiation. The extent of differentiation appears to be attenuated by HGF, suggesting a potential mechanism to support prior work indicating that HGF plays a protective role in reducing scar formation in vocal fold injuries. Paradoxically, IL-6, which has been shown to play a profibrotic role in dermal studies, also attenuated the TGF-beta1 response.

Dorsoradial capsulodesis for trapeziometacarpal joint instability.

PubMed

Rayan, Ghazi; Do, Viet

2013-02-01

We describe an alternative method for treating chronic trapeziometacarpal (TM) joint instability after acute injury or chronic repetitive use of the thumb by performing a dorsoradial capsulodesis procedure. The procedure is done by imbricating the redundant TM joint dorsoradial ligament and capsule after reducing the joint by pronating the thumb. The dorsoradial capsulodesis is a reasonable reconstructive option for chronic TM joint instability and subluxation. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Hypoxic remodelling of Ca{sup 2+} stores does not alter human cardiac myofibroblast invasion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riches, K.; Hettiarachchi, N.T.; Porter, K.E.

2010-12-17

Research highlights: {yields} Bradykinin promotes migration and proliferation of myofibroblasts. {yields} Such activity is Ca{sup 2+}-dependent and occurs under hypoxic conditions. {yields} Hypoxia increased myofibroblast Ca{sup 2+} stores but not influx evoked by bradykinin. {yields} Myofibroblast migration and proliferation was unaffected by hypoxia. -- Abstract: Cardiac fibroblasts are the most abundant cell type in the heart, and play a key role in the maintenance and repair of the myocardium following damage such as myocardial infarction by transforming into a cardiac myofibroblast (CMF) phenotype. Repair occurs through controlled proliferation and migration, which are Ca{sup 2+} dependent processes, and often requires themore » cells to operate within a hypoxic environment. Angiotensin converting enzyme (ACE) inhibitors reduce infarct size through the promotion of bradykinin (BK) stability. Although CMF express BK receptors, their activity under the reduced O{sub 2} conditions that occur following infarct are entirely unexplored. Using Fura-2 microfluorimetry on primary human CMF, we found that hypoxia significantly increased the mobilisation of Ca{sup 2+} from intracellular stores in response to BK whilst capacitative Ca{sup 2+} entry (CCE) remained unchanged. The enhanced store mobilisation was due to a striking increase in CMF intracellular Ca{sup 2+}-store content under hypoxic conditions. However, BK-induced CMF migration or proliferation was not affected following hypoxic exposure, suggesting that Ca{sup 2+} influx rather than mobilisation is of primary importance in CMF migration and proliferation.« less

Myofibroblast secretome and its auto-/paracrine signaling

PubMed Central

Bomb, Ritin; Heckle, Mark R.; Sun, Yao; Mancarella, Salvatore; Guntaka, Ramareddy V.; Gerling, Ivan C.; Weber, Karl T.

2016-01-01

Summary Myofibroblasts (myoFb) are phenotypically transformed, contractile fibroblast-like cells expressing α-smooth muscle actin microfilaments. They are integral to collagen fibrillogenesis with scar tissue formation at sites of repair irrespective of the etiologic origins of injury or tissue involved. MyoFb can persist long after healing is complete, where their ongoing turnover of collagen accounts for a progressive structural remodeling of an organ (a.k.a. fibrosis, sclerosis or cirrhosis). Such persistent metabolic activity is derived from a secretome consisting of requisite components in the de novo generation of angiotensin (Ang) II. Autocrine and paracrine signaling induced by tissue AngII is expressed via AT1 receptor ligand binding to respectively promote: i) regulation of myoFb collagen synthesis via the fibrogenic cytokine TGF-β1-Smad pathway; and ii) dedifferentiation and protein degradation of atrophic myocytes immobilized and ensnared by fibrillar collagen at sites of scarring. Several cardioprotective strategies in the prevention of fibrosis and involving myofibroblasts are considered. They include: inducing myoFb apoptosis through inactivation of antiapoptotic proteins; AT1 receptor antagonist to interfere with auto-/paracrine myoFb signaling or to induce counterregulatory expression of ACE2; and attacking the AngII-AT1R-TGF-β1-Smad pathway by antibody or the use of triplex-forming oligonucleotides. PMID:26818589

Capsule injection system for a hydraulic capsule pipelining system

DOEpatents

Liu, Henry

1982-01-01

An injection system for injecting capsules into a hydraulic capsule pipelining system, the pipelining system comprising a pipeline adapted for flow of a carrier liquid therethrough, and capsules adapted to be transported through the pipeline by the carrier liquid flowing through the pipeline. The injection system comprises a reservoir of carrier liquid, the pipeline extending within the reservoir and extending downstream out of the reservoir, and a magazine in the reservoir for holding capsules in a series, one above another, for injection into the pipeline in the reservoir. The magazine has a lower end in communication with the pipeline in the reservoir for delivery of capsules from the magazine into the pipeline.

Simultaneously Targeting Myofibroblast Contractility and Extracellular Matrix Cross-Linking as a Therapeutic Concept in Airway Fibrosis

PubMed Central

Lin, Yu-chun; Sung, Yon K.; Jiang, Xinguo; Peters-Golden, Marc; Nicolls, Mark R.

2016-01-01

Fibrosis after solid organ transplantation is considered an irreversible process and remains the major cause of graft dysfunction and death with limited therapies. This remodeling is characterized by aberrant accumulation of contractile myofibroblasts that deposit excessive extracellular matrix (ECM) and increase tissue stiffness. However, studies demonstrate that a stiff ECM, itself, promotes fibroblast-to-myofibroblast differentiation, stimulating further ECM production. This creates a positive feedback loop that perpetuates fibrosis. We hypothesized that simultaneously targeting myofibroblast contractility with relaxin and ECM stiffness with lysyl oxidase inhibitors could break the feedback loop, thereby, reversing established fibrosis. To test this, we used the orthotopic tracheal transplanted (OTT) mouse model, which develops robust fibrotic airway remodeling. Mice with established fibrosis were treated with saline, mono-, or combination therapies. While monotherapies had no effect, combining these agents decreased collagen deposition and promoted re-epithelialization of remodeled airways. Relaxin inhibited myofibroblast differentiation and contraction, in a matrix-stiffness-dependent manner through prostaglandin E2 (PGE2). Furthermore, the effect of combination therapy was lost in PGE2 receptor knockout and PGE2 inhibited OTT mice. This study reveals the important synergistic roles of cellular contractility and tissue stiffness in the maintenance of fibrotic tissue and suggests a new therapeutic principle for fibrosis. PMID:27804215

Inflammatory Myofibroblastic Tumor Presenting with Diabetes Insipidus in an Eight-Year-Old Boy: A Case Report.

PubMed

Sarı, Erkan; Ataş, Erman; Bulut, Engin Burak; Sarı, Sebahattin; Akın, Onur; Saldır, Mehmet; Karslıoğlu, Yıldırım; Yeşilkaya, Ediz

2015-12-01

Inflammatory myofibroblastic tumors (IMT) develop as a non-neoplastic proliferation of myofibroblasts in a myxoid to collagenous stroma admixed with inflammatory cells. The symptoms depend on the specific location of the tumor, which can be anywhere, but is particularly in the respiratory system. Thus, patients with IMT can present with a variety of findings. A pediatric patient with IMT who presented with cough, breathlessness, polyuria-polydipsia, and convulsions is described in this report.

Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene.

PubMed

Saiki, Masafumi; Ohyanagi, Fumiyoshi; Ariyasu, Ryo; Koyama, Junji; Sonoda, Tomoaki; Nishikawa, Shingo; Kitazono, Satoru; Yanagitani, Noriko; Horiike, Atsushi; Ninomiya, Hironori; Ishikawa, Yuichi; Nishio, Makoto

2017-12-01

Inflammatory myofibroblastic tumor (IMT) is a neoplasm characterized by the proliferaton of myofibroblasts with the infiltration of inflammatory cells. There is no standard treatment for patients with recurrent or metastatic IMT. We describe here a patient with hyper-progressive IMT with an anaplastic lymphoma kinase (ALK) fusion gene that dramatically responded to alectinib without adverse events. His dramatic and enduring response supports the observation that alectinib may be considered a good treatment option for rare aggressive ALK-positive tumors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Posterior subtalar joint synoviography and corticosteroid injection in rheumatoid arthritis.

PubMed Central

Beaudet, F; Dixon, A S

1981-01-01

Ten posterior subtalar joints of 8 patients with rheumatoid arthritis and 12 posterior subtalar joints of 6 cadavers were studied by contrast synoviography. In the rheumatoid group the abnormalities included posterior capsule distension, filling defects caused by hypertrophic synovitis, limited or irregular filling of the anterior recess of the joint in 5 out of 10, and communication with the ankle joint in 3 out of 10. None of the cadaveric joints showed posterior capsule distension or limited or irregular filling of the anterior recess of the joint, but communication with the ankle was present in 2 joints. The joints of the patients were injected with a 1:1 mixture of sodium iothalamate 70% (Conray 420) and triamcinolone hexacetonide (Lederspan) 20 mg/ml. All patients noticed a decrease in and an improvement in walking beginning 24-48 hours after the examination. Quantitative thermography was done immediately before and 1 after injection in 2 patients who showed an improvement in thermographic index. We conclude that hindfoot inflammatory pain arising from the posterior subtalar joint is caused by distension with hypertrophic synovitis which can be difficult to detect clinically. Images PMID:7224686

Correlation between Fibrillin-1 Degradation and mRNA Downregulation and Myofibroblast Differentiation in Cultured Human Dental Pulp Tissue

PubMed Central

Yoshiba, Nagako; Yoshiba, Kunihiko; Ohkura, Naoto; Takei, Erika; Edanami, Naoki; Oda, Youhei; Hosoya, Akihiro; Nakamura, Hiroaki; Okiji, Takashi

2015-01-01

Myofibroblasts and extracellular matrix are important components in wound healing. Alpha-smooth muscle actin (α-SMA) is a marker of myofibroblasts. Fibrillin-1 is a major constituent of microfibrils and an extracellular-regulator of TGF-β1, an important cytokine in the transdifferentiation of resident fibroblasts into myofibroblasts. To study the correlation between changes in fibrillin-1 expression and myofibroblast differentiation, we examined alterations in fibrillin-1 and α-SMA expression in organotypic cultures of dental pulp in vitro. Extracted healthy human teeth were cut to 1-mm-thick slices and cultured for 7 days. In intact dental pulp, fibrillin-1 was broadly distributed, and α-SMA was observed in pericytes and vascular smooth muscle cells. After 7 days of culture, immunostaining for fibrillin-1 became faint concomitant with a downregulation in its mRNA levels. Furthermore, fibroblasts, odontoblasts and Schwann cells were immunoreactive for α-SMA with a significant increase in α-SMA mRNA expression. Double immunofluorescence staining was positive for pSmad2/3, central mediators of TGF-β signaling, and α-SMA. The administration of inhibitors for extracellular matrix proteases recovered fibrillin-1 immunostaining; moreover, fibroblasts lost their immunoreactivity for α-SMA along with a downregulation in α-SMA mRNA. These findings suggest that the expression of α-SMA is TGF-β1 dependent, and fibrillin-1 degradation and downregulation might be implicated in the differentiation of myofibroblasts in dental pulp wound healing. PMID:25805839

[Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions].

PubMed

Neuhaus, J; Heinrich, M; Schlichting, N; Oberbach, A; Fitzl, G; Schwalenberg, T; Horn, L-C; Stolzenburg, J-U

2007-09-01

Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.

Retained Capsule Endoscope.

PubMed

Aihole, Jayalaxmi S; Vishnumurthy, G S; Babu, M Narendra

2016-11-15

Capsule endoscopy was invented to visualize the entire small intestine in a non- invasive manner in adults. 1 y, 9 mo-old boy presented with generalized edema for last 3 months. His routine investigations, including the upper gastrointestinal endoscopy, colonoscopy, and contrast enhanced computed tomography scan (CECT) were normal. In view of clinical suspicion of protein losing enteropathy, we planned capsule endoscopy. The capsule was not passed even after 3 weeks. Laparoscopy revealed impacted capsule in a dilated intestinal loop proximal to an ileal stricuture. Capsule endoscopy should be used judiciously in children.

Process Development and Micro-Machining of MARBLE Foam-Cored Rexolite Hemi-Shell Ablator Capsules

DOE PAGES

Randolph, Randall Blaine; Oertel, John A.; Schmidt, Derek William; ...

2016-06-30

For this study, machined CH hemi-shell ablator capsules have been successfully produced by the MST-7 Target Fabrication Team at Los Alamos National Laboratory. Process development and micro-machining techniques have been developed to produce capsules for both the Omega and National Ignition Facility (NIF) campaigns. These capsules are gas filled up to 10 atm and consist of a machined plastic hemi-shell outer layer that accommodates various specially engineered low-density polystyrene foam cores. Machining and assembly of the two-part, step-jointed plastic hemi-shell outer layer required development of new techniques, processes, and tooling while still meeting very aggressive shot schedules for both campaigns.more » Finally, problems encountered and process improvements will be discussed that describe this very unique, complex capsule design approach through the first Omega proof-of-concept version to the larger NIF version.« less

Modular "plug-and-play" capsules for multi-capsule environment in the gastrointestinal tract.

PubMed

Phee, S J; Ting, E K; Lin, L; Huynh, V A; Kencana, A P; Wong, K J; Tan, S L

2009-01-01

The invention of wireless capsule endoscopy has opened new ways of diagnosing and treating diseases in the gastrointestinal tract. Current wireless capsules can perform simple operations such as imaging and data collection (like temperature, pressure, and pH) in the gastrointestinal tract. Researchers are now focusing on adding more sophisticated functions such as drug delivery, surgical clips/tags deployment, and tissue samples collection. The finite on-board power on these capsules is one of the factors that limits the functionalities of these wireless capsules. Thus multiple application-specific capsules would be needed to complete an endoscopic operation. This would give rise to a multi-capsule environment. Having a modular "plug-and-play" capsule design would facilitate doctors in configuring multiple application-specific capsules, e.g. tagging capsule, for use in the gastrointestinal tract. This multi-capsule environment also has the advantage of reducing power consumption through asymmetric multi-hop communication.

Tamoxifen decreases the myofibroblast count in the healing bile duct tissue of pigs

PubMed Central

Siqueira, Orlando Hiroshi Kiono; Filho, Benedito Herani; de Paula, Rafael Erthal; Áscoli, Fábio Otero; da Nóbrega, Antonio Cláudio Lucas; Carvalho, Angela Cristina Gouvêa; Pires, Andréa Rodrigues Cordovil; Gaglionone, Nicolle Cavalcante; Cunha, Karin Soares Gonçalves; Granjeiro, José Mauro

2013-01-01

OBJECTIVE: The aim of this study was to evaluate the effect of oral tamoxifen treatment on the number of myofibroblasts present during the healing process after experimental bile duct injury. METHODS: The sample consisted of 16 pigs that were divided into two groups (the control and study groups). Incisions and suturing of the bile ducts were performed in the two groups. Tamoxifen (20 mg/day) was administered only to the study group. The animals were sacrificed after 30 days. Quantification of myofibroblasts in the biliary ducts was made through immunohistochemistry analysis using anti-alpha smooth muscle actin of the smooth muscle antibody. Immunohistochemical quantification was performed using a digital image system. RESULTS: In the animals treated with tamoxifen (20 mg/day), there was a significant reduction in immunostaining for alpha smooth muscle actin compared with the control group (0.1155 vs. 0.2021, p = 0.046). CONCLUSION: Tamoxifen reduced the expression of alpha smooth muscle actin in the healing tissue after bile duct injury, suggesting a decrease in myofibroblasts in the scarred area of the pig biliary tract. These data suggest that tamoxifen could be used in the prevention of biliary tract stenosis after bile duct surgeries. PMID:23420165

Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) promotes lung fibroblast proliferation, survival and differentiation to myofibroblasts.

PubMed

Hasaneen, Nadia A; Cao, Jian; Pulkoski-Gross, Ashleigh; Zucker, Stanley; Foda, Hussein D

2016-02-17

Idiopathic pulmonary fibrosis (IPF) is a chronic progressively fatal disease. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) is a glycosylated transmembrane protein that induces the expression of some matrix metalloproteinase (MMP) in neighboring stromal cells through direct epithelial-stromal interactions. EMMPRIN is highly expressed in type II alveolar epithelial cells at the edges of the fibrotic areas in IPF lung sections. However, the exact role of EMMPRIN in IPF is unknown. To determine if EMMPRIN contributes to lung fibroblast proliferation, resistance to apoptosis, and differentiation to myofibroblasts, normal Human lung fibroblasts (NHLF) transiently transfected with either EMMPRIN/GFP or GFP were treated with TGF- β1 from 0 to 10 ng/ml for 48 h and examined for cell proliferation (thymidine incorporation), apoptosis (FACS analysis and Cell Death Detection ELISA assay), cell migration (Modified Boyden chamber) and differentiation to myofibroblasts using Western blot for α-smooth actin of cell lysates. The effect of EMMPRIN inhibition on NHLF proliferation, apoptosis, migration and differentiation to myofibroblasts after TGF- β1 treatment was examined using EMMPRIN blocking antibody. We examined the mechanism by which EMMPRIN induces its effects on fibroblasts by studying the β-catenin/canonical Wnt signaling pathway using Wnt luciferase reporter assays and Western blot for total and phosphorylated β-catenin. Human lung fibroblasts overexpressing EMMPRIN had a significant increase in cell proliferation and migration compared to control fibroblasts. Furthermore, EMMPRIN promoted lung fibroblasts resistance to apoptosis. Lung fibroblasts overexpressing EMMPRIN showed a significantly increased expression of α- smooth muscle actin, a marker of differentiation to myofibroblasts compared to control cells. TGF-β1 increased the expression of EMMPRIN in lung fibroblasts in a dose-dependent manner. Attenuation of EMMPRIN expression with the use of an

Lactic Acid is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation Via pH-Dependent Activation of Transforming Growth Factor-β

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kottman, R. M.; Kulkarni, Ajit A.; Smolnycki, Katie A.

2012-10-15

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex disease for which the pathogenesis is poorly understood. In this study, we identified lactic acid as a metabolite that is elevated in the lung tissue of patients with IPF. Objectives: This study examines the effect of lactic acid on myofibroblast differentiation and pulmonary fibrosis. Methods:We used metabolomic analysis to examine cellular metabolism in lung tissuefrom patients with IPFanddeterminedthe effects of lactic acid and lactate dehydrogenase-5 (LDH5) overexpression on myofibroblast differentiation and transforming growth factor (TGF)-b activation in vitro. Measurements and Main Results: Lactic acid concentrations from healthy and IPF lung tissue weremore » determined by nuclear magnetic resonance spectroscopy; a-smooth muscle actin, calponin, and LDH5 expression were assessed by Western blot of cell culture lysates. Lactic acid and LDH5 were significantly elevated in IPF lung tissue compared with controls. Physiologic concentrations of lactic acid induced myofibroblast differentiation via activation of TGF-b. TGF-b induced expression of LDH5 via hypoxia-inducible factor 1a (HIF1a). Importantly, overexpression of both HIF1a and LDH5 in human lung fibroblasts induced myofibroblast differentiation and synergized with low dose TGF-b to induce differentiation. Furthermore, inhibition of both HIF1a and LDH5 inhibited TGF-b–induced myofibroblast differentiation. Conclusions: We have identified the metabolite lactic acid as an important mediator of myofibroblast differentiation via a pHdependent activation of TGF-b. We propose that the metabolic milieu of the lung, and potentially other tissues, is an important driving force behind myofibroblast differentiation and potentially the initiation and progression of fibrotic disorders.« less

Lactic Acid Is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation via pH-Dependent Activation of Transforming Growth Factor-β

PubMed Central

Kottmann, Robert Matthew; Kulkarni, Ajit A.; Smolnycki, Katie A.; Lyda, Elizabeth; Dahanayake, Thinesh; Salibi, Rami; Honnons, Sylvie; Jones, Carolyn; Isern, Nancy G.; Hu, Jian Z.; Nathan, Steven D.; Grant, Geraldine; Phipps, Richard P.

2012-01-01

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex disease for which the pathogenesis is poorly understood. In this study, we identified lactic acid as a metabolite that is elevated in the lung tissue of patients with IPF. Objectives: This study examines the effect of lactic acid on myofibroblast differentiation and pulmonary fibrosis. Methods: We used metabolomic analysis to examine cellular metabolism in lung tissue from patients with IPF and determined the effects of lactic acid and lactate dehydrogenase-5 (LDH5) overexpression on myofibroblast differentiation and transforming growth factor (TGF)-β activation in vitro. Measurements and Main Results: Lactic acid concentrations from healthy and IPF lung tissue were determined by nuclear magnetic resonance spectroscopy; α-smooth muscle actin, calponin, and LDH5 expression were assessed by Western blot of cell culture lysates. Lactic acid and LDH5 were significantly elevated in IPF lung tissue compared with controls. Physiologic concentrations of lactic acid induced myofibroblast differentiation via activation of TGF-β. TGF-β induced expression of LDH5 via hypoxia-inducible factor 1α (HIF1α). Importantly, overexpression of both HIF1α and LDH5 in human lung fibroblasts induced myofibroblast differentiation and synergized with low-dose TGF-β to induce differentiation. Furthermore, inhibition of both HIF1α and LDH5 inhibited TGF-β–induced myofibroblast differentiation. Conclusions: We have identified the metabolite lactic acid as an important mediator of myofibroblast differentiation via a pH-dependent activation of TGF-β. We propose that the metabolic milieu of the lung, and potentially other tissues, is an important driving force behind myofibroblast differentiation and potentially the initiation and progression of fibrotic disorders. PMID:22923663

Innervation of the wrist joint and surgical perspectives of denervation.

PubMed

Van de Pol, Gerrit J; Koudstaal, Maarten J; Schuurman, Arnold H; Bleys, Ronald L A W

2006-01-01

Because our experience with the techniques used in denervation surgery of the wrist joint often has proven insufficient in treating chronic pain we conducted an anatomic study to clarify the exact contributions of the nerves supplying the wrist joint. Our goal was to reveal all periosteal and capsular nerve connections and if necessary adjust our technique used in denervation surgery. Innervation of the wrist joint was investigated by microdissection and histologic examination of 18 human wrists. An acetylcholinesterase method was used to identify the nerves, both in whole-mount preparations and in sections. We found that the main innervation to the wrist capsule and periosteal nerve network came from the anterior interosseous nerve, lateral antebrachial cutaneous nerve, and posterior interosseous nerve. The palmar cutaneous branch of the median nerve, the deep branch of the ulnar nerve, the superficial branch of the radial nerve, and the dorsal branch of the ulnar nerve also were found to have connections with the capsule. The periosteal nerve branches did not appear to play a major role in the innervation of the capsule and ligaments; here the specific articular nerve branches proved more important. The posterior and medial antebrachial cutaneous nerves did not connect to the wrist capsule or periosteum but rather terminated in the extensor and flexor retinaculum. Based on our findings we propose to denervate the wrist by making 2 incisions. With one palmar and one dorsal incision it should be possible to disconnect the periosteum from the capsule and interrupt the majority of the capsular nerve branches.

Down-regulation of collagen synthesis and matrix metalloproteinase expression in myofibroblasts from Dupuytren nodule using adenovirus-mediated relaxin gene therapy.

PubMed

Kang, Young-Mi; Choi, Yun-Rak; Yun, Chae-Ok; Park, Jin-Oh; Suk, Kyung-Soo; Kim, Hak-Sun; Park, Moon-Soo; Lee, Byung-Ho; Lee, Hwan-Mo; Moon, Seong-Hwan

2014-04-01

Dupuytren's disease is a fibroproliferative connective tissue disorder characterized by contracture of the palmer fascia of the hand. Relaxin (RLN) is a multifunctional factor which contributes to the remodeling of the pelvic ligament by inhibiting fibrosis and inflammatory activities. The aim of this study was to investigate the effect of the RLN gene on the inhibition of fibrosis in myofibroblastic cells. Myofibroblast cells with adenovirus LacZ (Ad-LacZ) as a marker gene or adenovirus relaxin (Ad-RLN) as therapeutic gene showed transgene expressions in beta-galactosidase assay and Western blot analysis. Myofibroblastic cells with Ad-RLN demonstrated a 22% and 48% reduction in collagen I and III mRNA expressions respectively, a 50% decrease in MMP-1, 70% decrease in MMP-2, 80% decrease in MMP-9, and a 15% reduction in MMP-13 protein expression compared with cultures with viral control and saline control. In addition, myofibroblastic cells with Ad-RLN showed a 40% decrease in TIMP 1 and a 15% increase in TIMP 3 protein expression at 48 h compared to cultures with viral control and saline control. Also, myofibroblastic cell with Ad-RLN demonstrated a 74% inhibition of fibronectin and a 52% decrease in total collagen synthesis at 48 h compared with cultures with viral control and saline control. In conclusion, the RLN gene render antifibrogenic effect on myofibroblastic cells from Dupuytren's nodule via direct inhibition of collagen synthesis not through collagenolytic pathway such as MMP-1, -13, TIMP 1, and 3. Therefore relaxin can be an alternative therapeutic strategy in initial stage of Dupuytren's disease by its antifibrogenic effect. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro.

PubMed

Li, Fei-yan; Xie, Xi-sheng; Fan, Jun-ming; Li, Zi; Wu, Jiang; Zheng, Rong

2009-09-01

The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated. We applied hydraulic pressure (50 cm H2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-beta1 (TGF-beta1) of NRK52E cells were examined. Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of alpha-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-beta1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-beta1. We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-beta1 secretion.

In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype.

PubMed

Walker, J L; Bleaken, B M; Romisher, A R; Alnwibit, A A; Menko, A S

2018-05-02

Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing. These cells have the potential to differentiate to myofibroblasts, resulting in fibrosis and scarring. The signals underlying these differing pathways are complex and incompletely understood. The ex vivo mock cataract surgery cultures are an attractive model with which to address this question. With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment, and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform. Here, we show that upon injury, the cytoskeletal protein vimentin is released into the extracellular space, binds to the cell surface of the mesenchymal leader cells located at the wound edge in the native matrix environment, and supports wound closure. In pro-fibrotic environments, the extracellular vimentin pool also links specifically to the mesenchymal leader cells, and has an essential role in signaling their fate change to a myofibroblast. These findings suggest a novel role for extracellular, cell-surface-associated vimentin in mediating repair-cell function in wound repair and in transitioning these cells to a myofibroblast phenotype. Movie S1 Movie S1 Collective movement of mesenchymal leader and epithelial follower cells across the tissue culture substrate (ECZ) in response to injury was followed by time-lapse imaging from D0-D3. The mesenchymal cells at the leading edge were easily distinguished morphologically from the lens epithelial follower cells.

Diagnostic features of feline restrictive orbital myofibroblastic sarcoma.

PubMed

Bell, C M; Schwarz, T; Dubielzig, R R

2011-05-01

A progressive debilitating disease of the orbit and adjacent connective tissues of cats has historically been called feline orbital pseudotumor. The authors reviewed clinical, histopathologic, and diagnostic imaging features of this disease in 12 cases from the Comparative Ocular Pathology Laboratory of Wisconsin. The cats' ages ranged from 7 to 16 years (mean, 10.8 years). All cats had a history of severely restricted mobility of the globe and eyelids with secondary corneal disease. Eleven cats (92%) had concurrent involvement of the contralateral eye and/or the oral cavity. Diffuse scleral or episcleral thickening was seen with computed tomography in all clinically affected eyes. Histologically, an insidious infiltration of neoplastic spindle cells in the orbit, eyelids, and periorbital skin and soft tissues, with collagen deposition and a few perivascular lymphocytes, led to entrapment and restricted mobility of the eyelids and orbital tissues. The tumor failed to form a discrete mass, and it spread along fascial planes to the contralateral orbit and eyelids and/or the lips and oral cavity. In all tested cases (n = 10), neoplastic cells were immunohistochemically positive for vimentin, S100 protein, and smooth muscle actin. The authors adopted the term feline restrictive orbital myofibroblastic sarcoma to reflect the restricted mobility of the eyelids and globe and the imaging and histologic features of an invasive yet low-grade myofibroblastic sarcoma.

[Temporo-mandibular joint. Morpho-functional considerations].

PubMed

Scutariu, M D; Indrei, Anca

2004-01-01

The temporo-mandibular joint is distinguished from most other synovial joints of the body by two features: 1. the two jointed components carry teeth whose position and occlusion introduce a very strong influence on the movements of the temporo-mandibular joint and 2. its articular surfaces are not covered by hyaline cartilage, but by a dense, fibrous tissue. This paper describes the parts of the temporo-mandibular joint: the articular surfaces (the condylar process of the mandible and the glenoid part of the temporal bone), the fibrocartilaginous disc which is interposed between the mandibular and the temporal surface, the fibrous capsule of the temporo-mandibular joint and the ligaments of this joint. All these parts present a very strong adaptation at the important functions of the temporo-mandibular joint.

Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts.

PubMed Central

Pujuguet, P.; Hammann, A.; Moutet, M.; Samuel, J. L.; Martin, F.; Martin, M.

1996-01-01

Alternative splicing of primary fibronectin (FN) mRNA results in the synthesis of different isoforms. ED-A+ and ED-B+ FN isoforms are absent from plasma FN and are representative of cellular FN. Their expression was studied in human and rat normal colon, in human colorectal carcinomas, and in transplanted tumors derived from a chemically-induced rat colon cancer. In normal colon, only the ED-A+ FN isoform was expressed as a thin deposit between crypt colonocytes and pericryptal myofibroblasts. Conversely, heavy ED-A+ FN deposits and lighter ED-B+ FN expression were found in the stroma of colorectal tumors in association with myofibroblasts surrounding tumor glands. Some colonic cancer cells also contained intracellular FN isoform granules and expressed FN mRNA. Tumor-associated myofibroblasts and some cancer cell lines were able to synthesize and deposit extracellular ED-A+ and ED-B+ FN in vitro. FN isoform deposition by tumor-associated myofibroblasts was not modulated by colon cancer cell-conditioned medium, but was strongly enhanced when myofibroblasts were cultured on colon cancer cell extracellular matrix or on laminin. These results show that the ED-A+ and ED-B+ FN isoforms were overexpressed in colorectal cancer. Cancer cells can deposit these FN isoforms directly and also stimulate their deposition by tumor-associated myofibroblasts. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:8579120

Maintenance of arytenoid abduction following carbon dioxide laser debridement of the articular cartilage and joint capsule of the cricoarytenoid joint combined with prosthetic laryngoplasty in horses: an in vivo and in vitro study.

PubMed

Hawkins, J F; Couetil, L; Miller, M A

2014-02-01

The objective was to evaluate CO2 laser debridement of the cricoarytenoid joint (CAJ) combined with prosthetic laryngoplasty to prevent post-operative loss of arytenoid abduction in seven horses. Horses were assigned to either laser debridement of the left CAJ and laryngoplasty (laser treated, n=5) or control laryngoplasty (sham, n=2), and were evaluated with endoscopic examinations and measurement of right to left angle quotients (RLQ) to assess maintenance of arytenoid abduction. The animals were euthanased at intervals after surgery and larynges were harvested for post-mortem testing, including determination of translaryngeal flow, pressure, impedance and RLQ. Measurements were obtained under increasing vacuum-generated negative pressure with laryngoplasty sutures intact and with the knot/crimp of the laryngoplasty sutures removed. Following post-mortem testing the cricoarytenoid joints were examined histologically. Post-operative endoscopic examinations revealed no significant differences between RLQ measurements calculated for day 1 following surgery to the termination date of the study for the seven horses. Post-mortem RLQ at airflows of 10 and 60 L/s was significantly higher in sham than in laser treated horses both before and after knot/crimp removal. Translaryngeal impedance at 10 and 60 L/s was not statistically different between groups. Histopathology revealed necrosis and loss of articular cartilage in the laser treated horses. The lymphoid cell infiltration subsided but joint capsule and periarticular fibrosis increased over the course of the study. Post-operative loss of arytenoid abduction after laryngoplasty can be minimized with CO2 laser debridement of the CAJ joint. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pirfenidone and nintedanib modulate properties of fibroblasts and myofibroblasts in idiopathic pulmonary fibrosis.

PubMed

Lehtonen, Siri T; Veijola, Anniina; Karvonen, Henna; Lappi-Blanco, Elisa; Sormunen, Raija; Korpela, Saara; Zagai, Ulrika; Sköld, Magnus C; Kaarteenaho, Riitta

2016-02-04

Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease with a poor prognosis. Fibroblasts and myofibroblasts are the key cells in the fibrotic process. Recently two drugs, pirfenidone and nintedanib, were approved for clinical use as they are able to slow down the disease progression. The mechanisms by which these two drugs act in in vitro cell systems are not known. The aim of this study was therefore to examine the effects of pirfenidone and nintedanib on fibroblasts and myofibroblasts structure and function established from patients with or without IPF. Stromal cells were collected and cultured from control lung (n = 4) or IPF (n = 7). The cells were treated with pirfenidone and/or nintedanib and the effect of treatment was evaluated by measuring cell proliferation, alpha smooth muscle actin (α-SMA) and fibronectin expression by Western analysis and/or immunoelectron microscopy, ultrastructural properties by transmission electron microscopy and functional properties by collagen gel contraction and invasion assays. Both pirfenidone and nintedanib reduced in vitro proliferation of fibroblastic cells in a dose dependent manner. The number of cells from control lung was reduced to 47 % (p = 0.04) and of IPF cells to 42 % (p = 0.04) by 1 mM pirfenidone and correspondingly to 67 % (p = 0.04) and 68 % (p = 0.04), by 1 μM nintedanib. If both drugs were used together, a further reduced proliferation was observed. Both pirfenidone and nintedanib were able to reduce the amount of α-SMA and the myofibroblastic appearance although the level of reduction was cell line dependent. In functional assays, the effect of both drugs was also variable. We conclude that the ultrastructure and function of fibroblasts and myofibroblasts are affected by pirfenidone and nintedanib. Combination of the drugs reduced cell proliferation more than either of them individually. Human lung derived cell culture systems represent a potential platform for

Posterior capsule opacification.

PubMed

Wormstone, I Michael; Wang, Lixin; Liu, Christopher S C

2009-02-01

Posterior Capsule Opacification (PCO) is the most common complication of cataract surgery. At present the only means of treating cataract is by surgical intervention, and this initially restores high visual quality. Unfortunately, PCO develops in a significant proportion of patients to such an extent that a secondary loss of vision occurs. A modern cataract operation generates a capsular bag, which comprises a proportion of the anterior and the entire posterior capsule. The bag remains in situ, partitions the aqueous and vitreous humours, and in the majority of cases, houses an intraocular lens. The production of a capsular bag following surgery permits a free passage of light along the visual axis through the transparent intraocular lens and thin acellular posterior capsule. However, on the remaining anterior capsule, lens epithelial cells stubbornly reside despite enduring the rigours of surgical trauma. This resilient group of cells then begin to re-colonise the denuded regions of the anterior capsule, encroach onto the intraocular lens surface, occupy regions of the outer anterior capsule and most importantly of all begin to colonise the previously cell-free posterior capsule. Cells continue to divide, begin to cover the posterior capsule and can ultimately encroach on the visual axis resulting in changes to the matrix and cell organization that can give rise to light scatter. This review will describe the biological mechanisms driving PCO progression and discuss the influence of IOL design, surgical techniques and putative drug therapies in regulating the rate and severity of PCO.

Differential expression of myofibroblasts on CO2 laser wounds and scalpel wounds: an experimental model

NASA Astrophysics Data System (ADS)

Machado, R. M.; Oliveira, C. R. B.; Vitória, L. A.; Xavier, F. C. A.; Pinheiro, A. L. B.; Freitas, A. C.; Ramalho, L. M. P.

2018-04-01

Wound contraction of both traumatic and surgical origin may reduce or limit the function of the tissue. Myofibroblasts are cells involved on the process of wound contraction, which is smaller on CO2 Laser wounds. The aims of this study were to quantitative and statistically assess the presence of myofibroblasts on both conventional and CO2 Laser wounds. Thirty-two animals (rattus norvegicus) were divided into four groups and operated using either the CO2 Laser (groups A1 and A2) or conventional scalpel (groups B1 and B2). The animals were sacrificed eight days post-operatively (groups: A1 and B1) and 14th days after surgery (groups: A2 and B2). The spec imens we re routinely processed to wax and stained with a-Smooth Muscle Actin (aSMA) and analyzed under light microscopy (40X). Two standard areas around the wound of each slide were selected and used to count the number of myofribroblasts present using a calibrated eyepiece and a graticule. The number of myofibroblasts at day eight was significantly higher than at day 14th. Comparison of the two techniques at day eight showed significant differences between the two groups (Laser, p=0.007 and scalpel, p=0.001). The number of cells present on group B1 was significantly higher than group A1 (p=0.001). However at the 14th day there was no such difference (p=0,072). It is concluded that the small number of myofibroblasts at day eight after wounding with the CO2 Lasermay be the reason why contraction on this wound is smaller than the one observed in conventional surgery.

Retention of the capsule endoscope: a single-center experience of 1000 capsule endoscopy procedures.

PubMed

Li, Feng; Gurudu, Suryakanth R; De Petris, Giovanni; Sharma, Virender K; Shiff, Arthur D; Heigh, Russell I; Fleischer, David E; Post, Janice; Erickson, Paula; Leighton, Jonathan A

2008-07-01

Retention of the video capsule is the most significant complication associated with capsule endoscopy (CE). There are limited data on incidence, risk factors, and outcomes of capsule retention. We aimed to determine the incidence of capsule retention and to investigate the causes and clinical outcomes of capsule retention. Single tertiary referral medical center. All patients who underwent CE for suspected small bowel disease from June 2002 to March 2006. Retrospective case series. Capsule retention occurred in 1.4% of our patients (14/1000). Eleven patients failed to pass the capsule because of nonsteroidal anti-inflammatory drug (NSAID) enteropathy (diaphragm disease). One patient had capsule retention from an obstructing carcinoid tumor. Metastatic ovarian cancer with invasion of the ileum was the cause of retention in another patient. One patient who did not have surgical removal of the capsule because of loss of follow-up had retention caused by a small-bowel tumor suspicious for carcinoid tumor on CT enterography. All patients remained "asymptomatic" from the retained capsules. Thirteen patients underwent elective partial small-bowel resection and capsule removal. No deaths were associated with these surgeries. Eleven patients recovered promptly, whereas 2 patients had mild postoperative ileus. Retrospective study. Retention of the capsule endoscope appears to be infrequent. The most common cause is diaphragm disease resulting from NSAIDs in this study population. In most cases, capsule retention is asymptomatic, and it usually leads to surgical removal, which appears safe and also identifies and treats the underlying small-bowel condition.

Immunohistochemical analysis of stromal fibrocytes and myofibroblasts to envision the invasion and lymph node metastasis in oral squamous cell carcinoma.

PubMed

Rao, Sowmya J; Rao, Jyothi Bellur Madhava; Rao, Pp Jagadish

2017-01-01

Tumor cells work in close coordination with stromal elements from its stage of emergence to metastasis. The study was designed to assess the presence and distribution pattern of stromal fibrocytes and myofibroblasts in oral squamous cell carcinoma (OSCC). Possibility of using these stromal cells as a marker for invasion and lymphnode metastasis was evaluated. A total of 40 cases of OSCC consisting twenty cases of each lymph node positive (pN+) and lymph node negative (pN0) samples and ten normal oral mucosa (NOM) tissues were subjected to double immunostaining using CD34 and alpha-smooth muscle actin (α-SMA) antibodies. Stained sections were evaluated semiquantitatively. CD34 fibrocytes were seen in 70% of NOM and none of OSCC samples. α-SMA myofibroblasts were seen in 80% of OSCC and none of NOM samples. A statistically significant difference was found in fibrocyte values ( P < 0.001) and myofibroblast values ( P < 0.001) between NOM and OSCC study samples. No statistical significance in myofibroblast values between pN0 and pN+ study groups; however, their distribution pattern appreciably varied. This study suggested that fibrocytes could be used as one of the markers for early invasion. Abrupt loss of fibrocytes at the transition zone toward carcinoma and statistical significance in their values supported this inference. Heterogeneity in the distribution pattern of myofibroblasts in tumor stroma indicates that this variability may predict the tumor behavior toward nodal metastasis rather than their mere presence or absence.

Pain & resistance in patients with adhesive capsulitis during contrast material injection phase of MR arthrography.

PubMed

Yilmaz, Mehmet Halit; Kantarci, Fatih; Adaletli, Ibrahim; Ulus, Sila; Gulsen, Fatih; Ozer, Harun; Aktas, Ilknur; Akgun, Kenan; Kanberoglu, Kaya

2007-04-01

Adhesive capsulitis of the shoulder is a condition of unknown aetiology that results in the development of restricted active and passive glenohumeral motion. It has been reported that magnetic resonance (MR) imaging is useful in diagnosing adhesive capsulitis. We carried out this study to assess how pain and/or resistance during contrast material injection affects the diagnosis of adhesive capsulitis on magnetic resonance (MR) arthrography. The study included MR arthrography examinations of 21 patients with a diagnosis of adhesive capsulitis. The control group consisted of 20 patients who presented clinically with rotator cuff tear. The pain (visual analog scale, VAS), resistance to injection and the amount of contrast material that could be injected during injection phase of MR arthrography was assessed and compared between groups. The patients in adhesive capsulitis group (mean VAS score 66.5+/-25.5) experienced more pain when compared with the control group (mean VAS score 34.9+/-27.7, P<0.001). A statistically significant difference (P<0.001) in terms of the amount of the injected fluid (4.3+/-2.6 ml for adhesive capsulitis group, and 10.9+/-4.1 ml for control group) was seen into the joint cavity. Resistance to injection was significantly more (P<0.001) in patients with adhesive capsulitis when compared to control group. Experience of pain during injection, a decreased amount of contrast material injected and resistance to injection in patients during injection phase of MR arthrography may suggest adhesive capsulitis.

Bromelain down-regulates myofibroblast differentiation in an in vitro wound healing assay.

PubMed

Aichele, Kathrin; Bubel, Monika; Deubel, Gunther; Pohlemann, Tim; Oberringer, Martin

2013-10-01

Bromelain, a pineapple-derived enzyme mixture, is a widely used drug to improve tissue regeneration. Clinical and experimental data indicate a better outcome of soft tissue healing under the influence of bromelain. Proteolytic, anti-bacterial, anti-inflammatory, and anti-oedematogenic effects account for this improvement on the systemic level. It remains unknown, whether involved tissue cells are directly influenced by bromelain. In order to gain more insight into those mechanisms by which bromelain modulates tissue regeneration at the cellular level, we applied a well-established in vitro wound healing assay. Two main players of soft tissue healing--fibroblasts and microvascular endothelial cells--were used as mono- and co-cultures. Cell migration, proliferation, apoptosis, and the differentiation of fibroblasts to myofibroblasts as well as interleukin-6 were quantified in response to bromelain (36 × 10(-3) IU/ml) under normoxia and hypoxia. Bromelain attenuated endothelial cell and fibroblast proliferation in a moderate way. This proliferation decrease was not caused by apoptosis, rather, by driving cells into the resting state G0 of the cell cycle. Endothelial cell migration was not influenced by bromelain, whereas fibroblast migration was clearly slowed down, especially under hypoxia. Bromelain led to a significant decrease of myofibroblasts under both normoxic (from 19 to 12 %) and hypoxic conditions (from 22 to 15 %), coincident with higher levels of interleukin-6. Myofibroblast differentiation, a clear sign of fibrotic development, can be attenuated by the application of bromelain in vitro. Usage of bromelain as a therapeutic drug for chronic human wounds thus remains a very promising concept for the future.

The sacroiliac joint: anatomy, physiology and clinical significance.

PubMed

Forst, Stacy L; Wheeler, Michael T; Fortin, Joseph D; Vilensky, Joel A

2006-01-01

The sacroiliac joint (SIJ) is a putative source of low back pain. The objective of this article is to provide clinicians with a concise review of SIJ structure and function, diagnostic indicators of SIJ-mediated pain, and therapeutic considerations. The SIJ is a true diarthrodial joint with unique characteristics not typically found in other diarthrodial joints. The joint differs with others in that it has fibrocartilage in addition to hyaline cartilage, there is discontinuity of the posterior capsule, and articular surfaces have many ridges and depressions. The sacroiliac joint is well innervated. Histological analysis of the sacroiliac joint has verified the presence of nerve fibers within the joint capsule and adjoining ligaments. It has been variously described that the sacroiliac joint receives its innervation from the ventral rami of L4 and L5, the superior gluteal nerve, and the dorsal rami of L5, S1, and S2, or that it is almost exclusively derived from the sacral dorsal rami. Even though the sacroiliac joint is a known putative source of low back and lower extremity pain, there are few findings that are pathognomonic of sacroiliac joint pain. The controlled diagnostic blocks utilizing the International Association for the Study of Pain (IASP) criteria demonstrated the prevalence of pain of sacroiliac joint origin in 19% to 30% of the patients suspected to have sacroiliac joint pain. Conservative management includes manual medicine techniques, pelvic stabilization exercises to allow dynamic postural control, and muscle balancing of the trunk and lower extremities. Interventional treatments include sacroiliac joint, intra-articular joint injections, radiofrequency neurotomy, prolotherapy, cryotherapy, and surgical treatment. The evidence for intra-articular injections and radiofrequency neurotomy has been shown to be limited in managing sacroiliac joint pain.

Dermal fibroblast-to-myofibroblast transition sustained by αvß3 integrin-ILK-Snail1/Slug signaling is a common feature for hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders.

PubMed

Zoppi, Nicoletta; Chiarelli, Nicola; Binetti, Silvia; Ritelli, Marco; Colombi, Marina

2018-04-01

Hypermobile Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder with unknown molecular basis mainly characterized by generalized joint hypermobility, joint instability complications, and minor skin changes. The phenotypic spectrum is broad and includes multiple associated symptoms shared with chronic inflammatory systemic diseases. The stricter criteria defined in the 2017 EDS nosology leave without an identity many individuals with symptomatic joint hypermobility and/or features of hEDS; for these patients, the term Hypermobility Spectrum Disorders (HSD) was introduced. We previously reported that in vitro cultured hEDS and HSD patients' skin fibroblasts show a disarray of several extracellular matrix (ECM) components and dysregulated expression of genes involved in connective tissue homeostasis and inflammatory/pain/immune responses. Herein, we report that hEDS and HSD skin fibroblasts exhibit in vitro a similar myofibroblast-like phenotype characterized by the organization of α-smooth muscle actin cytoskeleton, expression of OB-cadherin/cadherin-11, enhanced migratory capability associated with augmented levels of the ECM-degrading metalloproteinase-9, and altered expression of the inflammation mediators CCN1/CYR61 and CCN2/CTGF. We demonstrate that in hEDS and HSD cells this fibroblast-to-myofibroblast transition is triggered by a signal transduction pathway that involves αvβ3 integrin-ILK complexes, organized in focal adhesions, and the Snail1/Slug transcription factor, thus providing insights into the molecular mechanisms related to the pathophysiology of these protean disorders. The indistinguishable phenotype identified in hEDS and HSD cells resembles an inflammatory-like condition, which correlates well with the systemic phenotype of patients, and suggests that these multisystemic disorders might be part of a phenotypic continuum rather than representing distinct clinical entities. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional Investigation of NCI-H460-Inducible Myofibroblasts on the Chemoresistance to VP-16 with a Microfluidic 3D Co-Culture Device

PubMed Central

He, Jiarui; Guo, Zhe; Ying, Li; Xu, Zhiyun; Zhang, Jianing; Lu, Jianxin; Wang, Qi

2013-01-01

Fibroblasts, the major cell type in tumor stroma, are essential for tumor growth and survival, and represent an important therapeutic target for cancers. Here we presented a microfluidic co-culture device in which the three-dimensional (3D) matrix was employed to reconstruct an in vivo-like fibroblast-tumor cell microenvironment for investigation of the role of myofibroblasts induced by lung cancer cells in the chemoresistance to VP-16. Composed of a double-layer chip and an injection pump, the device houses fibroblasts and lung cancer cells co-cultured in 3D matrix and 2D mode to induce fibroblasts to become myofibroblasts with the supplement of the medium continuously. With this device, we verified that the cytokines secreted by lung cancer cells could effectively transform the fibroblasts into myofibroblasts. Moreover, compared to fibroblasts, the myofibroblasts showed higher resistance to anticancer drug VP-16. We also demonstrated that this kind of acquired resistance in myofibroblasts was associated with the expression of Glucose-regulated protein 78 (GP78). We concluded that this device allows for the assay to characterize various cellular events in a single device sequentially, facilitating a better understanding of the interactions among heterotypic cells in a sophisticated microenvironment. PMID:23613925

Intrinsic Deregulation of Vascular Smooth Muscle and Myofibroblast Differentiation in Mesenchymal Stromal Cells from Patients with Systemic Sclerosis.

PubMed

Hegner, Björn; Schaub, Theres; Catar, Rusan; Kusch, Angelika; Wagner, Philine; Essin, Kirill; Lange, Claudia; Riemekasten, Gabriela; Dragun, Duska

2016-01-01

Obliterative vasculopathy and fibrosis are hallmarks of systemic sclerosis (SSc), a severe systemic autoimmune disease. Bone marrow-derived mesenchymal stromal cells (MSCs) from SSc patients may harbor disease-specific abnormalities. We hypothesized disturbed vascular smooth muscle cell (VSMC) differentiation with increased propensity towards myofibroblast differentiation in response to SSc-microenvironment defining growth factors and determined responsible mechanisms. We studied responses of multipotent MSCs from SSc-patients (SSc-MSCs) and healthy controls (H-MSCs) to long-term exposure to CTGF, b-FGF, PDGF-BB or TGF-β1. Differentiation towards VSMC and myofibroblast lineages was analyzed on phenotypic, biochemical, and functional levels. Intracellular signaling studies included analysis of TGF-β receptor regulation, SMAD, AKT, ERK1/2 and autocrine loops. VSMC differentiation towards both, contractile and synthetic VSMC phenotypes in response to CTGF and b-FGF was disturbed in SSc-MSCs. H-MSCs and SSc-MSCs responded equally to PDGF-BB with prototypic fibroblastic differentiation. TGF-β1 initiated myofibroblast differentiation in both cell types, yet with striking phenotypic and functional differences: In relation to H-MSC-derived myofibroblasts induced by TGF-β1, those obtained from SSc-MSCs expressed more contractile proteins, migrated towards TGF-β1, had low proliferative capacity, and secreted higher amounts of collagen paralleled by reduced MMP expression. Higher levels of TGF-β receptor 1 and enhanced canonical and noncanonical TGF-β signaling in SSc-MSCs accompanied aberrant differentiation response of SSc-MSCs in comparison to H-MSCs. Deregulated VSMC differentiation with a shift towards myofibroblast differentiation expands the concept of disturbed endogenous regenerative capacity of MSCs from SSc patients. Disease related intrinsic hyperresponsiveness to TGF-β1 with increased collagen production may represent one responsible mechanism. Better

Pediatric capsule endoscopy: review of the small bowel and patency capsules.

PubMed

Cohen, Stanley A; Ephrath, Hagit; Lewis, Jeffery D; Klevens, Alan; Bergwerk, Ari; Liu, Steven; Patel, Dinesh; Reed-Knight, Bonney; Stallworth, Angela; Wakhisi, Tamara; Gold, Benjamin D

2012-03-01

Because capsule endoscopy (CE) avoids ionizing radiation, deep sedation, and general anesthesia, CE may be valuable in pediatrics. We report a single pediatric center's experience with the use and safety of CE. In a retrospective review of consecutive CE studies, 284 CE studies were performed in 277 patients with a mean age of 15 (±3.7) years during a 5-year period. The youngest to swallow the capsule was 4.6 years old. Twenty capsules were placed. Overall, 245 (86%) patients underwent CE for suspected (184, 65%) or confirmed (61, 21%) Crohn disease (CD); 27 (9.5%) anemia or gastrointestinal bleeding; 6 (2%) polyposis; and 4 (1.4%) celiac disease. Positive findings were observed in 205 (72%) of the studies, with 152 (54%) having small bowel findings. Of these, 72 (47%) were diagnostic. Gastric (95, 33%) and colonic (31, 11%) abnormalities were also identified. Five CE studies (1.8%) resulted in retention of the capsule in nonsurgical patients. A patency capsule before CE in 23 patients allowed 19 CE to proceed with only 1 retained capsule. In 65 (21%) patients, the video capsule did not enter the colon before the video's end. Of these, 36 (65%) had significant findings, including 27 (49%) documenting small bowel (SB) CD. CE is useful to diagnose SB disease in children. Even in a study population with a high prevalence of confirmed and suspected CD, the risk of retention remains small. The patency capsule may lessen that risk. CE may identify gastric or colonic disease even when SB lesions are not present.

Comparative evaluation of gene delivery devices in primary cultures of rat hepatic stellate cells and rat myofibroblasts

PubMed Central

Weiskirchen, Ralf; Kneifel, Jens; Weiskirchen, Sabine; van de Leur, Eddy; Kunz, Dagmar; Gressner, Axel M

2000-01-01

Background The hepatic stellate cell is the primary cell type responsible for the excessive formation and deposition of connective tissue elements during the development of hepatic fibrosis in chronically injured liver. Culturing quiescent hepatic stellate cells on plastic causes spontaneous activation leading to a myofibroblastic phenotype similar to that seen in vivo. This provides a simple model system for studying activation and transdifferentiation of these cells. The introduction of exogenous DNA into these cells is discussed controversially mainly due to the lack of systematic analysis. Therefore, we examined comparatively five nonviral, lipid-mediated gene transfer methods and adenoviral based infection, as potential tools for efficient delivery of DNA to rat hepatic stellate cells and their transdifferentiated counterpart, i.e. myofibroblasts. Transfection conditions were determined using enhanced green fluorescent protein as a reporter expressed under the transcriptional control of the human cytomegalovirus immediate early gene 1 promoter/enhancer. Results With the use of chemically enhanced transfection methods, the highest relative efficiency was obtained with FuGENE™6 gene mediated DNA transfer. Quantitative evaluation of representative transfection experiments by flow cytometry revealed that approximately 6% of the rat hepatic stellate cells were transfected. None of the transfection methods tested was able to mediate gene delivery to rat myofibroblasts. To analyze if rat hepatic stellate cells and myofibroblasts are susceptible to adenoviral infection, we have inserted the transgenic expression cassette into a recombinant adenoviral type 5 genome as replacement for the E1 region. Viral particles of this replication-deficient Ad5-based reporter are able to infect 100% of rat hepatic stellate cells and myofibroblasts, respectively. Conclusions Our results indicate that FuGENE™6-based methods may be optimized sufficiently to offer a feasible

Biocompatible Capsules and Methods of Making

NASA Technical Reports Server (NTRS)

Loftus, David J. (Inventor)

2017-01-01

Embodiments of the invention include capsules for containing medical implants and delivery systems for release of active biological substances into a host body. Delivery systems comprise a capsule comprising an interior enclosed by walls, and a source of active biological substances enclosed within the capsule interior, wherein the active biological substances are free to diffuse across the capsule walls. The capsule walls comprise a continuous mesh of biocompatible fibers and a seal region where two capsule walls overlap. The interior of the capsule is substantially isolated from the medium surrounding the capsule, except for diffusion of at least one species of molecule between the capsule interior and the ambient medium, and prevents cell migration into or out of the capsule. Methods for preparing and using the capsules and delivery systems are provided.

Effects of food on a gastrically degraded drug: azithromycin fast-dissolving gelatin capsules and HPMC capsules.

PubMed

Curatolo, William; Liu, Ping; Johnson, Barbara A; Hausberger, Angela; Quan, Ernest; Vendola, Thomas; Vatsaraj, Neha; Foulds, George; Vincent, John; Chandra, Richa

2011-07-01

Commercial azithromycin gelatin capsules (Zithromax®) are known to be bioequivalent to commercial azithromycin tablets (Zithromax®) when dosed in the fasted state. These capsules exhibit a reduced bioavailability when dosed in the fed state, while tablets do not. This gelatin capsule negative food effect was previously proposed to be due to slow and/or delayed capsule disintegration in the fed stomach, resulting in extended exposure of the drug to gastric acid, leading to degradation to des-cladinose-azithromycin (DCA). Azithromycin gelatin capsules were formulated with "superdisintegrants" to provide fast-dissolving capsules, and HPMC capsule shells were substituted for gelatin capsule shells, in an effort to eliminate the food effect. Healthy volunteers were dosed with these dosage forms under fasted and fed conditions; pharmacokinetics were evaluated. DCA pharmacokinetics were also evaluated for the HPMC capsule subjects. In vitro disintegration of azithromycin HPMC capsules in media containing food was evaluated and compared with commercial tablets and commercial gelatin capsules. When the two fast-dissolving capsule formulations were dosed to fed subjects, the azithromycin AUC was 38.9% and 52.1% lower than after fasted-state dosing. When HPMC capsules were dosed to fed subjects, the azithromycin AUC was 65.5% lower than after fasted-state dosing. For HPMC capsules, the absolute fasting-state to fed-state decrease in azithromycin AUC (on a molar basis) was similar to the increase in DCA AUC. In vitro capsule disintegration studies revealed extended disintegration times for commercial azithromycin gelatin capsules and HPMC capsules in media containing the liquid foods milk and Ensure®. Interaction of azithromycin gelatin and HPMC capsules with food results in slowed disintegration in vitro and decreased bioavailability in vivo. Concurrent measurement of serum azithromycin and the acid-degradation product DCA demonstrates that the loss of azithromycin

Differential regulation of collagen secretion by kinin receptors in cardiac fibroblast and myofibroblast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catalán, Mabel; Smolic, Christian; Contreras, Ariel

Kinins mediate their cellular effects through B1 (B1R) and B2 (B2R) receptors, and the activation of B2R reduces collagen synthesis in cardiac fibroblasts (CF). However, the question of whether B1R and/or B2R have a role in cardiac myofibroblasts remains unanswered. Methods: CF were isolated from neonate rats and myofibroblasts were generated by an 84 h treatment with TGF-β1 (CMF). B1R was evaluated by western blot, immunocytochemistry and radioligand assay; B2R, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and cyclooxygenases 1and 2 (COX-1, and COX-2) were evaluated by western blot; intracellular Ca{sup +2} levels were evaluated with Fluo-4AM;more » collagen secretion was measured in the culture media using the picrosirius red assay kit. Results: B2R, iNOS, COX-1 and low levels of B1R but not eNOS, were detected by western blot in CF. Also, B1R, B2R, and COX-2 but not iNOS, eNOS or COX-1, were detected by western blot in CMF. By immunocytochemistry, our results showed lower intracellular B1R levels in CF and higher B1R levels in CMF, mainly localized on the cell membrane. Additionally, we found B1R only in CMF cellular membrane through radioligand displacement assay. Bradykinin (BK) B2R agonist increased intracellular Ca{sup 2+} levels and reduced collagen secretion both in CF and CMF. These effects were blocked by HOE-140, and inhibited by L-NAME, 1400W and indomethacin. Des-Arg-kallidin (DAKD) B1R agonist did not increase intracellular Ca{sup 2+} levels in CF; however, after preincubation for 1 h with DAKD and re-stimulation with the same agonist, we found a low increase in intracellular Ca{sup 2+} levels. Finally, DAKD increased intracellular Ca{sup 2+} levels and decreased collagen secretion in CMF, being this effect blocked by the B1R antagonist des-Arg9-Leu8-kallidin and indomethacin, but not by L-NAME or 1400 W. Conclusion: B1R, B2R, iNOS and COX-1 were expressed differently between CF and CMF, and collagen secretion

[Meniscoids of the intervertebral joints].

PubMed

Kos, J; Hert, J; Sevcík, P

2002-01-01

A large amount of material was used to study the distribution, location and shape of meniscoids in intervertebral joints of the human spine, from the atlanto-occipital joint to the sacrum, in order to find out how many of intervertebral joints had mobile meniscoids. These might be regarded as possible causes of spinal blockade or other vertebrogenous complaints. The materials provided by the Department of Anatomy and Department of Forensic Medicine at the Faculty of Medicine of Charles University in Pilznen included 20 cadaverous spines from humans aged 20 to 80 years. Access to each joint was provided by dissection of the articular capsule from the lower articular processes of the vertebra situated above. In the orthograde view, all meniscoids were described in terms of shape, size, consistence and location. Their structure was ascertained by histological examination of cross sections stained with haematoxylin and eosin. Meniscoids varying in shape and size were found in all of the intervertebral joints. They were classified by their histological structure as synovial, fat and fibrous meniscoids. The first category was observed frequently, the last only rarely. A total of 29 mobile meniscoids were recorded, most of them in the lumbar spine. Most of the meniscoids present in the cervical spine were of synovial and less frequently of fat types. Meniscoids found in the thoracic spine were poorly developed synovial ones and those present in the lumbar spine were of all types and were also largest in size. The most conspicuous meniscoids were seen in the spines that showed degenerative changes in intervertebral joints. Large fat pads were found in atlanto-occipital and atlanto-axial joints. Mobile meniscoids, most of them present in the lumbar spine (6.4% of all joints.), were connected with the capsule by a thin pedicle and it was possible to move them over a half of the articular surface. Some inter-individual changes were also found; in some spines, the most

Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells

PubMed Central

Cushing, Melinda C.; Mariner, Peter D.; Liao, Jo-Tsu; Sims, Evan A.; Anseth, Kristi S.

2008-01-01

This study aimed to identify signaling pathways that oppose connective tissue fibrosis in the aortic valve. Using valvular interstitial cells (VICs) isolated from porcine aortic valve leaflets, we show that basic fibroblast growth factor (FGF-2) effectively blocks transforming growth factor-β1 (TGF-β1)-mediated myofibroblast activation. FGF-2 prevents the induction of α-smooth muscle actin (αSMA) expression and the exit of VICs from the cell cycle, both of which are hallmarks of myofibroblast activation. By blocking the activity of the Smad transcription factors that serve as the downstream nuclear effectors of TGF-β1, FGF-2 treatment inhibits fibrosis in VICs. Using an exogenous Smad-responsive transcriptional promoter reporter, we show that Smad activity is repressed by FGF-2, likely an effect of the fact that FGF-2 treatment prevents the nuclear localization of Smads in these cells. This appears to be a direct effect of FGF signaling through mitogen-activated protein kinase (MAPK) cascades as the treatment of VICs with the MAPK/extracellular regulated kinase (MEK) inhibitor U0126 acted to induce fibrosis and blocked the ability of FGF-2 to inhibit TGF-β1 signaling. Furthermore, FGF-2 treatment of VICs blocks the development of pathological contractile and calcifying phenotypes, suggesting that these pathways may be utilized in the engineering of effective treatments for valvular disease.—Cushing, M. C., Mariner, P. D., Liao, J. T., Sims, E. A., Anseth, K. S. Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells. PMID:18218921

An interesting case of inflammatory myofibroblastic tumor presenting as cholangiocarcinoma.

PubMed

Karimi, Mehrdad; Tizmaghz, Adnan; Shabestanipour, Ghazaal

2018-04-06

Inflammatory myofibroblastic tumor (IMT) is a reactive or inflammatory state mostly affecting the pulmonary system and commonly occurs in children and young adults. IMT presentation in the hepatic duct bifurcation is very rare and has sporadically been reported before. A 12-year-old girl presented with jaundice, pruritus which had begun 5 weeks previously. Ultrasound revealed intrahepatic biliary ductal dilation and an isoechoic 25*30 mm lesion at or near the confluence of the right and left hepatic ducts that were suggestive of a hilar cholangiocarcinoma. Limited resection was decided intraoperatively because the intraoperative frozen section assessment of the CBD, right and left hepatic duct wall samples and porta hepatis lymph nodes was normal. Histologically the tumor proved an inflammatory myofibroblastic tumor (IMT). Almost all patients with resectable IMT should be managed with radical surgical resection or single nonsteroidal anti-inflammatory drugs. In addition, conservative treatments with NSAIDs, corticosteroids or chemotherapeutic agents could not be started in many cases due to the lack of definitive diagnosis of the mass preoperatively. Thus, surgical removal is frequently unavoidable. Biliary IBT is extremely rare and should be considered by all hepatobiliary surgeons dealing with the teens with cholangiocarcinoma, to avoid unnecessary major surgical resections. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Estrogen signaling in colorectal carcinoma microenvironment: expression of ERbeta1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression.

PubMed

Tzelepi, Vassiliki; Grivas, Petros; Kefalopoulou, Zinovia; Kalofonos, Haralabos; Varakis, John N; Melachrinou, Maria; Sotiropoulou-Bonikou, Georgia

2009-04-01

Epidemiological and molecular data suggest the involvement of estrogen signaling in colorectal tissue, mediated mainly through estrogen receptor beta (ERbeta). Estrogens may mediate their effects in epithelial cells indirectly by acting on stromal cells. Expression of ERalpha, ERbeta1, and the ER coregulators, amplified in breast cancer-1 (AIB-1) and transcriptional intermediary factor 2 (TIF-2), was evaluated in myofibroblasts of 107 colorectal carcinomas, 77 paired samples of normal mucosa, and 29 adenomas by immunohistochemistry. Double immunostaining with a-SMA was used to identify the myofibroblasts of normal tissue, adenomas, and cancer microenvironment. ERalpha was not expressed in stromal cells. Nuclear expression of ERbeta1, AIB-1, and TIF-2 in myofibroblasts gradually increased from normal mucosa, through adenomas, to carcinomas. Cytoplasmic ERbeta1 and TIF-2 expression was enhanced in carcinomas compared to normal mucosa and adenomas. Enhanced nuclear and cytoplasmic ERbeta1 expression and elevated nuclear AIB-1 expression were more frequently noted in myofibroblasts of carcinomas of advanced stage. ERbeta1 expression in cancer-associated myofibroblasts correlated to AIB-1 and TIF-2 expression. None of the markers correlated with patients' prognosis. Our findings imply that ERbeta1-dependent (genomic and non-genomic) and ER-coregulator-dependent (AIB-1, TIF-2) signal transductions in myofibroblasts may be involved in the initiation and progression of colorectal carcinomas.

Effects of selexipag and its active metabolite in contrasting the profibrotic myofibroblast activity in cultured scleroderma skin fibroblasts.

PubMed

Cutolo, Maurizio; Ruaro, Barbara; Montagna, Paola; Brizzolara, Renata; Stratta, Emanuela; Trombetta, Amelia Chiara; Scabini, Stefano; Tavilla, Pier Paolo; Parodi, Aurora; Corallo, Claudio; Giordano, Nicola; Paolino, Sabrina; Pizzorni, Carmen; Sulli, Alberto; Smith, Vanessa; Soldano, Stefano

2018-05-02

Myofibroblasts contribute to fibrosis through the overproduction of extracellular matrix (ECM) proteins, primarily type I collagen (COL-1) and fibronectin (FN), a process which is mediated in systemic sclerosis (SSc) by the activation of fibrogenic intracellular signaling transduction molecules, including extracellular signal-regulated kinases 1 and 2 (Erk1/2) and protein kinase B (Akt). Selexipag is a prostacyclin receptor agonist synthesized for the treatment of pulmonary arterial hypertension. The study investigated the possibility for selexipag and its active metabolite (ACT-333679) to downregulate the profibrotic activity in primary cultures of SSc fibroblasts/myofibroblasts and the fibrogenic signaling molecules involved. Fibroblasts from skin biopsies obtained with Ethics Committee (EC) approval from patients with SSc, after giving signed informed consent, were cultured until the 3 rd culture passage and then either maintained in normal growth medium (untreated cells) or independently treated with different concentrations of selexipag (from 30 μM to 0.3 μM) or ACT-333679 (from 10 μM to 0.1 μM) for 48 h. Protein and gene expressions of α-smooth muscle actin (α-SMA), fibroblast specific protein-1 (S100A4), COL-1, and FN were investigated by western blotting and quantitative real-time PCR. Erk1/2 and Akt phosphorylation was investigated in untreated and ACT-333679-treated cells by western botting. Selexipag and ACT-333679 significantly reduced protein synthesis and gene expression of α-SMA, S100A4, and COL-1 in cultured SSc fibroblasts/myofibroblasts compared to untreated cells, whereas FN was significantly downregulated at the protein level. Interestingly, ACT-333679 significantly reduced the phosphorylation of Erk1/2 and Akt in cultured SSc fibroblasts/myofibroblasts. Selexipag and mainly its active metabolite ACT-333679 were found for the first time to potentially interfere with the profibrotic activity of cultured SSc fibroblasts/myofibroblasts

Chromium content in the human hip joint tissues.

PubMed

Brodziak-Dopierała, Barbara; Kwapuliński, Jerzy; Sobczyk, Krzysztof; Wiechuła, Danuta

2015-02-01

Chromium has many important functions in the human body. For the osseous tissue, its role has not been clearly defined. This study was aimed at determining chromium content in hip joint tissues. A total of 91 hip joint samples were taken in this study, including 66 from females and 25 from males. The sample tissues were separated according to their anatomical parts. The chromium content was determined by the AAS method. The statistical analysis was performed with U Mann-Whitney's non-parametric test, P≤0.05. The overall chromium content in tissues of the hip joint in the study subjects was as follows: 5.73 µg/g in the articular cartilage, 5.33 µg/g in the cortical bone, 17.86 µg/g in the cancellous bone, 5.95 µg/g in the fragment of the cancellous bone from the intertrochanteric region, and 1.28 µg/g in the joint capsule. The chromium contents were observed in 2 group patients, it was 7.04 µg/g in people with osteoarthritis and 12.59 µg/g in people with fractures. The observed chromium content was highest in the cancellous bone and the lowest in the joint capsule. Chromium content was significantly different between the people with hip joint osteoarthritis and the people with femoral neck fractures. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Crosstalk Between Activated Myofibroblasts and β Cells in Injured Mouse Pancreas.

PubMed

Bayan, Jennifer-Ann; Peng, Zhechu; Zeng, Ni; He, Lina; Chen, Jingyu; Stiles, Bangyan L

2015-10-01

In injury conditions, myofibroblasts are induced to lay down matrix proteins and support the repair process. In this study, we investigated the role of myofibroblasts, particularly stellate cells, in the growth and regeneration of pancreatic β cells. We used both in vitro and in vivo approaches to address whether stellate cells may promote the growth of β cells. Our experiments demonstrated that activated stellate cells support the proliferation of β cells in vitro. In vivo, mesenchymals surrounding the pancreatic islets are activated (induced to proliferate) in the islet regeneration model of Pten null mice. These mesenchymals display markers of pancreatic stellate cells, such as desmin and to a lesser extent, smooth muscle actin α. We have shown previously that targeted β-cell deletion of Pten lead to a significant increase in total islet mass. This phenotype was accompanied by an increase in peri-islet mitotic activity, particularly in islets injured by streptozotocin, a β cell-specific toxin. Together with the in vitro observations, our data, here, suggest that that these mesenchymal cells may support the regeneration of the islets. Identifying how the communication occurs may provide clinically relevant mechanism for inducing β-cell regeneration.

Mercury Capsule Separation Tests

NASA Image and Video Library

1960-04-01

Mercury capsule separation from Redstone booster in the Altitude Wind Tunnel (AWT): NASA Lewis conducted full-scale separation tests of the posigrade rockets that were fired after the Redstone rockets burned out. The researchers studied the effect of the posigrade rockets firing on the Redstone booster and retrograde package. This film shows the Mercury capsule being mounted to the Redstone missile model in the Altitude Wind Tunnel. The capsule's engines are fired and it horizontally separates from the Atlas. After firing the capsule swings from an overhead crane.

Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells

PubMed Central

Lechuga, Susana; Baranwal, Somesh; Li, Chao; Naydenov, Nayden G.; Kuemmerle, John F.; Dugina, Vera; Chaponnier, Christine; Ivanov, Andrei I.

2014-01-01

Transdifferentiation of epithelial cells into mesenchymal cells and myofibroblasts plays an important role in tumor progression and tissue fibrosis. Such epithelial plasticity is accompanied by dramatic reorganizations of the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on epithelial transdifferentiation remain poorly understood. In the present study, we observed that selective siRNA-mediated knockdown of γ-cytoplasmic actin (γ-CYA), but not β-cytoplasmic actin, induced epithelial-to-myofibroblast transition (EMyT) of different epithelial cells. The EMyT manifested by increased expression of α-smooth muscle actin and other contractile proteins, along with inhibition of genes responsible for cell proliferation. Induction of EMyT in γ-CYA–depleted cells depended on activation of serum response factor and its cofactors, myocardial-related transcriptional factors A and B. Loss of γ-CYA stimulated formin-mediated actin polymerization and activation of Rho GTPase, which appear to be essential for EMyT induction. Our findings demonstrate a previously unanticipated, unique role of γ-CYA in regulating epithelial phenotype and suppression of EMyT that may be essential for cell differentiation and tissue fibrosis. PMID:25143399

Sweat collection capsule

NASA Technical Reports Server (NTRS)

Delaplaine, R. W.; Greenleaf, J. E.

1979-01-01

Capsule, with filter paper insert, is used to collect sweat for rate monitoring, chromatographic analysis, or active sweat gland location within specified area. Construction of capsule allows change of inserts while device remains strapped in place.

Engineering fluorescent poly(dopamine) capsules.

PubMed

Chen, Xi; Yan, Yan; Müllner, Markus; van Koeverden, Martin P; Noi, Ka Fung; Zhu, Wei; Caruso, Frank

2014-03-18

The recent development of poly(dopamine) (PDA) capsules provides new opportunities for their application in biology and medicine. To advance the biomedical application of PDA capsules, strategies that enable the preparation of fluorescently labeled PDA (F-PDA) capsules are required, as this will allow evaluation of their cellular interactions using a range of fluorescence-based techniques. Herein, we report a facile approach for the fabrication of F-PDA capsules via the polymerization of dopamine (DA) on sacrificial templates in the presence of hydrogen peroxide (H2O2). F-PDA capsules with well-defined sizes are prepared by templating different organic and inorganic particles. The resulting F-PDA capsules show negligible cytotoxicity in HeLa cells after incubation for 48 h. We also demonstrate visualization of the F-PDA capsules following internalization by HeLa cells using conventional fluorescence microscopy, en route toward detailed investigations on their biological interactions.

Comparison of myofibroblasts expression in oral squamous cell carcinoma, verrucous carcinoma, high risk epithelial dysplasia, low risk epithelial dysplasia and normal oral mucosa.

PubMed

Chaudhary, Minal; Gadbail, Amol Ramchandra; Vidhale, Gaurav; Mankar Gadbail, Mugdha P; Gondivkar, Shailesh M; Gawande, Madhuri; Patil, Swati

2012-09-01

The aim was to evaluate and compare the presence of myofibroblasts in oral squamous cell carcinoma (OSCC), verrucous carcinoma (VC), high-risk epithelial dysplasia (HRED), low-risk epithelial dysplasia (LRED), and normal oral mucosa (NOM). The study consisted of 37 OSCC, 15 VC, 15 HRED, 15 LRED and 15 NOM. α-smooth muscle actin (α-SMA) antibody was used to identify myofibroblasts. The α-SMA expression was not observed in NOM and LRED. The α-SMA was expressed in 97.29% of OSCC, 86.66% of VC, 46.66 % of HRED. The α-SMA expression was significantly higher in OSCC than VC (p = 0.023) and HRED (p < 0.000). The α-SMA expression was significantly higher in VC than HRED (p = 0.043). Myofibroblastic expression, as highlighted by α-SMA, is undetectable in NOM and LRED but increases as the disease progresses from potentially malignant disorders, as HRED to VC to invasive OSCC. Thus, proliferation of myofibroblasts may be used as a stromal marker of oral premalignancy and malignancy.

Spindle cell sarcoma of the vulva with myofibroblastic differentiation.

PubMed

Adeleye, Amanda J; Palmeri, Nicholas; Wang, Shih-Hsiu J; Liu-Jarin, Xiaolin; Wright, Jason D

2015-04-01

Primary vulvar sarcomas are rare lesions of the lower genital tract. We report the case of a patient with a spindle cell sarcoma of the vulva. A 44-year-old woman presented with a painless vulvar mass. Vulvar biopsy demonstrated a spindle cell sarcoma with myofibroblastic differentiation. Pretreatment evaluation revealed no evidence of metastatic disease, and magnetic resonance imaging found no local masses. The patient underwent right radical vulvectomy with negative margins and tolerated the procedure well. Women undergoing gynecologic care should have routine evaluation of the vulva to detect these rare neoplasms.

The effect of intra-articular hyaluronate and tramadol injection on patients with adhesive capsulitis of the shoulder.

PubMed

Kim, Kyung-Hee; Suh, Jung-Woo; Oh, Ki Young

2017-08-03

Local administration of opioids causes effective analgesia without adverse effects related to the central nervous system. After the beneficial demonstration of peripheral opioid receptors in joint synovia, intra-articular opioid injections were used for pain treatment. Clinical studies have reported the safety and efficacy of hyaluronate injection in the shoulder joint of patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive capsulitis. To estimate the efficacy of intra-articular hyaluronate and tramadol injection for adhesive capsulitis of the shoulder compared with that of intra-articular hyaluronate injection alone. Thirty patients with adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n= 16) or the tramadol group (n= 14). Hyaluronate group members were administered five weekly intra-articular hyaluronate injections; tramadol group members were administered three weekly intra-articular hyaluronate and tramadol injections and then two weekly intra-articular injections of hyaluronate. Visual Analog Scale (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3, 4, and 6 after the initial injection. A significant improvement was observed in VAS, PROM, and SPADI scores between time points in both groups. In comparison in both groups at weeks 1 and 2 after the initial injection the VAS scores of the tramadol group were significantly lower than those of the hyaluronate group. Intra-articular hyaluronate with tramadol showed more rapid and strong analgesic effects than intra-articular hyaluronate alone and did not induce any adverse effects.

The Lens Capsule

PubMed Central

Danysh, Brian P.; Duncan, Melinda K.

2009-01-01

The lens capsule is a modified basement membrane that completely surrounds the ocular lens. It is known that this extracellular matrix is important for both the structure and biomechanics of the lens in addition to providing informational cues to maintain lens cell phenotype. This review covers the development and structure of the lens capsule, lens diseases associated with mutations in extracellular matrix genes and the role of the capsule in lens function including those proposed for visual accommodation, selective permeability to infectious agents, and cell signaling. PMID:18773892

Magneto-responsive alginate capsules.

PubMed

Degen, Patrick; Zwar, Elena; Schulz, Imke; Rehage, Heinz

2015-05-20

Upon incorporation of magnetic nanoparticles (mNPs) into gels, composite materials called ferrogels are obtained. These magneto-responsive systems have a wide range of potential applications including switches and sensors as well as drug delivery systems. In this article, we focus on the properties of calcium alginate capsules, which are widely used as carrier systems in medicine and technology. We studied the incorporation of different kinds of mNPs in matrix capsules and in the core and the shell of hollow particles. We found out that not all particle-alginate or particle-CaCl2 solution combinations were suitable for a successful capsule preparation on grounds of a destabilization of the nanoparticles or the polymer. For those systems allowing the preparation of switchable beads or capsules, we systematically studied the size and microscopic structure of the capsules, their magnetic behavior and mechanical resistance.

ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis

PubMed Central

Lagares, David; Ghassemi-Kakroodi, Parisa; Tremblay, Caroline; Santos, Alba; Probst, Clemens K.; Franklin, Alicia; Santos, Daniela M.; Grasberger, Paula; Ahluwalia, Neil; Montesi, Sydney B.; Shea, Barry S.; Black, Katharine E.; Knipe, Rachel; Blati, Meryem; Baron, Murray; Wu, Brian; Fahmi, Hassan; Gandhi, Rajiv; Pardo, Annie; Selman, Moisés; Wu, Jiangping; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Tager, Andrew M.; Kapoor, Mohit

2017-01-01

Maladaptive wound healing responses to chronic tissue injury result in organ fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition and tissue remodelling by activated myofibroblasts, leads to loss of proper tissue architecture and organ function; however the molecular mediators of myofibroblast activation remain to be fully identified. Here we identify soluble ephrin-B2 as a novel pro-fibrotic mediator in lung and skin fibrosis. We provide molecular, functional and translational evidence that the ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar airspace after lung injury. Shedding of soluble ephrin-B2 (sEphrin-B2) promotes fibroblast chemotaxis and activation via EphB3/EphB4 receptor signaling. We found that mice lacking ephrin-B2 in fibroblasts are protected from skin and lung fibrosis and that a distintegrin and metalloproteinase 10 (ADAM10) is the major ephrin-B2 sheddase in fibroblasts. ADAM10 is induced by transforming growth factor-β1 (TGF-β1), and ADAM10-mediated sEphrin-B2 generation is required for TGF-β1–induced myofibroblast activation. Pharmacological inhibition of ADAM10 reduces sEphrin-B2 levels in bronchoalveolar lavage and prevents lung fibrosis in mice. Consistent with the mouse data, ADAM10/sEphrin-B2 signaling is upregulated in fibroblasts from human subjects with idiopathic pulmonary fibrosis. These results uncover a new molecular mechanism of tissue fibrogenesis and identify sEphrin-B2, its receptors Eph3/Eph4, and ADAM10 as potential therapeutic targets in the treatment of fibrotic diseases. PMID:29058717

Oxygen Fugacity in Large Metal Capsules

NASA Astrophysics Data System (ADS)

Faul, U.; Cline, C. J., II; Jackson, I.; Berry, A.

2016-12-01

During experiments with iron bearing silicates, equilibration between metal capsules and sample interior depends on diffusion of Fe if the capsule composition is not initially in equilibrium with the sample composition. For example, placing Pt or Ni capsules in contact with Fe-bearing olivine leads to Fe-loss from the olivine. In a fully equilibrated system the Fe contents of coexisting metal capsule and olivine reflect the oxygen fugacity (fO2) of the system. Experiments were conducted with olivine encapsulated or wrapped in four different metals (Fe, Ni70Fe30, Ni and Pt) to determine the fO2 in the cm-sized samples used for deformation and seismic property experiments. Small Pt particles mixed with olivine powder were used as fO2 sensors in the interior of the capsules. The results show an ordering of the fO2 in the interior that is consistent with the enclosing metals, i.e. the fO2 is lowest in a Fe capsule and highest in a Pt capsule. However, fO2 values in the more oxidizing metal capsules are substantially below their respective metal-oxide buffers. For example, solgel olivine encapsulated in Ni has an oxygen fugacity that is more than three orders of magnitude below Ni-NiO at 1200C and 0.3 GPa. The fO2 in a capsule interior is therefore to some extent self-buffering and only moderately influenced by the composition of the capsule. While the Pt particles in the interior are equilibrated, Fe gradients from the interior up to the Pt and Ni sample-capsule interfaces show that Fe loss into the capsules is diffusion limited. The fO2 at the interface also has implications for the water retention in unbuffered capsules. We infer that relatively high fO2 and hence fH2O observed adjacent to Pt capsules enables retention of water in these capsules, but the fO2 adjacent to Ni capsules is too low and water is lost.

The development of pyro shock test requirements for Viking Lander Capsule components

NASA Technical Reports Server (NTRS)

Barrett, S.

1975-01-01

The procedure used to derive component-level pyro shock specifications for the Viking Lander Capsule (VLC) is described. Effects of shock path distance and mechanical joints between the device and the point at which the environment is to be estimated are accounted for in the method. The validity of the prediction technique was verified by a series of shock tests on a full-scale structural model of the lander body.

The role of myofibroblasts in wound healing, contraction and its clinical implications in cleft palate repair.

PubMed

Chitturi, Ravi Teja; Balasubramaniam, A Murali; Parameswar, R Arjun; Kesavan, G; Haris, K T Muhamed; Mohideen, Khadijah

2015-03-01

Myofibroblasts after its discovery in 1971 as the principal cell for wound healing has come a long way as far as research is concerned. The primary focus of research has been regarding preventing certain unwanted effects of this cell such as wound contraction and scarring. As far as the oral and maxillofacial region is concerned, the primary concern of this untoward effect is during repair of cleft palate surgically which results impaired development of palate and the dentoalveolar structures. This review focuses on the basic aspects of myofibroblasts such as its origin, formation, function in wound healing, role in wound contraction and ways by which its unwanted effects can be overcome to improve the quality of the post surgical complications of cleft palate surgery.

Polydopamine-coated capsules

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Scott R.; Sottos, Nancy R.; Kang, Sen

One aspect of the invention is a polymer material comprising a capsule coated with PDA. In certain embodiments, the capsule encapsulates a functional agent. The encapsulated functional agent may be an indicating agent, healing agent, protecting agent, pharmaceutical drug, food additive, or a combination thereof.

Ganglion cyst of the temporomandibular joint.

PubMed

Heng-Kun, W; Yan-Ling, G; Wen-Feng, Z; Zhe, S; Ren-Xin, W; Xiao-Tao, Z

2014-02-01

Ganglion cyst of the temporomandibular joint is a rare disease, which may arise from myxoid degeneration of the collagenous tissue of the temporomandibular joint capsule, without epithelial or endothelial lining. We report a case of cystic lesion in a 40-year-old female patient. The patient had a left pre-auricular oval-shaped swelling without any articular symptoms. The pathological analysis after surgical removal allowed diagnosing the lesion as a ganglion cyst of the left temporomandibular joint. We made a literature review and noted that this condition was predominant in female patients. We recommend using MRI for diagnostic purposes and surgery as the best therapeutic alternative. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Determination of Parachute Joint Factors using Seam and Joint Testing

NASA Technical Reports Server (NTRS)

Mollmann, Catherine

2015-01-01

This paper details the methodology for determining the joint factor for all parachute components. This method has been successfully implemented on the Capsule Parachute Assembly System (CPAS) for the NASA Orion crew module for use in determining the margin of safety for each component under peak loads. Also discussed are concepts behind the joint factor and what drives the loss of material strength at joints. The joint factor is defined as a "loss in joint strength...relative to the basic material strength" that occurs when "textiles are connected to each other or to metals." During the CPAS engineering development phase, a conservative joint factor of 0.80 was assumed for each parachute component. In order to refine this factor and eliminate excess conservatism, a seam and joint testing program was implemented as part of the structural validation. This method split each of the parachute structural joints into discrete tensile tests designed to duplicate the loading of each joint. Breaking strength data collected from destructive pull testing was then used to calculate the joint factor in the form of an efficiency. Joint efficiency is the percentage of the base material strength that remains after degradation due to sewing or interaction with other components; it is used interchangeably with joint factor in this paper. Parachute materials vary in type-mainly cord, tape, webbing, and cloth -which require different test fixtures and joint sample construction methods. This paper defines guidelines for designing and testing samples based on materials and test goals. Using the test methodology and analysis approach detailed in this paper, the minimum joint factor for each parachute component can be formulated. The joint factors can then be used to calculate the design factor and margin of safety for that component, a critical part of the design verification process.

[Effects of exercise on joints.

PubMed

Moriyama, Hideki

Joints are composed of several different tissues(cartilage, capsule, meniscus, and ligament), and articular cartilage plays an important role in maintaining mechanical competence during exercise. Weight-bearing exercise has several benefit, including improved blood and synovial fluid circulation in a given joint. Consistent moderate activities facilitate cycles of anabolism and catabolism. Mechanical stresses are crucial for the maintenance of the morphologic and functional integrity of articular cartilage. Healthy cartilage is exposed by hydrostatic pressure and tensile strain, when cartilage degeneration develops, abnormal cartilage is exposed by shear stress. Moderate(physiological)exercise is characterized by a range of equilibrium between matrix anabolic and catabolic processes, or anabolism beyond catabolism. Joints are susceptible to insufficient or excessive activities, leading to joint degeneration. Lack of exercise is known to induce joint contracture seen clinically as a consequence of disuse changes, and excess mechanical stresses induce joint destruction such as osteoarthritis. Joint diseases resulting from insufficient or excessive activities are new and major challenging issues with our aging population. Thus, it is highly desirable to have an effective and efficient treatment to improve and protect against these joint diseases, and thereby to solve these clearly unanswered issues.

Inflammatory Myofibroblastic Tumors in a Case with Hypogastric Discomfort

PubMed Central

Mansour-Ghanaei, Fariborz; Gharibpoor, Alireza; Joukar, Farahnaz; Mavaddati, Sara; Askari, Kourosh; Askari, Seyed Ali; Gharibpoor, Faeze

2017-01-01

Patient: Male, 68 Final Diagnosis: Inflammatory myofibroblastic tumor Symptoms: 2–3 kg weight loss • Helicobacter pylori positive which were eradicated after treatment course • hypogastric region discomfort • no association between the pain, defecation and eating • no history of HIV, diabetes, smoking and alcohol consumption was recorded • no symptoms of nausea, vomiting, fever and shaking chills • normal vital signs • tenderness in the right lower quadrant of the abdomen with no rebound state was noted Medication: — Clinical Procedure: Lab examinationt-imaging-colonoscopy-surgery Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Inflammatory myofibroblastic tumors (IMTs) are scarce tumors with discrete immunohistochemical and molecular attributes which are not related to a particular location. There are different reports about the intrinsic nature of these tumors as benign to possibly malignant. Case Report: Here we report the case of a 68-year-old man referred to the Internal Medicine Department of Razi Hospital in Rasht (a city in the north of Iran) due to right lower quadrant (RLQ) discomfort with no specific symptoms. Colonoscopy revealed a mass-like lesion. Polymorphonuclear cells (PMNCs) admixed by some eosinophils were demonstrated histopathologically. Immunohistochemical evaluation was positive for vimentin, CD34, smooth muscle actin, and ALK, and negative for CD117 and desmin. The tumor was successfully removed by surgery with no chemotherapy. No recurrence was reported. Conclusions: We have performed surgical excision of the mass with no chemotherapy and no recurrence. Although recurrence is reported to be low, we recommend long-term follow-up after surgery. PMID:28250406

Inflammatory Myofibroblastic Bladder Tumor in a Patient with Wolf-Hirschhorn Syndrome

PubMed Central

Marte, Antonio; Indolfi, Paolo; Ficociello, Carmine; Oreste, Matilde; Bottigliero, Gaetano; Gualdiero, Giovanna; Barone, Ciro; Vigliar, Elena; Indolfi, Cristiana; Casale, Fiorina

2013-01-01

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm described in several tissues and organs including genitourinary system, lung, head, and neck. The etiology of IMT is contentious, and whether it is a postinflammatory process or a true neoplasm remains controversial. To our knowledge, we report the first reported case of IMT of urinary bladder in a pediatric patient with Wolf-Hirschhorn (WHS). We also review the literature about patients with associated neoplasia. PMID:24024066

Inflammatory myofibroblastic bladder tumor in a patient with wolf-hirschhorn syndrome.

PubMed

Marte, Antonio; Indolfi, Paolo; Ficociello, Carmine; Russo, Daniela; Oreste, Matilde; Bottigliero, Gaetano; Gualdiero, Giovanna; Barone, Ciro; Vigliar, Elena; Indolfi, Cristiana; Casale, Fiorina

2013-01-01

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm described in several tissues and organs including genitourinary system, lung, head, and neck. The etiology of IMT is contentious, and whether it is a postinflammatory process or a true neoplasm remains controversial. To our knowledge, we report the first reported case of IMT of urinary bladder in a pediatric patient with Wolf-Hirschhorn (WHS). We also review the literature about patients with associated neoplasia.

GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas.

PubMed

Kim, Hye Sung; Shin, Myung Soo; Cheon, Min Seok; Kim, Jae Wang; Lee, Cheol; Kim, Woo Ho; Kim, Young Sill; Jang, Bo Gun

2017-01-01

Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue.

Stiffening hydrogels for investigating the dynamics of hepatic stellate cell mechanotransduction during myofibroblast activation

NASA Astrophysics Data System (ADS)

Caliari, Steven R.; Perepelyuk, Maryna; Cosgrove, Brian D.; Tsai, Shannon J.; Lee, Gi Yun; Mauck, Robert L.; Wells, Rebecca G.; Burdick, Jason A.

2016-02-01

Tissue fibrosis contributes to nearly half of all deaths in the developed world and is characterized by progressive matrix stiffening. Despite this, nearly all in vitro disease models are mechanically static. Here, we used visible light-mediated stiffening hydrogels to investigate cell mechanotransduction in a disease-relevant system. Primary hepatic stellate cell-seeded hydrogels stiffened in situ at later time points (following a recovery phase post-isolation) displayed accelerated signaling kinetics of both early (Yes-associated protein/Transcriptional coactivator with PDZ-binding motif, YAP/TAZ) and late (alpha-smooth muscle actin, α-SMA) markers of myofibroblast differentiation, resulting in a time course similar to observed in vivo activation dynamics. We further validated this system by showing that α-SMA inhibition following substrate stiffening resulted in attenuated stellate cell activation, with reduced YAP/TAZ nuclear shuttling and traction force generation. Together, these data suggest that stiffening hydrogels may be more faithful models for studying myofibroblast activation than static substrates and could inform the development of disease therapeutics.

Effect of rotator cuff strengthening as an adjunct to standard care in subjects with adhesive capsulitis: A randomized controlled trial.

PubMed

Rawat, Pallavi; Eapen, Charu; Seema, Kulathuran Pillai

Randomized controlled trial. To study the effect of adding rotator cuff (RC) muscles strengthening to joint mobilization and transcutaneous electrical nerve stimulation (TENS) in patients with adhesive capsulitis. A prospective, parallel-group, randomised clinical trial was conducted on 42 patients. One group received TENS and joint mobilization and in the other group RC muscles strengthening was added. Treatment was given for 12 sessions within 4 weeks. When compared between the groups statistically significant changes were seen in all the outcome measures in the group that received RC muscle strengthening exercises vs TENS and mobilization. VAS 12.76 ± 1.04 vs 4.05 ± 1.32; SPADI 34.66 ± 6.69 vs 54.29 ± 12.17; PFPS 3.06 ± 0.80 vs 4.70 ± 0.81; and ROM (elevation >125 vs >110 degrees and rotations >70 vs >48 degrees). Addition of a structured RC strengthening program to TENS and joint mobilization in the treatment of adhesive capsulitis resulted in improvement in pain, ROM and function. 1b. Copyright © 2016 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Ethical aspects of capsule endoscopy.

PubMed

Niv, Yaron

2008-01-01

Capsule endoscopy is the most recent innovation in gastrointestinal endoscopy. The capsule contains a video camera that photographs the bowel for 8 h after the capsule has been orally ingested and transmits the images for interpretation to a computerized workstation. Ethical considerations of the use of capsule endoscopy should cover the following main issues: justification of the procedure, its potential benefits and harm, and patient autonomy. Capsule endoscopy has several advantages over traditional endoscopy. The procedure is painless, does not require sedation, is easy to perform and for the first time enables exploration of the entire small bowel at high magnification. However, the clinician cannot control its passive advance along the bowel. In addition, the examination may be incomplete, as the capsule reaches the cecum in only 80% of cases. This paper discusses the problems related to the new endoscopic procedure, the diagnostic yield in comparison with other procedures, proper indications for the procedure, outcome and complications. Copyright 2008 S. Karger AG, Basel.

Polyelectrolyte capsules preloaded with interconnected alginate matrix: An effective capsule system for encapsulation and release of macromolecules.

PubMed

Sundaramurthy, Anandhakumar; Sundramoorthy, Ashok K

2018-02-01

In recent years, the design of stimuli-responsive hollow polymeric capsules is of tremendous interest for the scientific community because of the broad application of these capsules in the biomedical field. The use of weak polyelectrolytes as layer components for capsule fabrication is especially interesting as it results in hollow capsules that show unique release characteristics under physiological conditions. In this work, a methodology to prepare sub-micron sized alginate doped calcium carbonate (CaCO 3 ) particles through controlled precipitation in the presence of alginate is reported. Hollow capsules obtained by Layer-by-Layer (LbL) assembly of poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) are showing an interconnected alginate matrix in the interior of the capsules. Investigations showed that the presence of alginate matrix enhances the encapsulation of cationic molecules (e.g. doxorubicin hydrochloride) manifold by charge controlled attraction mechanism. Capsule permeability investigated by confocal laser scanning microscopy revealed that the transformation from an open state to closed state is accompanied by an intermediate state where capsules are neither open nor closed. Furthermore, time dependent study indicated that the encapsulation process is linear as a function of time. The cell viability experiments demonstrated excellent biocompatibility of hollow capsules with mouse embryonic fibroblast cells. Anticancer investigations showed that DOX loaded capsules have significant anti-proliferative characteristics against HeLa cells. Such capsules have high potential for use as drug carrier for cationic drugs in cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.

PubMed

Dabiri, Shahriar; Talebi, Amin; Shahryari, Jahanbanoo; Meymandi, Manzoumeh Shamsi; Safizadeh, Hossein

2013-02-01

This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue.  There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P < 0.001). We observed positive significant correlations between stromal myofibroblasts, HER2 expression, and the numbers of involved lymph nodes in invasive cancer, DCIS, and FCD ± DIN (P < 0.001). More myofibroblasts were present in grade III cases, with the least frequent observed among grade I cases in the stroma of those with invasive disease, DCIS, and FCD ± DIN (P < 0.001).  MVC was inversely related to stromal myofibroblasts in invasive cancer (P < 0.001) and DCIS (P < 0.001), whereas there was a positive correlation in the stroma of FCD ± DIN (P = 0.002) and normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001).  Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts

Efficacy of Dorsoradial Capsulodesis for Trapeziometacarpal Joint Instability: A Cadaver Study.

PubMed

Chenoweth, Brian A; O'Mahony, Gavin D; Fitzgerald, Casey; Stoner, Julie A; O'Donoghue, Daniel L; Rayan, Ghazi M

2017-01-01

To test the biomechanical properties of the dorsoradial capsulodesis procedure. Six cadaveric hands were used. After exposing the trapeziometacarpal (TMC) joint, we placed Kirschner wires in the distal radius and thumb metacarpal. The rotation shear test was then performed to test the joint axial laxity, and angular measurements using Kirschner wires as reference points were documented. The dorsoradial (DR) ligament and capsule were released, followed by the intermetacarpal (IM) ligament; angular measurements were obtained. Finally, the DR capsulodesis procedure was performed, and final measurements were obtained. Comparisons were made among the various stages of ligament integrity to determine the amount of stability provided by DR capsulodesis. All cadavers demonstrated axial laxity with transection of the DR ligament; an increase in stability was obtained after DR capsulodesis. Transection of the capsule and IM ligament caused increased laxity relative to the native joint (median, 24° and 35°, respectively, on rotational testing). After we performed DR capsulodesis, rotational stability improved by a median of 41° compared with DR ligament transection, 49° compared with DR and IM ligament transection, and 18° relative to the native joint. Dorsoradial capsulodesis restores rotational stability for TMC joint after division of the DR and IM ligaments. The stability achieved was statistically significant compared with both an intact native TMC joint and induced laxity of the TMC joint. The DR capsulodesis procedure may improve rotational stability to the TMC joint. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Patency© and agile© capsules

PubMed Central

Caunedo-Álvarez, Ángel; Romero-Vazquez, Javier; Herrerias-Gutierrez, Juan M

2008-01-01

Small bowel strictures can be missed by current diagnostic methods. The Patency capsule is a new non-endoscopic dissolvable capsule which has as an objective of checking the patency of digestive tract, in a non-invasive manner. The available clinical trials have demonstrated that the Patency© capsule is a good tool for assessment of the functional patency of the small bowel, and it allows identification of those patients who can safely undergo a capsule endoscopy, despite clinical and radiographic evidence of small-bowel obstruction. Some cases of intestinal occlusion have been reported with the Patency© capsule, four of them needed surgery. So, a new capsule with two timer plugs (Agile© capsule) has been recently developed in order to minimize the risk of occlusion. This new device stars its dissolution process earlier (30 h after ingestion) and its two timer plugs have been designed to begin the disintegration even when the device is blocked in a tight stricture. PMID:18785278

Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

PubMed Central

Eldred, Julie A.; McDonald, Matthew; Wilkes, Helen S.; Spalton, David J.; Wormstone, I. Michael

2016-01-01

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs. PMID:27076230

Nitrated fatty acids reverse pulmonary fibrosis by dedifferentiating myofibroblasts and promoting collagen uptake by alveolar macrophages

PubMed Central

Reddy, Aravind T.; Lakshmi, Sowmya P.; Zhang, Yingze; Reddy, Raju C.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease, thought to be largely transforming growth factor β (TGFβ) driven, for which there is no effective therapy. We assessed the potential benefits in IPF of nitrated fatty acids (NFAs), which are unique endogenous agonists of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor that exhibits wound-healing and antifibrotic properties potentially useful for IPF therapy. We found that pulmonary PPARγ is down-regulated in patients with IPF. In vitro, knockdown or knockout of PPARγ expression in isolated human and mouse lung fibroblasts induced a profibrotic phenotype, whereas treating human fibroblasts with NFAs up-regulated PPARγ and blocked TGFβ signaling and actions. NFAs also converted TGFβ to inactive monomers in cell-free solution, suggesting an additional mechanism through which they may inhibit TGFβ. In vivo, treating mice bearing experimental pulmonary fibrosis with NFAs reduced disease severity. Also, NFAs up-regulated the collagen-targeting factor milk fat globule-EGF factor 8 (MFG-E8), stimulated collagen uptake and degradation by alveolar macrophages, and promoted myofibroblast dedifferentiation. Moreover, treating mice with established pulmonary fibrosis using NFAs reversed their existing myofibroblast differentiation and collagen deposition. These findings raise the prospect of treating IPF with NFAs to halt and perhaps even reverse the progress of IPF.—Reddy, A. T., Lakshmi, S. P., Zhang, Y., Reddy, R. C. Nitrated fatty acids reverse pulmonary fibrosis by dedifferentiating myofibroblasts and promoting collagen uptake by alveolar macrophages. PMID:25252739

Magnetically guided capsule endoscopy.

PubMed

Shamsudhin, Naveen; Zverev, Vladimir I; Keller, Henrik; Pane, Salvador; Egolf, Peter W; Nelson, Bradley J; Tishin, Alexander M

2017-08-01

Wireless capsule endoscopy (WCE) is a powerful tool for medical screening and diagnosis, where a small capsule is swallowed and moved by means of natural peristalsis and gravity through the human gastrointestinal (GI) tract. The camera-integrated capsule allows for visualization of the small intestine, a region which was previously inaccessible to classical flexible endoscopy. As a diagnostic tool, it allows to localize the sources of bleedings in the middle part of the gastrointestinal tract and to identify diseases, such as inflammatory bowel disease (Crohn's disease), polyposis syndrome, and tumors. The screening and diagnostic efficacy of the WCE, especially in the stomach region, is hampered by a variety of technical challenges like the lack of active capsular position and orientation control. Therapeutic functionality is absent in most commercial capsules, due to constraints in capsular volume and energy storage. The possibility of using body-exogenous magnetic fields to guide, orient, power, and operate the capsule and its mechanisms has led to increasing research in Magnetically Guided Capsule Endoscopy (MGCE). This work shortly reviews the history and state-of-art in WCE technology. It highlights the magnetic technologies for advancing diagnostic and therapeutic functionalities of WCE. Not restricting itself to the GI tract, the review further investigates the technological developments in magnetically guided microrobots that can navigate through the various air- and fluid-filled lumina and cavities in the body for minimally invasive medicine. © 2017 American Association of Physicists in Medicine.

Successful treatment of an unresectable inflammatory myofibroblastic tumor of the frontal bone using a cyclooxygenase-2 inhibitor and methotrexate.

PubMed

Kusunoki-Nakamoto, Fumiko; Matsukawa, Takashi; Tanaka, Masaki; Miyagawa, Toji; Yamamoto, Tomotaka; Shimizu, Jun; Ikemura, Masako; Shibahara, Junji; Tsuji, Shoji

2013-01-01

Inflammatory myofibroblastic tumor (IMT) is a disease characterized by tumorous lesions consisting of myofibroblastic spindle cells and inflammatory cells that occur primarily in the soft tissues and viscera of children and young adults. Total excision is the most effective therapy. Steroids have been used to treat unresectable lesions with some success. We herein report a case of IMT involving the frontal bone accompanied by pachymeningitis. The tumor was characterized by an aggressive clinical course that was refractory to prednisolone. Performing total excision seemed difficult. Celecoxib and methotrexate were effective treatments. Our experience suggests the efficacy of celecoxib and methotrexate as alternatives for treating unresectable IMT.

Histological study of the human temporo-mandibular joint and its surrounding muscles.

PubMed

Bravetti, P; Membre, H; El Haddioui, A; Gérard, H; Fyard, J P; Mahler, P; Gaudy, J F

2004-10-01

This is a histological study of the human temporo-mandibular joint and its surrounding muscles. Using a microscopic study of serial sections from anatomical specimens from six subjects, the detailed anatomy of the joint is presented with particular regard to the histology. This study has allowed, in particular, the description of the ligaments and capsule as well as the insertions of the masticatory muscles (temporalis, masseter, lateral pterygoid) on this joint. These observations are then compared with the anatomical and histological data already reported on this subject. This study shows that the bulk of the muscular fibres of the lateral pterygoid passes under the foot of the disc is attached over the whole height of the condylar, unite and extend as far as the medial pole of the joint under the insertion of the articular disc. An insertion of the temporo-masseter musculo-tendinous complex on the anterior and lateral capsulo-discal structures was observed. The lateral pterygoid is composed of a succession of tendinous and fleshy fibres. This study confirms the thickening of the lateral capsule that corresponds to a lateral collateral ligament, and the absence of a medial collateral ligament. Medial stability is conferred by the lateral ligament of the contralateral joint.

Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumour of the mediastinum: A favourable response to treatment and review of the literature.

PubMed

Ghandi, Narges; Ghanadan, Alireza; Azizian, Mohammad-Reza; Hejazi, Pardis; Aghazadeh, Nessa; Tavousi, Parvin; Daneshpazhooh, Maryam

2015-05-01

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disorder that occurs in association with an underlying neoplasm. Inflammatory myofibroblastic tumour (IMT) is a rare low-grade sarcoma of fibroblasts and myofibroblasts associated with inflammatory cells, most commonly occurring in the lung. In this study, a case of PNP associated with IMT of the mediastinum is reported. The patient had a favourable outcome following surgical resection and treatment with a systemic steroid, azathioprine, and i.v. immunoglobulin. The occurrence of PNP with sarcomas, specifically IMT, is noteworthy although it is not well studied in the existing literature. © 2014 The Australasian College of Dermatologists.

Low-energy gamma ray inspection of brazed aluminum joints

NASA Technical Reports Server (NTRS)

Brown, J. A.

1967-01-01

Americium 241 serves as a suitable radioisotope /gamma ray source/ and exposure probe for radiographic inspection of brazed aluminum joints in areas of limited accessibility. The powdered isotope is contained in a sealed capsule mounted at the end of a spring-loaded pushrod in the probe assembly.

Biomechanical Effects of Acromioplasty on Superior Capsule Reconstruction for Irreparable Supraspinatus Tendon Tears.

PubMed

Mihata, Teruhisa; McGarry, Michelle H; Kahn, Timothy; Goldberg, Iliya; Neo, Masashi; Lee, Thay Q

2016-01-01

% of intact [P = .002]) and subacromial peak contact pressure (0° of abduction: 47% of intact [P = .0002]; 30° of abduction: 83% of intact [P = .0005]; 60° of abduction: 38% of intact [P = .04]) compared with after the creation of a supraspinatus tear. Adding acromioplasty significantly decreased the subacromial contact area compared with superior capsule reconstruction without acromioplasty (0° of abduction: 26% decrease [P = .01]; 30° of abduction: 21% decrease [P = .009]; 60° of abduction: 61% decrease [P = .003]) and did not alter humeral head position, superior translation, or subacromial peak contact pressure. Superior capsule reconstruction repositioned the superiorly migrated humeral head and restored superior stability in the shoulder joint. Adding acromioplasty decreased the subacromial contact area without increasing the subacromial contact pressure. When superior capsule reconstruction is performed for irreparable rotator cuff tears, acromioplasty may help to decrease the postoperative risk of abrasion and tearing of the graft beneath the acromion. © 2015 The Author(s).

Stennis time capsule

NASA Image and Video Library

2011-10-15

Stennis Space Center Director Patrick Scheuermann (right) and Naval Meteorology and Oceanography Command Chief of Staff James Pettigrew drop the first shovelfuls of dirt on a time capsule to be opened on the rocket engine test facility's 100th anniversary in 2061. The time capsule was placed in front of the Roy S. Estess Building on Oct. 25 as Stennis concluded celebrations of its 50th anniversary.

Enteric-coating of pulsatile-release HPC capsules prepared by injection molding.

PubMed

Macchi, E; Zema, L; Maroni, A; Gazzaniga, A; Felton, L A

2015-04-05

Capsular devices based on hydroxypropyl cellulose (Klucel® LF) intended for pulsatile release were prepared by injection molding (IM). In the present work, the possibility of exploiting such capsules for the development of colonic delivery systems based on a time-dependent approach was evaluated. For this purpose, it was necessary to demonstrate the ability of molded cores to undergo a coating process and that coated systems yield the desired performance (gastric resistance). Although no information was available on the coating of IM substrates, some issues relevant to that of commercially-available capsules are known. Thus, preliminary studies were conducted on molded disks for screening purposes prior to the spray-coating of HPC capsular cores with Eudragit® L 30 D 55. The ability of the polymeric suspension to wet the substrate, spread, start penetrating and initiate hydration/swelling, as well as to provide a gastroresistant barrier was demonstrated. The coating of prototype HPC capsules was carried out successfully, leading to coated systems with good technological properties and able to withstand the acidic medium with no need for sealing at the cap/body joint. Such systems maintained the original pulsatile release performance after dissolution of the enteric film in pH 6.8 fluid. Therefore, they appeared potentially suitable for the development of a colon delivery platform based on a time-dependent approach. Copyright © 2015 Elsevier B.V. All rights reserved.

Systemic injection of AAV9 carrying a periostin promoter targets gene expression to a myofibroblast-like lineage in mouse hearts after reperfused myocardial infarction.

PubMed

Piras, B A; Tian, Y; Xu, Y; Thomas, N A; O'Connor, D M; French, B A

2016-05-01

Adeno-associated virus (AAV) has been used to direct gene transfer to a variety of tissues, including heart, liver, skeletal muscle, brain, kidney and lung, but it has not previously been shown to effectively target fibroblasts in vivo, including cardiac fibroblasts. We constructed expression cassettes using a modified periostin promoter to drive gene expression in a cardiac myofibroblast-like lineage, with only occasional spillover into cardiomyocyte-like cells. We compared AAV serotypes 6 and 9 and found robust gene expression when the vectors were delivered by systemic injection after myocardial infarction (MI), with little expression in healthy, non-infarcted mice. AAV9 provided expression in a greater number of cells than AAV6, with reporter gene expression visible in the cardiac infarct and border zones from 5 to 62 days post MI, as assessed by luciferase and Cre-activated green fluorescent protein expression. Although common myofibroblast markers were expressed in low abundance, most of the targeted cells expressed myosin IIb, an embryonic form of smooth muscle myosin heavy chain that has previously been associated with myofibroblasts after reperfused MI. This study is the first to demonstrate AAV-mediated expression in a potentially novel myofibroblast-like lineage in mouse hearts post MI and may open new avenues of gene therapy to treat patients surviving MI.

Agile patency system eliminates risk of capsule retention in patients with known intestinal strictures who undergo capsule endoscopy.

PubMed

Herrerias, Juan M; Leighton, Jonathan A; Costamagna, Guido; Infantolino, Anthony; Eliakim, Rami; Fischer, Doron; Rubin, David T; Manten, Howard D; Scapa, Eitan; Morgan, Douglas R; Bergwerk, Ari J; Koslowsky, Binyamin; Adler, Samuel N

2008-05-01

Capsule endoscopy (CE) of the small bowel has become a standard diagnostic tool, but there have been concerns regarding the risk of capsule retention in certain high-risk groups. The Agile patency system, an ingestible and dissolvable capsule with an external scanner, was developed to allow physicians to perform CE with greater confidence that the capsule will be safely excreted in patients at risk for capsule retention. Our purpose was to assess the ability of the device to help physicians identify which patients with known strictures may safely undergo CE. Patients with known strictures ingested the new patency capsule and underwent periodic scanning until it was excreted. The intestinal tract was considered to be sufficiently patent if the capsule was excreted intact or if the capsule was not detected by the scanner at 30 hours after ingestion. If patency was established, then standard CE was performed. International multicenter study. A total of 106 patients with known strictures. Agile patency system. Performance and safety of Agile patency system. A total of 106 patients ingested the patency capsule. Fifty-nine (56%) excreted it intact and subsequently underwent CE. There were no cases of capsule retention. Significant findings on CE were found in 24 (41%). There were 3 severe adverse events. These results suggest that the Agile patency system is a useful tool for physicians to use before CE in patients with strictures to avoid retention. This group of patients may have a high yield of clinically significant findings at CE. This capsule may determine whether patients who have a contraindication to CE may safely undergo CE and obtain useful diagnostic information.

STAT-3 contributes to pulmonary fibrosis through epithelial injury and fibroblast-myofibroblast differentiation

PubMed Central

Pedroza, Mesias; Le, Thuy T.; Lewis, Katherine; Karmouty-Quintana, Harry; To, Sarah; George, Anuh T.; Blackburn, Michael R.; Tweardy, David J.; Agarwal, Sandeep K.

2016-01-01

Lung fibrosis is the hallmark of the interstitial lung diseases. Alveolar epithelial cell (AEC) injury is a key step that contributes to a profibrotic microenvironment. Fibroblasts and myofibroblasts subsequently accumulate and deposit excessive extracellular matrix. In addition to TGF-β, the IL-6 family of cytokines, which signal through STAT-3, may also contribute to lung fibrosis. In the current manuscript, the extent to which STAT-3 inhibition decreases lung fibrosis is investigated. Phosphorylated STAT-3 was elevated in lung biopsies from patients with idiopathic pulmonary fibrosis and bleomycin (BLM)-induced fibrotic murine lungs. C-188-9, a small molecule STAT-3 inhibitor, decreased pulmonary fibrosis in the intraperitoneal BLM model as assessed by arterial oxygen saturation (control, 84.4 ± 1.3%; C-188-9, 94.4 ± 0.8%), histology (Ashcroft score: untreated, 5.4 ± 0.25; C-188-9, 3.3 ± 0.14), and attenuated fibrotic markers such as diminished α–smooth muscle actin, reduced collagen deposition. In addition, C-188-9 decreased the expression of epithelial injury markers, including hypoxia-inducible factor-1α (HIF-1α) and plasminogen activator inhibitor-1 (PAI-1). In vitro studies show that inhibition of STAT-3 decreased IL-6– and TGF-β–induced expression of multiple genes, including HIF-1α and PAI-1, in AECs. Furthermore, C-188-9 decreased fibroblast-to-myofibroblast differentiation. Finally, TGF-β stimulation of lung fibroblasts resulted in SMAD2/SMAD3-dependent phosphorylation of STAT-3. These findings demonstrate that STAT-3 contributes to the development of lung fibrosis and suggest that STAT-3 may be a therapeutic target in pulmonary fibrosis.—Pedroza, M., Le, T. T., Lewis, K., Karmouty-Quintana, H., To, S., George, A. T., Blackburn, M. R., Tweardy, D. J., Agarwal, S. K. STAT-3 contributes to pulmonary fibrosis through epithelial injury and fibroblast-myofibroblast differentiation. PMID:26324850

Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

PubMed

Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

2004-01-01

Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

Endoscopic placement of the small-bowel video capsule by using a capsule endoscope delivery device.

PubMed

Holden, Jeremy P; Dureja, Parul; Pfau, Patrick R; Schwartz, Darren C; Reichelderfer, Mark; Judd, Robert H; Danko, Istvan; Iyer, Lalitha V; Gopal, Deepak V

2007-05-01

Capsule endoscopy performed via the traditional peroral route is technically challenging in patients with dysphagia, gastroparesis, and/or abnormal upper-GI (UGI) anatomy. To describe the indications and outcomes of cases in which the AdvanCE capsule endoscope delivery device, which has recently been cleared by the Food and Drug Administration, was used. Retrospective, descriptive, case series. Tertiary care, university hospital. We report a case series of 16 consecutive patients in whom the AdvanCE delivery device was used. The study period was May 2005 through July 2006. Endoscopic delivery of the video capsule to the proximal small bowel by using the AdvanCE delivery device. Indications, technique, and completeness of small bowel imaging in patients who underwent endoscopic video capsule delivery. The AdvanCE delivery device was used in 16 patients ranging in age from 3 to 74 years. The primary indications for endoscopic delivery included inability to swallow the capsule (10), altered UGI anatomy (4), and gastroparesis (2). Of the 4 patients with altered UGI anatomy, 3 had dual intestinal loop anatomy (ie, Bilroth-II procedure, Whipple surgery, Roux-en-Y gastric bypass) and 1 had a failed Nissen fundoplication. In all cases, the capsule was easily deployed without complication, and complete small intestinal imaging was achieved. Small patient size. Endoscopic placement of the Given PillCam by use of the AdvanCE delivery device was safe and easily performed in patients for whom capsule endoscopy would otherwise have been contraindicated or technically challenging.

Hepatic stellate cell and myofibroblast-like cell gene expression in the explanted cirrhotic livers of patients undergoing liver transplantation.

PubMed

Estep, J Michael; O'Reilly, Linda; Grant, Geraldine; Piper, James; Jonsson, Johann; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair M

2010-02-01

Hepatic stellate cells (HSC) are involved in hepatic fibrogenesis. Cell signaling associated with an insult to the liver affects an HSC transdifferentiation to fibrogenic myofibroblast-like cells. To investigate the transcriptional expression distinguishing HSC and myofibroblast-like cells between livers with and without cirrhosis. Tissue from ten cirrhotic livers (undergoing transplant) and four non-cirrhotic livers from the National Disease Research Interchange underwent cell separation to extract HSC and myofibroblast-like cell populations. Separated cell types as well as LI-90 cells were subjected to microarray analysis. Selected microarray results were verified by quantitative real-time PCR. Differential expression of some genes, such as IL-1beta, IL-1alpha, and IL-6, was associated with both transdifferentiation and disease. Other genes, such as fatty acid 2-hydroxylase only show differential expression in association with disease. Functional analysis supported these findings, indicating some signal transduction pathways (IL-6) are involved in disease and activation, whereas retinoid X receptor signaling in HSC from cirrhotic and non-cirrhotic livers varies in scope and quality. These findings indicate distinct phenotypes for HSC from cirrhotic and non-cirrhotic livers. Furthermore, coordinated differential expression between genes involved in the same signal transduction pathways provides some insight into the mechanisms that may control the balance between fibrogenesis and fibrolysis.

TGF-β1/FGF-2 signaling mediates the 15-HETE-induced differentiation of adventitial fibroblasts into myofibroblasts.

PubMed

Zhang, Li; Chen, Yan; Li, Guixia; Chen, Minggang; Huang, Wei; Liu, Yanrui; Li, Yumei

2016-01-05

Pulmonary adventitial fibroblasts (PAFs) are activated under stress stimuli leading to their differentiation into myofibroblasts, which is involved in vessel remodeling. 15-HETE is known as an important factor in vessel remodeling under hypoxia; however, the role of 15-HETE in PAF phenotypic alteration is not clear. The effect of 15-HETE on PAF phenotypic alterations was investigated in the present study. PAFs were treated with 15-HETE (0.5 μM) for 24 h, and the myofibroblast marker α-smooth muscle actin (α-SMA) was analyzed. The 15-HETE induced α-SMA expression and cell morphology. 15-HETE upregulated FGF-2 levels in PAFs, and knockdown FGF-2 by siRNAs blocked the enhanced α-SMA expression induced by 15-HETE. p38 kinase was activated, and blocked depressed 15-HETE-induced FGF-2 expression. The downstream of p38 pathway, Egr-1 activation, was also raised by 15-HETE treatment, and silenced Egr-1 suppressed the 15-HETE-induced upregulation of FGF-2. TGF-β1 was upregulated with FGF-2 treatment, and α-SMA expression induced by FGF-2 was inhibited after the cell was transferred with TGF-β1 siRNA. Meanwhile, FGF-2 increased α-SMA expression and improved proliferation, which was associated with p27(kip1) and cyclin E variation. The above results suggest that p38/Egr-1 pathway-mediated FGF-2 is involved in 15-HETE-induced differentiation of PAFs into myofibroblasts and cell proliferation.

Sagittal distal limb kinematics inside the hoof capsule captured using high-speed fluoroscopy in walking and trotting horses.

PubMed

Roach, J M; Pfau, T; Bryars, J; Unt, V; Channon, S B; Weller, R

2014-10-01

Kinematic evaluation of the distal limb of the horse using standard methods is challenging, mainly due to the hoof capsule restricting visualisation, but the recent development of a high-speed fluoroscopy (HSF) system has allowed in vivo cineradiographic assessment of moving skeletal structures at high speeds. The application of this non-invasive method to the equine distal limb is used to describe 'internal' distal limb kinematics including intra-horse and inter-horse variability, and variability between walk and trot. Distal limb kinematic data were collected at walk and trot from six non-lame horses using HSF set over a force plate. The dorsal proximal interphalangeal joint (PIPJ) angle and the dorsal distal interphalangeal joint (DIPJ) angle were measured at toe-on and at 25%, 50% and 75% of stance. The PIPJ and DIPJ showed overall extension through stance. The mean ± SD range of motion (ROM) during stance of the PIPJ was 9.7 ± 2.7° (walk) and 8.7 ± 3.0° (trot) and of the DIPJ was 28.6 ± 4.6° (walk) and 26.5 ± 6.3° (trot) showing significant differences between gaits and changes through stance (P < 0.001). Inter- and intra- horse variations were also significant for both joint angles (P < 0.001). HSF allowed for kinematic assessment of the distal limb within the hoof capsule. The ROM of the PIPJ observed was similar to results published in the literature whilst the ROM for the DIPJ was less than values previously reported. Future studies will use HSF to estimate strain in the tendons and ligaments within the hoof capsule, which are a common site of lameness in the horse. Copyright © 2014. Published by Elsevier Ltd.

Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

PubMed Central

Mia, Masum M.; Boersema, Miriam; Bank, Ruud A.

2014-01-01

One of the most potent pro-fibrotic cytokines is transforming growth factor (TGFβ). TGFβ is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1β (IL1β) can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1β, TGFβ1, and IL1β in combination with TGFβ1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase), and matrix metalloproteinases (MMPs). We found that IL1β alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1β is able to inhibit the TGFβ1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1), the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGFβ1. The addition of IL1β reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1β that were observed are the increased levels of MMP1, −2, −9 and −14 produced by fibroblasts exposed to TGFβ1/IL1β in comparison with fibroblasts exposed to TGFβ1 alone. In addition, IL1β decreased the TGFβ1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1β. Suppression of COL1A1 by IL1β in the presence of TGFβ1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1β in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future anti

Capsule Escape Tests - Wallops Island

NASA Image and Video Library

1959-05-14

Caption: Off the pad abort shot at Wallops using Langley PARD designed full scale capsule with Recruit rocket and extended skirt main parachute. Shows sequential images of launch and capsule splashdown.

Contraception with subdermal ST-1435 capsules: side-effects, endocrine profiles and liver function related to different lengths of capsules.

PubMed

Kurunmäki, H; Toivonen, J; Lähteenmäki, P; Luukkainen, T

1985-03-01

One Silastic capsule of 15 mm, 20 mm or 30 mm length was inserted subcutaneously into the ventral aspect of the left forearm or upper arm of 28 healthy women during menstrual bleeding or not later than on the seventh day of the menstrual cycle. A new capsule of the same length was inserted after six months and both capsules were removed twelve months after the first insertion. Side-effects, including changes in body weight, blood pressure, menstrual bleeding and liver function test results, were registered. Blood samples were taken from selected subjects twice a week during the 1st, 2nd, 3rd, 6th, 7th and 12th month of use. Plasma concentrations of ST-1435 were measured by radioimmunoassay and the effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. There were no differences in hormonal side-effects between subjects who had a 30 mm capsule or subjects who had 20 mm or 15 mm capsules, but subjects who had 20 or 15 mm capsules had significantly longer bleeding or spotting periods in comparison with subjects who had a 30 mm capsule. There were no changes in blood pressure, body weight or liver function test results in comparison with pre-insertion values. The plasma level of ST-1435 was not significantly higher during the use of 30 mm capsules than during the use of 20 or 15 mm capsules. During the use of the shorter ST-1435 capsules, plasma estradiol elevation and slightly suppressed FSH were seen, while the use of longer capsules resulted in a slight suppression of LH. Progesterone concentrations during monitored cycles indicated anovulation. No pregnancies occurred during the study period of one year. The continuation rate at one year was 71% in the 30 mm capsule group and 57% in the 20 and 15 mm capsule groups taken together.

Dynamic properties of human incudostapedial joint-Experimental measurement and finite element modeling.

PubMed

Jiang, Shangyuan; Gan, Rong Z

2018-04-01

The incudostapedial joint (ISJ) is a synovial joint connecting the incus and stapes in the middle ear. Mechanical properties of the ISJ directly affect sound transmission from the tympanic membrane to the cochlea. However, how ISJ properties change with frequency has not been investigated. In this paper, we report the dynamic properties of the human ISJ measured in eight samples using a dynamic mechanical analyzer (DMA) for frequencies from 1 to 80 Hz at three temperatures of 5, 25 and 37 °C. The frequency-temperature superposition (FTS) principle was used to extrapolate the results to 8 kHz. The complex modulus of ISJ was measured with a mean storage modulus of 1.14 MPa at 1 Hz that increased to 3.01 MPa at 8 kHz, and a loss modulus that increased from 0.07 to 0.47 MPa. A 3-dimensional finite element (FE) model consisting of the articular cartilage, joint capsule and synovial fluid was then constructed to derive mechanical properties of ISJ components by matching the model results to experimental data. Modeling results showed that mechanical properties of the joint capsule and synovial fluid affected the dynamic behavior of the joint. This study contributes to a better understanding of the structure-function relationship of the ISJ for sound transmission. Copyright © 2018. Published by Elsevier Ltd.

Strength Variation of Parachute Joints

NASA Technical Reports Server (NTRS)

Mollmann, Catherine

2017-01-01

A parachute joint is defined as a location where a component is sewn or connected to another component. During the design and developmental phase of a parachute system, the joints for each structural component are isolated and tested through a process called seam and joint testing. The objective of seam and joint testing is to determine the degradation on a single component due to interaction with other components; this data is then used when calculating the margin of safety for that component. During the engineering developmental phase of CPAS (Capsule Parachute Assembly System), the parachute system for the NASA Orion Crew Module, testing was completed for every joint of the six subsystems: the four parachutes (main, drogue, pilot, and FBCP [forward bay cover parachute]), the retention release bridle, and the retention panels. The number of joint tests for these subsystems totaled 92, which provides a plethora of data and results for further analysis. In this paper, the data and results of these seam and joint tests are examined to determine the effects, if any, of different operators and sewing machines on the strength of parachute joints. Other variables are also studied to determine their effect on joint strength, such as joint complexity, joint strength magnitude, material type, and material construction. Findings reveal that an optimally-run seam and joint test program could result in an increased understanding of the structure of the parachute; this should lead to a parachute built with optimal components, potentially saving system weight and volume.

The effect of montelukast and antiadhesion barrier solution on the capsule formation after insertion of silicone implants in a white rat model.

PubMed

Yang, J-D; Kwon, O-H; Lee, J-W; Chung, H-Y; Cho, B-C; Park, H-Y; Kim, T-G

2013-01-01

TGF-β and collagen I were higher in the control group than in the experimental groups. Group IV (the synergic effect group) had a more pronounced effect on all the parameters examined than that in groups II and III with separate drug administration. Montelukast and AABS reduced the thickness, the inflammatory cell infiltrate and the myofibroblast content of the peri-implant capsules around silicone implants in this white rat model. They lowered the expression of the fibrotic mediator, TGF-β, and inhibited the peri-implant capsular fibrosis. Therefore, montelukast and AABS are effective in the reduction of silicone-induced peri-implant capsular formation.

First order capsules comparative arrangements

NASA Technical Reports Server (NTRS)

1963-01-01

Pen and ink views of comparative arragements of several capsules including the existing 'Big Joe' design, the compromise 'Big Joe' design, and the 'Little Joe'. All capsule designs are labeled and include dimensions.

Nanocomposite capsules with directional, pulsed nanoparticle release.

PubMed

Udoh, Christiana E; Cabral, João T; Garbin, Valeria

2017-12-01

The precise spatiotemporal delivery of nanoparticles from polymeric capsules is required for applications ranging from medicine to materials science. These capsules derive key performance aspects from their overall shape and dimensions, porosity, and internal microstructure. To this effect, microfluidics provide an exceptional platform for emulsification and subsequent capsule formation. However, facile and robust approaches for nanocomposite capsule fabrication, exhibiting triggered nanoparticle release, remain elusive because of the complex coupling of polymer-nanoparticle phase behavior, diffusion, phase inversion, and directional solidification. We investigate a model system of polyelectrolyte sodium poly(styrene sulfonate) and 22-nm colloidal silica and demonstrate a robust capsule morphology diagram, achieving a range of internal morphologies, including nucleated and bicontinuous microstructures, as well as isotropic and non-isotropic external shapes. Upon dissolution in water, we find that capsules formed with either neat polymers or neat nanoparticles dissolve rapidly and isotropically, whereas bicontinuous, hierarchical, composite capsules dissolve via directional pulses of nanoparticle clusters without disrupting the scaffold, with time scales tunable from seconds to hours. The versatility, facile assembly, and response of these nanocomposite capsules thus show great promise in precision delivery.

Gelatin capsule in stomach (image)

MedlinePlus

... detect the presence of intestinal parasites. A weighted gelatin capsule attached to a string is swallowed and left in place. After about 4 hours, the gelatin capsule is pulled out of the stomach by ...

Thermoregulation of Capsule Production by Streptococcus pyogenes

PubMed Central

Kang, Song Ok; Wright, Jordan O.; Tesorero, Rafael A.; Lee, Hyunwoo; Beall, Bernard; Cho, Kyu Hong

2012-01-01

The capsule of Streptococcus pyogenes serves as an adhesin as well as an anti-phagocytic factor by binding to CD44 on keratinocytes of the pharyngeal mucosa and the skin, the main entry sites of the pathogen. We discovered that S. pyogenes HSC5 and MGAS315 strains are further thermoregulated for capsule production at a post-transcriptional level in addition to the transcriptional regulation by the CovRS two-component regulatory system. When the transcription of the hasABC capsular biosynthetic locus was de-repressed through mutation of the covRS system, the two strains, which have been used for pathogenesis studies in the laboratory, exhibited markedly increased capsule production at sub-body temperature. Employing transposon mutagenesis, we found that CvfA, a previously identified membrane-associated endoribonuclease, is required for the thermoregulation of capsule synthesis. The mutation of the cvfA gene conferred increased capsule production regardless of temperature. However, the amount of the capsule transcript was not changed by the mutation, indicating that a post-transcriptional regulator mediates between CvfA and thermoregulated capsule production. When we tested naturally occurring invasive mucoid strains, a high percentage (11/53, 21%) of the strains exhibited thermoregulated capsule production. As expected, the mucoid phenotype of these strains at sub-body temperature was due to mutations within the chromosomal covRS genes. Capsule thermoregulation that exhibits high capsule production at lower temperatures that occur on the skin or mucosal surface potentially confers better capability of adhesion and invasion when S. pyogenes penetrates the epithelial surface. PMID:22615992

Big Joe Capsule Assembly Activities

NASA Image and Video Library

1959-08-01

Big Joe Capsule Assembly Activities in 1959 at NASA Glenn Research Center (formerly NASA Lewis). Big Joe was an Atlas missile that successfully launched a boilerplate model of the Mercury capsule on September 9, 1959.

The effects of hematoma on implant capsules.

PubMed

Caffee, H H

1986-02-01

Hematoma surrounding an implant is one of the many factors that have been suggested as possible causes for scar capsule contracture. In this study, experiments were designed to determine the influence of hematoma on the incidence and severity of capsule contracture in rabbits. Two implants were placed in each animal, 1 with a surrounding hematoma and 1 control. Capsules were evaluated subjectively and compared objectively with measurements of deformability, surface area, and capsule thickness. No differences were found with any of the objective criteria, which suggests that hematoma may not be a noteworthy cause of implant capsule contracture.

Deletion of H-Ras decreases renal fibrosis and myofibroblast activation following ureteral obstruction in mice.

PubMed

Grande, M Teresa; Fuentes-Calvo, Isabel; Arévalo, Miguel; Heredia, Fabiana; Santos, Eugenio; Martínez-Salgado, Carlos; Rodríguez-Puyol, Diego; Nieto, M Angela; López-Novoa, José M

2010-03-01

Tubulointerstitial fibrosis is characterized by the presence of myofibroblasts that contribute to extracellular matrix accumulation. These cells may originate from resident fibroblasts, bone-marrow-derived cells, or renal epithelial cells converting to a mesenchymal phenotype. Ras GTPases are activated during renal fibrosis and play crucial roles in regulating both cell proliferation and TGF-beta-induced epithelial-mesenchymal transition. Here we set out to assess the contribution of Ras to experimental renal fibrosis using the well-established model of unilateral ureteral obstruction. Fifteen days after obstruction, both fibroblast proliferation and inducers of epithelial-mesenchymal transition were lower in obstructed kidneys of H-ras knockout mice and in fibroblast cell lines derived from these mice. Interestingly, fibronectin, collagen I accumulation, overall interstitial fibrosis, and the myofibroblast population were also lower in the knockout than in the wild-type mice. As expected, we found lower levels of activated Akt in the kidneys and cultured fibroblasts of the knockout. Whether Ras inhibition will turn out to prevent progression of renal fibrosis will require more direct studies.

Thickening of the inferior glenohumeral capsule: an ultrasound sign for shoulder capsular contracture.

PubMed

Michelin, Paul; Delarue, Yohann; Duparc, Fabrice; Dacher, Jean Nicolas

2013-10-01

The aim of this retrospective study was to measure the inferior glenohumeral capsule thickness of shoulders clinically affected by capsular contracture by comparison to the contralateral asymptomatic side. Bilateral shoulder ultrasound (US) examinations of 20 patients with clinically or MRI proven unilateral capsular contracture were retrospectively assessed. Inferior capsule evaluation was performed with a transducer placed within the axilla in maximally abducted shoulders. Measurements were symmetrically performed orthogonally to the inferior glenohumeral ligament (IGHL) in the axial plane; the coronal plane was used to ensure the tension of the IGHL. The significance of any difference in thickening was assessed with the Mann-Whitney test. The average thickness was 4.0 mm in shoulders with capsular contracture vs. 1.3 mm in asymptomatic contralateral shoulders (P < 0.0001). Twenty per cent of patients with capsular contracture and inferior capsule thickness increase showed US features of other painful diseases of the rotator cuff. The thickness of the inferior capsule is measurable through ultrasound examination and appears to be increased in shoulders with capsular contracture. Exploration of the inferior aspect of the shoulder joint could be added to shoulder US examination protocols for capsular contracture assessment even if other rotator cuff abnormalities are diagnosed by US. • Ultrasound is increasingly used to diagnose shoulder problems. • The thickness of the inferior glenohumeral ligament is measurable in the axilla. • The inferior glenohumeral ligament appears thickened in shoulders with capsular contracture. • Capsular contracture ultrasound features can be associated with other rotator cuff problems.

Immunohistochemical expression of myofibroblasts, TGF-β1 and IFN-γ in oral fibrous lesions.

PubMed

Santos, Pedro Paulo de Andrade; Barroso, Keila Martha Amorim; Nonaka, Cassiano Francisco Weege; Pereira Pinto, Leão; Souza, Lélia Batista de

2018-05-29

Analyze the presence of myofibroblasts (MFBs) in oral fibrous lesions and investigate TGF-β1 and IFN-γ expression by immunohistochemistry during their differentiation. Twenty giant cell fibromas (GCFs), 20 fibromas (FIBs), and 20 fibrous hyperplasias (FHs) were selected. To evaluate the presence of MFBs, anti-α-SMA-immunoreactive cells were quantified in connective tissue. TGF-β1 and IFN-γ expressions were evaluated in epithelial and connective tissue by determining the percentage of immunoreactive cells. Higher MFBs concentrations were observed in GCFs (median of 20.00), followed by FHs (15.00) and FIBs (14.00) (P = 0.072). No significant correlation between TGF-β1 or IFN-γ immunoexpression and the number of MFBs in oral fibrous lesions was observed (P > 0.05). The higher density of MFBs found in GCFs, followed by FHs and FIBs, reaffirms the fibrogenic role of these cells, while the higher concentrations detected in GCFs, including evidence of giant MFBs, also suggest a role in the neoplastic behavior of these lesions. No correlation was observed between TGF-β1 and IFN-γ in the myofibroblastic transdifferentiation process of the analyzed lesions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stennis time capsule

NASA Image and Video Library

2011-10-15

Stennis Space Center Director Patrick Scheuermann (right) and Naval Meteorology and Oceanography Command Chief of Staff James Pettigrew drop the first shovelfuls of dirt on a time capsule to be opened on the rocket engine test facility's 100th anniversary in 2061. The time capsule was placed in front of the Roy S. Estess Building on Oct. 25 as Stennis concluded celebrations of its 50th anniversary. NASA publicly announced plans to build the rocket engine test site Oct. 25, 1961.

Small intestinal model for electrically propelled capsule endoscopy

PubMed Central

2011-01-01

The aim of this research is to propose a small intestine model for electrically propelled capsule endoscopy. The electrical stimulus can cause contraction of the small intestine and propel the capsule along the lumen. The proposed model considered the drag and friction from the small intestine using a thin walled model and Stokes' drag equation. Further, contraction force from the small intestine was modeled by using regression analysis. From the proposed model, the acceleration and velocity of various exterior shapes of capsule were calculated, and two exterior shapes of capsules were proposed based on the internal volume of the capsules. The proposed capsules were fabricated and animal experiments were conducted. One of the proposed capsules showed an average (SD) velocity in forward direction of 2.91 ± 0.99 mm/s and 2.23 ± 0.78 mm/s in the backward direction, which was 5.2 times faster than that obtained in previous research. The proposed model can predict locomotion of the capsule based on various exterior shapes of the capsule. PMID:22177218

Contraindications for video capsule endoscopy

PubMed Central

Bandorski, Dirk; Kurniawan, Niehls; Baltes, Peter; Hoeltgen, Reinhard; Hecker, Matthias; Stunder, Dominik; Keuchel, Martin

2016-01-01

Video capsule endoscopy (VCE) has been applied in the last 15 years in an increasing field of applications. Although many contraindications have been put into perspective, some precautions still have to be considered. Known stenosis of the gastrointestinal tract is a clear contraindication for VCE unless surgery is already scheduled or at least has been considered as an optional treatment modality. In patients with a higher incidence of stenosis, as in an established diagnosis of Crohn’s disease, clinical signs of obstruction, prior radiation or surgical small bowel resection, a preceding test with the self-dissolving patency capsule can override this contraindication. Endoscopic placement of the capsule should be considered in patients with swallowing disorders to avoid aspiration. Esophageal or gastric motility disorders may require endoscopic capsule transport or application of prokinetics if the real-time viewer proofs delayed transit. In pregnant women, VCE should be restricted to urgent cases where diagnosis cannot be postponed after delivery, as data on safety are missing. There is theoretical and clinical evidence that patients with implanted cardiac devices such as a pacemaker, cardioverters or left heart assist devices, can safely undergo VCE in spite of still existing contraindication by manufacturers. Children from the age of 2 years have safely undergone VCE. Although video capsules are not proven safe with magnetic resonance imaging (MRI), first single cases of patients incidentally undergoing MRI with an incorporated capsule have been reported, showing susceptibility artifacts but no signs of clinical harm. PMID:28018097

21 CFR 520.1660b - Oxytetracycline hydrochloride capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride capsules. 520.1660b... Oxytetracycline hydrochloride capsules. (a) Specifications. The drug is in capsule form with each capsule containing 125 or 250 milligrams of oxytetracycline hydrochloride. Oxytetracycline is the antibiotic...

Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis

PubMed Central

Park, Ah-Mee; Kanai, Kyosuke; Itoh, Tatsuki; Sato, Takao; Tsukui, Tatsuya; Inagaki, Yutaka; Selman, Moises; Matsushima, Kouji; Yoshie, Osamu

2016-01-01

Heat shock protein 27 (HSP27) is a member of the small molecular weight HSP family. Upon treatment with transforming growth factor β1 (TGF-β1), we observed upregulation of HSP27 along with that of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation, in cultured human and mouse lung fibroblasts. Furthermore, by using siRNA knockdown, we demonstrated that HSP27 was involved in cell survival and upregulation of fibronectin, osteopontin (OPN) and type 1 collagen, all functional markers of myofibroblast differentiation, in TGF-β1-treated MRC-5 cells. In lung tissues of bleomycin-treated mice, HSP27 was strongly upregulated and substantially co-localized with α-SMA, OPN and type I collagen but not with proSP-C (a marker of type II alveolar epithelial cells), E-cadherin (a marker of epithelial cells) or F4/80 (a marker of macrophages). A similar co-localization of HSP27 and α-SMA was observed in lung tissues of patients with idiopathic pulmonary fibrosis. Furthermore, airway delivery of HSP27 siRNA effectively suppressed bleomycin-induced pulmonary fibrosis in mice. Collectively, our findings indicate that HSP27 is critically involved in myofibroblast differentiation of lung fibroblasts and may be a promising therapeutic target for lung fibrotic diseases. PMID:26859835

Basic ammonothermal GaN growth in molybdenum capsules

NASA Astrophysics Data System (ADS)

Pimputkar, S.; Speck, J. S.; Nakamura, S.

2016-12-01

Single crystal, bulk gallium nitride (GaN) crystals were grown using the basic ammonothermal method in a high purity growth environment created using a non-hermetically sealed molybdenum (Mo) capsule and compared to growths performed in a similarly designed silver (Ag) capsule and capsule-free René 41 autoclave. Secondary ion mass spectrometry (SIMS) analysis revealed transition metal free (<1×1017 cm-3) GaN crystals. Anomalously low oxygen concentrations ((2-6)×1018 cm-3) were measured in a {0001} seeded crystal boule grown using a Mo capsule, despite higher source material oxygen concentrations ((1-5)×1019 cm-3) suggesting that molybdenum (or molybdenum nitrides) may act to getter oxygen under certain conditions. Total system pressure profiles from growth runs in a Mo capsule system were comparable to those without a capsule, with pressures peaking within 2 days and slowly decaying due to hydrogen diffusional losses. Measured Mo capsule GaN growth rates were comparable to un-optimized growth rates in capsule-free systems and appreciably slower than in Ag-capsule systems. Crystal quality replicated that of the GaN seed crystals for all capsule conditions, with high quality growth occurring on the (0001) Ga-face. Optical absorption and impurity concentration characterization suggests reduced concentrations of hydrogenated gallium vacancies (VGa-Hx).

Initial experimental evaluation of wireless capsule endoscopes in the bladder: implications for capsule cystoscopy.

PubMed

Gettman, Matthew T; Swain, Paul

2009-05-01

Cystoscopy remains one of the most important diagnostic procedures for the lower urinary tract. Wireless capsule endoscopy was introduced in the 1990s but use to date is limited to gastroenterology. We evaluated the feasibility in the pig model of using wireless capsule endoscopes (WCEs) for cystoscopy. Experimental evaluation of capsule cystoscopy was performed in a 50-kg farm pig. The capsule was deployed into the bladder through a custom access sheath. Images were continuously transmitted at a rate of four frames per second to a laptop computer and processed using proprietary software. Manipulation of the WCE within the bladder was performed using a set protocol. The animal was then euthanized and gross inspection was performed. We measured the ability to deploy and manipulate the capsule within the bladder. Feasibility of capturing and retrieving images in real time was also assessed. The WCE was efficiently deployed and manipulated within the bladder passively and with the use of external magnets. The entire bladder mucosa was visualized. Real-time image transmission and capture were successful. No complications were seen during capsule cystoscopy. Minor urethral bleeding was observed after the experiment, likely related to placement of the access sheath required for deployment of the WCE. Limitations are that the evaluation of WCE was performed in the pig model, in only one female animal, using a nonsurvival approach. Furthermore, the study was not designed to differentiate normal from abnormal mucosal findings and focused solely on inspection of the bladder. This report suggests that cystoscopy with a WCE is feasible. With this device, all aspects of the bladder mucosa could be visualized, and ongoing technologic and procedural developments are warranted for this new approach.

Anterior capsule relaxing incisions with neodymium:YAG laser for patients at high-risk for anterior capsule contraction.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Hirata, Akira; Hayashi, Hideyuki

2011-01-01

To examine the effect of anterior capsule relaxing incisions created with a neodymium:YAG (Nd:YAG) laser on prevention of anterior capsule contraction after cataract surgery in high-risk patients. Hayashi Eye Hospital, Fukuoka, Japan. Randomized masked clinical trials. Patients at high risk for anterior capsule contraction had anterior capsule relaxing incisions in either eye 3 days postoperatively. The anterior capsule opening was measured using a Scheimpflug videophotography system (EAS-1000) immediately and 1, 3, and 6 months after capsulotomy, and the percentage reduction in area was calculated. The degree of intraocular lens (IOL) decentration and tilt, posterior capsule opacification (PCO), and other complications were also assessed. Of the 84 patients included, 30 had primary angle closure, 28 had pseudoexfoliation, and 26 had diabetic retinopathy. There was no significant difference in the mean opening area between fellow eyes at baseline. In patients with primary angle closure, the area was significantly greater and the percentage reduction in area was significantly less in the capsulotomy group than in the no-capsulotomy group (P≤.0428). In patients with pseudoexfoliation or diabetic retinopathy, the percentage reduction was significantly less in the capsulotomy group than in the no-capsulotomy group (P≤.0493), although there was no significant difference in area. No significant difference was found in IOL decentration or tilt, PCO, or incidence of other complications. Neodymium:YAG laser anterior capsule relaxing incisions in the early period after cataract surgery were effective in preventing anterior capsule contraction in high-risk patients and had no adverse effects. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Effects of transforming growth factor-beta1 on cell motility, collagen gel contraction, myofibroblastic differentiation, and extracellular matrix expression of human adipose-derived stem cell.

PubMed

Kakudo, Natsuko; Kushida, Satoshi; Suzuki, Kenji; Ogura, Tsunetaka; Notodihardjo, Priscilla Valentin; Hara, Tomoya; Kusumoto, Kenji

2012-12-01

Human adipose-derived stem cells (ASCs) are adult pluripotent stem cells, and their usefulness in plastic surgery has garnered attention in recent years. Although, there have been expectations that ASCs might function in wound repair and regeneration, no studies to date have examined the role of ASCs in the mechanism that promotes wound-healing. Transforming growth factor-beta1 (TGF-β1) is a strong candidate cytokine for the triggering of mesenchymal stem cell migration, construction of extracellular matrices, and differentiation of ASCs into myofibroblasts. Cell proliferation, motility, and differentiation, as well as extracellular matrix production, play an important role in wound-healing. We have evaluated the capacity of ASCs to proliferate and their potential to differentiate into phenotypic myofibroblasts, as well as their cell motility and collagen gel contraction ability, when cultured with TGF-β1. Cell motility was analyzed using a wound-healing assay. ASCs that differentiated into myofibroblasts expressed the gene for alpha-smooth muscle actin, and its protein expression was detected immunohistochemically. The extracellular matrix expression in ASCs was evaluated using real-time RT-PCR. Based on the results, we conclude that human ASCs have the potential for cell motility, extracellular matrix gene expression, gel contraction, and differentiation into myofibroblasts and, therefore, may play an important role in the wound-healing process.

Preservation of the articular capsule and short lateral rotator in direct anterior approach to total hip arthroplasty.

PubMed

Kanda, Akio; Kaneko, Kazuo; Obayashi, Osamu; Mogami, Atsuhiko; Morohashi, Itaru

2018-03-09

In total hip arthroplasty via a direct anterior approach, the femur must be elevated at the time of femoral implant placement. For adequate elevation, division of the posterior soft tissues is necessary. However, if we damage and separate the posterior muscle tissue, we lose the benefits of the intermuscular approach. Furthermore, damage to the posterior soft tissue can result in posterior dislocation. We investigate that protecting the posterior soft tissue increases the joint stability in the early postoperative period and results in a lower dislocation rate. We evaluated muscle strength recovery by measuring the maximum width of the internal obturator muscle on CT images (GE-Healthcare Discovery CT 750HD). We compared the maximum width of the muscle belly preoperatively versus 10 days and 6 months postoperatively. As clinical evaluations, we also investigated the range of motion of the hip joint, hip joint function based on the Japanese Orthopaedic Association hip score (JOA score), and the dislocation rate 6 months after surgery. The width of the internal obturator muscle increased significantly from 15.1 ± 3.1 mm before surgery to 16.4 ± 2.8 mm 6 months after surgery. The JOA score improved significantly from 50.8 ± 15.1 points to 95.6 ± 7.6 points. No dislocations occurred in this study. We cut only the posterosuperior articular capsule and protected the internal obturator muscle to preserve muscle strength. We repaired the entire posterosuperior and anterior articular capsule. These treatments increase joint stability in the early postoperative period, thus reducing the dislocation rate. Therapeutic, Level IV.

Inflammatory Myofibroblastic Tumor Mimicking Apical Periodontitis.

PubMed

Adachi, Makoto; Kiho, Kazuki; Sekine, Genta; Ohta, Takahisa; Matsubara, Makoto; Yoshida, Takakazu; Katsumata, Akitoshi; Tanuma, Jun-ichi; Sumitomo, Shinichiro

2015-12-01

Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Reinforcing effects of caffeine in coffee and capsules.

PubMed

Griffiths, R R; Bigelow, G E; Liebson, I A

1989-09-01

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee.

Reinforcing effects of caffeine in coffee and capsules.

PubMed Central

Griffiths, R R; Bigelow, G E; Liebson, I A

1989-01-01

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee. PMID:2794839

Sensor capsule for diagnosis of gastric disorders

NASA Technical Reports Server (NTRS)

Holen, J. T.

1972-01-01

Motility and pH sensor capsule is developed to monitor gastric acidity, pressure, and temperature. Capsule does not interfere with digestion. Sensor is capsule which includes pH electrode, Pitran pressure transducer, and thermistor temperature sensor all potted in epoxy and enclosed in high density polyethylene sheath.

Capsule endoscopy: no longer limited to the small bowel.

PubMed

Niv, Yaron

2010-03-01

Capsule endoscopy is the latest evolution in gastrointestinal endoscopy and the first to enable complete investigation of the small bowel. Recent new developments in the field of capsule endoscopy include the esophageal capsule (Pilcam ESO) and the colonic capsule (PillCam Colon). esophageal and colonic capsules have two heads with two lenses and cameras. The new capsules have the capability of taking more frames from both sides. The indications for the esophageal capsule examination are diagnosis and follow-up of Barrett's esophagus and esophageal varices. The colonic capsule can be used for colorectal cancer screening and for incomplete colonoscopy. Regarding other new technologies, continuous quality control is needed for the performance, appropriateness of the indications, diagnostic yield, procedure-specific outcome assessment, and cost-effectiveness.

Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells.

PubMed

Lechuga, Susana; Baranwal, Somesh; Li, Chao; Naydenov, Nayden G; Kuemmerle, John F; Dugina, Vera; Chaponnier, Christine; Ivanov, Andrei I

2014-10-15

Transdifferentiation of epithelial cells into mesenchymal cells and myofibroblasts plays an important role in tumor progression and tissue fibrosis. Such epithelial plasticity is accompanied by dramatic reorganizations of the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on epithelial transdifferentiation remain poorly understood. In the present study, we observed that selective siRNA-mediated knockdown of γ-cytoplasmic actin (γ-CYA), but not β-cytoplasmic actin, induced epithelial-to-myofibroblast transition (EMyT) of different epithelial cells. The EMyT manifested by increased expression of α-smooth muscle actin and other contractile proteins, along with inhibition of genes responsible for cell proliferation. Induction of EMyT in γ-CYA-depleted cells depended on activation of serum response factor and its cofactors, myocardial-related transcriptional factors A and B. Loss of γ-CYA stimulated formin-mediated actin polymerization and activation of Rho GTPase, which appear to be essential for EMyT induction. Our findings demonstrate a previously unanticipated, unique role of γ-CYA in regulating epithelial phenotype and suppression of EMyT that may be essential for cell differentiation and tissue fibrosis. © 2014 Lechuga, Baranwal, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

PGE(2) inhibition of TGF-beta1-induced myofibroblast differentiation is Smad-independent but involves cell shape and adhesion-dependent signaling.

PubMed

Thomas, Peedikayil E; Peters-Golden, Marc; White, Eric S; Thannickal, Victor J; Moore, Bethany B

2007-08-01

Myofibroblasts are pathogenic in pulmonary fibrotic disease due to their exuberant production of matrix rich in collagen that interferes with gas exchange and the ability of these cells to contract and distort the alveolar space. Transforming growth factor-beta1 (TGF-beta1) is a well-known inducer of myofibroblast differentiation. TGF-beta1-induced transformation of fibroblasts to apoptosis-resistant myofibroblasts is adhesion-dependent and focal adhesion kinase (FAK)-mediated. Prostaglandin E(2) (PGE(2)) inhibits this differentiation via E prostanoid receptor 2 (EP2) signaling and cAMP elevation, but whether PGE(2) does so by interfering with TGF-beta1 signaling is unknown. Thus we examined the effects of PGE(2) in the presence and absence of TGF-beta1 stimulation on candidate signaling pathways in human lung fibroblasts. We now demonstrate that PGE(2) does not interfere with TGF-beta1-induced Smad phosphorylation or its translocation to the nucleus. Rather, PGE(2) has dramatic effects on cell shape and cytoskeletal architecture and disrupts the formation of appropriate focal adhesions. PGE(2) treatment diminishes TGF-beta1-induced phosphorylation of paxillin, STAT-3, and FAK and, in turn, limits activation of the protein kinase B (PKB/Akt) pathway. These alterations do not, however, result in increased apoptosis within the first 24 h of treatment. Interestingly, the effects of PGE(2) stimulation alone do not always mirror the effects of PGE(2) in the presence of TGF-beta1, indicating that the context for EP2 signaling is different in the presence of TGF-beta1. Taken together, our results demonstrate that PGE(2) has the potential to limit TGF-beta1-induced myofibroblast differentiation via adhesion-dependent, but Smad-independent, pathways.

Structure and Composition of the Bacillus anthracis Capsule

PubMed Central

Avakyan, A. A.; Katz, L. N.; Levina, K. N.; Pavlova, I. B.

1965-01-01

Avakyan, A. A. (Academy of Medical Sciences, Moscow, USSR), L. N. Katz, K. N. Levina, and I. B. Pavlova. Structure and composition of the Bacillus anthracis capsule. J. Bacteriol. 90:1082–1095. 1965.—Observations by various methods of light microscopy (phase contrast, dark-field, and fluorescence) revealed the complex structure of the Bacillus anthracis capsule, which changes regularly during the growth cycle of the culture. Special cytological methods of staining the capsule made it possible to study its fine structure, which is not revealed by negative staining with India ink. For example, the capsule shows a membranelike outline, fine transverse lines, and interruptions and transverse septa traversing the entire capsule. By using cytochemical methods, it was found that the capsule has a stratified structure and that the various layers of the capsule differ as to the value of the isoelectric point, metachromatic ability, sensitivity to various enzymes, and, consequently, chemical composition. It was thus shown that the membranelike outline of the capsule consists of peptides and neutral mucopolysaccharides. The middle part of the capsule consists of a complex of substances of both polysaccharide and protein nature, and the inner part consists of acid mucopolysaccharides. Observation of the capsular forms of B. anthracis by means of an electron microscope revealed differences in the osmiophilia and submicroscopic structure of the membranelike outline and the middle and inner parts of the capsule. Immunochemical studies conducted by the fluorescent-antibody method revealed localization of antigens in different parts of the capsule, and made it possible to differentiate the capsular antigens according to their serum-staining ability and according of their relations to enzymes, i.e., their chemical composition. This paper concerns the possibility of studying the fine structure of bacterial capsules in fixed preparations, and the differences and similarities of

A New Family of Capsule Polymerases Generates Teichoic Acid-Like Capsule Polymers in Gram-Negative Pathogens.

PubMed

Litschko, Christa; Oldrini, Davide; Budde, Insa; Berger, Monika; Meens, Jochen; Gerardy-Schahn, Rita; Berti, Francesco; Schubert, Mario; Fiebig, Timm

2018-05-29

Group 2 capsule polymers represent crucial virulence factors of Gram-negative pathogenic bacteria. They are synthesized by enzymes called capsule polymerases. In this report, we describe a new family of polymerases that combine glycosyltransferase and hexose- and polyol-phosphate transferase activity to generate complex poly(oligosaccharide phosphate) and poly(glycosylpolyol phosphate) polymers, the latter of which display similarity to wall teichoic acid (WTA), a cell wall component of Gram-positive bacteria. Using modeling and multiple-sequence alignment, we showed homology between the predicted polymerase domains and WTA type I biosynthesis enzymes, creating a link between Gram-negative and Gram-positive cell wall biosynthesis processes. The polymerases of the new family are highly abundant and found in a variety of capsule-expressing pathogens such as Neisseria meningitidis , Actinobacillus pleuropneumoniae , Haemophilus influenzae , Bibersteinia trehalosi , and Escherichia coli with both human and animal hosts. Five representative candidates were purified, their activities were confirmed using nuclear magnetic resonance (NMR) spectroscopy, and their predicted folds were validated by site-directed mutagenesis. IMPORTANCE Bacterial capsules play an important role in the interaction between a pathogen and the immune system of its host. During the last decade, capsule polymerases have become attractive tools for the production of capsule polymers applied as antigens in glycoconjugate vaccine formulations. Conventional production of glycoconjugate vaccines requires the cultivation of the pathogen and thus the highest biosafety standards, leading to tremendous costs. With regard to animal husbandry, where vaccines could avoid the extensive use of antibiotics, conventional production is not sufficiently cost-effective. In contrast, enzymatic synthesis of capsule polymers is pathogen-free and fast, offers high stereo- and regioselectivity, and works with high efficacy

Oxygen fugacity and piston cylinder capsule assemblies

NASA Astrophysics Data System (ADS)

Jakobsson, S.

2011-12-01

A double capsule assembly designed to control oxygen fugacity in piston cylinder experiments has been tested at 1200 °C and 10 kbar. The assembly consists of an outer Pt-capsule containing a solid buffer (Ni-NiO or Co-CoO plus H2O) and an inner AuPd-capsule containing the sample, H2O and a Pt-wire. To prevent direct contact with the buffer phases the AuPd-capsule is embedded in finely ground Al2O3 along with some coarser, fractured Al2O3 facilitating fluid inclusion formation. No water loss is observed in the sample even after 48 hrs but a slight increase in water content is observed in longer duration runs due to oxygen and hydrogen diffusion into the AuPd-capsule. Carbon from the furnace also diffuses through the outer Pt-capsule but reacts with H2O in the outer capsule to form CO2 and never reaches the inner capsule. Oxygen fugacity of runs in equilibrium with the Ni-NiO and Co-CoO buffers was measured by analyzing the Fe content of the Pt-wire in the sample1 and by analyzing Fe dissolved in the AuPd capsule2. The second method gives values that are in good agreement with established buffer whereas results from the first method are one half to one log units higher than the established values. References 1. E. Medard, C. A. McCammon, J. A. Barr, T. L. Grove, Am. Mineral. 93, 1838 (2008). 2. J. Barr, T. Grove, Contrib. Mineral. Petrol. 160, 631 (2010)

Swimming Exercise Prevents Fibrogenesis in Chronic Kidney Disease by Inhibiting the Myofibroblast Transdifferentiation

PubMed Central

Peng, Chiung-Chi; Chen, Kuan-Chou; Hsieh, Chiu-Lan; Peng, Robert Y.

2012-01-01

Background The renal function of chronic kidney disease (CKD) patients may be improved by a number of rehabilitative mechanisms. Swimming exercise training was supposed to be beneficial to its recovery. Methodology/Principal Findings Doxorubicin-induced CKD (DRCKD) rat model was performed. Swimming training was programmed three days per week, 30 or 60 min per day for a total period of 11 weeks. Serum biochemical and pathological parameters were examined. In DRCKD, hyperlipidemia was observed. Active mesangial cell activation was evidenced by overexpression of PDGFR, P-PDGFR, MMP-2, MMP-9, α-SMA, and CD34 with a huge amount collagen deposition. Apparent myofibroblast transdifferentiation implicating fibrogenesis in the glomerular mesangium, glomerulonephritis and glomeruloscelorosis was observed with highly elevated proteinuria and urinary BUN excretion. The 60-min swimming exercise but not the 30 min equivalent rescued most of the symptoms. To quantify the effectiveness of exercise training, a physical parameter, i.e. “the strenuosity coefficient” or “the myokine releasing coefficient”, was estimated to be 7.154×10−3 pg/mL-J. Conclusions The 60-min swimming exercise may ameliorate DRCKD by inhibiting the transdifferentiation of myofibroblasts in the glomerular mesangium. Moreover, rehabilitative exercise training to rescue CKD is a personalized remedy. Benefits depend on the duration and strength of exercise, and more importantly, on the individual physiological condition. PMID:22761655

Vortex rings from Sphagnum moss capsules

NASA Astrophysics Data System (ADS)

Whitaker, Dwight; Strassman, Sam; Cha, Jung; Chang, Emily; Guo, Xinyi; Edwards, Joan

2010-11-01

The capsules of Sphagnum moss use vortex rings to disperse spores to suitable habitats many kilometers away. Vortex rings are created by the sudden release of pressurized air when the capsule ruptures, and are an efficient way to carry the small spores with low terminal velocities to heights where they can be carried by turbulent wind currents. We will present our computational model of these explosions, which are carried out using a 2-D large eddy simulation (LES) on FLUENT. Our simulations can reproduce the observed motion of the spore clouds observed from moss capsules with high-speed videos, and we will discuss the roles of bursting pressure, cap mass, and capsule morphology on the formation and quality of vortex rings created by this plant.

Lipoxin A4 Attenuates Constitutive and TGF-β1–Dependent Profibrotic Activity in Human Lung Myofibroblasts

PubMed Central

Feghali-Bostwick, Carol A.; Amrani, Yassine; Bradding, Peter

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a common, progressive, and invariably lethal interstitial lung disease with no effective therapy. The key cell driving the development of fibrosis is the myofibroblast. Lipoxin A4 (LXA4) is an anti-inflammatory lipid, important in the resolution of inflammation, and it has potential antifibrotic activity. However, the effects of LXA4 on primary human lung myofibroblasts (HLMFs) have not previously been investigated. Therefore, the aim of this study was to examine the effects of LXA4 on TGF-β1–dependent responses in IPF- and nonfibrotic control (NFC)–derived HLMFs. HLMFs were isolated from IPF and NFC patients and grown in vitro. The effects of LXA4 on HLMF proliferation, collagen secretion, α-smooth muscle actin (αSMA) expression, and Smad2/3 activation were examined constitutively and following TGF-β1 stimulation. The LXA4 receptor (ALXR) was expressed in both NFC- and IPF-derived HLMFs. LXA4 (10−10 and 10−8 mol) reduced constitutive αSMA expression, actin stress fiber formation, contraction, and nuclear Smad2/3, indicating regression from a myofibroblast to fibroblast phenotype. LXA4 also significantly inhibited FBS-dependent proliferation and TGF-β1–dependent collagen secretion, αSMA expression, and Smad2/3 nuclear translocation in IPF-derived HLMFs. LXA4 did not inhibit Smad2/3 phosphorylation. In summary, LXA4 attenuated profibrotic HLMF activity and promoted HLMF regression to a quiescent fibroblast phenotype. LXA4 or its stable analogs delivered by aerosol may offer a novel approach to the treatment of IPF. PMID:26276873

Relationship between ultrasound elastography and myofibroblast distribution in breast cancer and its clinical significance

PubMed Central

Hao, Yi; Guo, Xia; Ma, Binlin; Zhu, Lin; Liu, Lisha

2016-01-01

The study investigated the relationship between ultrasound elastography (USE) scoring and myofibroblast distribution with expression features of α-SMA + /CD34− in patients of Uyghur and Han ethnicities with breast masses in Xinjiang, China. The data was used to evaluate its clinical significance in the early diagnosis of breast cancer. A total of 300 patients with breast masses were included in the study, which involved conventional sonography and USE, with histopathologic diagnosis as the reference standard. Myofibroblast distribution was investigated by detecting the expression levels of α-SMA and CD34 in lesions using immunohistochemistry and real-time PCR. Out of 300 lesions, 185 were histologically malignant and 115 benign. The mean elasticity score for malignant lesions was significantly higher than for benign lesions. The expression level of α-SMA was elevated while the expression level of CD34 was lower in malignancies, compared with benign lesions. The expression of α-SMA was positively associated with the USE scores, while a negative relationship was observed between CD34 expression and USE scoring. The combination of USE and molecular diagnosis provides a promising modality for the early diagnosis and evaluation of the risks in particular types of breast cancer. PMID:26846996

Induction of myofibroblastic differentiation in vitro by covalently immobilized transforming growth factor-beta(1).

PubMed

Metzger, Wolfgang; Grenner, Nadine; Motsch, Sandra E; Strehlow, Rothin; Pohlemann, Tim; Oberringer, Martin

2007-11-01

Growth factors are an important tool in tissue engineering. Bone morphogenetic protein-2 and transforming growth factor-beta(1) (TGF-beta(1)) are used to provide bioactivity to surgical implants and tissue substitute materials. Mostly growth factors are used in soluble or adsorbed form. However, simple adsorption of proteins to surfaces is always accompanied by reduced stability and undefined pharmacokinetics. This study aims to prove that TGF-beta(1) can be covalently immobilized to functionalized surfaces, maintaining its ability to induce myofibroblastic differentiation of normal human dermal fibroblasts. In vivo, fibroblasts differentiate to myofibroblasts (MFs) during soft tissue healing by the action of TGF-beta(1). As surfaces for our experiments, we used slides bearing aldehyde, epoxy, or amino groups. For our in vitro cell culture experiments, we used the expression of alpha-smooth muscle actin as a marker for MFs after immunochemical staining. Using the aldehyde and the epoxy slides, we were able to demonstrate the activity of immobilized TGF-beta(1) through a significant increase in MF differentiation rate. A simple immunological test was established to detect TGF-beta(1) on the surfaces. This technology enables the creation of molecular "landscapes" consisting of several factors arranged in a distinct spatial pattern and immobilized on appropriate surfaces.

Polyelectrolyte multilayer capsules as vehicles with tunable permeability.

PubMed

Antipov, Alexei A; Sukhorukov, Gleb B

2004-11-29

This review is devoted to a novel type of polymer micro- and nanocapsules. The shell of the capsule is fabricated by alternate adsorption of oppositely charged polyelectrolytes (PEs) onto the surface of colloidal particles. Cores of different nature (organic or inorganic) with size varied from 0.1 to 10 mum can be used for templating such PE capsules. The shell thickness can be tuned in nanometer range by assembling of defined number of PE layers. The permeability of capsules depends on the pH, ionic strength, solvent, polymer composition, and shell thickness; it can be controlled and varied over wide range of substances regarding their molecular weight and charge. Including functional polymers into capsule wall, such as weak PEs or thermosensitive polymers, makes the capsule permeability sensitive to correspondent external stimuli. Permeability of the capsules is of essential interest in diverse areas related to exploitation of systems with controlled and sustained release properties. The envisaged applications of such capsules/vesicles cover biotechnology, medicine, catalysis, food industry, etc.

Cell cycle constraints on capsulation and bacteriophage susceptibility.

PubMed

Ardissone, Silvia; Fumeaux, Coralie; Bergé, Matthieu; Beaussart, Audrey; Théraulaz, Laurence; Radhakrishnan, Sunish Kumar; Dufrêne, Yves F; Viollier, Patrick H

2014-11-25

Despite the crucial role of bacterial capsules in pathogenesis, it is still unknown if systemic cues such as the cell cycle can control capsule biogenesis. In this study, we show that the capsule of the synchronizable model bacterium Caulobacter crescentus is cell cycle regulated and we unearth a bacterial transglutaminase homolog, HvyA, as restriction factor that prevents capsulation in G1-phase cells. This capsule protects cells from infection by a generalized transducing Caulobacter phage (φCr30), and the loss of HvyA confers insensitivity towards φCr30. Control of capsulation during the cell cycle could serve as a simple means to prevent steric hindrance of flagellar motility or to ensure that phage-mediated genetic exchange happens before the onset of DNA replication. Moreover, the multi-layered regulatory circuitry directing HvyA expression to G1-phase is conserved during evolution, and HvyA orthologues from related Sinorhizobia can prevent capsulation in Caulobacter, indicating that alpha-proteobacteria have retained HvyA activity.

21 CFR 872.3110 - Dental amalgam capsule.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental amalgam capsule. 872.3110 Section 872.3110...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3110 Dental amalgam capsule. (a) Identification. A dental amalgam capsule is a container device in which silver alloy is intended to be mixed with mercury...

21 CFR 872.3110 - Dental amalgam capsule.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental amalgam capsule. 872.3110 Section 872.3110...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3110 Dental amalgam capsule. (a) Identification. A dental amalgam capsule is a container device in which silver alloy is intended to be mixed with mercury...

21 CFR 872.3110 - Dental amalgam capsule.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental amalgam capsule. 872.3110 Section 872.3110...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3110 Dental amalgam capsule. (a) Identification. A dental amalgam capsule is a container device in which silver alloy is intended to be mixed with mercury...

21 CFR 872.3110 - Dental amalgam capsule.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental amalgam capsule. 872.3110 Section 872.3110...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3110 Dental amalgam capsule. (a) Identification. A dental amalgam capsule is a container device in which silver alloy is intended to be mixed with mercury...

21 CFR 872.3110 - Dental amalgam capsule.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental amalgam capsule. 872.3110 Section 872.3110...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3110 Dental amalgam capsule. (a) Identification. A dental amalgam capsule is a container device in which silver alloy is intended to be mixed with mercury...

Biomimetic/Bioinspired Design of Enzyme@capsule Nano/Microsystems.

PubMed

Shi, J; Jiang, Y; Zhang, S; Yang, D; Jiang, Z

2016-01-01

Enzyme@capsule nano/microsystems, which refer to the enzyme-immobilized capsules, have received tremendous interest owing to the combination of the high catalytic activities of encapsulated enzymes and the hierarchical structure of the capsule. The preparation of capsules and simultaneous encapsulation of enzymes is recognized as the core process for the rational design and construction of enzyme@capsule nano/microsystems. The strategy used has three major steps: (a) generation of the templates, (b) surface coating on the templates, and (c) removal of the templates, and it has been proven to be effective and versatile for the construction of enzyme@capsule nano/microsystems. Several conventional methods, including layer-by-layer assembly of polyelectrolytes, liquid crystalline templating method, etc., were used to design and construct enzyme@capsule nano/microsystems, but these have two major drawbacks. One is the low mechanical stability of the systems and the second is the harsh conditions used in the construction process. Learning from nature, several biomimetic/bioinspired methods such as biomineralization, biomimetic/bioinspired adhesion, and their combination have been exploited for the construction of enzyme@capsule nano/microsystems. In this chapter, we will present a general protocol for the construction of enzyme@capsule nano/microsystems using the latter approach. Some suggestions for improved design, construction, and characterization will also be presented with detailed procedures for specific examples. © 2016 Elsevier Inc. All rights reserved.

3D Printed Programmable Release Capsules.

PubMed

Gupta, Maneesh K; Meng, Fanben; Johnson, Blake N; Kong, Yong Lin; Tian, Limei; Yeh, Yao-Wen; Masters, Nina; Singamaneni, Srikanth; McAlpine, Michael C

2015-08-12

The development of methods for achieving precise spatiotemporal control over chemical and biomolecular gradients could enable significant advances in areas such as synthetic tissue engineering, biotic-abiotic interfaces, and bionanotechnology. Living organisms guide tissue development through highly orchestrated gradients of biomolecules that direct cell growth, migration, and differentiation. While numerous methods have been developed to manipulate and implement biomolecular gradients, integrating gradients into multiplexed, three-dimensional (3D) matrices remains a critical challenge. Here we present a method to 3D print stimuli-responsive core/shell capsules for programmable release of multiplexed gradients within hydrogel matrices. These capsules are composed of an aqueous core, which can be formulated to maintain the activity of payload biomolecules, and a poly(lactic-co-glycolic) acid (PLGA, an FDA approved polymer) shell. Importantly, the shell can be loaded with plasmonic gold nanorods (AuNRs), which permits selective rupturing of the capsule when irradiated with a laser wavelength specifically determined by the lengths of the nanorods. This precise control over space, time, and selectivity allows for the ability to pattern 2D and 3D multiplexed arrays of enzyme-loaded capsules along with tunable laser-triggered rupture and release of active enzymes into a hydrogel ambient. The advantages of this 3D printing-based method include (1) highly monodisperse capsules, (2) efficient encapsulation of biomolecular payloads, (3) precise spatial patterning of capsule arrays, (4) "on the fly" programmable reconfiguration of gradients, and (5) versatility for incorporation in hierarchical architectures. Indeed, 3D printing of programmable release capsules may represent a powerful new tool to enable spatiotemporal control over biomolecular gradients.

Characteristics of patients with a retained wireless capsule endoscope (WCE) necessitating laparotomy for removal of the capsule.

PubMed

Purdy, Martin; Heikkinen, Markku; Juvonen, Petri; Voutilainen, Markku; Eskelinen, Matti

2011-01-01

A capsule endoscope is a wireless miniature camera used to take images of the small bowel mucosa. Retention of the wireless capsule endoscope (WCE), defined as at least two weeks' retention or an obstruction demanding removal by laparotomy, is the main and practically only complication of the procedure. The aim of this study was to evaluate the characteristics of patients with a retained WCE necessitating laparotomy for removal of the capsule or capsule fragments. The medical records of 555 patients who had undergone the WCE procedure over a 7-year period (2002-2008) were reviewed. The indications for the WCE procedure were, obscure gastrointestinal bleeding, Crohn's disease, abdominal pain and suspicion of malignancy. A retained WCE requiring operative treatment was found in 10 cases (in nine patients, twice in one patient). The WCE retention frequency of 1.8% (10/555) equalled that in the literature. The retention rate of WCE capsules is low and routine examination of the small bowel with MRI or CT is not necessary before WCE. These examinations were enable to predict WCE retention according to our results.

Capsules made from prefabricated thin films

NASA Astrophysics Data System (ADS)

Amstad, Esther

2018-02-01

Capsules are composed of a core, typically a liquid containing active substances, and a surrounding shell. They are used to delay the degradation of active ingredients, protect them from reacting or interacting with substances contained in the surrounding shell, or to prevent premature consumption of encapsulants (1, 2). The performance of capsules is often determined by their permeability toward encapsulants and stability against rupture; these parameters can be adjusted with the composition, structure, and thickness of the shell (3, 4). Mechanically robust capsules with a minimal permeability even toward low molecular weight substances often have rather thick shells (5). On page 775 of this issue, Kumar et al. (6) report an elegant process to fabricate capsules with very thin, rigid shells that display a low permeability even toward small encapsulants.

[Evaluation of nopal capsules in diabetes mellitus].

PubMed

Frati Munari, A C; Vera Lastra, O; Ariza Andraca, C R

1992-01-01

To find out if commercial capsules with dried nopal (prickle-pear cactus, Opuntia ficus indica may have a role in the management of diabetes mellitus, three experiments were performed: 30 capsules where given in fasting condition to 10 diabetic subjects and serum glucose was measured through out 3 hours; a control test was performed with 30 placebo capsules. OGTT with previous intake of 30 nopal or placebo capsules was performed in ten healthy individuals. In a crossover and single blinded study 14 diabetic patients withdrew the oral hypoglycemic treatment and received 10 nopal or placebo capsules t.i.d. during one week; serum glucose, cholesterol and tryglycerides levels were measured before and after each one-week period. Five healthy subjects were also studied in the same fashion. Opuntia capsules did not show acute hypoglycemic effect and did not influence OGTT. In diabetic patients serum glucose, cholesterol and tryglycerides levels did not change with Opuntia, but they increased with placebo (P < 0.01 glucose and cholesterol, P = NS triglycerides). In healthy individuals glycemia did not change with nopal, while cholesterol and triglycerides decreased (P < 0.01 vs. placebo). The intake of 30 Opuntia capsules daily in patients with diabetes mellitus had a discrete beneficial effect on glucose and cholesterol. However this dose is unpractical and at present it is not recommended in the management of diabetes mellitus.

Emerging Issues and Future Developments in Capsule Endoscopy

PubMed Central

Slawinski, Piotr R.; Obstein, Keith L.; Valdastri, Pietro

2015-01-01

Capsule endoscopy (CE) has transformed from a research venture into a widely used clinical tool and the primary means for diagnosing small bowel pathology. These orally administered capsules traverse passively through the gastrointestinal tract via peristalsis and are used in the esophagus, stomach, small bowel, and colon. The primary focus of CE research in recent years has been enabling active CE manipulation and extension of the technology to therapeutic functionality; thus, widening the scope of the procedure. This review outlines clinical standards of the technology as well as recent advances in CE research. Clinical capsule applications are discussed with respect to each portion of the gastrointestinal tract. Promising research efforts are presented with an emphasis on enabling active capsule locomotion. The presented studies suggest, in particular, that the most viable solution for active capsule manipulation is actuation of a capsule via exterior permanent magnet held by a robot. Developing capsule procedures adhering to current healthcare standards, such as enabling a tool channel or irrigation in a therapeutic device, is a vital phase in the adaptation of CE in the clinical setting. PMID:26028956

Cell cycle constraints on capsulation and bacteriophage susceptibility

PubMed Central

Ardissone, Silvia; Fumeaux, Coralie; Bergé, Matthieu; Beaussart, Audrey; Théraulaz, Laurence; Radhakrishnan, Sunish Kumar; Dufrêne, Yves F; Viollier, Patrick H

2014-01-01

Despite the crucial role of bacterial capsules in pathogenesis, it is still unknown if systemic cues such as the cell cycle can control capsule biogenesis. In this study, we show that the capsule of the synchronizable model bacterium Caulobacter crescentus is cell cycle regulated and we unearth a bacterial transglutaminase homolog, HvyA, as restriction factor that prevents capsulation in G1-phase cells. This capsule protects cells from infection by a generalized transducing Caulobacter phage (φCr30), and the loss of HvyA confers insensitivity towards φCr30. Control of capsulation during the cell cycle could serve as a simple means to prevent steric hindrance of flagellar motility or to ensure that phage-mediated genetic exchange happens before the onset of DNA replication. Moreover, the multi-layered regulatory circuitry directing HvyA expression to G1-phase is conserved during evolution, and HvyA orthologues from related Sinorhizobia can prevent capsulation in Caulobacter, indicating that alpha-proteobacteria have retained HvyA activity. DOI: http://dx.doi.org/10.7554/eLife.03587.001 PMID:25421297

Capsule endoscopy—A mechatronics perspective

NASA Astrophysics Data System (ADS)

Lin, Lin; Rasouli, Mahdi; Kencana, Andy Prima; Tan, Su Lim; Wong, Kai Juan; Ho, Khek Yu; Phee, Soo Jay

2011-03-01

The recent advances in integrated circuit technology, wireless communication, and sensor technology have opened the door for development of miniature medical devices that can be used for enhanced monitoring and treatment of medical conditions. Wireless capsule endoscopy is one of such medical devices that has gained significant attention during the past few years. It is envisaged that future wireless capsule endoscopies replace traditional endoscopy procedures by providing advanced functionalities such as active locomotion, body fluid/tissue sampling, and drug delivery. Development of energy-efficient miniaturized actuation mechanisms is a key step toward achieving this goal. Here, we review some of the actuators that could be integrated into future wireless capsules and discuss the existing challenges.

Noninflammatory Joint Contractures Arising from Immobility: Animal Models to Future Treatments

PubMed Central

Wong, Kayleigh; Trudel, Guy; Laneuville, Odette

2015-01-01

Joint contractures, defined as the limitation in the passive range of motion of a mobile joint, can be classified as noninflammatory diseases of the musculoskeletal system. The pathophysiology is not well understood; limited information is available on causal factors, progression, the pathophysiology involved, and prediction of response to treatment. The clinical heterogeneity of joint contractures combined with the heterogeneous contribution of joint connective tissues to joint mobility presents challenges to the study of joint contractures. Furthermore, contractures are often a symptom of a wide variety of heterogeneous disorders that are in many cases multifactorial. Extended immobility has been identified as a causal factor and evidence is provided from both experimental and epidemiology studies. Of interest is the involvement of the joint capsule in the pathophysiology of joint contractures and lack of response to remobilization. While molecular pathways involved in the development of joint contractures are being investigated, current treatments focus on physiotherapy, which is ineffective on irreversible contractures. Future treatments may include early diagnosis and prevention. PMID:26247029

Subperiosteal Transmission Of Intra-Articular Pressure Between Articulated And Stationary Joints

PubMed Central

Pitkin, Mark; Muppavarapu, Raghuveer; Cassidy, Charles; Pitkin, Emil

2015-01-01

Hydrostatic pressures can be transmitted between synovial capsules. In each of ten rabbits, we simultaneously measured pressure in two joints, one of which was passively ranged, and the other of which was kept stationary. The intra-articular pressure inside the stationary joint changed every time its companion joint was ranged. But the pressure in the stationary joint did not change when the periosteum was transected above the ranged joint. This phenomenon was observed in all four animals that served as their own controls. The study suggests that the intra-articular pressure was transmitted through the space between the periosteum and the bone surface. Alternative explanations, like measurements of venous blood pressure, did not show correlation with hydrostatic pressure changes in the joints. The Floating Skeleton concept suggests a biomechanical rationale for this newly observed phenomenon: that there exists a subperiosteal hydrostatic connection of synovial joints, and that this “net” distributes excess pressures among joints through the periosteal sheath to sustain the integrity of the joint contacting surfaces over a lifetime. PMID:25632015

Experimental measurement on movement of spiral-type capsule endoscope

PubMed Central

Yang, Wanan; Dai, Houde; He, Yong; Qin, Fengqing

2016-01-01

Wireless capsule endoscope achieved great success, however, the maneuvering of wireless capsule endoscope is challenging at present. A magnetic driving instrument, including two bar magnets, a stepper motor, a motor driver, a motor controller, and a power supplier, was developed to generate rotational magnetic fields. Permanent magnet ring, magnetized as S and N poles radially and mounted spiral structure on the surface, acted as a capsule. The maximum torque passing to the capsule, rotational synchronization of capsule and motor, and the translational speed of capsule, were measured in ex vivo porcine large intestine. The experimental results illustrate that the rotational movement of the spiral-type capsule in the intestine is feasible and the cost of the magnetic driving equipment is low. As a result, the solution is promising in the future controllability. PMID:26848279

Experimental measurement on movement of spiral-type capsule endoscope.

PubMed

Yang, Wanan; Dai, Houde; He, Yong; Qin, Fengqing

2016-01-01

Wireless capsule endoscope achieved great success, however, the maneuvering of wireless capsule endoscope is challenging at present. A magnetic driving instrument, including two bar magnets, a stepper motor, a motor driver, a motor controller, and a power supplier, was developed to generate rotational magnetic fields. Permanent magnet ring, magnetized as S and N poles radially and mounted spiral structure on the surface, acted as a capsule. The maximum torque passing to the capsule, rotational synchronization of capsule and motor, and the translational speed of capsule, were measured in ex vivo porcine large intestine. The experimental results illustrate that the rotational movement of the spiral-type capsule in the intestine is feasible and the cost of the magnetic driving equipment is low. As a result, the solution is promising in the future controllability.

Inflammatory Myofibroblastic Tumor of the Kidney: A Rare Renal Tumor.

PubMed

Pothadiyil, Alvin Jose; Bhat, Suresh; Paul, Fredrick; Mampatta, Jithesh; Srinivas, Mahesh

2016-11-01

Inflammatory Myofibroblastic Tumour (IMT) or 'pseudotumour' of the kidney is a rare benign tumour of unknown aetiology affecting mostly young adults. A subset of IMT is neoplastic and harbours translocations of activin receptor-like kinase-1 (ALK-1) gene and can recur or rarely metastasize. Presentation varies from an incidentaloma to gross haematuria. Clinical examination and radiological investigations are usually inconclusive. Often, biopsy is inconclusive necessitating a management similar to that of Renal Cell Cancer (RCC). Diagnosis is based on immunohistochemistry. We are reporting a case of IMT in a 50-year-old male patient who presented with left flank mass which on evaluation was suggestive of left renal cell carcinoma. Excision of the tumour, histopathological examination and Immunohistochemistry proved the tumour to be IMT.

Fabrication of capsule assemblies, phase 3

NASA Technical Reports Server (NTRS)

Keeton, A. R.; Stemann, L. G.

1973-01-01

Thirteen capsule assemblies were fabricated for evaluation of fuel pin design concepts for a fast spectrum lithium cooled compact space power reactor. These instrumented assemblies were designed for real time test of prototype fuel pins. Uranium mononitride fuel pins were encased in AISI 304L stainless steel capsules. Fabrication procedures were fully qualified by process development and assembly qualification tests. Instrumentation reliability was achieved utilizing specially processed and closely controlled thermocouple hot zone fabrication and by thermal screening tests. Overall capsule reliability was achieved with an all electron beam welded assembly.

Stopping mechanism for capsule endoscope using electrical stimulus.

PubMed

Woo, Sang Hyo; Kim, Tae Wan; Cho, Jin Ho

2010-01-01

An ingestible capsule, which has the ability to stop at certain locations in the small intestine, was designed and implemented to monitor intestinal diseases. The proposed capsule can contract the small intestine by using electrical stimuli; this contraction causes the capsule to stop when the maximum static frictional force (MSFF) is larger than the force of natural peristalsis. In vitro experiments were carried out to verify the feasibility of the capsule, and the results showed that the capsule was successfully stopped in the small intestine. Various electrodes and electrical stimulus parameters were determined on the basis of the MSFF. A moderate increment of the MSFF (12.7 +/- 4.6 gf at 5 V, 10 Hz, and 5 ms) and the maximum increment of the MSFF (56.5 +/- 9.77 gf at 20 V, 10 Hz, and 5 ms) were obtained, and it is sufficient force to stop the capsule.

Age-Dependent Decline in Mouse Lung Regeneration with Loss of Lung Fibroblast Clonogenicity and Increased Myofibroblastic Differentiation

PubMed Central

Paxson, Julia A.; Gruntman, Alisha; Parkin, Christopher D.; Mazan, Melissa R.; Davis, Airiel; Ingenito, Edward P.; Hoffman, Andrew M.

2011-01-01

While aging leads to a reduction in the capacity for regeneration after pneumonectomy (PNX) in most mammals, this biological phenomenon has not been characterized over the lifetime of mice. We measured the age-specific (3, 9, 24 month) effects of PNX on physiology, morphometry, cell proliferation and apoptosis, global gene expression, and lung fibroblast phenotype and clonogenicity in female C57BL6 mice. The data show that only 3 month old mice were fully capable of restoring lung volumes by day 7 and total alveolar surface area by 21 days. By 9 months, the rate of regeneration was slower (with incomplete regeneration by 21 days), and by 24 months there was no regrowth 21 days post-PNX. The early decline in regeneration rate was not associated with changes in alveolar epithelial cell type II (AECII) proliferation or apoptosis rate. However, significant apoptosis and lack of cell proliferation was evident after PNX in both total cells and AECII cells in 24 mo mice. Analysis of gene expression at several time points (1, 3 and 7 days) post-PNX in 9 versus 3 month mice was consistent with a myofibroblast signature (increased Tnc, Lox1, Col3A1, Eln and Tnfrsf12a) and more alpha smooth muscle actin (αSMA) positive myofibroblasts were present after PNX in 9 month than 3 month mice. Isolated lung fibroblasts showed a significant age-dependent loss of clonogenicity. Moreover, lung fibroblasts isolated from 9 and 17 month mice exhibited higher αSMA, Col3A1, Fn1 and S100A expression, and lower expression of the survival gene Mdk consistent with terminal differentiation. These data show that concomitant loss of clonogenicity and progressive myofibroblastic differentiation contributes to the age-dependent decline in the rate of lung regeneration. PMID:21912590

Identification of a functional capsule locus in Streptococcus mitis.

PubMed

Rukke, H V; Hegna, I K; Petersen, F C

2012-04-01

The polysaccharide capsule of Streptococcus pneumoniae is a hallmark for virulence in humans. In its close relative Streptococcus mitis, a common human commensal, analysis of the sequenced genomes of six strains revealed the presence of a putative capsule locus in four of them. We constructed an isogenic S. mitis mutant from the type strain that lacked the 19 open reading frames in the capsule locus (Δcps mutant), using a deletion strategy similar to previous capsule functional studies in S. pneumoniae. Transmission electron microscopy and atomic force microscopy revealed a capsule-like structure in the S. mitis type strain that was absent or reduced in the Δcps mutant. Since S. mitis are predominant oral colonizers of tooth surfaces, we addressed the relevance of the capsule locus for the S. mitis overall surface properties, autoaggregation and biofilm formation. The capsule deletion resulted in a mutant with approximately two-fold increase in hydrophobicity. Binding to the Stains-all cationic dye was reduced by 40%, suggesting a reduction in the overall negative surface charge of the mutant. The mutant exhibited also increased autoaggregation in coaggregation buffer, and up to six-fold increase in biofilm levels. The results suggested that the capsule locus is associated with production of a capsule-like structure in S. mitis and indicated that the S. mitis capsule-like structure may confer surface attributes similar to those associated with the capsule in S. pneumoniae. © 2011 John Wiley & Sons A/S.

21 CFR 520.608 - Dicloxacillin sodium monohydrate capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dicloxacillin sodium monohydrate capsules. 520.608 Section 520.608 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dicloxacillin sodium monohydrate capsules. (a) Specifications. Each capsule contains dicloxacillin sodium...

21 CFR 520.608 - Dicloxacillin sodium monohydrate capsules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dicloxacillin sodium monohydrate capsules. 520.608 Section 520.608 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dicloxacillin sodium monohydrate capsules. (a) Specifications. Each capsule contains dicloxacillin sodium...

21 CFR 520.608 - Dicloxacillin sodium monohydrate capsules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dicloxacillin sodium monohydrate capsules. 520.608 Section 520.608 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dicloxacillin sodium monohydrate capsules. (a) Specifications. Each capsule contains dicloxacillin sodium...

Production, deformation and mechanical investigation of magnetic alginate capsules

NASA Astrophysics Data System (ADS)

Zwar, Elena; Kemna, Andre; Richter, Lena; Degen, Patrick; Rehage, Heinz

2018-02-01

In this article we investigated the deformation of alginate capsules in magnetic fields. The sensitivity to magnetic forces was realised by encapsulating an oil in water emulsion, where the oil droplets contained dispersed magnetic nanoparticles. We solved calcium ions in the aqueous emulsion phase, which act as crosslinking compounds for forming thin layers of alginate membranes. This encapsulating technique allows the production of flexible capsules with an emulsion as the capsule core. It is important to mention that the magnetic nanoparticles were stable and dispersed throughout the complete process, which is an important difference to most magnetic alginate-based materials. In a series of experiments, we used spinning drop techniques, capsule squeezing experiments and interfacial shear rheology in order to determine the surface Young moduli, the surface Poisson ratios and the surface shear moduli of the magnetically sensitive alginate capsules. In additional experiments, we analysed the capsule deformation in magnetic fields. In spinning drop and capsule squeezing experiments, water droplets were pressed out of the capsules at elevated values of the mechanical load. This phenomenon might be used for the mechanically triggered release of water-soluble ingredients. After drying the emulsion-filled capsules, we produced capsules, which only contained a homogeneous oil phase with stable suspended magnetic nanoparticles (organic ferrofluid). In the dried state, the thin alginate membranes of these particles were rather rigid. These dehydrated capsules could be stored at ambient conditions for several months without changing their properties. After exposure to water, the alginate membranes rehydrated and became flexible and deformable again. During this swelling process, water diffused back in the capsule. This long-term stability and rehydration offers a great spectrum of different applications as sensors, soft actuators, artificial muscles or drug delivery systems.

Effect of [6]-gingerol on myofibroblast differentiation in transforming growth factor beta 1-induced nasal polyp-derived fibroblasts.

PubMed

Park, Sook A; Park, Il-Ho; Cho, Jung-Sun; Moon, You-Mi; Lee, Seung Hoon; Kim, Tae Hoon; Lee, Sang Hag; Lee, Heung-Man

2012-01-01

[6]-Gingerol is one of the major pungent principles of ginger and has diverse effects, including anti-inflammatory, and antioxidative effects. Reactive oxygen species (ROS) are released during the phenotypic transformation of fibroblasts to myofibroblasts, a process that is involved in the growth of nasal polyps by inducing extracellular matrix (ECM) accumulation. The purpose of this study was to determine the effect of [6]-gingerol on myofibroblast differentiation and collagen production of nasal polyp-derived fibroblasts (NPDFs) and to determine if the effect of [6]-gingerol is linked to an antioxidant effect. NPDFs were incubated and treated with transforming growth factor (TGF) beta 1. The ROS generated by NPDFs were determined using 2″,7″-dichlorfluorescein-diacetate. The fluorescence was captured by a fluorescent microscope and measured using a fluorometer. The expression of alpha-smooth muscle actin (SMA) and collagen type IV mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of α-SMA protein and pSmad2/3 was determined by immunofluorescence microscopy and or Western blotting. The amount of total soluble collagen production was analyzed by the SirCol collagen dye-binding assay. TGF-beta 1 stimulation increased ROS production by NPDFs. [6]-Gingerol decreased the production of ROS in TGF-beta 1-induced NPDFs. Myofibroblast differentiation, collagen production, and phosphorylation of Smad2/3 were prevented by [6]-gingerol and inhibition of ROS generation with antioxidant such as diphenyliodonium, N-acetylcysteine, and ebselen. These results suggest the possibility that [6]-gingerol may play an important role in inhibiting the production of the ECM in the development of nasal polyps through an antioxidant effect.

Design and synthesis of organic-inorganic hybrid capsules for biotechnological applications.

PubMed

Shi, Jiafu; Jiang, Yanjun; Wang, Xiaoli; Wu, Hong; Yang, Dong; Pan, Fusheng; Su, Yanlei; Jiang, Zhongyi

2014-08-07

Organic-inorganic hybrid capsules, which typically possess a hollow lumen and a hybrid wall, have emerged as a novel and promising class of hybrid materials and have attracted enormous attention. In comparison to polymeric capsules or inorganic capsules, the hybrid capsules combine the intrinsic physical/chemical properties of the organic and inorganic moieties, acquire more degrees of freedom to manipulate multiple interactions, create hierarchical structures and integrate multiple functionalities. Thus, the hybrid capsules exhibit superior mechanical strength (vs. polymeric capsules) and diverse functionalities (vs. inorganic capsules), which may give new opportunities to produce high-performance materials. Much effort has been devoted to exploring innovative and effective methods for the synthesis of hybrid capsules that exhibit desirable performance in target applications. This tutorial review firstly presents a brief description of the capsular structure and hybrid materials in nature, then classifies the hybrid capsules into molecule-hybrid capsules and nano-hybrid capsules based upon the size of the organic and inorganic moieties in the capsule wall, followed by a detailed discussion of the design and synthesis of the hybrid capsules. For each kind of hybrid capsule, the state-of-the-art synthesis methods are described in detail and a critical comment is embedded. The applications of these hybrid capsules in biotechnological areas (biocatalysis, drug delivery, etc.) have also been summarized. Hopefully, this review will offer a perspective and guidelines for the future research and development of hybrid capsules.

Gettering capsule for removing oxygen from liquid lithium systems

NASA Technical Reports Server (NTRS)

Tower, L. K.; Breitwieser, R.

1973-01-01

Capsule consisting of tantalum shell lined with tantalum screen and partially filled with lithium and pieces of yttrium is immersed in hot lithium stream. Oxygen is removed from stream by being absorbed by gettering capsule. Oxygen passes through capsule wall and into lithium inside capsule where it reacts with yttrium to form Y2O3.

[Dorsal capsular imbrication for dorsal instability of the distal radioulnar joint].

PubMed

Unglaub, F; Manz, S; Bruckner, T; Leclère, F M; Hahn, P; Wolf, M B

2013-12-01

To stabilize the distal radioulnar joint (DRUJ) by performing dorsal capsular imbrication in patients presenting with dorsal instability. The goal was to reduce pain and prevent the occurrence of posttraumatic arthrosis. Posttraumatic dorsal instability of the DRUJ with missing block while performing translational activities in the DRUJ or subluxation while actively rotating the forearm. Cases, in which other stabilizing techniques, such as, sutures of the triangular fibrocartilage complex failed. DRUJ arthrosis, previous surgical interventions to the capsule area of the DRUJ, instabilities due to osseous reasons (malposition or pseudarthrosis) should already have been treated. Dorsal approach and opening of the 5th extensor compartment to expose the dorsal joint capsule. A longitudinal division of the capsule was performed and sufficient tissue on the radial and ulnar border was retained to ensure a solid suture technique. Then 2 U-shaped sutures using FiberWire suture material were made. Correction of the malposition and repositioning the forearm into supination. Tightening of the prepared capsule sutures and closing of the retinaculum with a resorbable suture. Patients wore a long-arm cast with the forearm being in supination for a period of 4 weeks. Following cast removal, patients wore a forearm splint for a period of 4 weeks to limit forearm pronation/supination at 45°. Full load on the wrist was allowed after 12 weeks. The subjective and functional outcomes of 20 patients having received capsular imbrication using this technique were good and entailed no significant complications. The postoperative DASH was 15.8 points. Of the 20 patients, 17 patients (85%) had a reduction of pain. Symptoms of DRUJ instability could be reduced in 18 patients (90%). Pronation/supination of the wrist was not restricted postoperatively.

Relative ratios of collagen composition of periarticular tissue of joints of the upper limb.

PubMed

Cheah, A; Harris, A; Le, W; Huang, Y; Yao, J

2017-07-01

We investigated the relative ratios of collagen composition of periarticular tissue of the elbow, wrist, metacarpophalangeal, proximal and distal interphalangeal joints. Periarticulat tissue, which we defined as the ligaments, palmar plate and capsule, was harvested from ten fresh-frozen cadaveric upper limbs, yielding 50 samples. The mean paired differences (95% confidence interval) of the relative ratios of collagen between the five different joints were estimated using mRNA expression of collagen in the periarticular tissue. We found that the relative collagen composition of the elbow was not significantly different to that of the proximal interphalangeal joint, nor between the proximal interphalangeal joint and distal interphalangeal joint, whereas the differences in collagen composition between all the other paired comparisons of the joints had confidence intervals that did not include zero.

Motion of an elastic capsule in a square microfluidic channel.

PubMed

Kuriakose, S; Dimitrakopoulos, P

2011-07-01

In the present study we investigate computationally the steady-state motion of an elastic capsule along the centerline of a square microfluidic channel and compare it with that in a cylindrical tube. In particular, we consider a slightly over-inflated elastic capsule made of a strain-hardening membrane with comparable shearing and area-dilatation resistance. Under the conditions studied in this paper (i.e., small, moderate, and large capsules at low and moderate flow rates), the capsule motion in a square channel is similar to and thus governed by the same scaling laws with the capsule motion in a cylindrical tube, even though in the channel the cross section in the upstream portion of large capsules is nonaxisymmetric (i.e., square-like with rounded corners). When the hydrodynamic forces on the membrane increase, the capsule develops a pointed downstream edge and a flattened rear (possibly with a negative curvature) so that the restoring tension forces are increased as also happens with droplets. Membrane tensions increase significantly with the capsule size while the area near the downstream tip is the most probable to rupture when a capsule flows in a microchannel. Because the membrane tensions increase with the interfacial deformation, a suitable Landau-Levich-Derjaguin-Bretherton analysis reveals that the lubrication film thickness h for large capsules depends on both the capillary number Ca and the capsule size a; our computations determine the latter dependence to be (in dimensionless form) h ~ a(-2) for the large capsules studied in this work. For small and moderate capsule sizes a, the capsule velocity Ux and additional pressure drop ΔP+ are governed by the same scaling laws as for high-viscosity droplets. The velocity and additional pressure drop of large thick capsules also follow the dynamics of high-viscosity droplets, and are affected by the lubrication film thickness. The motion of our large thick capsules is characterized by a Ux-U ~ h ~ a(-2

Motion of an elastic capsule in a square microfluidic channel

PubMed Central

Kuriakose, S.; Dimitrakopoulos, P.

2013-01-01

In the present study we investigate computationally the steady-state motion of an elastic capsule along the centerline of a square microfluidic channel and compare it with that in a cylindrical tube. In particular, we consider a slightly over-inflated elastic capsule made of a strain-hardening membrane with comparable shearing and area-dilatation resistance. Under the conditions studied in this paper (i.e. small, moderate and large capsules at low and moderate flow rates), the capsule motion in a square channel is similar to, and thus governed by the same scaling laws with the capsule motion in a cylindrical tube, even though in the channel the cross-section in the upstream portion of large capsules is non-axisymmetric (i.e. square-like with rounded corners). When the hydrodynamic forces on the membrane increase, the capsule develops a pointed downstream edge and a flattened rear (possibly with a negative curvature) so that the restoring tension forces are increased as also happens with droplets. Membrane tensions increase significantly with the capsule size while the area near the downstream tip is the most probable to rupture when a capsule flows in a microchannel. Because the membrane tensions increase with the interfacial deformation, a suitable Landau-Levich-Derjaguin-Bretherton analysis reveals that the lubrication film thickness h for large capsules depends on both the capillary number Ca and the capsule size a; our computations determine the latter dependence to be (in dimensionless form) h ~ a−2 for the large capsules studied in this work. For small and moderate capsule sizes a, the capsule velocity Ux and additional pressure drop ΔP+ are governed by the same scaling laws as for high-viscosity droplets. The velocity and additional pressure drop of large thick capsules also follow the dynamics of high-viscosity droplets, and are affected by the lubrication film thickness. The motion of our large thick capsules is characterized by a Ux−u~h~a−2

Cutaneous amelanotic signet-ring cell malignant melanoma with interspersed myofibroblastic differentiation in a young cat.

PubMed

Hirz, Manuela; Herden, Christiane

2016-07-01

The diagnosis of malignant melanoma can be difficult because these tumors can be amelanotic and may contain diverse variants and divergent differentiations, of which the signet-ring cell subtype is very rare and has only been described in humans, dogs, cats, and a hamster. We describe herein histopathologic and immunohistochemical approaches taken to diagnose a case of signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. A tumor within the abdominal skin of a 2-year-old cat was composed of signet-ring cells and irregularly interwoven streams of spindle cells. Both neoplastic cell types were periodic-acid-Schiff, Fontana, and Sudan black B negative. Signet-ring cells strongly expressed vimentin and S100 protein. Spindle cells strongly expressed vimentin and smooth muscle actin; some cells expressed S100, moderately neuron-specific enolase, and others variably actin and desmin. A few round cells expressed melan A, and a few plump spindle cells expressed melan A and PNL2, confirming the diagnosis of amelanotic signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. Differential diagnoses were excluded, including signet-ring cell forms of adenocarcinomas, lymphomas, liposarcomas, leiomyosarcomas, squamous cell carcinomas, basal cell carcinomas, and adnexal tumors. © 2016 The Author(s).

Axial traction magnetic resonance imaging (MRI) of the glenohumeral joint in healthy volunteers: initial experience.

PubMed

Garwood, Elisabeth R; Souza, Richard B; Zhang, Amy; Zhang, Alan L; Ma, C Benjamin; Link, Thomas M; Motamedi, Daria

Evaluate technical feasibility and potential applications of glenohumeral (GH) joint axial traction magnetic resonance imaging (MRI) in healthy volunteers. Eleven shoulders were imaged in neutral and with 4kg axial traction at 3T. Quantitative measurements were assessed. Axial traction was well tolerated. There was statistically significant widening of the superior GH joint space (p=0.002) and acromial angle (p=0.017) with traction. Inter-rater agreement was high. GH joint axial traction MRI is technically feasible and well tolerated in volunteers. Traction of the capsule, widening of the superior GH joint space and acromial angle were observed. Copyright © 2017 Elsevier Inc. All rights reserved.

Light weight escape capsule for fighter aircraft

NASA Technical Reports Server (NTRS)

Robert, James A.

1988-01-01

Emergency crew escape capabilities have been less than adequate for fighter aircraft since before WW II. From the over-the-side bailout of those days through the current ejection seat with a rocket catapult, escaping from a disabled aircraft has been risky at best. Current efforts are underway toward developing a high-tech, smart ejection seat that will give fighter pilots more room to live in the sky, but an escape capsule is needed to meet current and future fighter envelopes. Escape capsules have a bad reputation due to past examples of high weight, poor performance and great complexity. However, the advantages available demand that a capsule be developed. This capsule concept will minimize the inherent disavantages and incorporate the benefits while integrating all aspects of crew station design. The resulting design is appropriate for a crew station of the year 2010 and includes improved combat acceleration protection, chemical or biological combat capability, improved aircraft to escape system interaction, and the highest level of escape performance achievable. The capsule is compact, which can allow a reduced aircraft size and weighs only 1200 lb. The escape system weight penalty is only 120 lb higher than that for the next ejection seat and the capsule has a corresponding increase in performance.

Development of remote welding techniques for in-pile IASCC capsules and evaluation of material integrity on capsules for long irradiation period

NASA Astrophysics Data System (ADS)

Shibata, A.; Nakano, J.; Ohmi, M.; Kawamata, K.; Nakagawa, T.; Tsukada, T.

2012-03-01

To simulate irradiation assisted stress corrosion cracking (IASCC) behavior by in-pile experiments, it is necessary to irradiate specimens up to a neutron fluence that is higher than the IASCC threshold fluence. Pre-irradiated specimens must be relocated from pre-irradiation capsules to in-pile capsules. Hence, a remote welding machine has been developed. And the integrity of capsule housing for a long term irradiation was evaluated by tensile tests in air and slow strain rate tests in water. Two type specimens were prepared. Specimens were obtained from the outer tubes of capsule irradiated to 1.0-3.9 × 1026 n/m2 (E > 1 MeV). And specimens were irradiated in a leaky capsule to 0.03-1.0 × 1026 n/m2. Elongation more than 15% in tensile test at 423 K was confirmed and no IGSCC fraction was shown in SSRT at 423 K which was estimated as temperature at the outer tubes of the capsule under irradiation.

Polar tent for reduced perturbation of NIF ignition capsules

NASA Astrophysics Data System (ADS)

Hammel, B. A.; Pickworth, L.; Stadermann, M.; Field, J.; Robey, H.; Scott, H. A.; Smalyuk, V.

2016-10-01

In simulations, a tent that contacts the capsule near the poles and departs tangential to the capsule surface greatly reduces the capsule perturbation, and the resulting mass injected into the hot-spot, compared to current capsule support methods. Target fabrication appears feasible with a layered tent (43-nm polyimide + 8-nm C) for increased stiffness. We are planning quantitative measurements of the resulting shell- ρR perturbation near peak implosion velocity (PV) using enhanced self-emission backlighting, achieved by adding 1% Ar to the capsule fill in Symcaps (4He + H). Layered DT implosions are also planned for an integrated test of capsule performance. We will describe the design and simulation predictions. Prepared by LLNL under Contract DE-AC52-07NA27344.

General route for the assembly of functional inorganic capsules.

PubMed

Akartuna, Ilke; Tervoort, Elena; Studart, André R; Gauckler, Ludwig J

2009-11-03

Semipermeable, hollow capsules are attractive materials for the encapsulation and delivery of active agents in food processing, pharmaceutical and agricultural industries, and biomedicine. These capsules can be produced by forming a solid shell of close packed colloidal particles, typically polymeric particles, at the surface of emulsion droplets. However, current methods to prepare such capsules may involve multistep chemical procedures to tailor the surface chemistry of particles or are limited to particles that exhibit inherently the right hydrophobic-hydrophilic balance to adsorb around emulsion droplets. In this work, we describe a general and simple method to fabricate semipermeable, inorganic capsules from emulsion droplets stabilized by a wide variety of colloidal metal oxide particles. The assembly of particles at the oil-water interface is induced by the in situ hydrophobization of the particle surface through the adsorption of short amphiphilic molecules. The adsorption of particles at the interface leads to stable capsules comprising a single layer of particles in the outer shell. Such capsules can be used in the wet state or can be further processed into dry capsules. The permeability of the capsules can be modified by filling the interstices between the shell particles with polymeric or inorganic species. Functional capsules with biocompatible, bioresorbable, heat-resistant, chemical-resistant, and magnetic properties were prepared using alumina, silica, iron oxide, or tricalcium phosphate as particles in the shell.

21 CFR 520.260 - n-Butyl chloride capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false n-Butyl chloride capsules. 520.260 Section 520.260... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.260 n-Butyl chloride capsules. (a)(1) Specifications. n-Butyl chloride capsules, veterinary contain 272 milligrams or 816 milligrams...

IRRADIATION-CAPSULE STUDY OF URANIUM MONOCARBIDE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, R.B.; Stahl, D.; Stang, J.H.

1960-03-01

Small cylindrical specimens of enriched UC were irradiated to evaluate usefulness as a high-temperature fuel for stationary power reactors. Detailed thermal and nuclear analyses were made to arrive at an appropriate capsule design on the basis of target specimen center-line temperature ( approximately 1500 deg F), specimen surface temperature (1100 deg F), specimen composition (U--5 wt.% C), and acapsule o.d. of 1.125 in. Temperature data from thermocouples inside the capsule indicated that five of the six capsules irradiated operated at close to the design conditions. Irradiation periods for individual capsules were varied to give burnups ranging from 1,000 to 20,000more » Mwd/t of U. Preliminary evidence indicates that this range of burnups was achieved. By using temperature and heat-flux data from the actual irradiations to estimate effective in-pile specimen thermal conductivities, it was found that the conductivity did not appear to vary during the exposures. (auth)« less

[Improvement of Digital Capsule Endoscopy System and Image Interpolation].

PubMed

Zhao, Shaopeng; Yan, Guozheng; Liu, Gang; Kuang, Shuai

2016-01-01

Traditional capsule image collects and transmits analog image, with weak anti-interference ability, low frame rate, low resolution. This paper presents a new digital image capsule, which collects and transmits digital image, with frame rate up to 30 frames/sec and pixels resolution of 400 x 400. The image is compressed in the capsule, and is transmitted to the outside of the capsule for decompression and interpolation. A new type of interpolation algorithm is proposed, which is based on the relationship between the image planes, to obtain higher quality colour images. capsule endoscopy, digital image, SCCB protocol, image interpolation

Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung.

PubMed

Sava, Parid; Ramanathan, Anand; Dobronyi, Amelia; Peng, Xueyan; Sun, Huanxing; Ledesma-Mendoza, Adrian; Herzog, Erica L; Gonzalez, Anjelica L

2017-12-21

Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology characterized by a compositionally and mechanically altered extracellular matrix. Poor understanding of the origin of α-smooth muscle actin (α-SMA) expressing myofibroblasts has hindered curative therapies. Though proposed as a source of myofibroblasts in mammalian tissues, identification of microvascular pericytes (PC) as contributors to α-SMA-expressing populations in human IPF and the mechanisms driving this accumulation remain unexplored. Here, we demonstrate enhanced detection of α-SMA+ cells coexpressing the PC marker neural/glial antigen 2 in the human IPF lung. Isolated human PC cultured on decellularized IPF lung matrices adopt expression of α-SMA, demonstrating that these cells undergo phenotypic transition in response to direct contact with the extracellular matrix (ECM) of the fibrotic human lung. Using potentially novel human lung-conjugated hydrogels with tunable mechanical properties, we decoupled PC responses to matrix composition and stiffness to show that α-SMA+ PC accumulate in a mechanosensitive manner independent of matrix composition. PC activated with TGF-β1 remodel the normal lung matrix, increasing tissue stiffness to facilitate the emergence of α-SMA+ PC via MKL-1/MTRFA mechanotranduction. Nintedanib, a tyrosine-kinase inhibitor approved for IPF treatment, restores the elastic modulus of fibrotic lung matrices to reverse the α-SMA+ phenotype. This work furthers our understanding of the role that microvascular PC play in the evolution of IPF, describes the creation of an ex vivo platform that advances the study of fibrosis, and presents a potentially novel mode of action for a commonly used antifibrotic therapy that has great relevance for human disease.

Progenitors of Secondary Crest Myofibroblasts are Developmentally Committed in Early Lung Mesoderm

PubMed Central

Li, Changgong; Li, Min; Li, Sha; Xing, Yiming; Yang, Chang-Yo; Li, Aimin; Borok, Zea; De Langhe, Stijn; Minoo, Parviz

2015-01-01

Development of the mammalian lung is predicated on cross-communications between two highly interactive tissues, the endodermally-derived epithelium and the mesodermally-derived pulmonary mesenchyme. While much attention has been paid the lung epithelium, the pulmonary mesenchyme, partly due to lack of specific tractable markers remains under-investigated. The lung mesenchyme is derived from the lateral plate mesoderm and is the principal recipient of Hedgehog (Hh) signaling, a morphogenetic network that regulates multiple aspects of embryonic development. Using the Hh-responsive Gli1-creERT2 mouse line, we identified the mesodermal targets of Hh signaling at various time points during embryonic and postnatal lung development. Cell lineage analysis showed these cells serve as progenitors to contribute to multiple lineages of mesodermally-derived differentiated cell types that include parenchymal or interstitial myofibroblasts, parabronchial and perivascular smooth muscle as well as rare populations of cells within the mesothelium. Most importantly, Gli1-creERT2 identified the progenitors of secondary crest myofibroblasts, a hitherto intractable cell type that plays a key role in alveolar formation, a vital process about which little is currently known. Transcriptome analysis of Hh-targeted progenitor cells transitioning from the pseudoglandular to the saccular phase of lung development revealed important modulations of key signaling pathways. Amongst these, there was significant down-regulation of canonical WNT signaling. Ectopic stabilization of β-Catenin via inactivation of Apc by Gli1-creERT2 expanded the Hh-targeted progenitor pools, which caused the formation of fibroblastic masses within the lung parenchyma. The Gli1-creERT2 mouse line represents a novel tool in the analysis of mesenchymal cell biology and alveolar formation during lung development. PMID:25448080

Video capsule endoscopy: Perspectives of a revolutionary technique

PubMed Central

Bouchard, Simon; Ibrahim, Mostafa; Van Gossum, Andre

2014-01-01

Video capsule endoscopy (VCE) was launched in 2000 and has revolutionized direct endoscopic imaging of the gut. VCE is now a first-line procedure for exploring the small bowel in cases of obscure digestive bleeding and is also indicated in some patients with Crohn’s disease, celiac disease, and polyposis syndrome. A video capsule has also been designed for visualizing the esophagus in order to detect Barrett’s esophagus or esophageal varices. Different capsules are now available and differ with regard to dimensions, image acquisition rate, battery life, field of view, and possible optical enhancements. More recently, the use of VCE has been extended to exploring the colon. Within the last 5 years, tremendous developments have been made toward increasing the capabilities of the colon capsule. Although colon capsule cannot be proposed as a first-line colorectal cancer screening procedure, colon capsule may be used in patients with incomplete colonoscopy or in patients who are unwilling to undergo colonoscopy. In the near future, new technological developments will improve the diagnostic yield of VCE and broaden its therapeutic capabilities. PMID:25516644

A multicenter, prospective, randomized comparison of a novel signal transmission capsule endoscope to an existing capsule endoscope.

PubMed

Choi, Eric H; Mergener, Klaus; Semrad, Carol; Fisher, Laurel; Cave, David R; Dodig, Milan; Burke, Carol; Leighton, Jonathan A; Kastenberg, David; Simpson, Peter; Sul, James; Bhattacharya, Kanishka; Charles, Roger; Gerson, Lauren; Weber, Luke; Eisen, Glenn; Reidel, Warren; Vargo, John J; Wakim-Fleming, Jamile; Lo, Simon K

2013-08-01

MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission. To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB). Prospective, multicenter, comparative study. Six academic hospitals. A total of 105 patients with OGIB. Patients ingested both the MC and PC capsules sequentially in a randomized fashion. Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination. Data analysis resulted in 43 (48%) "abnormal" cases identifying a source of OGIB by either capsule. Twenty-four cases (55.8%) were positive by both capsules. There was negative agreement in 46 of 58 cases (79.3%). The κ index was 0.547 (χ(2) = 1.32; P = .36). In 12 cases, MC positively identified a source that was not seen on PC, whereas in 7 cases, PC positively identified a source that was not seen on MC. MC had a 5.6% higher rate of detecting small-bowel lesions (P = .54). MC captured images at 3 frames per second for 11.1 hours, and PC captured images at 2 frames per second for 7.8 hours (P < .0001). Complete small-bowel examination was achieved in 93.3% for MC and 84.3% for PC (P = .10). Readers were not blinded to the particular capsule they were reading. A positive diagnostic finding for OGIB was identified by either capsule in 48% of cases. The concordance rate between the 2 capsules was comparable to that of prior studies in identifying sources of small-bowel bleeding. The longer operational time of the MC may result in higher rates of complete small-bowel examination, which may, in turn, translate into a higher rate of detecting small-bowel lesions. ( NCT00878982.). Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Effects of whole-body cryotherapy in the management of adhesive capsulitis of the shoulder.

PubMed

Ma, Sang-Yeol; Je, Hyun Dong; Jeong, Ji Hoon; Kim, Hae-Young; Kim, Hyeong-Dong

2013-01-01

To compare 2 different treatment approaches, physical therapy modalities, and joint mobilization versus whole-body cryotherapy (WBC) combined with physical therapy modalities and joint mobilization, for symptoms of adhesive capsulitis (AC) of the shoulder. A randomized trial. Hospital. Patients with AC of the shoulder (N=30). Patients were randomly assigned to 2 groups. The WBC group received physical therapy modalities, passive joint mobilization of the shoulder, and WBC, whereas the non-WBC group received only physical therapy modalities and passive joint mobilization of the shoulder. Visual analog scale (VAS), active range of motion (ROM) of flexion, abduction, internal and external rotation of the shoulder, and the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) were measured before and after the intervention. A statistically significant difference between groups was found for the VAS, active ROM of flexion, abduction, internal rotation, and external rotation, and the ASES with greater improvements in the WBC group (Ps<.01). Overall, both groups showed a significant improvement in all outcome measures and ROM measures from pre to post at a level of P<.01. There is significant improvement with the addition of WBC to treatment interventions in this sample of patients. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Analysis of Fission Products on the AGR-1 Capsule Components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paul A. Demkowicz; Jason M. Harp; Philip L. Winston

2013-03-01

The components of the AGR-1 irradiation capsules were analyzed to determine the retained inventory of fission products in order to determine the extent of in-pile fission product release from the fuel compacts. This includes analysis of (i) the metal capsule components, (ii) the graphite fuel holders, (iii) the graphite spacers, and (iv) the gas exit lines. The fission products most prevalent in the components were Ag-110m, Cs 134, Cs 137, Eu-154, and Sr 90, and the most common location was the metal capsule components and the graphite fuel holders. Gamma scanning of the graphite fuel holders was also performed tomore » determine spatial distribution of Ag-110m and radiocesium. Silver was released from the fuel components in significant fractions. The total Ag-110m inventory found in the capsules ranged from 1.2×10 2 (Capsule 3) to 3.8×10 1 (Capsule 6). Ag-110m was not distributed evenly in the graphite fuel holders, but tended to concentrate at the axial ends of the graphite holders in Capsules 1 and 6 (located at the top and bottom of the test train) and near the axial center in Capsules 2, 3, and 5 (in the center of the test train). The Ag-110m further tended to be concentrated around fuel stacks 1 and 3, the two stacks facing the ATR reactor core and location of higher burnup, neutron fluence, and temperatures compared with Stack 2. Detailed correlation of silver release with fuel type and irradiation temperatures is problematic at the capsule level due to the large range of temperatures experienced by individual fuel compacts in each capsule. A comprehensive Ag 110m mass balance for the capsules was performed using measured inventories of individual compacts and the inventory on the capsule components. For most capsules, the mass balance was within 11% of the predicted inventory. The Ag-110m release from individual compacts often exhibited a very large range within a particular capsule.« less

Capsule endoscope localization based on computer vision technique.

PubMed

Liu, Li; Hu, Chao; Cai, Wentao; Meng, Max Q H

2009-01-01

To build a new type of wireless capsule endoscope with interactive gastrointestinal tract examination, a localization and orientation system is needed for tracking 3D location and 3D orientation of the capsule movement. The magnetic localization and orientation method produces only 5 DOF, but misses the information of rotation angle along capsule's main axis. In this paper, we presented a complementary orientation approach for the capsule endoscope, and the 3D rotation can be determined by applying computer vision technique on the captured endoscopic images. The experimental results show that the complementary orientation method has good accuracy and high feasibility.

Performance evaluation of wireless communications through capsule endoscope.

PubMed

Takizawa, Kenichi; Aoyagi, Takahiro; Hamaguchi, Kiyoshi; Kohno, Ryuji

2009-01-01

This paper presents a performance evaluation of wireless communications applicable into a capsule endoscope. A numerical model to describe the received signal strength (RSS) radiated from a capsule-sized signal generator is derived through measurements in which a liquid phantom that has equivalent electrical constants is used. By introducing this model and taking into account the characteristics of its direction pattern of the capsule and propagation distance between the implanted capsule and on-body antenna, a cumulative distribution function (CDF) of the received SNR is evaluated. Then, simulation results related to the error ratio in the wireless channel are obtained. These results show that the frequencies of 611 MHz or lesser would be useful for the capsule endoscope applications from the view point of error rate performance. Further, we show that the use of antenna diversity brings additional gain to this application.

Wilms' tumor 1 (Wt1) regulates pleural mesothelial cell plasticity and transition into myofibroblasts in idiopathic pulmonary fibrosis

PubMed Central

Karki, Suman; Surolia, Ranu; Hock, Thomas David; Guroji, Purusotham; Zolak, Jason S.; Duggal, Ryan; Ye, Tong; Thannickal, Victor J.; Antony, Veena B.

2014-01-01

Pleural mesothelial cells (PMCs), which are derived from the mesoderm, exhibit an extraordinary capacity to undergo phenotypic changes during development and disease. PMC transformation and trafficking has a newly defined role in idiopathic pulmonary fibrosis (IPF); however, the contribution of Wilms' tumor 1 (Wt1)-positive PMCs to the generation of pathognomonic myofibroblasts remains unclear. PMCs were obtained from IPF lung explants and healthy donor lungs that were not used for transplantation. Short hairpin Wt1-knockdown PMCs (sh Wt1) were generated with Wt1 shRNA, and morphologic and functional assays were performed in vitro. Loss of Wt1 abrogated the PMC phenotype and showed evidence of mesothelial-to-mesenchymal transition (MMT), with a reduced expression of E-cadherin and an increase in the profibrotic markers α-smooth muscle actin (α-SMA) and fibronectin, along with increased migration and contractility, compared with that of the control. Migration of PMCs in response to active transforming growth factor (TGF)-β1 was assessed by live-cell imaging with 2-photon microscopy and 3D imaging, of Wt1-EGFP transgenic mice. Lineage-tracing experiments to map the fate of Wt1+ PMCs in mouse lung in response to TGF-β1 were also performed by using a Cre-loxP system. Our results, for the first time, demonstrate that Wt1 is necessary for the morphologic integrity of pleural membrane and that loss of Wt1 contributes to IPF via MMT of PMCs into a myofibroblast phenotype.—Karki, S., Surolia, R., Hock, T. D., Guroji, P., Zolak, J. S., Duggal, R., Ye, T., Thannickal, V., J., Antony, V. B. Wilms' tumor 1 (Wt1) regulates pleural mesothelial cell plasticity and transition into myofibroblasts in idiopathic pulmonary fibrosis. PMID:24265486

Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells.

PubMed

Kastl, Lena; Sasse, Daniel; Wulf, Verena; Hartmann, Raimo; Mircheski, Josif; Ranke, Christiane; Carregal-Romero, Susana; Martínez-López, José Antonio; Fernández-Chacón, Rafael; Parak, Wolfgang J; Elsasser, Hans-Peter; Rivera Gil, Pilar

2013-08-27

Polyelectrolyte multilayer (PEM) capsules are carrier vehicles with great potential for biomedical applications. With the future aim of designing biocompatible, effective therapeutic delivery systems (e.g., for cancer), the pathway of internalization (uptake and fate) of PEM capsules was investigated. In particular the following experiments were performed: (i) the study of capsule co-localization with established endocytic markers, (ii) switching-off endocytotic pathways with pharmaceutical/chemical inhibitors, and (iii) characterization and quantification of capsule uptake with confocal and electron microscopy. As result, capsules co-localized with lipid rafts and with phagolysosomes, but not with other endocytic vesicles. Chemical interference of endocytosis with chemical blockers indicated that PEM capsules enter the investigated cell lines through a mechanism slightly sensitive to electrostatic interactions, independent of clathrin and caveolae, and strongly dependent on cholesterol-rich domains and organelle acidification. Microscopic characterization of cells during capsule uptake showed the formation of phagocytic cups (vesicles) to engulf the capsules, an increased number of mitochondria, and a final localization in the perinuclear cytoplasma. Combining all these indicators we conclude that PEM capsule internalization in general occurs as a combination of different sequential mechanisms. Initially, an adsorptive mechanism due to strong electrostatic interactions governs the stabilization of the capsules at the cell surface. Membrane ruffling and filopodia extensions are responsible for capsule engulfing through the formation of a phagocytic cup. Co-localization with lipid raft domains activates the cell to initiate a lipid-raft-mediated macropinocytosis. Internalization vesicles are very acidic and co-localize only with phagolysosome markers, excluding caveolin-mediated pathways and indicating that upon phagocytosis the capsules are sorted to

A wireless narrowband imaging chip for capsule endoscope.

PubMed

Lan-Rong Dung; Yin-Yi Wu

2010-12-01

This paper presents a dual-mode capsule gastrointestinal endoscope device. An endoscope combined with a narrowband image (NBI), has been shown to be a superior diagnostic tool for early stage tissue neoplasms detection. Nevertheless, a wireless capsule endoscope with the narrowband imaging technology has not been presented in the market up to now. The narrowband image acquisition and power dissipation reduction are the main challenges of NBI capsule endoscope. In this paper, we present the first narrowband imaging capsule endoscope that can assist clinical doctors to effectively diagnose early gastrointestinal cancers, profited from our dedicated dual-mode complementary metal-oxide semiconductor (CMOS) sensor. The dedicated dual-mode CMOS sensor can offer white-light and narrowband images. Implementation results show that the proposed 512 × 512 CMOS sensor consumes only 2 mA at a 3-V power supply. The average current of the NBI capsule with an 8-Mb/s RF transmitter is nearly 7 ~ 8 mA that can continuously work for 6 ~ 8 h with two 1.5-V 80-mAh button batteries while the frame rate is 2 fps. Experimental results on backside mucosa of a human tongue and pig's small intestine showed that the wireless NBI capsule endoscope can significantly improve the image quality, compared with a commercial-of-the-shelf capsule endoscope for gastrointestinal tract diagnosis.

Positron radiography of ignition-relevant ICF capsules

DOE PAGES

Williams, G. J.; Chen, Hui; Field, J. E.; ...

2017-12-11

Laser-generated positrons are evaluated as a probe source to radiograph in-flight ignition-relevant inertial confinement fusion capsules. Current ultraintense laser facilities are capable of producing 2 ×10 12 relativistic positrons in a narrow energy bandwidth and short time duration. Monte Carlo simulations suggest that the unique characteristics of such positrons allow for the reconstruction of both capsule shell radius and areal density between 0.002 and 2g/cm 2. The energy-downshifted positron spectrum and angular scattering of the source particles are sufficient to constrain the conditions of the capsule between preshot and stagnation. Here, we evaluate the effects of magnetic fields near themore » capsule surface using analytic estimates where it is shown that this diagnostic can tolerate line integrated field strengths of 100 T mm.« less

Positron radiography of ignition-relevant ICF capsules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, G. J.; Chen, Hui; Field, J. E.

Laser-generated positrons are evaluated as a probe source to radiograph in-flight ignition-relevant inertial confinement fusion capsules. Current ultraintense laser facilities are capable of producing 2 ×10 12 relativistic positrons in a narrow energy bandwidth and short time duration. Monte Carlo simulations suggest that the unique characteristics of such positrons allow for the reconstruction of both capsule shell radius and areal density between 0.002 and 2g/cm 2. The energy-downshifted positron spectrum and angular scattering of the source particles are sufficient to constrain the conditions of the capsule between preshot and stagnation. Here, we evaluate the effects of magnetic fields near themore » capsule surface using analytic estimates where it is shown that this diagnostic can tolerate line integrated field strengths of 100 T mm.« less

Positron radiography of ignition-relevant ICF capsules

NASA Astrophysics Data System (ADS)

Williams, G. J.; Chen, Hui; Field, J. E.; Landen, O. L.; Strozzi, D. J.

2017-12-01

Laser-generated positrons are evaluated as a probe source to radiograph in-flight ignition-relevant inertial confinement fusion capsules. Current ultraintense laser facilities are capable of producing 2 × 1012 relativistic positrons in a narrow energy bandwidth and short time duration. Monte Carlo simulations suggest that the unique characteristics of such positrons allow for the reconstruction of both capsule shell radius and areal density between 0.002 and 2 g/cm2. The energy-downshifted positron spectrum and angular scattering of the source particles are sufficient to constrain the conditions of the capsule between preshot and stagnation. We evaluate the effects of magnetic fields near the capsule surface using analytic estimates where it is shown that this diagnostic can tolerate line integrated field strengths of 100 T mm.

Uterine inflammatory myofibroblastic tumor: more common than expected

PubMed Central

Mandato, Vincenzo Dario; Valli, Riccardo; Mastrofilippo, Valentina; Bisagni, Alessandra; Aguzzoli, Lorenzo; La Sala, Giovanni Battista

2017-01-01

Abstract Rationale: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm composed of spindled to epithelioid cells with prominent myxoid stroma and inflammatory infiltrate. It has a low but definite malignant potential. However, its management has never been standardized. Patient Concerns and Diagnosis: We present the first case of uterine IMT laparoscopically treated. Moreover, we reviewed the English literature regarding uterine IMT published between 1987 and June 2017. A total of 72 cases of uterine IMT were included. Clinical and pathological characteristics, treatments and outcomes were recorded. Interventions and Outcomes: A total laparoscopic hysterectomy with opportunistic bilateral salpingectomy was performed. Patient is free of disease at 6 months of follow-up. Lessons: Uterine IMT may be identified by anaplastic lymphoma kinase overexpression, its prognosis is usually good, complete excision seems to be effective to avoid relapse and mini invasive surgery seems to be effective and safe to treat uterine IMT. However, considering the age of women affected by disease, conservative management, or medical therapy could be taken in account to avoid surgical injuries and to preserve fertility. PMID:29310405

Capsule-odometer: a concept to improve accurate lesion localisation.

PubMed

Karargyris, Alexandros; Koulaouzidis, Anastasios

2013-09-21

In order to improve lesion localisation in small-bowel capsule endoscopy, a modified capsule design has been proposed incorporating localisation and - in theory - stabilization capabilities. The proposed design consists of a capsule fitted with protruding wheels attached to a spring-mechanism. This would act as a miniature odometer, leading to more accurate lesion localization information in relation to the onset of the investigation (spring expansion e.g., pyloric opening). Furthermore, this capsule could allow stabilization of the recorded video as any erratic, non-forward movement through the gut is minimised. Three-dimensional (3-D) printing technology was used to build a capsule prototype. Thereafter, miniature wheels were also 3-D printed and mounted on a spring which was attached to conventional capsule endoscopes for the purpose of this proof-of-concept experiment. In vitro and ex vivo experiments with porcine small-bowel are presented herein. Further experiments have been scheduled.

Wireless communication link for capsule endoscope at 600 MHz.

PubMed

Khaleghi, A; Balasingham, I

2015-01-01

Simulation of a wireless communication link for a capsule endoscopy is presented for monitoring of small intestine in humans. The realized communication link includes the transmitting capsule antenna, the outside body receiving antenna and the model of the human body. The capsule antenna is designed for operating at the frequency band of 600 MHz with an impedance bandwidth of 10 MHz and omnidirectional radiation pattern. The quality of the communication link is improved by using directive antenna outside body inside matching layer for electromagnetic wave tuning to the body. The outside body antenna has circular polarization that guaranteeing the communication link for different orientations of the capsule inside intestine. It is shown that the path loss for the capsule in 60 mm from the abdomen surface varies between 37-47 dB in relation to the antenna orientation. This link can establish high data rate wireless communications for capsule endoscopy.

Primate lens capsule elasticity assessed using Atomic Force Microscopy

PubMed Central

Ziebarth, Noël M.; Arrieta, Esdras; Feuer, William J.; Moy, Vincent T.; Manns, Fabrice; Parel, Jean-Marie

2011-01-01

The purpose of this project is to measure the elasticity of the human and non-human primate lens capsule at the microscopic scale using Atomic Force Microscopy (AFM). Elasticity measurements were performed using AFM on the excised anterior lens capsule from 9 cynomolgus monkey (5.9–8.0 years), 8 hamadryas baboon (2.8–10.1 years), and 18 human lenses (33–79 years). Anterior capsule specimens were obtained by performing a 5mm continuous curvilinear capsulorhexis and collecting the resulting disk of capsular tissue. To remove the lens epithelial cells the specimen was soaked in 0.1% trypsin and 0.02% EDTA for five minutes, washed, and placed on a Petri dish and immersed in DMEM. Elasticity measurements of the capsule were performed with a laboratory-built AFM system custom designed for force measurements of ophthalmic tissues. The capsular specimens were probed with an AFM cantilever tip to produce force-indentation curves for each specimen. Young’s modulus was calculated from the force-indentation curves using the model of Sneddon for a conical indenter. Young’s modulus of elasticity was 20.1–131kPa for the human lens capsule, 9.19–117kPa for the cynomolgus lens capsule, and 13.1–62.4kPa for the baboon lens capsule. Young’s modulus increased significantly with age in humans (p=0.03). The age range of the monkey and baboon samples was not sufficient to justify an analysis of age dependence. The capsule elasticity of young humans (<45 years) was not statistically different from that of the monkey and baboon. In humans, there is an increase in lens capsule stiffness at the microscale that could be responsible for an increase in lens capsule bulk stiffness. PMID:21420953

Closeup View - Sigma "7" Capsule - Recovery Ship

NASA Image and Video Library

1962-10-03

S62-06175 (3 Oct. 1962) --- Closeup view of the Mercury-Atlas 8 (MA-8) Sigma 7 capsule being lowered to recovery ship's deck. Navy personnel remove the floatation device before opening the capsule. Photo credit: NASA

Capsule endoscopy: Current practice and future directions

PubMed Central

Hale, Melissa F; Sidhu, Reena; McAlindon, Mark E

2014-01-01

Capsule endoscopy (CE) has transformed investigation of the small bowel providing a non-invasive, well tolerated means of accurately visualising the distal duodenum, jejunum and ileum. Since the introduction of small bowel CE thirteen years ago a high volume of literature on indications, diagnostic yields and safety profile has been presented. Inclusion in national and international guidelines has placed small bowel capsule endoscopy at the forefront of investigation into suspected diseases of the small bowel. Most commonly, small bowel CE is used in patients with suspected bleeding or to identify evidence of active Crohn’s disease (CD) (in patients with or without a prior history of CD). Typically, CE is undertaken after upper and lower gastrointestinal flexible endoscopy has failed to identify a diagnosis. Small bowel radiology or a patency capsule test should be considered prior to CE in those at high risk of strictures (such as patients known to have CD or presenting with obstructive symptoms) to reduce the risk of capsule retention. CE also has a role in patients with coeliac disease, suspected small bowel tumours and other small bowel disorders. Since the advent of small bowel CE, dedicated oesophageal and colon capsule endoscopes have expanded the fields of application to include the investigation of upper and lower gastrointestinal disorders. Oesophageal CE may be used to diagnose oesophagitis, Barrett’s oesophagus and varices but reliability in identifying gastroduodenal pathology is unknown and it does not have biopsy capability. Colon CE provides an alternative to conventional colonoscopy for symptomatic patients, while a possible role in colorectal cancer screening is a fascinating prospect. Current research is already addressing the possibility of controlling capsule movement and developing capsules which allow tissue sampling and the administration of therapy. PMID:24976712

Inadvertent trypan blue posterior capsule staining during cataract surgery.

PubMed

Burkholder, Bryn M; Srikumaran, Divya; Nanji, Afshan; Lee, Bryan; Weinberg, Robert S

2013-04-01

To report 5 cases of inadvertent posterior capsule staining with trypan blue during phacoemulsification. Retrospective, observational case series. Five cases of posterior capsule staining with trypan blue were identified from cataract surgeries performed at an academic institution. All 5 eyes underwent phacoemulsification with use of iris retractors. The surgical videos from each case were reviewed to better understand the mechanisms and risk factors for posterior capsule staining with trypan blue and techniques to avoid this complication. No eyes had clinical evidence of zonular pathology during their preoperative examination. Only 1 patient reported a possible childhood history of trauma to both eyes. One eye had uveitis, requiring posterior synechialysis. All 5 cases involved the use of iris retractors. No other intraoperative complications occurred, and the intraocular lens was successfully placed in the capsular bag in all cases. All eyes had resolution of posterior capsule staining by postoperative day 8. Inadvertent posterior capsule staining with trypan blue can occur in eyes that appear structurally normal. The use of iris retractors may facilitate posterior capsule staining by allowing the posterior flow of trypan blue under the iris and through the zonules to the posterior capsule. Surgeons should consider techniques to minimize the risk of posterior capsule staining, particularly in cases involving the use of iris retractors. Copyright © 2013 Elsevier Inc. All rights reserved.

Aspiration of capsule endoscope and successful bronchoscopic extraction.

PubMed

Girdhar, Ankur; Usman, Faisal; Bajwa, Abubakr

2012-10-01

Capsule endoscopy is a novel tool for the diagnosis of small intestinal disorders. Recently, a new complication of the procedure in the form of the capsule's aspiration into the lungs has been reported. The aspiration of capsule endoscope can lead to a variety of complications including respiratory failure. A low threshold to suspect this complication and urgent bronchoscopic extraction in appropriate patients can prevent serious sequelae.

Bronchial Aspiration of Capsule Endoscope.

PubMed

Buscot, Matthieu; Leroy, Sylvie; Pradelli, Johanna; Chaabane, Nouha; Hebuterne, Xavier; Marquette, Charles-Hugo; Filippi, Jerôme

2017-01-01

Capsule endoscope aspiration is an increasingly reported complication, potentially responsible for respiratory distress and asphyxia. This adverse event is primarily managed by rigid bronchoscopy when spontaneous expulsion does not occur. This complication is all the more detrimental to patients as it can delay or jeopardize further digestive exploration. We report direct repositioning of the capsule in the stomach at the same time as bronchoscopy, thus making second-line gastrointestinal endoscopy needless. © 2017 S. Karger AG, Basel.

Low intensity 635 nm diode laser irradiation inhibits fibroblast-myofibroblast transition reducing TRPC1 channel expression/activity: New perspectives for tissue fibrosis treatment.

PubMed

Sassoli, Chiara; Chellini, Flaminia; Squecco, Roberta; Tani, Alessia; Idrizaj, Eglantina; Nosi, Daniele; Giannelli, Marco; Zecchi-Orlandini, Sandra

2016-03-01

Low-level laser therapy (LLLT) or photobiomodulation therapy is emerging as a promising new therapeutic option for fibrosis in different damaged and/or diseased organs. However, the anti-fibrotic potential of this treatment needs to be elucidated and the cellular and molecular targets of the laser clarified. Here, we investigated the effects of a low intensity 635 ± 5 nm diode laser irradiation on fibroblast-myofibroblast transition, a key event in the onset of fibrosis, and elucidated some of the underlying molecular mechanisms. NIH/3T3 fibroblasts were cultured in a low serum medium in the presence of transforming growth factor (TGF)-β1 and irradiated with a 635 ± 5 nm diode laser (continuous wave, 89 mW, 0.3 J/cm(2) ). Fibroblast-myofibroblast differentiation was assayed by morphological, biochemical, and electrophysiological approaches. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 and of Tissue inhibitor of MMPs, namely TIMP-1 and TIMP-2, after laser exposure was also evaluated by confocal immunofluorescence analyses. Moreover, the effect of the diode laser on transient receptor potential canonical channel (TRPC) 1/stretch-activated channel (SAC) expression and activity and on TGF-β1/Smad3 signaling was investigated. Diode laser treatment inhibited TGF-β1-induced fibroblast-myofibroblast transition as judged by reduction of stress fibers formation, α-smooth muscle actin (sma) and type-1 collagen expression and by changes in electrophysiological properties such as resting membrane potential, cell capacitance and inwardly rectifying K(+) currents. In addition, the irradiation up-regulated the expression of MMP-2 and MMP-9 and downregulated that of TIMP-1 and TIMP-2 in TGF-β1-treated cells. This laser effect was shown to involve TRPC1/SAC channel functionality. Finally, diode laser stimulation and TRPC1 functionality negatively affected fibroblast-myofibroblast transition by interfering with TGF-β1 signaling, namely reducing the

Therapeutic Application of Phage Capsule Depolymerases against K1, K5, and K30 Capsulated E. coli in Mice.

PubMed

Lin, Han; Paff, Matthew L; Molineux, Ian J; Bull, James J

2017-01-01

Capsule depolymerase enzymes offer a promising class of new antibiotics. In vivo studies are encouraging but it is unclear how well this type of phage product will generalize in therapeutics, or whether different depolymerases against the same capsule function similarly. Here, in vivo efficacy was tested using cloned bacteriophage depolymerases against Escherichia coli strains with three different capsule types: K1, K5, and K30. When treating infections with the cognate capsule type in a mouse thigh model, the previously studied K1E depolymerase rescued poorly, whereas K1F, K1H, K5, and K30 depolymerases rescued well. K30 gp41 was identified as the catalytically active protein. In contrast to the in vivo studies, K1E enzyme actively degraded K1 capsule polysaccharide in vitro and sensitized K1 bacteria to serum killing. The only in vitro correlate of poor K1E performance in vivo was that the purified enzyme did not form the expected trimer. K1E appeared as an 18-mer which might limit its in vivo distribution. Overall, depolymerases were easily identified, cloned from phage genomes, and as purified proteins they proved generally effective.

Lung fibrosis-associated soluble mediators and bronchoalveolar lavage from idiopathic pulmonary fibrosis patients promote the expression of fibrogenic factors in subepithelial lung myofibroblasts.

PubMed

Bouros, Evangelos; Filidou, Eirini; Arvanitidis, Konstantinos; Mikroulis, Dimitrios; Steiropoulos, Paschalis; Bamias, George; Bouros, Demosthenes; Kolios, George

2017-10-01

Idiopathic pulmonary fibrosis (IPF) is characterized by infiltration of inflammatory cells, excessive collagen production and accumulation of myofibroblasts. We explored the possible role of subepithelial lung myofibroblasts (SELMs) in the development of fibrosis in IPF. SELMs, isolated from surgical specimens of healthy lung tissue, were cultured with pro-inflammatory factors or bronchoalveolar lavage fluid (BALF) from patients with IPF or idiopathic non-specific interstitial pneumonia (iNSIP) and their fibrotic activity was assessed. Stimulation of SELMs with pro-inflammatory factors induced a significant increase of Tissue Factor (TF) and Tumor necrosis factor-Like cytokine 1 A (TL1A) expression and collagen production in culture supernatants. Stimulation with BALF from IPF patients with mild to moderate, but not severe disease, and from iNSIP patients induced a significant increase of TF expression. BALF from all IPF patients induced a significant increase of TL1A expression and collagen production, while BALF from iNSIP patients induced a significant increase of TL1A, but not of collagen production. Interestingly, TGF-β1 and BALF from all IPF, but not iNSIP patients, induced a significant increase in SELMs migration. In conclusion, BALF from IPF patients induces fibrotic activity in lung myofibroblasts, similar to mediators associated with lung fibrosis, indicating a key role of SELMs in IPF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epithelioid inflammatory myofibroblastic sarcoma responsive to surgery and an ALK inhibitor in a patient with panhypopituitarism.

PubMed

Kurihara-Hosokawa, Kotomi; Kawasaki, Isao; Tamai, Anna; Yoshida, Yoko; Yakushiji, Yosuke; Ueno, Hiroki; Fukumoto, Mariko; Fukushima, Hiroko; Inoue, Takeshi; Hosoi, Masayuki

2014-01-01

We encountered a case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) originating from an abdominal organ that rapidly regrew twice. The patient underwent two surgeries. Large tumors grew within three months after the second surgery. The patient subsequently received chemotherapy with an anaplastic lymphoma kinase (ALK) inhibitor. Although EIMS has a poor prognosis, the patient continues to be alive with disease 14 months after surgical treatment and the administration of the ALK inhibitor.

Spheroidal and conical shapes of ferrofluid-filled capsules in magnetic fields

NASA Astrophysics Data System (ADS)

Wischnewski, Christian; Kierfeld, Jan

2018-04-01

We investigate the deformation of soft spherical elastic capsules filled with a ferrofluid in external uniform magnetic fields at fixed volume by a combination of numerical and analytical approaches. We develop a numerical iterative solution strategy based on nonlinear elastic shape equations to calculate the stretched capsule shape numerically and a coupled finite element and boundary element method to solve the corresponding magnetostatic problem and employ analytical linear response theory, approximative energy minimization, and slender-body theory. The observed deformation behavior is qualitatively similar to the deformation of ferrofluid droplets in uniform magnetic fields. Homogeneous magnetic fields elongate the capsule and a discontinuous shape transition from a spheroidal shape to a conical shape takes place at a critical field strength. We investigate how capsule elasticity modifies this hysteretic shape transition. We show that conical capsule shapes are possible but involve diverging stretch factors at the tips, which gives rise to rupture for real capsule materials. In a slender-body approximation we find that the critical susceptibility above which conical shapes occur for ferrofluid capsules is the same as for droplets. At small fields capsules remain spheroidal and we characterize the deformation of spheroidal capsules both analytically and numerically. Finally, we determine whether wrinkling of a spheroidal capsule occurs during elongation in a magnetic field and how it modifies the stretching behavior. We find the nontrivial dependence between the extent of the wrinkled region and capsule elongation. Our results can be helpful in quantitatively determining capsule or ferrofluid material properties from magnetic deformation experiments. All results also apply to elastic capsules filled with a dielectric liquid in an external uniform electric field.

The transport of wear particles in the prosthetic hip joint: a computational fluid dynamics investigation.

PubMed

Hölzer, Andreas; Schröder, Christian; Woiczinski, Matthias; Sadoghi, Patrick; Müller, Peter E; Jansson, Volkmar

2012-02-02

The joint fluid mechanics and transport of wear particles in the prosthetic hip joint were analyzed for subluxation and flexion motion using computational fluid dynamics (CFD). The entire joint space including a moving capsule boundary was considered. It was found that particles suspended in the joint space are drawn into the joint gap between prosthesis cup and head during subluxation, which was also documented by Lundberg et al. (2007; Journal of Biomechanics 40, 1676-1685), however, wear particles remain in the joint gap. Wear particles leave the joint gap during flexion and can finally migrate to the proximal boundaries including the acetabular bone, where the particle deposition can cause osteolysis according to the established literature. Thus, the present study supports the theory of polyethylene wear particle induced osteolysis of the acetabular bone as a major factor in the loosening of hip prosthesis cups. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of three-layered rumen escapable capsules for cattle

PubMed Central

SEYAMA, Tomohiro; HIRAYASU, Hirofumi; YAMAWAKI, Kenji; ADACHI, Takuhiko; SUGIMOTO, Takayuki; KASAI, Koji

2016-01-01

A new rumen escapable tool is presented for cattle in prospect of developing medical treatment or supplementing trace elements for disease prevention. This tool consists of a three-layered capsule that dissolves in the lower digestive tract, but not in the rumen. The capsule was manufactured by capsule-forming techniques through the use of liquid surface tension. This method does not involve high-temperature treatment, so the capsule can contain not only lipophilic substances but also hydrophilic or heat-sensitive substances. Furthermore, the capsule has a specific gravity of 1.3 and diameter of 6.0 mm, which were previously shown to be appropriate to avoid rumination. The objective of this study was to confirm the effectiveness of the capsule pertinent to rumen escaping. In order to validate rumen escape, capsules containing 30 g of water-soluble vitamin (thiamine hydrochloride) per head were administered to four lactating cows assigned in a crossover trial. In the group administered encapsulated thiamine hydrochloride, blood thiamine levels increased from 12.4 ± 1.03 ng/ml before administration to 54.8 ± 2.21 ng/ml at 6 hr following administration, whereas the level remained at 13.3 ± 2.05 ng/ml in the control group administered via aqueous solution. This indicates that the three-layered capsules passed through the rumen and dissolved in the lower digestive tract, thus functioning as a rumen escapable tool. PMID:27546371

A histological study on the effect of pressure therapy on the activities of myofibroblasts and keratinocytes in hypertrophic scar tissues after burn.

PubMed

Li-Tsang, Cecilia W P; Feng, Beibei; Huang, Lin; Liu, Xusheng; Shu, Bin; Chan, Yvonne T Y; Cheung, Kwok-Kuen

2015-08-01

Although pressure therapy (PT) has been widely used as the first-line treatment for hypertrophic scars (HS), the histopathological changes involved have seldom been studied. This study aimed to examine the longitudinal effect of PT on the histopathological changes in HS. Ten scar samples were selected from six patients with HS after burn and they were given a standardized PT intervention for 3 months while 16 scar samples were obtained on those without PT. The scar biopsies were collected pre-treatment, 1 and 3 months post-intervention for both clinical and histopathological examinations. Clinical assessments demonstrated significant improvement in the thickness and redness of the scars after PT. Histological examination revealed that cell density in the dermal layer was markedly reduced in the 3-months post-pressurized scar tissues, while the arrangement of the collagen fiber was changed from nodular to wave-like pattern. The α-smooth muscle actin immunoreactivity was significantly decreased after 1-month pressure treatment. There was a significant reduction of myofibroblasts population and a concomitant increase in the apoptotic index in the dermal layer in the 3-months' post-pressurized scars. A significant negative correlation was found between the myofibroblasts population and the apoptotic index. The keratinocyte proliferation was found inhibited after PT. Results demonstrated that PT appeared to promote HS maturation by inhibiting the keratinocyte proliferation and suppressing myofibroblasts population, the latter possibly via apoptosis. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Unusual Internal Astigmatism Due to Severe Capsule Contraction Syndrome.

PubMed

Zéboulon, Pierre; Gatinel, Damien

2018-01-01

To describe a case of severe capsule contraction syndrome causing significant astigmatism due to intraocular lens (IOL) folding. Case report. Capsule fibrosis and contraction resulted in bending of the hydrophilic IOL along its long axis. Anterior Nd:YAG capsulotomy resolved the situation and restored the patient's visual acuity. Hydrophilic IOLs are more susceptible to capsule contraction due to the increased flexibility of highly hydrated materials. They should be avoided in patients at risk of capsule contraction to prevent ocular complications. [J Refract Surg. 2018;34(1):65-67.]. Copyright 2018, SLACK Incorporated.

Albumin/asparaginase capsules prepared by ultrasound to retain ammonia.

PubMed

Tinoco, Ana; Ribeiro, Artur; Oliveira, César; Parpot, Pier; Gomes, Andreia; Cavaco-Paulo, Artur

2016-11-01

Asparaginase reduces the levels of asparagine in blood, which is an essential amino acid for the proliferation of lymphoblastic malign cells. Asparaginase converts asparagine into aspartic acid and ammonia. The accumulation of ammonia in the bloodstream leads to hyperammonemia, described as one of the most significant side effects of asparaginase therapy. Therefore, there is a need for asparaginase formulations with the potential to reduce hyperammonemia. We incorporated 2 % of therapeutic enzyme in albumin-based capsules. The presence of asparaginase in the interface of bovine serum albumin (BSA) capsules showed the ability to hydrolyze the asparagine and retain the forming ammonia at the surface of the capsules. The incorporation of Poloxamer 407 in the capsule formulation further increased the ratio aspartic acid/ammonia from 1.92 to 2.46 (and 1.10 from the free enzyme), decreasing the levels of free ammonia. This capacity to retain ammonia can be due to electrostatic interactions and retention of ammonia at the surface of the capsules. The developed BSA/asparaginase capsules did not cause significant cytotoxic effect on mouse leukemic macrophage cell line RAW 264.7. The new BSA/asparaginase capsules could potentially be used in the treatment of acute lymphoblastic leukemia preventing hyperammonemia associated with acute lymphoblastic leukemia (ALL) treatment with asparaginase.

Analysing intracellular deformation of polymer capsules using structured illumination microscopy

NASA Astrophysics Data System (ADS)

Chen, Xi; Cui, Jiwei; Sun, Huanli; Müllner, Markus; Yan, Yan; Noi, Ka Fung; Ping, Yuan; Caruso, Frank

2016-06-01

Understanding the behaviour of therapeutic carriers is important in elucidating their mechanism of action and how they are processed inside cells. Herein we examine the intracellular deformation of layer-by-layer assembled polymer capsules using super-resolution structured illumination microscopy (SIM). Spherical- and cylindrical-shaped capsules were studied in three different cell lines, namely HeLa (human epithelial cell line), RAW264.7 (mouse macrophage cell line) and differentiated THP-1 (human monocyte-derived macrophage cell line). We observed that the deformation of capsules was dependent on cell line, but independent of capsule shape. This suggests that the mechanical forces, which induce capsule deformation during cell uptake, vary between cell lines, indicating that the capsules are exposed to higher mechanical forces in HeLa cells, followed by RAW264.7 and then differentiated THP-1 cells. Our study demonstrates the use of super-resolution SIM in analysing intracellular capsule deformation, offering important insights into the cellular processing of drug carriers in cells and providing fundamental knowledge of intracellular mechanobiology. Furthermore, this study may aid in the design of novel drug carriers that are sensitive to deformation for enhanced drug release properties.Understanding the behaviour of therapeutic carriers is important in elucidating their mechanism of action and how they are processed inside cells. Herein we examine the intracellular deformation of layer-by-layer assembled polymer capsules using super-resolution structured illumination microscopy (SIM). Spherical- and cylindrical-shaped capsules were studied in three different cell lines, namely HeLa (human epithelial cell line), RAW264.7 (mouse macrophage cell line) and differentiated THP-1 (human monocyte-derived macrophage cell line). We observed that the deformation of capsules was dependent on cell line, but independent of capsule shape. This suggests that the mechanical forces

The capsule of the fungal pathogen Cryptococcus neoformans

PubMed Central

Zaragoza, Oscar; Rodrigues, Marcio L.; De Jesus, Magdia; Frases, Susana; Dadachova, Ekaterina; Casadevall, Arturo

2009-01-01

The capsule of the fungal pathogen Cryptococcus neoformans has been studied extensively in recent decades, and a large body of information is now available to the scientific community. Well-known aspects of the capsule include its structure, antigenic properties and its function as a virulence factor. The capsule is composed primarily of two polysaccharides, glucuronoxylomannan (GXM) and galactoxylomannan (GalXM), in addition to a smaller proportion of mannoproteins (MP). Most of the studies on the composition of the capsule have focused on GXM, which comprises more than 90% of the capsule's polysaccharide mass. It is GalXM, however, that is of particular scientific interest because of its immunological properties. The molecular structure of these polysaccharides is very complex and has not yet been fully elucidated. Both GXM and GalXM are high molecular mass polymers with the mass of GXM equaling roughly 10 times that of GalXM. Recent findings suggest, however, that the actual Mw might be different to what it has traditionally been thought to be. In addition to their structural roles in the polysaccharide capsule, these molecules have been associated with many deleterious effects on the immune response. Capsular components are therefore considered key virulence determinants in Cryptococcus neoformans, which has motivated their use in vaccines and made them targets for monoclonal antibody treatments. In this review we will provide an update on the current knowledge of the C. neoformans capsule, covering aspects related to its structure, synthesis, and particularly, its role as a virulence factor. PMID:19426855

Connective tissue cells expressing fibro/adipogenic progenitor markers increase under chronic damage: relevance in fibroblast-myofibroblast differentiation and skeletal muscle fibrosis.

PubMed

Contreras, Osvaldo; Rebolledo, Daniela L; Oyarzún, Juan Esteban; Olguín, Hugo C; Brandan, Enrique

2016-06-01

Fibrosis occurs in skeletal muscle under various pathophysiological conditions such as Duchenne muscular dystrophy (DMD), a devastating disease characterized by fiber degeneration that results in progressive loss of muscle mass, weakness and increased extracellular matrix (ECM) accumulation. Fibrosis is also observed after skeletal muscle denervation and repeated cycles of damage followed by regeneration. The ECM is synthesized largely by fibroblasts in the muscle connective tissue under normal conditions. Myofibroblasts, cells that express α-smooth muscle actin (α-SMA), play a role in many tissues affected by fibrosis. In skeletal muscle, fibro/adipogenic progenitors (FAPs) that express cell-surface platelet-derived growth factor receptor-α (PDGFR-α) and the transcription factor Tcf4 seem to be responsible for connective tissue synthesis and are good candidates for the origin of myofibroblasts. We show that cells positive for Tcf4 and PDGFR-α are expressed in skeletal muscle under normal conditions and are increased in various skeletal muscles of mdx mice, a murine model for DMD, wild type muscle after sciatic denervation and muscle subjected to chronic damage. These cells co-label with the myofibroblast marker α-SMA in dystrophic muscle but not in normal tissue. The Tcf4-positive cells lie near macrophages mainly concentrated in dystrophic necrotic-regenerating foci. The close proximity of Tcf4-positive cells to inflammatory cells and their previously described role in muscle regeneration might reflect an active interaction between these cell types and growth factors, possibly resulting in a muscular regenerative or fibrotic condition.

The mechanoreceptors of the costo-vertebral joints

PubMed Central

Godwin-Austen, R. B.

1969-01-01

1. Unitary recording in the thoracic dorsal roots of mechanoreceptor discharges from the costo-vertebral joints was carried out in the cat and rabbit. Criteria for the identification of costo-vertebral joint mechanoreceptors were established. 2. The majority of rib joint mechanoreceptors are slowly adapting and fifty-three such receptors were studied. Five rapidly adapting receptors were also identified. 3. The responses of these receptors have been correlated with rib position and movement. The slowly adapting receptors gave a monotonic response to different rib positions. 72% showed an increase of discharge rate with displacements towards expiratory rib positions. 4. In response to manually imposed rib movements slowly adapting joint mechanoreceptors gave a dynamic response which was directly related to the velocity of the movement and adapted within 2 sec. The movements of breathing produced a corresponding alteration of the discharge frequency of the slowly adapting receptors. 5. Slowly adapting receptors were localized to the capsule of the costo-transverse joint by probing. They responded to increased intra-articular pressure with an increase of discharge rate and were silenced by intra-articular lignocaine, 0·4%. 6. Rapidly adapting joint mechanoreceptors responded to rib movement with a brief burst of discharges. 7. The rib joint mechanoreceptors signal rib joint position, and the direction and velocity of rib movement. It is suggested that these afferent discharges provide the basis for the perception of respiratory movements of the chest. The significance of these receptors to the `sense of effort' resulting from a resistance to breathing is discussed. PMID:5789947

Tag gas capsule with magnetic piercing device

DOEpatents

Nelson, Ira V.

1976-06-22

An apparatus for introducing a tag (i.e., identifying) gas into a tubular nuclear fuel element. A sealed capsule containing the tag gas is placed in the plenum in the fuel tube between the fuel and the end cap. A ferromagnetic punch having a penetrating point is slidably mounted in the plenum. By external electro-magnets, the punch may be caused to penetrate a thin rupturable end wall of the capsule and release the tag gas into the fuel element. Preferably the punch is slidably mounted within the capsule, which is in turn loaded as a sealed unit into the fuel element.

Alternative method for enteric coating of HPMC capsules resulting in ready-to-use enteric-coated capsules.

PubMed

Huyghebaert, Nathalie; Vermeire, An; Remon, Jean Paul

2004-04-01

The aim of this study was to develop an alternative method for enteric coating of HPMC capsules that avoids the sealing step before coating, resulting in ready-to-use enteric-coated capsules for the use in retail or hospital pharmacy or R&D sections of pharmaceutical industry and for the production of enteric-coated heat and moisture sensitive biomaterials. HPMC caps and bodies 00 (Vcaps, Capsugel) were coated separately in a fluid bed apparatus prior to filling (GPCG-1, Glatt) with Eudragit L30D-55 or Eudragit FS 30 D (Röhm), Aqoat AS-HF (Shin-Etsu) and Sureteric (Colorcon), using an optimised coating process. The coated bodies were filled and closed with the coated caps without encountering problems of coating damage. The release in 0.1N HCl after 2h from capsules coated with Eudragit L30D-55, Eudragit FS 30 D, Aqoat AS-HF and Sureteric was 0.6+/-.03, 0.6+/-0.3, 1.2+/-0.2 and 7.3+/-1.9%, respectively. The alternative method was reproducible and offered a way to overcome the time-consuming and expensive sealing step required using the conventional coating procedure. The obtained enteric-coated HPMC capsules can be stored (un)-filled for at least 6 months without loosing enteric properties.

Capsule Shimming Developments for National Ignition Facility (NIF) Hohlraum Asymmetry Experiments

DOE PAGES

Rice, Neal G.; Vu, M.; Kong, C.; ...

2017-12-20

Capsule drive in National Ignition Facility (NIF) indirect drive implosions is generated by x-ray illumination from cylindrical hohlraums. The cylindrical hohlraum geometry is axially symmetric but not spherically symmetric causing capsule-fuel drive asymmetries. We hypothesize that fabricating capsules asymmetric in wall thickness (shimmed) may compensate for drive asymmetries and improve implosion symmetry. Simulations suggest that for high compression implosions Legendre mode P 4 hohlraum flux asymmetries are the most detrimental to implosion performance. General Atomics has developed a diamond turning method to form a GDP capsule outer surface to a Legendre mode P 4 profile. The P 4 shape requiresmore » full capsule surface coverage. Thus, in order to avoid tool-lathe interference flipping the capsule part way through the machining process is required. This flipping process risks misalignment of the capsule causing a vertical step feature on the capsule surface. Recent trials have proven this step feature height can be minimized to ~0.25 µm.« less

Scaling effects in spiral capsule robots.

PubMed

Liang, Liang; Hu, Rong; Chen, Bai; Tang, Yong; Xu, Yan

2017-04-01

Spiral capsule robots can be applied to human gastrointestinal tracts and blood vessels. Because of significant variations in the sizes of the inner diameters of the intestines as well as blood vessels, this research has been unable to meet the requirements for medical applications. By applying the fluid dynamic equations, using the computational fluid dynamics method, to a robot axial length ranging from 10 -5 to 10 -2  m, the operational performance indicators (axial driving force, load torque, and maximum fluid pressure on the pipe wall) of the spiral capsule robot and the fluid turbulent intensity around the robot spiral surfaces was numerically calculated in a straight rigid pipe filled with fluid. The reasonableness and validity of the calculation method adopted in this study were verified by the consistency of the calculated values by the computational fluid dynamics method and the experimental values from a relevant literature. The results show that the greater the fluid turbulent intensity, the greater the impact of the fluid turbulence on the driving performance of the spiral capsule robot and the higher the energy consumption of the robot. For the same level of size of the robot, the axial driving force, the load torque, and the maximum fluid pressure on the pipe wall of the outer spiral robot were larger than those of the inner spiral robot. For different requirements of the operating environment, we can choose a certain kind of spiral capsule robot. This study provides a theoretical foundation for spiral capsule robots.

Mechanical characterization of capsule properties using abrupt-step channels

NASA Astrophysics Data System (ADS)

Salsac, Anne-Virginie; Le Goff, Anne; Kaoui, Badr; Barthè-Biesel, Dominique; Biomechanics; Bioengineering Lab Team

2017-11-01

Capsules consisting of a liquid droplet enclosed by a thin polymerized membrane are commonly encountered in nature (cells) or in industrial process (pharmaceutical, cosmetic or food products). The mechanical properties of the capsule wall are essential to guarantee the particle integrity and release of the internal contents when and where necessary. The difficulty is to assess the mechanical properties of the thin membrane. We will show how abrupt-step channels can be used to identify the membrane viscoelastic properties and point of rupture. This can be achieved by using a channel presenting a step change in cross-section and inverting the direction of the flow of the capsule suspension within the tube. To deduce information on the viscoelasticity, we will exploit the relaxation of the capsules as they flow through the expansion. To study membrane rupture, we will instead invert the channel, block the capsules at the neck of the constriction and determine the pressure difference needed for breakup. All the experiments will be conducted on initially spherical capsules with a thin cross-linked protein membrane for a proof of concept.

Anterior capsule tear after laser iridotomy complicating phacoemulsification

PubMed Central

Vivien Cherng Hui, Yip; Sanjay, Srinivasan; Benjamin Chong-Ming, Chang

2011-01-01

A 70-year-old Indian lady had a history of bilateral laser peripheral iridotomy (LPI) for primary angle closure. Subsequently she developed cataract in both the eyes. Right eye cataract surgery was complicated by an anterior capsule rupture, which was discovered intra-operatively at the site of the LPI. Trypan blue was used to stain the anterior capsule to delineate the anterior capsule defect. An attempt at continuous curvilinear capsulorhexis was unsuccessful, and the anterior capsulotomy was completed with scissors. To the best of our knowledge the surgical management of cataract in the presence of anterior capsule rupture as a result of LPI has not been reported. Awareness of this potential complication of LPI will aid in planning for successful phacoemulsification cataract surgery. PMID:23960943

Antioxidant functionalized polymer capsules to prevent oxidative stress.

PubMed

Larrañaga, Aitor; Isa, Isma Liza Mohd; Patil, Vaibhav; Thamboo, Sagana; Lomora, Mihai; Fernández-Yague, Marc A; Sarasua, Jose-Ramon; Palivan, Cornelia G; Pandit, Abhay

2018-02-01

Polymeric capsules exhibit significant potential for therapeutic applications as microreactors, where the bio-chemical reactions of interest are efficiently performed in a spatial and time defined manner due to the encapsulation of an active biomolecule (e.g., enzyme) and control over the transfer of reagents and products through the capsular membrane. In this work, catalase loaded polymer capsules functionalized with an external layer of tannic acid (TA) are fabricated via a layer-by-layer approach using calcium carbonate as a sacrificial template. The capsules functionalised with TA exhibit a higher scavenging capacity for hydrogen peroxide and hydroxyl radicals, suggesting that the external layer of TA shows intrinsic antioxidant properties, and represents a valid strategy to increase the overall antioxidant potential of the developed capsules. Additionally, the hydrogen peroxide scavenging capacity of the capsules is enhanced in the presence of the encapsulated catalase. The capsules prevent oxidative stress in an in vitro inflammation model of degenerative disc disease. Moreover, the expression of matrix metalloproteinase-3 (MMP-3), and disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5), which represents the major proteolytic enzymes in intervertebral disc, are attenuated in the presence of the polymer capsules. This platform technology exhibits potential to reduce oxidative stress, a key modulator in the pathology of a broad range of inflammatory diseases. Oxidative stress damages important cell structures leading to cellular apoptosis and senescence, for numerous disease pathologies including cancer, neurodegeneration or osteoarthritis. Thus, the development of biomaterials-based systems to control oxidative stress has gained an increasing interest. Herein, polymer capsules loaded with catalase and functionalized with an external layer of tannic acid are fabricated, which can efficiently scavenge important reactive oxygen species (i

Flake-shell capsules: adjustable inorganic structures.

PubMed

Ji, Qingmin; Guo, Chunyan; Yu, Xiaoyan; Ochs, Christopher J; Hill, Jonathan P; Caruso, Frank; Nakazawa, Hiromoto; Ariga, Katsuhiko

2012-08-06

Structure-adjustable capsules are fabricated from inorganic components by using a self-template dissolution-regrowth mechanism to give flake-shell silica microcapsules. The capsules shrink under thermal stimulus and their structures can be adjusted by treatment at different pH values. Tuning of shell pore diameters leads to tailored drug release over prolonged periods. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Moisture diffusion and permeability characteristics of hydroxypropylmethylcellulose and hard gelatin capsules.

PubMed

Barham, Ahmad S; Tewes, Frederic; Healy, Anne Marie

2015-01-30

The primary objective of this paper is to compare the sorption characteristics of hydroxypropylmethylcellulose (HPMC) and hard gelatin (HG) capsules and their ability to protect capsule contents. Moisture sorption and desorption isotherms for empty HPMC and HG capsules have been investigated using dynamic vapour sorption (DVS) at 25°C. All sorption studies were analysed using the Young-Nelson model equations which distinguishes three moisture sorption types: monolayer adsorption moisture, condensation and absorption. Water vapour diffusion coefficients (D), solubility (S) and permeability (P) parameters of the capsule shells were calculated. ANOVA was performed with the Tukey comparison test to analyse the effect of %RH and capsule type on S, P, and D parameters. The moisture uptake of HG capsules were higher than HPMC capsules at all %RH conditions studied. It was found that values of D and P across HPMC capsules were greater than for HG capsules at 0-40 %RH; whereas over the same %RH range S values were higher for HG than for HPMC capsules. S values decreased gradually as the %RH was increased up to 60% RH. To probe the effect of moisture ingress, spray dried lactose was loaded into capsules. Phase evolution was characterised by scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). The capsules under investigation are not capable of protecting spray dried lactose from induced solid state changes as a result of moisture uptake. For somewhat less moisture sensitive formulations, HPMC would appear to be a better choice than HG in terms of protection of moisture induced deterioration. Copyright © 2014 Elsevier B.V. All rights reserved.

Management of acromioclavicular joint injuries.

PubMed

Li, Xinning; Ma, Richard; Bedi, Asheesh; Dines, David M; Altchek, David W; Dines, Joshua S

2014-01-01

Acromioclavicular joint injuries are among the most common shoulder girdle injuries in athletes and most commonly result from a direct force to the acromion with the arm in an adducted position. Acromioclavicular joint injuries often present with associated injuries to the glenohumeral joint, including an increased incidence of superior labrum anterior posterior (SLAP) tears that may warrant further evaluation and treatment. Anteroposterior stability of the acromioclavicular joint is conferred by the capsule and acromioclavicular ligaments, of which the posterior and superior ligaments are the strongest. Superior-inferior stability is maintained by the coracoclavicular (conoid and trapezoid) ligaments. Type-I or type-II acromioclavicular joint injuries have been treated with sling immobilization, early shoulder motion, and physical therapy, with favorable outcomes. Return to activity can occur when normal shoulder motion and strength are obtained and the shoulder is asymptomatic as compared with the contralateral normal extremity. The management of type-III injuries remains controversial and is individualized. While a return to the previous level of functional activity with nonsurgical treatment has been documented in a number of case series, surgical reduction and coracoclavicular ligament reconstruction has been associated with a favorable outcome and can be considered in patients who place high functional demands on their shoulders or in athletes who participate in overhead sports. Surgical management is indicated for high-grade (≥type IV) acromioclavicular joint injuries to achieve anatomic reduction of the acromioclavicular joint, reconstruction of the coracoclavicular ligaments, and repair of the deltotrapezial fascia. Outcomes after surgical reconstruction of the coracoclavicular ligaments have been satisfactory with regard to achieving pain relief and return to functional activities, but further improvements in the biomechanical strength of these

Improvement in Capsule Abort Performance Using Supersonic Aerodynamic Interaction by Fences

NASA Astrophysics Data System (ADS)

Koyama, Hiroto; Wang, Yunpeng; Ozawa, Hiroshi; Doi, Katsunori; Nakamura, Yoshiaki

The space transportation system will need advanced abort systems to secure crew against serious accidents. Here this study deals with the capsule-type space transportation systems with a Launch Abort System (LAS). This system is composed of a conic capsule as a Launch Abort Vehicle (LAV) and a cylindrical rocket as a Service Module (SM), and the capsule is moved away from the rocket by supersonic aerodynamic interactions in an emergency. We propose a method to improve the performance of the LAV by installing fences at the edges of surfaces on the rocket and capsule sides. Their effects were investigated by experimental measurements and numerical simulations. Experimental results show that the fences on the rocket and capsule surfaces increase the aerodynamic thrust force on the capsule by 70% in a certain clearance between the capsule and rocket. Computational results show the detailed flow fields where the centripetal flow near the surface on the rocket side is induced by the fence on the rocket side and the centrifugal flow near the surface on the capsule side is blocked by the fence on the capsule side. These results can confirm favorable effects of the fences on the performance of the LAS.

Engineering multifunctional capsules through the assembly of metal-phenolic networks.

PubMed

Guo, Junling; Ping, Yuan; Ejima, Hirotaka; Alt, Karen; Meissner, Mirko; Richardson, Joseph J; Yan, Yan; Peter, Karlheinz; von Elverfeldt, Dominik; Hagemeyer, Christoph E; Caruso, Frank

2014-05-26

Metal-organic coordination materials are of widespread interest because of the coupled benefits of inorganic and organic building blocks. These materials can be assembled into hollow capsules with a range of properties, which include selective permeability, enhanced mechanical/thermal stability, and stimuli-responsiveness. Previous studies have primarily focused on the assembly aspects of metal-coordination capsules; however, the engineering of metal-specific functionality for capsule design has not been explored. A library of functional metal-phenolic network (MPN) capsules prepared from a phenolic ligand (tannic acid) and a range of metals is reported. The properties of the MPN capsules are determined by the coordinated metals, allowing for control over film thickness, disassembly characteristics, and fluorescence behavior. Furthermore, the functional properties of the MPN capsules were tailored for drug delivery, positron emission tomography (PET), magnetic resonance imaging (MRI), and catalysis. The ability to incorporate multiple metals into MPN capsules demonstrates that a diverse range of functional materials can be generated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Latrunculin B and substratum stiffness regulate corneal fibroblast to myofibroblast transformation.

PubMed

Thomasy, Sara M; Raghunathan, Vijay Krishna; Miyagi, Hidetaka; Evashenk, Alexander T; Sermeno, Jasmyne C; Tripp, Geneva K; Morgan, Joshua T; Murphy, Christopher J

2018-05-01

The transformation of keratocytes and fibroblasts to myofibroblasts is important to corneal wound healing as well as formation of stromal haze. The purpose of this study was to determine the effect of latrunculin B, an actin cytoskeleton disruptor in conjunction with a fundamental biophysical cue, substrate stiffness, on myofibroblast transformation in vitro and in vivo. Rabbit corneal fibroblasts were cultured on substrates of differing compliance (1.5, 22, and 71 kPa) and tissue culture plastic (TCP; > 1 GPa) in media containing 0 or 10 ng/ml TGFβ1 for 72 h. Cells were treated with 0.4 μM Lat-B or DMSO for 30 min every 24 h for 72 h. RNA was collected from cells and expression of alpha-smooth muscle actin (α-SMA), keratocan, and ALDH1A1 determined using qPCR; immunocytochemistry was used to assess α-SMA protein expression. A rabbit phototherapeutic keratectomy (PTK) model was used to assess the impact of 0.1% Lat-B (n = 3) or 25% DMSO (vehicle control, n = 3) on corneal wound healing by assessment of epithelial wound size with fluorescein stain and semi-quantitative stromal haze scoring by an observer masked to treatment group as well as Fourier-domain optical coherence tomography (FD-OCT) at set time points. Statistical analysis was completed using one-way or two-way analysis of variance. Treatment with Lat-B versus DMSO resulted in significantly less αSMA mRNA (P ≤ 0.007) for RCF cells grown on 22 and 71 kPa substrates as well as TCP without or with TGFβ1, and significantly decreased α-SMA protein expression in RCFs cultured on the intermediate (22 kPa) stiffness in the absence (P = 0.028) or presence (P = 0.018) of TGFβ1. Treatment with Lat-B versus DMSO but did not significantly alter expression of keratocan or ALDH1A1 mRNA in RCFs (P > 0.05) in the absence or presence of TGFβ1, but RCFs grown on stiff hydrogels (71 kPa) had significantly more keratocan mRNA expression versus the 22 kPa hydrogel or

Sigmoid sinus occlusion infiltrated by inflammatory myofibroblastic tumor from mastoid.

PubMed

Wang, Jingye; Sun, Zhongwu; Zhuo, Shengxia; Wang, Kai

2015-01-01

Inflammatory myofibroblastic tumor (IMT) and some types of immunoglobulin (Ig) G4-related disease are often involved in the spectrum of inflammatory pseudotumor (IPT) and the concept of IgG4-related IPT/IMT has recently been proposed. A 38-year-old man complained of initial symptoms of blurred vision and headache. A tumor was found in the right mastoid, which caused occlusion of the right sigmoid sinus and intracranial hypertension. A diagnosis of IMT with IgG4+ plasma cell infiltration was established by surgical, pathological, and immunohistochemistry findings. His symptoms were completely relieved after corticosteroid therapy and no recurrence was detected during 22 months of follow-up. A case with cerebral venous sinus infiltrated by IMTs in the head and neck has never been reported; corticosteroid therapy proved satisfactory in IMT with IgG4+ plasma cell infiltration. © 2014 Wiley Periodicals, Inc.

Bioequivalence of a methylphenidate hydrochloride extended-release preparation: comparison of an intact capsule and an opened capsule sprinkled on applesauce.

PubMed

Fischer, R; Schütz, H; Grossmann, M; Leis, H J; Ammer, R

2006-03-01

To assess bioequivalence between an intact capsule and the content of a capsule sprinkled on applesauce. Medikinet retard 20 mg capsules were obtained from Medice (Iserlohn, Germany). This was a single-center, completely randomized, open, 2-period, 2-sequence, balanced crossover study with a washout period of 1 week between administrations, in 12 healthy male and female subjects, aged 18-45 years. Blood samples were collected over 24 hours and methylphenidate plasma concentration-time data were used to calculate pharmacokinetic parameters for both administrations. The main parameters were (confirmatory) AUC0-tz (extent of BA), Cmax, tmax (rate of BA) and (descriptively) AUC0-infinity and t1/2. Equivalence was concluded if the 90% confidence interval (CI) for the ratio between test and reference was 0.80-1.25 (AUC0-tz). All 12 dosed subjects finished both treatment periods and were included in pharmacokinetic and safety analyses. 90% geometric confidence intervals for AUC0-tz and Cmax data were well within accepted bioequivalence limits. The study has shown that both treatment modes lead to similar pattern of absorption and elimination following single-dose administration in the fed state. The test treatment (content of capsule sprinkled over 15 ml applesauce) is bioequivalent to the reference treatment (intact capsule) in terms of extent and rate of absorption. Data collected from this study demonstrate that Medikinet retard capsules can be opened and the content sprinkled on a tablespoon of applesauce without influencing the rate and extent of bioavailability.

[Clinical Efficacy of Supplementary Treatment of Gukang Capsules to the Elder Patients with Fracture of Distal Radius].

PubMed

Wang, Wei; Liao, Su-ping; Wei, Lei

2015-01-01

To study the clinical efficacy of supplementary treatment of tukang Capsules to the elder patients with fracture of the distal radius. A total of 108 elder patients with fracture of the distal radius diagnosed by X-ray,who visited orthopedics department of Pu' ai Hospital in January 2012 - December 2013, were randomly divided into observation group and control group. Cases in both groups received the operation of internal fixation by T-type plate. Cases in control group received oral Calcium Carbonate Tablets, and cases in observation group received Gukang Capsules besides Calcium Carbonate Tablets. Treatment duration was four weeks. The painful and swelling degree of wrist joints, levels of type I propeptide carboxy-terminal procollagen (P I CP) and bone glaprotein(BGP) in serum were compared. Hospitalization and fracture healing time, as well as recovery condition of wrist joints in the sixth month after operation were compared. The VAS of both groups was not significantly different before operation and in the 28th day after operation(P >0. 05), but the VAS in observation group was significantly lower than that in control group in the 3rd,5th, 7th, 14th and 21th day after operation(P <0. 01). The swelling scale of both groups was not significantly different before operation and in the 28th day after operation(P >0. 05), but the swelling scale in observation group was significantly lower than that in control group in the 3rd, 5th, 7th, 14th and 21th day after operation(P <0. 01). The levels of P I CP and BGP in serum of both groups were not significantly different before operation(P >0. 05), but the levels of P I CP and BGP in serum of observation groups were significantly higher than that in control group one and two months after operation (P <0. 01). Hospitalization and fracture healing time in observation group was significantly shortened compared with control group (P <0. 05). The effective ratio in observation group was 79. 63%, significantly higher than that

Spectral measurements of asymmetrically irradiated capsule backlighters

DOE PAGES

Keiter, P. A.; Drake, R. P.

2016-09-09

Capsule backlighters provide a quasi-continuum x-ray spectrum over a wide range of photon energies. Ideally one irradiates the capsule backlighter symmetrically, however, in complex experimental geometries, this is not always possible. In recent experiments we irradiated capsule backlighters asymmetrically and measured the x-ray spectrum from multiple directions. We will present time-integrated spectra over the photon energy range of ~2-13 keV and time-resolved spectra over the photon energy range of ~2-3 keV. Lastly, we will compare the spectra from different lines of sight to determine if the laser asymmetry results in an angular dependence in the x-ray emission.

State diagram for adhesion dynamics of deformable capsules under shear flow.

PubMed

Luo, Zheng Yuan; Bai, Bo Feng

2016-08-17

Due to the significance of understanding the underlying mechanisms of cell adhesion in biological processes and cell capture in biomedical applications, we numerically investigate the adhesion dynamics of deformable capsules under shear flow by using a three-dimensional computational fluid dynamic model. This model is based on the coupling of the front tracking-finite element method for elastic mechanics of the capsule membrane and the adhesion kinetics simulation for adhesive interactions between capsules and functionalized surfaces. Using this model, three distinct adhesion dynamic states are predicted, such as detachment, rolling and firm-adhesion. Specifically, the effects of capsule deformability quantified by the capillary number on the transitions of these three dynamic states are investigated by developing an adhesion dynamic state diagram for the first time. At low capillary numbers (e.g. Ca < 0.0075), whole-capsule deformation confers the capsule a flattened bottom in contact with the functionalized surface, which hence promotes the rolling-to-firm-adhesion transition. It is consistent with the observations from previous studies that cell deformation promotes the adhesion of cells lying in the rolling regime. However, it is surprising to find that, at relatively high capillary numbers (e.g. 0.0075 < Ca < 0.0175), the effect of capsule deformability on its adhesion dynamics is far more complex than just promoting adhesion. High deformability of capsules makes their bottom take a concave shape with no adhesion bond formation in the middle. The appearance of this specific capsule shape inhibits the transitions of both rolling-to-firm-adhesion and detachment-to-rolling, and it means that capsule deformation no longer promotes the capsule adhesion. Besides, it is interesting to note that, when the capillary number exceeds a critical value (e.g. Ca = 0.0175), the rolling state no longer appears, since capsules exhibit large deviation from the spherical shape.

Epithelioid inflammatory myofibroblastic sarcoma: An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK.

PubMed

Mariño-Enríquez, Adrián; Wang, Wei-Lien; Roy, Angshumoy; Lopez-Terrada, Dolores; Lazar, Alexander J F; Fletcher, Christopher D M; Coffin, Cheryl M; Hornick, Jason L

2011-01-01

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate biological potential, which may recur and rarely metastasize. Pathologic features do not correlate well with behavior. Approximately 50% of conventional IMTs harbor ALK gene rearrangement and overexpress ALK, most showing diffuse cytoplasmic staining. Rare IMTs with a distinct nuclear membrane or perinuclear pattern of ALK staining and epithelioid or round cell morphology have been reported. These cases pursued an aggressive clinical course, suggesting that such patterns may predict malignant behavior. We describe 11 cases of IMT with epithelioid morphology and a nuclear membrane or perinuclear pattern of immunostaining for ALK. Ten patients were male and 1 was female, ranging from 7 months to 63 years in age (median, 39 y). All tumors were intra-abdominal; most arose in the mesentery or omentum, measuring 8 to 26 cm (median, 15 cm). Six tumors were multifocal at presentation. The tumors were composed predominantly of sheets of round-to-epithelioid cells with vesicular nuclei, large nucleoli, and amphophilic-to-eosinophilic cytoplasm. In all cases, a minor spindle cell component was present. Nine tumors had abundant myxoid stroma. In 7 cases neutrophils were prominent and in 3 cases lymphocytes were prominent. Plasma cells were often absent. Median mitotic rate was 4/10 HPF; 6 tumors had necrosis. By immunohistochemistry, all tumors were positive for ALK, 9 tumors showing a nuclear membrane staining pattern and 2 tumors showing a cytoplasmic pattern with perinuclear accentuation. Other positive markers were desmin (10 of 11), focal smooth muscle actin (4 of 8), and CD30 (8 of 8). All tumors were negative for MYF4, caldesmon, keratins, EMA, and S-100. Fluorescence in situ hybridization was positive for ALK gene rearrangement in 9 cases, and in 3 cases tested, a RANBP2-ALK fusion was detected by reverse transcription polymerase chain reaction. Ten patients underwent surgical resection

Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis

PubMed Central

Roulis, Manolis; Nikolaou, Christoforos; Kotsaki, Elena; Kaffe, Eleanna; Karagianni, Niki; Koliaraki, Vasiliki; Salpea, Klelia; Ragoussis, Jiannis; Aidinis, Vassilis; Martini, Eva; Becker, Christoph; Herschman, Harvey R.; Vetrano, Stefania; Danese, Silvio; Kollias, George

2014-01-01

Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with inflammatory bowel diseases (IBDs). Here we show that Tpl2 may exert a dominant homeostatic rather than inflammatory function in the intestine mediated specifically by subepithelial intestinal myofibroblasts (IMFs). Mice with complete or IMF-specific Tpl2 ablation are highly susceptible to epithelial injury-induced colitis showing impaired compensatory proliferation in crypts and extensive ulcerations without significant changes in inflammatory responses. Following epithelial injury, IMFs sense innate or inflammatory signals and activate, via Tpl2, the cyclooxygenase-2 (Cox-2)-prostaglandin E2 (PGE2) pathway, which we show here to be essential for the epithelial homeostatic response. Exogenous PGE2 administration rescues mice with complete or IMF-specific Tpl2 ablation from defects in crypt function and susceptibility to colitis. We also show that Tpl2 expression is decreased in IMFs isolated from the inflamed ileum of IBD patients indicating that Tpl2 function in IMFs may be highly relevant to human disease. The IMF-mediated mechanism we propose also involves the IBD-associated genes IL1R1, MAPK1, and the PGE2 receptor-encoding PTGER4. Our results establish a previously unidentified myofibroblast-specific innate pathway that regulates intestinal homeostasis and may underlie IBD susceptibility in humans. PMID:25316791

Magnetized HDC ignition capsules for yield enhancement and implosion magnetohydrodynamics

NASA Astrophysics Data System (ADS)

Zimmerman, G.; Ho, D.; Perkins, J.; Logan, G.; Hawkins, S.; Rhodes, M.

2014-10-01

Imposing a magnetic field on capsules can turn capsules that fail, because of low 1-D margin, into igniting capsules that give yield in the MegaJoule range. The imposed magnetic field can be amplified by up to O(103) as it is being compressed by the imploding shell, e.g. if the initial field is 50 T, then the field in the hot spot of the assembled configuration can reach >104 T. (We are currently designing hardware that can provide a field in the 50 T range inside NIF hohlraums.) With this highly compressed field strength, the gyro radius of alpha particles becomes smaller than the hot spot size. Consequently, the heating of the hot spot becomes more efficient. The imposed field can also prevent hot electrons in the holhraum from reaching the capsule. We choose capsules with high-density carbon (HDC) ablators for this study. HDC capsules have good 1-D performance and also have short pulses (10 ns or less), allowing the use of low gas-filled or near-vacuum hohlraums which provide high coupling efficiency. We describe a 2-D simulation of a 3-shock HDC capsule. We will show detailed magnetohydrodynamic evolution of the implosion. HDC capsules with 2-shock pulses have low margin because of their high adiabat, and it is difficult to achieve ignition in realistic 2-D simulations. The improvement in performance for 2-shock magnetized capsules will be presented. This work was supported by LLNL Laboratory Directed Research and Development LDRD 14-ER-028 under Contract DE-AC52-07NA27344.

Genome wide gene expression analysis of the posterior capsule in patients with osteoarthritis and knee flexion contracture.

PubMed

Campbell, Thomas Mark; Trudel, Guy; Wong, Kayleigh Kristin; Laneuville, Odette

2014-11-01

Knee flexion contractures (KFC) are limitations in the ability to fully extend the knee joint. In people with knee osteoarthritis (OA), KFC are common, impair function, and worsen outcomes after arthroplasty. In KFC, the posterior knee capsule is believed to play a key role, but the pathophysiology remains poorly understood. We sought to identify gene expression differences in the posterior knee capsule of patients with OA with and without KFC. Capsule tissue was obtained from the knees of 12 subjects diagnosed with advanced-stage OA at the time of knee arthroplasty surgery. The presence or absence of KFC allocated patients into 2 groups using a case-control design. Genomewide capsular gene expression was compared between the 2 patient groups. Confirmation of differential expression of the corresponding proteins was performed by immunohistochemistry on tissue sections. There were no significant demographic differences between the patients with OA with KFC and without KFC save for reduced extension in their surgical knee (p<0.01). KFC patients showed a 6.4-fold decrease in CSN1S1 (p=0.017) gene expression and a 3.7-, 2.0-, and 2.6-fold increase in CHAD, Sox9, and Cyr61 gene expression, respectively (p=0.001, 0.004, 0.001, respectively). There were corresponding increases in protein levels for chondroadherin, sex determining region Y-box 9, and casein alphaS1 (all p<0.05). Functional analysis of the differentially expressed genes indicated a strong association with pathways related to the extracellular matrix and to tissue fibrosis. Posterior capsules in endstage OA knees with KFC exhibited differential expression of 4 genes all previously documented to be associated with tissue fibrosis.

Identification of the duodenal papilla by colon capsule endoscope.

PubMed

Karagiannis, S; Dücker, C; Dautel, P; Strubenhoff, J; Faiss, S

2010-07-01

The sensitivity of small-bowel capsule endoscopy in visualizing a single finding present in everyone, the duodenal papilla, is limited. In this retrospective case series study we evaluated whether the duodenal papilla can be better visualized by a capsule endoscope equipped with cameras on both ends. The recordings of 45 colonic capsule endoscopies (PillCam Colon) performed in a single tertiary center were re-evaluated seeking for the duodenal papilla. The two-hour sleeping period of the colon capsule endoscopy system led to the imaging of duodenum in 10 / 45 patients. The duodenal papilla was identified in 6 / 10 (60 %) patients while the number of frames where the papilla was clearly visualized ranged from 2 - 9. Consequently, a small-bowel capsule endoscope containing two cameras could better identify the duodenal papilla and theoretically other obscure areas of the small bowel, expanding its diagnostic accuracy.

Laundry detergent capsules and pediatric poisoning.

PubMed

Bonney, Asha G; Mazor, Suzan; Goldman, Ran D

2013-12-01

A 4-year-old girl was brought into the emergency department vomiting after having had ingested a laundry detergent capsule (LDC) from under the sink at her house. What is the risk of LDC poisoning? What can be done to treat these children? Laundry detergent capsules are relatively new to supermarket shelves in North America, and there has been an emergence of case reports in the literature describing LDC poisoning, which is worse than poisoning from other laundry detergents. Very little is known about the mechanisms causing these severe reactions, which include airway compromise and esophageal perforation, but the attractive appearance of these capsules and easy access at home has governments and health officials concerned about an increase in poisoning. No residual problems have been associated with these cases to date; however, further research is needed to assess long-term effects.

Lens capsule structure assessed with atomic force microscopy

PubMed Central

Sueiras, Vivian M.; Moy, Vincent T.

2015-01-01

Purpose To image the ultrastructure of the anterior lens capsule at the nanoscale level using atomic force microscopy (AFM). Methods Experiments were performed on anterior lens capsules maintained in their in situ location surrounding the lens from six human cadavers (donor age range: 44–88 years), four cynomolgus monkeys (Macaca fascicularis age range: 4.83–8.92 years), and seven pigs (<6 months). Hydration of all samples was maintained using Dulbecco’s Modified Eagle Medium (DMEM). Whole lenses were removed from the eye and placed anterior side up in agarose gel before gel hardening where only the posterior half of the lens was contained within the gel. After the gel hardened, the Petri dish was filled with DMEM until the point where the intact lens was fully submerged. AFM was used to image the anterior lens surface in contact mode. An integrated analysis program was used to calculate the interfibrillar spacing, fiber diameter, and surface roughness of the samples. Results The AFM images depict a highly ordered fibrous structure at the surface of the lens capsule in all three species. The interfibrillar spacing for the porcine, cynomolgus monkey, and human lens capsules was 0.68±0.25, 1.80±0.39, and 1.08±0.25 μm, respectively. In the primate, interfibrillar spacing significantly decreased linearly as a function of age. The fiber diameters ranged from 50 to 950 nm. Comparison of the root mean square (RMS) and average deviation demonstrate that the surface of the porcine lens capsule is the smoothest, and that the human and cynomolgus monkey capsules are significantly rougher. Conclusions AFM was successful in providing high-resolution images of the nanostructure of the lens capsule samples. Species-dependent differences were observed in the overall structure and surface roughness. PMID:25814829

Capsule endoscopy in the diagnosis of Crohn's disease.

PubMed

Niv, Yaron

2013-01-01

Crohn's disease is a chronic inflammatory disorder affecting any part of the gastrointestinal tract, but frequently involves the small and large bowel. Typical presenting symptoms include abdominal pain and diarrhea. Patients with this disorder may also have extraintestinal manifestations, including arthritis, uveitis, and skin lesions. The PillCam™SB capsule is an ingestible disposable video camera that transmits high quality images of the small intestinal mucosa. This enables the small intestine to be readily accessible to physicians investigating for the presence of small bowel disorders, such as Crohn's disease. Four meta-analyses have demonstrated that capsule endoscopy identifies Crohn's disease when other methods are not helpful. It should be noted that it is the best noninvasive procedure for assessing mucosal status, but is not superior to ileocolonoscopy, which remains the gold standard for assessment of ileocolonic disease. Mucosal healing along the small bowel can only be demonstrated by an endoscopic procedure such as capsule endoscopy. Achievement of long-term mucosal healing has been associated with a trend towards a decreased need for hospitalization and a decreased requirement for corticosteroid treatment in patients with Crohn's disease. Recently, we have developed and validated the Capsule Endoscopy Crohn's Disease Activity Index (also known as the Niv score) for Crohn's disease of the small bowel. The next step is to expand our score to the colon, and to determine the role and benefit of a capsule endoscopy activity score in patients suffering from Crohn's ileocolitis and/or colitis. This scoring system will also serve to improve our understanding of the impact of capsule endoscopy, and therefore treatment, on the immediate outcome of this disorder. As the best procedure available for assessing mucosal status, capsule endoscopy will provide important information about the course and outcome of Crohn's disease.

Arthrofibrosis involving the middle facet of the talocalcaneal joint in children and adolescents.

PubMed

El Rassi, George; Riddle, Eric C; Kumar, S Jay

2005-10-01

Pain over the anterolateral aspect of the ankle in a patient with a history of repeated ankle sprains and with restricted subtalar movement may be associated with a tarsal coalition. Nineteen patients presented with such a history, but conventional imaging did not reveal a cartilaginous or osseous coalition. Since symptoms persisted despite nonoperative treatment, the middle facet was explored surgically. The purpose of this study was to discuss the operative findings and to report the results of treatment. Nineteen patients (twenty-three feet) with pain over the anterolateral aspect of the ankle or a history of repeated ankle sprains had restricted subtalar joint motion and inconclusive findings on diagnostic imaging, except for bone-scanning. Their ages ranged from 9.1 to 18.5 years. The middle facet of the subtalar joint was explored surgically through a 3 to 4-cm-long incision centered over the sustentaculum tali. The results at a mean of 5.8 years were classified as good, fair, or poor on the basis of pain, talocalcaneal joint motion, and shoe wear. Routine radiographs, computed tomography, and magnetic resonance imaging revealed no major abnormality, whereas technetium-99m bone scintigraphy consistently showed slightly increased isotope uptake in the middle facet. Surgical removal of a hypervascular and thickened capsule and synovium in the area of the middle facet of the subtalar joint decreased pain and improved subtalar motion. The final result was good in seventeen patients (twenty feet) and fair in two patients (three feet). There were no poor results. A diagnosis of inflammatory arthrofibrosis should be considered when a patient with a painful rigid flatfoot has normal findings on radiographs and hematological studies but increased isotope uptake in the middle facet of the talocalcaneal joint on bone scintigraphy. Excision of the hypervascular capsule and synovium from this area can result in resolution of the symptoms. Therapeutic Level IV.

Role of capsule endoscopy in inflammatory bowel disease.

PubMed

Kopylov, Uri; Seidman, Ernest G

2014-02-07

Videocapsule endoscopy (VCE) has revolutionized our ability to visualize the small bowel mucosa. This modality is a valuable tool for the diagnosis of obscure small bowel Crohn's disease (CD), and can also be used for monitoring of disease activity in patients with established small-bowel CD, detection of complications such as obscure bleeding and neoplasms, evaluation of response to anti-inflammatory treatment and postoperative recurrence following small bowel resection. VCE could also be an important tool in the management of patients with unclassified inflammatory bowel disease, potentially resulting in reclassification of these patients as having CD. Reports on postoperative monitoring and evaluation of patients with ileal pouch-anal anastomosis who have developed pouchitis have recenty been published. Monitoring of colonic inflammatory activity in patients with ulcerative colitis using the recently developed colonic capsule has also been reported. Capsule endoscopy is associated with an excellent safety profile. Although retention risk is increased in patients with small bowel CD, this risk can be significanty decreased by a routine utilization of a dissolvable patency capsule preceding the ingestion of the diagnostic capsule. This paper contains an overview of the current and future clinical applications of capsule endoscopy in inflammatory bowel disease.

Ultrasound capsule endoscopy: sounding out the future

PubMed Central

Stewart, Fraser; Lay, Holly; Cummins, Gerard; Newton, Ian P.; Desmulliez, Marc P. Y.; Steele, Robert J. C.; Näthke, Inke; Cochran, Sandy

2017-01-01

Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (µUS) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently. PMID:28567381

Unsteady Pressures on a Generic Capsule Shape

NASA Technical Reports Server (NTRS)

Burnside, Nathan; Ross, James C.

2015-01-01

While developing the aerodynamic database for the Orion spacecraft, the low-speed flight regime (transonic and below) proved to be the most difficult to predict and measure accurately. The flow over the capsule heat shield in descent flight was particularly troublesome for both computational and experimental efforts due to its unsteady nature and uncertainty about the boundary layer state. The data described here were acquired as part of a study to improve the understanding of the overall flow around a generic capsule. The unsteady pressure measurements acquired on a generic capsule shape are presented along with a discussion about the effects of various flight conditions and heat-shield surface roughness on the resulting pressure fluctuations.

A locomotion mechanism with external magnetic guidance for active capsule endoscope.

PubMed

Wang, Xiaona; Meng, Max Q H; Chen, Xijun

2010-01-01

Gastrointestinal (GI) disorder is one of the most common diseases in human body. The swallowable wireless capsule endoscopy has been proved to be a convenient, painless and effective way to examine the whole GI tract. However, lack of motion control makes the movement of the capsule substantially random, resulting in missing diagnosis. In this paper, a locomotion mechanism is developed for the next-generation active capsule endoscope. An internal actuator integrated on-board the capsule is designed to provide driving force and improve the dexterity. A small permanent magnet enclosed inside the capsule interacts with an external magnetic field to control the capsule's orientation and offer extra driving force. This mechanism avoids sophisticated and bulky control system and reduces power consumption inside the capsule. Ex-vivo experimental results showed that it can make a controllable movement inside the porcine large intestine. The mechanism also has the potential to be a platform for further development, such as devices of operations, spraying medicine, biopsy etc.

Capsule-Fixated Intraocular Lens Implantation in Small Pupil Cases.

PubMed

Schojai, Merita; Schultz, Tim; Burkhard Dick, H

2017-08-01

To describe a new technique for implantation of capsule-fixated intraocular lenses (IOLs) (FEMTIS; Oculentis, Berlin, Germany) in patients with small pupils. In 4 eyes with small pupils, an anterior capsule-fixated IOL was implanted into the capsular bag after femtosecond laser treatment. The two large and two small flaps of the IOL were elevated to the front of the iris and the anterior capsule. Finally, the iris was flipped over the flaps to ensure a fixation of the capsule inside of the capsulotomy. In all cases, the implantation of anterior capsule-fixated IOLs was possible. No complications occurred during surgery or within the first months after surgery. With the described technique, capsulefixated IOLs can be implanted in eyes with small pupil easily and safely. This type of IOL has great potential to improve the refractive outcome by better prediction of the postoperative IOL position and eliminating IOL rotation after cataract surgery. [J Refract Surg. 2017;33(8):568-570.]. Copyright 2017, SLACK Incorporated.

Investigation of albumin-derived perfluorocarbon-based capsules by holographic optical trapping

PubMed Central

Köhler, Jannis; Ruschke, Jegor; Ferenz, Katja Bettina; Esen, Cemal; Kirsch, Michael; Ostendorf, Andreas

2018-01-01

Albumin-derived perfluorocarbon-based capsules are promising as artificial oxygen carriers with high solubility. However, these capsules have to be studied further to allow initial human clinical tests. The aim of this paper is to provide and characterize a holographic optical tweezer to enable contactless trapping and moving of individual capsules in an environment that mimics physiological (in vivo) conditions most effectively in order to learn more about the artificial oxygen carrier behavior in blood plasma without recourse to animal experiments. Therefore, the motion behavior of capsules in a ring shaped or vortex beam is analyzed and optimized on account of determination of the optical forces in radial and axial direction. In addition, due to the customization and generation of dynamic phase holograms, the optical tweezer is used for first investigations on the aggregation behavior of the capsules and a statistical evaluation of the bonding in dependency of different capsule sizes is performed. The results show that the optical tweezer is sufficient for studying individual perfluorocarbon-based capsules and provide information about the interaction of these capsules for future use as artificial oxygen carriers. PMID:29552409

Evolving Insights on Metabolism, Autophagy, and Epigenetics in Liver Myofibroblasts.

PubMed

Nwosu, Zeribe C; Alborzinia, Hamed; Wölfl, Stefan; Dooley, Steven; Liu, Yan

2016-01-01

Liver myofibroblasts (MFB) are crucial mediators of extracellular matrix (ECM) deposition in liver fibrosis. They arise mainly from hepatic stellate cells (HSCs) upon a process termed "activation." To a lesser extent, and depending on the cause of liver damage, portal fibroblasts, mesothelial cells, and fibrocytes may also contribute to the MFB population. Targeting MFB to reduce liver fibrosis is currently an area of intense research. Unfortunately, a clog in the wheel of antifibrotic therapies is the fact that although MFB are known to mediate scar formation, and participate in liver inflammatory response, many of their molecular portraits are currently unknown. In this review, we discuss recent understanding of MFB in health and diseases, focusing specifically on three evolving research fields: metabolism, autophagy, and epigenetics. We have emphasized on therapeutic prospects where applicable and mentioned techniques for use in MFB studies. Subsequently, we highlighted uncharted territories in MFB research to help direct future efforts aimed at bridging gaps in current knowledge.

Double-balloon endoscopy as the primary method for small-bowel video capsule endoscope retrieval.

PubMed

Van Weyenberg, Stijn J B; Van Turenhout, Sietze T; Bouma, Gerd; Van Waesberghe, Jan Hein T M; Van der Peet, Donald L; Mulder, Chris J J; Jacobs, Maarten A J M

2010-03-01

Capsule retention in the small bowel is a known complication of small-bowel video capsule endoscopy. Surgery is the most frequently used method of capsule retrieval. To determine the incidence and causes of capsule retention and to describe double-balloon endoscopy (DBE) as the primary technique used for capsule retrieval. Retrospective analysis of all video capsule studies was performed at our center, and evaluation of the outcome of DBE was the first method used to retrieve entrapped video capsules. Tertiary referral center. A total of 904 patients who underwent small-bowel video capsule endoscopy. Capsule retrieval by DBE. The number of patients in whom capsule retention occurred and the number of patients in whom an entrapped capsule could be retrieved by using DBE. Capsule retention occurred in 8 patients (incidence 0.88%; 95% CI, 0.41%-1.80%) and caused acute small-bowel obstruction in 6 patients. All retained capsules were successfully removed during DBE. Five patients underwent elective surgery to treat the underlying cause of capsule retention. One patient required emergency surgery because of multiple small-bowel perforations. Retrospective design. In our series, the incidence of capsule retention was low. DBE is a reliable method for removing retained capsules and might prevent unnecessary surgery. If surgery is required, preoperative capsule retrieval allows preoperative diagnosis, adequate staging in case of malignancy, and optimal surgical planning. 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Design of illumination system in ring field capsule endoscope

NASA Astrophysics Data System (ADS)

Jeng, Wei-De; Mang, Ou-Yang; Chen, Yu-Ta; Wu, Ying-Yi

2011-03-01

This paper is researching about the illumination system in ring field capsule endoscope. It is difficult to obtain the uniform illumination on the observed object because the light intensity of LED will be changed along its angular displacement and same as luminous intensity distribution curve. So we use the optical design software which is Advanced Systems Analysis Program (ASAP) to build a photometric model for the optimal design of LED illumination system in ring field capsule endoscope. In this paper, the optimal design of illumination uniformity in the ring field capsule endoscope is from origin 0.128 up to optimum 0.603 and it would advance the image quality of ring field capsule endoscope greatly.

Laundry detergent capsules and pediatric poisoning

PubMed Central

Bonney, Asha G.; Mazor, Suzan; Goldman, Ran D.

2013-01-01

Abstract Question A 4-year-old girl was brought into the emergency department vomiting after having had ingested a laundry detergent capsule (LDC) from under the sink at her house. What is the risk of LDC poisoning? What can be done to treat these children? Answer Laundry detergent capsules are relatively new to supermarket shelves in North America, and there has been an emergence of case reports in the literature describing LDC poisoning, which is worse than poisoning from other laundry detergents. Very little is known about the mechanisms causing these severe reactions, which include airway compromise and esophageal perforation, but the attractive appearance of these capsules and easy access at home has governments and health officials concerned about an increase in poisoning. No residual problems have been associated with these cases to date; however, further research is needed to assess long-term effects. PMID:24336541

A review of drug delivery systems for capsule endoscopy.

PubMed

Munoz, Fredy; Alici, Gursel; Li, Weihua

2014-05-01

The development of a highly controllable drug delivery system (DDS) for capsule endoscopy has become an important field of research due to its promising applications in therapeutic treatment of diseases in the gastrointestinal (GI) tract and drug absorption studies. Several factors need to be considered to establish the minimum requirements for a functional DDS. Environmental factors of the GI tract and also pharmaceutical factors can help determine the requirements to be met by a DDS in an endoscopic capsule. In order to minimize the influence of such factors on the performance of an effective DDS, at least two mechanisms should be incorporated into a capsule endoscope: an anchoring mechanism to control the capsule position and a drug release mechanism to control variables such as the drug release rate, number of doses and amount of drug released. The implementation of such remotely actuated mechanisms is challenging due to several constraints, including the limited space available in a swallowable capsule endoscope and the delicate and complex environment within the GI tract. This paper presents a comprehensive overview of existing DDS. A comparison of such DDS for capsule endoscopy based on the minimum DDS requirements is presented and future work is also discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Magnetically Actuated Soft Capsule With the Multimodal Drug Release Function

PubMed Central

Yim, Sehyuk; Goyal, Kartik; Sitti, Metin

2014-01-01

In this paper, we present a magnetically actuated multimodal drug release mechanism using a tetherless soft capsule endoscope for the treatment of gastric disease. Because the designed capsule has a drug chamber between both magnetic heads, if it is compressed by the external magnetic field, the capsule could release a drug in a specific position locally. The capsule is designed to release a drug in two modes according to the situation. In the first mode, a small amount of drug is continuously released by a series of pulse type magnetic field (0.01–0.03 T). The experimental results show that the drug release can be controlled by the frequency of the external magnetic pulse. In the second mode, about 800 mm3 of drug is released by the external magnetic field of 0.07 T, which induces a stronger magnetic attraction than the critical force for capsule’s collapsing. As a result, a polymeric coating is formed around the capsule. The coated area is dependent on the drug viscosity. This paper presents simulations and various experiments to evaluate the magnetically actuated multimodal drug release capability. The proposed soft capsules could be used as minimally invasive tetherless medical devices with therapeutic capability for the next generation capsule endoscopy. PMID:25378896

Asymptomatic bronchial aspiration and prolonged retention of a capsule endoscope: a case report.

PubMed

Pezzoli, Alessandro; Fusetti, Nadia; Carella, Alessandra; Gullini, Sergio

2011-08-02

Capsule endoscopy has, over the last few years, become a first-line test to visualize the mucosa of the small intestine. This technique is generally considered safe and does not cause discomfort for patients. However, although patients may have difficulty in swallowing the capsule, bronchial aspiration of a capsule endoscope is a very rare complication. We report the case of an 82-year-old man who experienced prolonged bronchial aspiration of a capsule endoscope without relevant symptoms, followed by a spontaneous return of the capsule to the gastrointestinal tract. An 82-year-old Caucasian man was referred to our unit from another local hospital to undergo capsule endoscopy. He swallowed the capsule without any apparent difficulties and did not show any overt symptoms. The following day, when we reviewed the capsule endoscopy images, we realized that the capsule was in the bronchial system and remained there for the duration of the study. An urgent X-ray of the chest confirmed the presence of the capsule in the left side of the bronchopulmonary tree. Two days later a repeat chest X-ray showed the capsule in the right bronchus. After two days the capsule was retrieved in the feces. Our patient remained asymptomatic during the entire admission period. Aspiration of a capsule endoscope is a rare complication; to the best of our knowledge this is the first reported case in which a capsule endoscope remained for six days in the bronchial system of a patient without causing airway compromise or pneumonitis and spontaneously returned to the gastrointestinal tract.

Description and Nomenclature of Neisseria meningitidis Capsule Locus

PubMed Central

Claus, Heike; Jiang, Ying; Bennett, Julia S.; Bratcher, Holly B.; Jolley, Keith A.; Corton, Craig; Care, Rory; Poolman, Jan T.; Zollinger, Wendell D.; Frasch, Carl E.; Stephens, David S.; Feavers, Ian; Frosch, Matthias; Parkhill, Julian; Vogel, Ulrich; Quail, Michael A.; Bentley, Stephen D.; Maiden, Martin C.J.

2013-01-01

Pathogenic Neisseria meningitidis isolates contain a polysaccharide capsule that is the main virulence determinant for this bacterium. Thirteen capsular polysaccharides have been described, and nuclear magnetic resonance spectroscopy has enabled determination of the structure of capsular polysaccharides responsible for serogroup specificity. Molecular mechanisms involved in N. meningitidis capsule biosynthesis have also been identified, and genes involved in this process and in cell surface translocation are clustered at a single chromosomal locus termed cps. The use of multiple names for some of the genes involved in capsule synthesis, combined with the need for rapid diagnosis of serogroups commonly associated with invasive meningococcal disease, prompted a requirement for a consistent approach to the nomenclature of capsule genes. In this report, a comprehensive description of all N. meningitidis serogroups is provided, along with a proposed nomenclature, which was presented at the 2012 XVIIIth International Pathogenic Neisseria Conference. PMID:23628376

Inflammatory myofibroblastic tumor: an entity of CT and MR imaging to differentiate from malignant tumors of the sinonasal cavity.

PubMed

Yan, Zhongyu; Wang, Yongzhe; Zhang, Zhengyu

2014-01-01

Inflammatory myofibroblastic tumor (IMT) is chronic inflammatory lesions of unknown origins. The preoperative diagnosis for tumors in the sinonasal cavity is difficult to distinguish between IMT and aggressive malignancy in most cases. The purpose of this study was to evaluate the imaging features of IMT distinguishing the 2 types of tumors. Computed tomography and magnetic resonance imaging were identified retrospectively with IMT in 14 cases and with aggressive malignancy in 38 cases in the sinonasal cavity proven by pathology. Imaging findings were evaluated, including the configuration, extent, margin, calcification, bone involvement, T1WI and T2WI signal intensity, and degree of enhancement. There was a significant difference between IMT and aggressive malignancy regarding the configuration, extension, calcification, bone change, signal intensity and homogeneous on T2-weighted imaging, and degree of enhancement (P < 0.05). Inflammatory myofibroblastic tumor and aggressive malignancy have some different imaging features that could be helpful in the differentiation between the lesions. Bone erosion with sclerosis, calcification when present, typically homogenous and never hyperintense of T2 appearance, and mild enhancement played an important role in differentiating sinonasal IMT from malignancies.

TNF-α-induced NF-κB activation promotes myofibroblast differentiation of LR-MSCs and exacerbates bleomycin-induced pulmonary fibrosis.

PubMed

Hou, Jiwei; Ma, Tan; Cao, Honghui; Chen, Yabing; Wang, Cong; Chen, Xiang; Xiang, Zou; Han, Xiaodong

2018-03-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease of unknown cause. It has been reported that both lung resident mesenchymal stem cells (LR-MSCs) and tumor necrosis factor-α (TNF-α) play important roles in the development of pulmonary fibrosis. However, the underlying connections between LR-MSCs and TNF-α in the pathogenesis of pulmonary fibrosis are still elusive. In this study, we found that the pro-inflammatory cytokine TNF-α and the transcription factor nuclear factor kappa B (NF-κB) p65 subunit were both upregulated in bleomycin-induced fibrotic lung tissue. In addition, we discovered that TNF-α promotes myofibroblast differentiation of LR-MSCs through activating NF-κB signaling. Interestingly, we also found that TNF-α promotes the expression of β-catenin. Moreover, we demonstrated that suppression of the NF-κB signaling could attenuate myofibroblast differentiation of LR-MSCs and bleomycin-induced pulmonary fibrosis which were accompanied with decreased expression of β-catenin. Our data implicates that inhibition of the NF-κB signaling pathway may provide a therapeutic strategy for pulmonary fibrosis, a disease that warrants more effective treatment approaches. © 2017 Wiley Periodicals, Inc.

The Effects of Knee Joint Effusion on Quadriceps Electromyography During Jogging

PubMed Central

Torry, Michael R.; Decker, Michael J.; Millett, Peter J.; Steadman, J. Richard; Sterett, William I.

2005-01-01

To investigate and describe the influence of intra-articular effusion on knee joint kinematics and electromyographic (EMG) profiles during jogging. Thirteen individuals underwent a 20 cc 0.9% saline insufflation of the knee joint capsule and completed 8 jogging trials. Stance phase, sagittal plane knee joint kinematics and thigh muscular EMG profiles were compared pre- and post-insufflation utilizing a paired t-test ( = 0.05). Mild knee effusion caused a reduction in vastus medialis (p = 0.005) and lateralis (p = 0.006) EMG activity. The rectus femoris, biceps femoris and medial hamstring muscles did not exhibit changes due to this protocol. There were no changes in the sagittal plane knee joint kinematic pattern. Twenty cc effusion can cause quadriceps inhibition in the vastus medialis and the vastus lateralis in otherwise healthy individuals during jogging. This study provides baseline data for the effects of mild knee joint effusion on thigh musculature during jogging. Key Points 20 cc of knee effusion can cause vastus medialis and lateralis inhibition as noted by decreases in EMG amplitude. This effusion does not appear to alter sagittal plane knee joint kinematics during jogging. This finding if different from previous work investigating knee joint kinematic changes during a less dynamic activity (gait) with 20 cc of effusion. PMID:24431955

Residual mercury content and leaching of mercury and silver from used amalgam capsules.

PubMed

Stone, M E; Pederson, E D; Cohen, M E; Ragain, J C; Karaway, R S; Auxer, R A; Saluta, A R

2002-06-01

The objective of this investigation was to carry out residual mercury (Hg) determinations and toxicity characteristic leaching procedure (TCLP) analysis of used amalgam capsules. For residual Hg analysis, 25 capsules (20 capsules for one brand) from each of 10 different brands of amalgam were analyzed. Total residual Hg levels per capsule were determined using United States Environmental Protection Agency (USEPA) Method 7471. For TCLP analysis, 25 amalgam capsules for each of 10 brands were extracted using a modification of USEPA Method 1311. Hg analysis of the TCLP extracts was done with USEPA Method 7470A. Analysis of silver (Ag) concentrations in the TCLP extract was done with USEPA Method 6010B. Analysis of the residual Hg data resulted in the segregation of brands into three groups: Dispersalloy capsules, Group A, retained the most Hg (1.225 mg/capsule). These capsules were the only ones to include a pestle. Group B capsules, Valliant PhD, Optaloy II, Megalloy and Valliant Snap Set, retained the next highest amount of Hg (0.534-0.770 mg/capsule), and were characterized by a groove in the inside of the capsule. Group C, Tytin regular set double-spill, Tytin FC, Contour, Sybraloy regular set, and Tytin regular set single-spill retained the least amount of Hg (0.125-0.266 mg/capsule). TCLP analysis of the triturated capsules showed Sybraloy and Contour leached Hg at greater than the 0.2 mg/l Resource Conservation and Recovery Act (RCRA) limit. This study demonstrated that residual mercury may be related to capsule design features and that TCLP extracts from these capsules could, in some brands, exceed RCRA Hg limits, making their disposal problematic. At current RCRA limits, the leaching of Ag is not a problem.

A comparative study on liquid core formulation on the diameter on the alginate capsules

NASA Astrophysics Data System (ADS)

Ong, Hui-Yen; Lee, Boon-Beng; Radzi, AkmalHadi Ma'; Zakaria, Zarina; Chan, Eng-Seng

2015-08-01

Liquid core capsule has vast application in biotechnology related industries such as pharmaceutical, medical, agriculture and food. Formulation of different types of capsule was important to determine the performance of the capsule. Generally, the liquid core capsule with different formulations generated different size of capsule.Therefore, the aim of this project is to investigate the effect of different liquid core solution formulations on the diameter of capsule. The capsule produced by extruding liquid core solutions into sodium alginate solution. Three types of liquid core solutions (chitosan, xanthan gum, polyethylene glycol (PEG)) were investigated. The results showed that there is significant change in capsule diameter despite in different types of liquid core solution were used and a series of capsule range in diameter of 3.1 mm to 4.5 mm were produced. Alginate capsule with chitosan formulation appeared to be the largest capsule among all.

[Exploring the clinical characters of Shugan Jieyu capsule through text mining].

PubMed

Pu, Zheng-Ping; Xia, Jiang-Ming; Xie, Wei; He, Jin-Cai

2017-09-01

The study was main to explore the clinical characters of Shugan Jieyu capsule through text mining. The data sets of Shugan Jieyu capsule were downloaded from CMCC database by the method of literature retrieved from May 2009 to Jan 2016. Rules of Chinese medical patterns, diseases, symptoms and combination treatment were mined out by data slicing algorithm, and they were demonstrated in frequency tables and two dimension based network. Then totally 190 literature were recruited. The outcomess suggested that SC was most frequently correlated with liver Qi stagnation. Primary depression, depression due to brain disease, concomitant depression followed by physical diseases, concomitant depression followed by schizophrenia and functional dyspepsia were main diseases treated by Shugan Jieyu capsule. Symptoms like low mood, psychic anxiety, somatic anxiety and dysfunction of automatic nerve were mainy relieved bv Shugan Jieyu capsule.For combination treatment. Shugan Jieyu capsule was most commonly used with paroxetine, sertraline and fluoxetine. The research suggested that syndrome types and mining results of Shugan Jieyu capsule were almost the same as its instructions. Syndrome of malnutrition of heart spirit was the potential Chinese medical pattern of Shugan Jieyu capsule. Primary comorbid anxiety and depression, concomitant comorbid anxiety and depression followed by physical diseases, and postpartum depression were potential diseases treated by Shugan Jieyu capsule.For combination treatment, Shugan Jieyu capsule was most commonly used with paroxetine, sertraline and fluoxetine. Copyright© by the Chinese Pharmaceutical Association.

The double capsules in macro-textured breast implants.

PubMed

Giot, Jean-Philippe; Paek, Laurence S; Nizard, Nathanael; El-Diwany, Mostafa; Gaboury, Louis A; Nelea, Monica; Bou-Merhi, Joseph S; Harris, Patrick G; Danino, Michel A

2015-10-01

Breast implants are amongst the most widely used types of permanent implants in modern medicine and have both aesthetic and reconstructive applications with excellent biocompatibility. The double capsule is a complication associated with textured prostheses that leads to implant displacement; however, its etiology has yet to be elucidated. In this study, 10 double capsules were sampled from breast expander implants for in-depth analysis; histologically, the inner capsular layer demonstrated highly organized collagen in sheets with delamination of fibers. At the prosthesis interface (PI) where the implant shell contacts the inner capsular layer, scanning electron microscopy (SEM) revealed a thin layer which mirrored the three-dimensional characteristics of the implant texture; the external surface of the inner capsular layer facing the intercapsular space (ICS) was flat. SEM examination of the inner capsule layer revealed both a large bacterial presence as well as biofilm deposition at the PI; a significantly lower quantity of bacteria and biofilm were found at the ICS interface. These findings suggest that the double capsule phenomenon's etiopathogenesis is of mechanical origin. Delamination of the periprosthetic capsule leads to the creation of the ICS; the maintained separation of the 2 layers subsequently alters the biostability of the macro-textured breast implant. Copyright © 2015 Elsevier Ltd. All rights reserved.

Versatile Loading of Diverse Cargo into Functional Polymer Capsules.

PubMed

Richardson, Joseph J; Maina, James W; Ejima, Hirotaka; Hu, Ming; Guo, Junling; Choy, Mei Y; Gunawan, Sylvia T; Lybaert, Lien; Hagemeyer, Christoph E; De Geest, Bruno G; Caruso, Frank

2015-02-01

Polymer microcapsules are of particular interest for applications including self-healing coatings, catalysis, bioreactions, sensing, and drug delivery. The primary way that polymer capsules can exhibit functionality relevant to these diverse fields is through the incorporation of functional cargo in the capsule cavity or wall. Diverse functional and therapeutic cargo can be loaded into polymer capsules with ease using polymer-stabilized calcium carbonate (CaCO 3 ) particles. A variety of examples are demonstrated, including 15 types of cargo, yielding a toolbox with effectively 500+ variations. This process uses no harsh reagents and can take less than 30 min to prepare, load, coat, and form the hollow capsules. For these reasons, it is expected that the technique will play a crucial role across scientific studies in numerous fields.

Deformation of an elastic capsule in a uniform electric field

NASA Astrophysics Data System (ADS)

Karyappa, Rahul B.; Deshmukh, Shivraj. D.; Thaokar, Rochish. M.

2014-12-01

The deformation of a thin elastic capsule subjected to a uniform electric field is investigated in the Stokes flow regime. The electrohydrodynamic flow is analyzed using a perfect conductor and a perfect dielectric model for the capsule and the fluid phase, respectively. A theoretical analysis is carried out using an asymptotic expansion in the electric capillary number (Ca) (a ratio of the electric stress to the elastic tension) in the small deformation limit using the finite deformation Hooke's law. The analysis is used to determine the elasticity of polysiloxane capsules suspended in oil, the deformation of which is obtained using videography. The boundary element method is implemented to seek numerical solutions to the hydrodynamic, elastic, and electrostatics equations. The finite deformation Hooke's law, the Mooney-Rivlin, and Skalak's model for elasticity are employed. The effect of electric capillary number, unstressed geometry, and the type of membrane material on the deformation of a capsule is presented in the high Ca number limit using numerical simulation. Capsules synthesized with higher monomer concentration displayed electric stress induced wrinkling process at high electric field strengths. Burst of a capsule is characterized by poration of the polymer membrane, which could be symmetric or asymmetric at the two poles, depending upon the value of the capillary number. The results should be useful in understanding the response of elastic capsules such as red blood cells and polymerized membranes, to an electric field, in applications such as electrodeformation and electroporation. It also provides a theoretical framework for a possible way of determining the elastic parameters of a capsule.

Glenohumeral corticosteroid injections in adhesive capsulitis: a systematic search and review

PubMed Central

Song, Amos; Higgins, Laurence D.; Newman, Joel; Jain, Nitin B.

2014-01-01

OBJECTIVES To assess the literature on outcomes of corticosteroid injections for adhesive capsulitis, and in particular, image-guided corticosteroid injections. TYPE Systematic search and review LITERATURE SURVEY The databases used were PubMed (1966-present), Embase (1947-present), Web of Science (1900–present), and the Cochrane Central Register of Controlled Trials. Upon reviewing full text articles of these studies, a total of 25 studies were identified for inclusion. The final yield included 7 prospective studies, 16 randomized trials, and 2 retrospective studies. METHODOLOGY This systematic review was formatted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study criteria were limited to clinical trials, prospective studies, and retrospective studies that specifically evaluated intra-articular corticosteroid injections, both alone and in combination with other treatment modalities, for shoulder adhesive capsulitis. We included studies that were not randomized control trials because our review was not a meta-analysis. Data items extracted from each study included: study design, study population, mean patient age, duration of study, duration of symptoms, intervention, single or multiple injections, location of injections, control population, follow up duration, and outcome measurements. A percent change in outcome measures was calculated when corresponding data was available. Risk of bias in individual studies was assessed when appropriate. SYNTHESIS All studies involved at least one corticosteroid injection intended for placement in the glenohumeral joint but only eight studies used image-guidance for all injections. Seven of these studies reported statistically significant improvements in ROM at 12 weeks of follow-up or earlier. Ninety-two percent of all studies documented a greater improvement in either visual analog pain scores or range of motion after corticosteroid injections in the first 1–6 weeks as

Elevation of transforming growth factor beta (TGFbeta) and its downstream mediators in subcutaneous foreign body capsule tissue.

PubMed

Li, Allen G; Quinn, Matthew J; Siddiqui, Yasmin; Wood, Michael D; Federiuk, Isaac F; Duman, Heather M; Ward, W Kenneth

2007-08-01

Foreign body encapsulation represents a chronic fibrotic response and has been a major obstacle that reduces the useful life of implanted biomedical devices. The precise mechanism underlying such an encapsulation is still unknown. We hypothesized that, considering its central role in many other fibrotic conditions, transforming growth factor beta (TGFbeta) may play an important role during the formation of foreign body capsule (FBC). In the present study, we implanted mock sensors in rats subcutaneously and excised FBC samples at day 7, 21, and 48-55 postimplantation. The most abundant TGFbeta isoform in all tissues was TGFbeta1, which was expressed minimally in control tissue. The expression of both TGFbeta1 RNA and protein was significantly increased in FBC tissues at all time points, with the highest level in day 7 FBC. The number of cells stained for phosphorylated Smad2, an indication of activated TGFbeta signaling, paralleled the expression of TGFbeta. A similar dynamic change was also observed in the numbers of FBC myofibroblasts, which in response to TGFbeta, differentiate from quiescent fibroblasts and synthesize collagen. Type I collagen, the most prominent downstream target of TGFbeta in fibrosis, was found in abundance in the FBC, especially during the latter time periods. We suggest that TGFbeta plays an important role in the FBC formation. Inhibition of TGFbeta signaling could be a promising strategy in the prevention of FBC formation, thereby extending the useful life of subcutaneous implants.

Wireless capsule endoscopy: perspectives beyond gastrointestinal bleeding.

PubMed

Redondo-Cerezo, Eduardo; Sánchez-Capilla, Antonio Damián; De La Torre-Rubio, Paloma; De Teresa, Javier

2014-11-14

Wireless capsule endoscopy (CE) is a technology developed for the endoscopic exploration of the small bowel. The first capsule model was approved by the Food and Drug Administration in 2001, and its first and essential indication was occult gastrointestinal (GI) bleeding. Over subsequent years, this technology has been refined to provide superior resolution, increased battery life, and capabilities to view different parts of the GI tract. Indeed, cases for which CE proved useful have increased significantly over the last few years, with new indications for the small bowel and technical improvements that have expanded its use to other parts of the GI tract, including the esophagus and colon. The main challenges in the development of CE are new devices with the ability to provide therapy, air inflation for a better vision of the small bowel, biopsy sampling systems attached to the capsule and the possibility to guide and move the capsule with an external motion control. In this article we review the current and new indications of CE, and the evolving technological changes shaping this technology, which has a promising potential in the coming future of gastroenterology.

Method of forming capsules containing a precise amount of material

DOEpatents

Grossman, Mark W.; George, William A.; Maya, Jakob

1986-01-01

A method of forming a sealed capsule containing a submilligram quantity of mercury or the like, the capsule being constructed from a hollow glass tube, by placing a globule or droplet of the mercury in the tube. The tube is then evacuated and sealed and is subsequently heated so as to vaporize the mercury and fill the tube therewith. The tube is then separated into separate sealed capsules by heating spaced locations along the tube with a coiled heating wire means to cause collapse spaced locations therealong and thus enable separation of the tube into said capsules.

Method of forming capsules containing a precise amount of material

DOEpatents

Grossman, M.W.; George, W.A.; Maya, J.

1986-06-24

A method of forming a sealed capsule containing a submilligram quantity of mercury or the like, the capsule being constructed from a hollow glass tube, by placing a globule or droplet of the mercury in the tube. The tube is then evacuated and sealed and is subsequently heated so as to vaporize the mercury and fill the tube therewith. The tube is then separated into separate sealed capsules by heating spaced locations along the tube with a coiled heating wire means to cause collapse spaced locations there along and thus enable separation of the tube into said capsules. 7 figs.

Supercooling Water in Cylindrical Capsules

NASA Astrophysics Data System (ADS)

Guzman, J. J. Milón; Braga, S. L.

2005-11-01

An experimental apparatus was developed to investigate the supercooling phenomenon of water inside cylindrical capsules used for a cold storage process. The coolant is a water-alcohol mixture controlled by a constant temperature bath (CTB). Temperatures varying with time are measured inside and outside the capsule. Cylinders with an internal diameter and thickness of 45 and 1.5 mm, respectively, were made from four different materials: acrylic, PVC, brass, and aluminum. The supercooling period of the water and the nucleation temperature were investigated for different coolant temperatures. The supercooling and nucleation probabilities are shown as a function of the coolant temperature for the four different materials.

Video-based measurements for wireless capsule endoscope tracking

NASA Astrophysics Data System (ADS)

Spyrou, Evaggelos; Iakovidis, Dimitris K.

2014-01-01

The wireless capsule endoscope is a swallowable medical device equipped with a miniature camera enabling the visual examination of the gastrointestinal (GI) tract. It wirelessly transmits thousands of images to an external video recording system, while its location and orientation are being tracked approximately by external sensor arrays. In this paper we investigate a video-based approach to tracking the capsule endoscope without requiring any external equipment. The proposed method involves extraction of speeded up robust features from video frames, registration of consecutive frames based on the random sample consensus algorithm, and estimation of the displacement and rotation of interest points within these frames. The results obtained by the application of this method on wireless capsule endoscopy videos indicate its effectiveness and improved performance over the state of the art. The findings of this research pave the way for a cost-effective localization and travel distance measurement of capsule endoscopes in the GI tract, which could contribute in the planning of more accurate surgical interventions.

Medical capsule robots: A renaissance for diagnostics, drug delivery and surgical treatment.

PubMed

Mapara, Sanyat S; Patravale, Vandana B

2017-09-10

The advancements in electronics and the progress in nanotechnology have resulted in path breaking development that will transform the way diagnosis and treatment are carried out currently. This development is Medical Capsule Robots, which has emerged from the science fiction idea of robots travelling inside the body to diagnose and cure disorders. The first marketed capsule robot was a capsule endoscope developed to capture images of the gastrointestinal tract. Today, varieties of capsule endoscopes are available in the market. They are slightly larger than regular oral capsules, made up of a biocompatible case and have electronic circuitry and mechanisms to capture and transmit images. In addition, robots with diagnostic features such as in vivo body temperature detection and pH monitoring have also been launched in the market. However, a multi-functional unit that will diagnose and cure diseases inside the body has not yet been realized. A remote controlled capsule that will undertake drug delivery and surgical treatment has not been successfully launched in the market. High cost, inadequate power supply, lack of control over drug release, limited space for drug storage on the capsule, inadequate safety and no mechanisms for active locomotion and anchoring have prevented their entry in the market. The capsule robots can revolutionize the current way of diagnosis and treatment. This paper discusses in detail the applications of medical capsule robots in diagnostics, drug delivery and surgical treatment. In diagnostics, detailed analysis has been presented on wireless capsule endoscopes, issues associated with the marketed versions and their corresponding solutions in literature. Moreover, an assessment has been made of the existing state of remote controlled capsules for targeted drug delivery and surgical treatment and their future impact is predicted. Besides the need for multi-functional capsule robots and the areas for further research have also been

Phenotypic Heterogeneity in Expression of the K1 Polysaccharide Capsule of Uropathogenic Escherichia coli and Downregulation of the Capsule Genes during Growth in Urine.

PubMed

King, Jane E; Aal Owaif, Hasan A; Jia, Jia; Roberts, Ian S

2015-07-01

Uropathogenic Escherichia coli (UPEC) is the major causative agent of uncomplicated urinary tract infections (UTI). The K1 capsule on the surface of UPEC strains is a key virulence factor, and its expression may be important in the onset and progression of UTI. In order to understand capsule expression in more detail, we analyzed its expression in the UPEC strain UTI89 during growth in rich medium (LB medium) and urine and during infection of a bladder epithelial cell line. Comparison of capsule gene transcription using a chromosomal gfp reporter fusion showed a significant reduction in transcription during growth in urine compared to that during growth in LB medium. When examined at the single-cell level, following growth in both media, capsule gene expression appears to be heterogeneous, with two distinct green fluorescent protein (GFP)-expressing populations. Using anti-K1 antibody, we showed that this heterogeneity in gene expression results in two populations of encapsulated and unencapsulated cells. We demonstrated that the capsule hinders attachment to and invasion of epithelial cells and that the unencapsulated cells within the population preferentially adhere to and invade bladder epithelial cells. We found that once internalized, UTI89 starts to produce capsule to aid in its intracellular survival and spread. We propose that this observed phenotypic diversity in capsule expression is a fitness strategy used by the bacterium to deal with the constantly changing environment of the urinary tract. Copyright © 2015 King et al.

Antiobesity effects of Undaria lipid capsules prepared with scallop phospholipids.

PubMed

Okada, Tomoko; Mizuno, Yasuyuki; Sibayama, Shinichi; Hosokawa, Masashi; Miyashita, Kazuo

2011-01-01

Based on previous research findings, a capsule was developed containing n-3 polyunsaturated fatty acid rich scallop phospholipids (PLs) with an incorporation of brown seaweed (Undaria pinnatifida) lipids (ULs) containing fucoxanthin. The antiobesity effects of the capsules were evaluated with an animal model using 3-wk-old male KK-A(y) mice. Each group received different combinations of lipid (UL, PL, UL + PL, or UL + PL capsule) either incorporated into the diet or into drinking water. Animals were sacrificed after a 4-wk experimental feeding period, and adipose tissues and organs were dissected and weighed. Blood samples were obtained to determine plasma lipid profiles. Uncoupling protein 1 (UCP1) mRNA expression levels were determined by real-time polymerase chain reaction analysis, and UCP1 expression was determined by western blotting analysis. Treatment with either UL alone or UL + PL (capsule) through drinking water resulted in a significant reduction in body weight, compared to the control group. The total white adipose tissue weight of mice fed the UL + PL capsule in drinking water was significantly reduced. Both UCP1 and UCP1 mRNA expression in epididymal fat from mice fed the capsule were significantly higher than in the control group. These results suggest that incorporation of UL into scallop-derived PL by means of capsulation may lead to an additive increase in the antiobesity properties of these bioactive lipids.

Water Landing Characteristics of a Reentry Capsule

NASA Technical Reports Server (NTRS)

1958-01-01

Experimental and theoretical investigations have been made to determine the water-landing characteristics of a conical-shaped reentry capsule having a segment of a sphere as the bottom. For the experimental portion of the investigation, a 1/12-scale model capsule and a full-scale capsule were tested for nominal flight paths of 65 deg and 90 deg (vertical), a range of contact attitudes from -30 deg to 30 deg, and a full-scale vertical velocity of 30 feet per second at contact. Accelerations were measured by accelerometers installed at the centers of gravity of the model and full-scale capsules. For the model test the accelerations were measured along the X-axis (roll) and Z-axis (yaw) and for the full-scale test they were measured along the X-axis (roll), Y-axis (pitch), and Z-axis (yaw). Motions and displacements of the capsules that occurred after contact were determined from high-speed motion pictures. The theoretical investigation was conducted to determine the accelerations that might occur along the X-axis when the capsule contacted the water from a 90 deg flight path at a 0 deg attitude. Assuming a rigid body, computations were made from equations obtained by utilizing the principle of the conservation of momentum. The agreement among data obtained from the model test, the full-scale test, and the theory was very good. The accelerations along the X-axis, for a vertical flight path and 0 deg attitude, were in the order of 40g. For a 65 deg flight path and 0 deg attitude, the accelerations along the X-axis were in the order of 50g. Changes in contact attitude, in either the positive or negative direction from 0 deg attitude, considerably reduced the magnitude of the accelerations measured along the X-axis. Accelerations measured along the Y- and Z-axes were relatively small at all test conditions.

Water-Landing Characteristics of a Reentry Capsule

NASA Technical Reports Server (NTRS)

McGehee, John R.; Hathaway, Melvin E.; Vaughan, Victor L., Jr.

1959-01-01

Experimental and theoretical investigations have been made to determine the water-landing characteristics of a conical-shaped reentry capsule having a segment of a sphere as the bottom. For the experimental portion of the investigation, a 1/12-scale model capsule and a full-scale capsule were tested for nominal flight paths of 65 deg and 90 deg (vertical), a range of contact attitudes from -30 deg to 30 deg, and a full-scale vertical velocity of 30 feet per second at contact. Accelerations were measured by accelerometers installed at the centers of gravity of the model and full-scale capsules. For the model test the accelerations were measured along the X-axis (roll) and Z-axis (yaw) and for the full-scale test they were measured along the X-axis (roll), Y-axis (pitch), and Z-axis (yaw). Motions and displacements of the capsules that occurred after contact were determined from high-speed motion pictures. The theoretical investigation was conducted to determine the accelerations that might occur along the X-axis when the capsule contacted the water from a 90 deg flight path at a 0 deg attitude. Assuming a rigid body, computations were made from equations obtained by utilizing the principle of the conservation of momentum. The agreement among data obtained from the model test, the full-scale test, and the theory was very good. The accelerations along the X-axis, for a vertical flight path and 0 deg attitude, were in the order of 40g. For a 65 deg flight path and 0 deg attitude, the accelerations along the X-axis were in the order of 50g. Changes in contact attitude, in either the positive or negative direction from 0 deg attitude, considerably reduced the magnitude of the accelerations measured along the X-axis. Accelerations measured along the Y- and Z-axes were relatively small at all test conditions.

The effect of glicerol and sorbitol plasticizers toward disintegration time of phyto-capsules

NASA Astrophysics Data System (ADS)

Pudjiastuti, Pratiwi; Hendradi, Esti; Wafiroh, Siti; Harsini, Muji; Darmokoesoemo, Handoko

2016-03-01

The aim of research is determining the effect of glycerol and sorbitol toward the disintegration time of phyto-capsules, originated capsules from plant polysaccharides. Phyto-capsules were made from polysaccharides and 0.5% (v/v) of glycerol and sorbitol of each. The seven capsules of each were determined the disintegration time using Erweka disintegrator. The mean of disintegration time of phyto-capsules without plasticizers, with glycerol and sorbitol were 25'30"; 45'15" and 35'30" respectively. The color and colorless gelatin capsules showed the mean of disintegration time 7'30" and 2'35" respectively.

Capsule Endoscopy in the Assessment of Obscure Gastrointestinal Bleeding: An Economic Analysis

PubMed Central

Palimaka, S; Blackhouse, Gord; Goeree, Ron

2015-01-01

Background Small-bowel capsule endoscopy is a tool used to visualize the small bowel to identify the location of bleeds in obscure gastrointestinal bleeding (OGIB). Capsule endoscopy is currently funded in Ontario in cases where there has been a failure to identify a source of bleeding via conventional diagnostic procedures. In Ontario, capsule endoscopy is a diagnostic option for patients whose findings on esophagogastroduodenoscopy, colonoscopy, and push enteroscopy have been negative (i.e., the source of bleeding was not found). Objectives This economic analysis aims to estimate the budget impact of different rates of capsule endoscopy use as a complement to push enteroscopy procedures in patients aged 18 years and older. Data Sources Population-based administrative databases for Ontario were used to identify patients receiving push enteroscopy and small-bowel capsule endoscopy in the fiscal years 2008 to 2012. Review Methods A systematic literature search was performed to identify economic evaluations of capsule endoscopy for the investigation of OGIB. Studies were assessed for their methodological quality and their applicability to the Ontarian setting. An original budget impact analysis was performed using data from Ontarian administrative sources and published literature. The budget impact was estimated for different levels of use of capsule endoscopy as a complement to push enteroscopy due to the uncertain clinical utility of the capsule based on current clinical evidence. The analysis was conducted from the provincial public payer perspective. Results With varying rates of capsule endoscopy use, the budgetary impact spans from savings of $510,000,1 when no (0%) push enteroscopy procedures are complemented with capsule endoscopy, to $2,036,000, when all (100%) push enteroscopy procedures are complemented with capsule endoscopy. A scenario where 50% of push enteroscopy procedures are complemented with capsule endoscopy (expected use based on expert opinion

Alginate/sodium caseinate aqueous-core capsules: a pH-responsive matrix.

PubMed

Ben Messaoud, Ghazi; Sánchez-González, Laura; Jacquot, Adrien; Probst, Laurent; Desobry, Stéphane

2015-02-15

Alginate capsules have several applications. Their functionality depends considerably on their permeability, chemical and mechanical stability. Consequently, the creation of composite system by addition of further components is expected to control mechanical and release properties of alginate capsules. Alginate and alginate-sodium caseinate composite liquid-core capsules were prepared by a simple extrusion. The influence of the preparation pH and sodium caseinate concentration on capsules physico-chemical properties was investigated. Results showed that sodium caseinate influenced significantly capsules properties. As regards to the membrane mechanical stability, composite capsules prepared at pH below the isoelectric point of sodium caseinate exhibited the highest surface Young's modulus, increasing with protein content, explained by potential electrostatic interactions between sodium caseinate amino-groups and alginate carboxylic group. The kinetic of cochineal red A release changed significantly for composite capsules and showed a pH-responsive release. Sodium caseinate-dye mixture studied by absorbance and fluorescence spectroscopy confirmed complex formation at pH 2 by electrostatic interactions between sodium caseinate tryptophan residues and cochineal red sulfonate-groups. Consequently, the release mechanism was explained by membrane adsorption process. This global approach is useful to control release mechanism from macro and micro-capsules by incorporating guest molecules which can interact with the entrapped molecule under specific conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Magnesium Ion Acts as a Signal for Capsule Induction in Cryptococcus neoformans.

PubMed

Rathore, Sudarshan S; Raman, Thiagarajan; Ramakrishnan, Jayapradha

2016-01-01

Cryptococcal meningitis caused by Cryptococcus neoformans, is a common opportunistic neural infection in immunocompromised individuals. Cryptococcus meningitis is associated with fungal burden with larger capsule size in cerebrospinal fluid (CSF). To understand the role of CSF constituents in capsule enlargement, we have evaluated the effect of artificial CSF on capsule induction in comparison with various other capsule inducing media. Two different strains of C. neoformans, an environmental and a clinical isolates were used in the present study. While comparing the various capsule inducing media for the two different strains of C. neoformans, it was observed that the capsule growth was significantly increased when grown in artificial CSF at pH 5.5, temperature 34°C for ATCC C. neoformans and 37°C for Clinical C. neoformans and with an incubation period of 72 h. In addition, artificial CSF supports biofilm formation in C. neoformans. While investigating the individual components of artificial CSF, we found that Mg(2+) ions influence the capsule growth in both environmental and clinical strains of C. neoformans. To confirm our results we studied the expression of four major CAP genes namely, CAP10, CAP59, CAP60, and CAP64 in various capsule inducing media and in different concentrations of Mg(2+) and Ca(2+). Our results on gene expression suggest that, Mg(2+) does have an effect on CAP gene expression, which are important for capsule biosynthesis and virulence. Our findings on the role of Mg(2+) ion as a signal for capsule induction will promote a way to elucidate the control mechanisms for capsule biosynthesis in C. neoformans.

Magnesium Ion Acts as a Signal for Capsule Induction in Cryptococcus neoformans

PubMed Central

Rathore, Sudarshan S.; Raman, Thiagarajan; Ramakrishnan, Jayapradha

2016-01-01

Cryptococcal meningitis caused by Cryptococcus neoformans, is a common opportunistic neural infection in immunocompromised individuals. Cryptococcus meningitis is associated with fungal burden with larger capsule size in cerebrospinal fluid (CSF). To understand the role of CSF constituents in capsule enlargement, we have evaluated the effect of artificial CSF on capsule induction in comparison with various other capsule inducing media. Two different strains of C. neoformans, an environmental and a clinical isolates were used in the present study. While comparing the various capsule inducing media for the two different strains of C. neoformans, it was observed that the capsule growth was significantly increased when grown in artificial CSF at pH 5.5, temperature 34°C for ATCC C. neoformans and 37°C for Clinical C. neoformans and with an incubation period of 72 h. In addition, artificial CSF supports biofilm formation in C. neoformans. While investigating the individual components of artificial CSF, we found that Mg2+ ions influence the capsule growth in both environmental and clinical strains of C. neoformans. To confirm our results we studied the expression of four major CAP genes namely, CAP10, CAP59, CAP60, and CAP64 in various capsule inducing media and in different concentrations of Mg2+ and Ca2+. Our results on gene expression suggest that, Mg2+ does have an effect on CAP gene expression, which are important for capsule biosynthesis and virulence. Our findings on the role of Mg2+ ion as a signal for capsule induction will promote a way to elucidate the control mechanisms for capsule biosynthesis in C. neoformans. PMID:27014245

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

PubMed

KuKanich, Butch; Warner, Matt; Hahn, Kevin

2017-02-01

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Capsule endoscopy: in search of the ideal image.

PubMed

Enns, Robert

2008-01-01

Capsule studies can be reviewed by varying rates and speeds; however, the presence of significant debris is frustrating to the reviewer much like the excessive stool that tends to hinder the progress of a colonoscopist. Numerous studies have been published in regards to the advantages of an ideal preparation in the setting of capsule endoscopy. This most recent study by Wei et al. is another study that has demonstrated that a colonic preparation, in this situation, combined with simethicone given just prior to the capsule study results in improved visibility of the mucosa. In theory, this will lead to an improved diagnostic ability to limit excessive reading duration.

Limited distal clavicle excision of acromioclavicular joint osteoarthritis.

PubMed

Gokkus, K; Saylik, M; Atmaca, H; Sagtas, E; Aydin, A T

2016-05-01

Resection of the distal aspect of clavicle has a well-documented treatment modality in case of acromioclavicular joint osteoarthritis resistant to conservative treatment. Limited (mean ∼0.5cm distal end of clavicle resection) distal clavicle excision of A-C joint arthritis in cases resistant to conservative treatment may reduce the pain and improve the shoulder function. In this study, we retrospectively evaluated the results of limited distal clavicle excision of acromioclavicular joint osteoarthritis resistant to conservative treatment. All patients were evaluated by using the Visual Analogue Scale (VAS) and UCLA shoulder rating scale (University of California Los Angeles), either before surgery or final follow-up period for pain and functional results, respectively. A total of 110 patients (48 male, 62 female) with AC joint arthritis, treated between the years of 2008-2012, were retrospectively analyzed. A total of 30 patients (12 male, 18 female) who failed to show improvement with conservative treatment underwent limited surgical open excision of distal clavicle. The mean age of the study population was 52.5±1.2 years. The mean follow-up period was 27±1.3 months. The mean preoperative VAS score was 83.6±5.58 (range, 70-90) while mean VAS was 26.6±9.3 (range, 10-50) at the final follow-up. There was a statistically significant difference between pre- and postoperative VAS scores in patients who had treated by surgical approach (P<0.001). The mean UCLA score of the patients increased postoperatively from 11.5 (range, 9-14) to 29.2 (range, 27-32) at the final follow-up. There was a statistically significant difference between the two time periods with respect to UCLA scores (P<0.001). In patients with AC osteoarthritis resistant to conservative therapy, the hypothesized limited clavicle excision (mean ∼0.5cm distal end of clavicle resection with preserving coracoclavicular ligaments and inferior capsule) reduced the pain and improved the shoulder function

The Antiphagocytic Activity of SeM of Streptococcus equi Requires Capsule.

PubMed

Timoney, John F; Suther, Pranav; Velineni, Sridhar; Artiushin, Sergey C

2014-01-01

Resistance to phagocytosis is a crucial virulence property of Streptococcus equi (Streptococcus equi subsp. equi; Se), the cause of equine strangles. The contribution and interdependence of capsule and SeM to killing in equine blood and neutrophils were investigated in naturally occurring strains of Se. Strains CF32, SF463 were capsule and SeM positive, strains Lex90, Lex93 were capsule negative and SeM positive and strains Se19, Se1-8 were capsule positive and SeM deficient. Phagocytosis and killing of Se19, Se1-8, Lex90 and Lex93 in equine blood and by neutrophils suspended in serum were significantly (P ≤ 0.02) greater compared to CF32 and SF463. The results indicate capsule and SeM are both required for resistance to phagocytosis and killing and that the anti-phagocytic property of SeM is greatly reduced in the absence of capsule.

Ultrasonic technique for inspection of GPHS capsule girth weld integrity

NASA Astrophysics Data System (ADS)

Placr, Arnost

1993-05-01

An innovative nondestructive examination (NDE) technique for the inspection of integrity of General Purpose Heat Source (GPHS) capsule girth welds was developed employing a Lamb wave as the mode of the sound propagation. Reliability of the Lamb wave technique was tested on GPHS capsules using plutonium pallet simulators. All ten capsules, which were previously rejected, passed ultrasonic (UT) inspection using the Lamb wave technique.

The history of time for capsule endoscopy.

PubMed

Adler, Samuel N

2017-05-01

Capsule endoscopy was conceived by inventive minds of good people. In the beginning there was a will to do something for medicine. The idea fomented after a discourse between the talented engineer with his physician friend. It took years to develop the concept. Then excellent engineers created de novo the necessary components to turn the capsule into a viable reality. The story is a tribute to human ingenuity.

Solid State Stability of Extemporaneously Prepared Levothyroxine Aliquots and Capsules.

PubMed

Fortner, Jeff; Salton, Jason; Carlson, Christie; Wheeler, Rich; Cote, Brianna; Rao, Deepa

2015-01-01

The purpose of this research was to collect, analyze, and compare stability data for levothyroxine (T4) powder in the anhydrous and pentahydrate form when prepared as an aliquot and in capsules. Two different compounding pharmacies, Central Iowa Compounding and Gateway Medical Pharmacy, used different forms of T4 and aliquot formulations, which were studied to determine the beyond-use date at ±5% or ±10% of labeled strength. T4 was extracted from aliquot and capsule formulations and assessed using reverse-phase high- performance liquid chromatography validated to differentiate between the degraded and original forms of T4. The results indicate that T4 1:100 aliquot formulation prepared with silica gel or Avicel as filler are stable for 120 days at ±10% labeled potency, but at ±5% labeled potency, the silica gel and Avicel aliquot formulations are stable for 45 and 30 days, respectively. The silica gel capsules prepared from fresh aliquot were stable for 120 days at ±10% labeled potency and 90 days at ±5% labeled potency, while the Avicel capsules prepared from fresh aliquot were stable for 180 days at both ±10% and ±5% labeled potency. Avicel capsules prepared from old aliquot (120 days) and fresh aliquot (1 day) were also compared for stability. The old aliquot Avicel capsules were stable for 14 days at ±5% labeled potency and 150 days at ±10% labeled potency, while new aliquot Avicel capsules were stable for 180 days at both ±10% and ±5% labeled potency. Based on our data, there can be significant variation in the beyond-use dates assigned to T4 capsules based on the diluents used for aliquots, the final capsule formulations, and the potency standards applied. These results also indicate that pharmacists must exercise caution when using older aliquots and may have to assign shorter beyond-use dates.

Safety of capsule endoscopy using human body communication in patients with cardiac devices.

PubMed

Chung, Joo Won; Hwang, Hye Jin; Chung, Moon Jae; Park, Jeong Youp; Pak, Hui-Nam; Song, Si Young

2012-06-01

The MiroCam (IntroMedic, Ltd., Seoul, Korea) is a small-bowel capsule endoscope that uses human body communication to transmit data. The potential interactions between cardiac devices and the capsule endoscope are causes for concern, but no data are available for this matter. This clinical study was designed to evaluate the potential influence of the MiroCam capsules on cardiac devices. Patients with cardiac pacemakers or implantable cardiac defibrillators referred for evaluation of small bowel disease were prospectively enrolled in this study. Before capsule endoscopy, a cardiologist checked baseline electrocardiograms and functions of the cardiac devices. Cardiac rhythms were continuously monitored by 24-h telemetry during capsule endoscopy in the hospital. After completion of procedures, functions of the cardiac devices were checked again for interference. Images from the capsule endoscopy were reviewed and analyzed for technical problems. Six patients, three with pacemakers and three with implantable cardiac defibrillators, were included in the study. We identified no disturbances in the cardiac devices and no arrhythmias detected on telemetry monitoring during capsule endoscopy. No significant changes in the programmed parameters of the cardiac devices were noted after capsule endoscopy. There were no imaging disturbances from the cardiac devices on capsule endoscopy. Capsule endoscopy using human body communication to transmit data was safely performed in patients with cardiac pacemakers or implantable cardiac defibrillators. Images from the capsule endoscopy were not affected by cardiac devices. A further large-scale study is required to confirm the safety of capsule endoscopy with various types of cardiac devices.

Nitrogen Source-Dependent Capsule Induction in Human-Pathogenic Cryptococcus Species

PubMed Central

Frazzitta, Aubrey E.; Vora, Haily; Price, Michael S.; Tenor, Jennifer L.; Betancourt-Quiroz, Marisol; Toffaletti, Dena L.; Cheng, Nan

2013-01-01

Cryptococcus neoformans and C. gattii cause meningoencephalitis and are an increasing human health threat. These pathogenic Cryptococcus species are neurotropic and persist in the cerebrospinal fluid (CSF) of the mammalian host during infection. In order to survive in the host, pathogenic fungi must procure nutrients, such as carbon and nitrogen, from the CSF. To enhance our understanding of nutrient acquisition during central nervous system infection by Cryptococcus species, we examined the utilization of nitrogen sources available in CSF. We screened for the growth and capsule production of 817 global environmental and clinical isolates on various sources of nitrogen. Both environmental and clinical strains grew robustly on uric acid, Casamino Acids, creatinine, and asparagine as sole nitrogen sources. Urea induced the greatest magnitude of capsule induction. This induction was greater in Cryptococcus gattii than in C. neoformans. We confirmed the ability of nonpreferred nitrogen sources to increase capsule production in pathogenic species of Cryptococcus. Since urea is metabolized to ammonia and CO2 (a known signal for capsule induction), we examined urea metabolism mutants for their transcriptional response to urea regarding capsule production. The transcriptional profile of C. neoformans under urea-supplemented conditions revealed both similar and unique responses to other capsule-inducing conditions, including both intra- and extracellular urea utilization. As one of the most abundant nitrogen sources in the CSF, the ability of Cryptococcus to import urea and induce capsule production may substantially aid this yeast's survival and propagation in the host. PMID:23975889

Nitrogen source-dependent capsule induction in human-pathogenic cryptococcus species.

PubMed

Frazzitta, Aubrey E; Vora, Haily; Price, Michael S; Tenor, Jennifer L; Betancourt-Quiroz, Marisol; Toffaletti, Dena L; Cheng, Nan; Perfect, John R

2013-11-01

Cryptococcus neoformans and C. gattii cause meningoencephalitis and are an increasing human health threat. These pathogenic Cryptococcus species are neurotropic and persist in the cerebrospinal fluid (CSF) of the mammalian host during infection. In order to survive in the host, pathogenic fungi must procure nutrients, such as carbon and nitrogen, from the CSF. To enhance our understanding of nutrient acquisition during central nervous system infection by Cryptococcus species, we examined the utilization of nitrogen sources available in CSF. We screened for the growth and capsule production of 817 global environmental and clinical isolates on various sources of nitrogen. Both environmental and clinical strains grew robustly on uric acid, Casamino Acids, creatinine, and asparagine as sole nitrogen sources. Urea induced the greatest magnitude of capsule induction. This induction was greater in Cryptococcus gattii than in C. neoformans. We confirmed the ability of nonpreferred nitrogen sources to increase capsule production in pathogenic species of Cryptococcus. Since urea is metabolized to ammonia and CO(2) (a known signal for capsule induction), we examined urea metabolism mutants for their transcriptional response to urea regarding capsule production. The transcriptional profile of C. neoformans under urea-supplemented conditions revealed both similar and unique responses to other capsule-inducing conditions, including both intra- and extracellular urea utilization. As one of the most abundant nitrogen sources in the CSF, the ability of Cryptococcus to import urea and induce capsule production may substantially aid this yeast's survival and propagation in the host.

A biodegradable, immunoprotective, dual nanoporous capsule for cell-based therapies.

PubMed

Zhang, Xulang; He, Hongyan; Yen, Chi; Ho, Wiston; Lee, L James

2008-11-01

To demonstrate the transplantation of drug-secreting cells with immunoprotection, a biodegradable delivery device combining two nanoporous capsules is developed using secretory alkaline phosphatase gene (SEAP) transfected mouse embryonic stem (mES) cells as a model system. The outer capsule is a poly (ethylene glycol) (PEG)-coated poly (epsilon-caprolactone) (PCL) chamber covered with a PEG grafted PCL nanoporous membrane made by phase inversion technique. SEAP gene transfected mES cells encapsulated in alginate-poly-L-lysine (AP) microcapsules are placed in the PCL capsule. Both nanoporous capsules showed good immunoprotection in the IgG solution. In microcapsules, mES cells could form a spheroid embryonic body (EB) and grow close to the microcapsule size. The secreted SEAP from encapsulated mES cells increased gradually to a maximum value before reaching a steady level, following the cell growth pattern in the microcapsule. Without microcapsules, mES cells only formed a monolayer in the large PCL capsule. The secreted SEAP release was very low. The integrated device showed a similar cell growth pattern to that in microcapsules alone, while the SEAP release rate could be regulated by the pore size of the large capsule. This integrated device can achieve multi-functionalities for cell-based therapy, i.e. a 3-D microenvironment provided by microcapsules for cell growth, superior immunoprotection and controllable release performance provided by the two nanoporous membranes, and good fibrosis prevention by PEG surface modification of the large capsule.

Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling

PubMed Central

Allen, Jessica; Ryu, Jubin; Maggi, Alessandro; Flores, Bianca; Greer, Julia R.

2016-01-01

Fibrotic encapsulation limits the efficacy and lifetime of implantable biomedical devices. Microtopography has shown promise in the regulation of myofibroblast differentiation, a key driver of fibrotic encapsulation. However, existing studies have not systematically isolated the requisite geometric parameters for suppression of myofibroblast differentiation via microtopography, and there has not been in vivo validation of this technology to date. To address these issues, a novel lamination method was developed to afford more control over topography dimensions. Specifically, in this study we focus on fiber length and its effect on myofibroblast differentiation. Fibroblasts cultured on films with microfibers exceeding 16 μm in length lost the characteristic morphology associated with myofibroblast differentiation, while shorter microfibers of 6 μm length failed to produce this phenotype. This increase in length corresponded to a 50% decrease in fiber stiffness, which acts as a mechanical cue to influence myofibroblast differentiation. Longer microfiber films suppressed expression of myofibroblast-specific genes (αSMA, Col1α2, and Col3α1) and TGFβ signaling components (TGFβ1, TβR2, and Smad3). About 16 μm long microfiber films subcutaneously implanted in a mouse wound-healing model generated a substantially thinner fibrotic capsule and less deposition of collagen in the wound bed. Together, these results identify a critical feature length threshold for microscale topography-mediated repression of fibrotic encapsulation. This study also demonstrates a simple and powerful strategy to improve surface biocompatibility and reduce fibrotic encapsulation around implanted materials. PMID:26507808

Capsule- and disk-filter procedure

USGS Publications Warehouse

Skrobialowski, Stanley C.

2016-01-01

Capsule and disk filters are disposable, self-contained units composed of a pleated or woven filter medium encased in a polypropylene or other plastic housing that can be connected inline to a sample-delivery system (such as a submersible or peristaltic pump) that generates sufficient pressure (positive or negative) to force water through the filter. Filter media are available in several pore sizes, but 0.45 µm is the pore size used routinely for most studies at this time. Capsule or disk filters (table 5.2.1.A.1) are required routinely for most studies when filtering samples for trace-element analyses and are recommended when filtering samples for major-ion or other inorganic-constituent analyses.

Capsule endoscopy in the diagnosis of Crohn’s disease

PubMed Central

Niv, Yaron

2013-01-01

Crohn’s disease is a chronic inflammatory disorder affecting any part of the gastrointestinal tract, but frequently involves the small and large bowel. Typical presenting symptoms include abdominal pain and diarrhea. Patients with this disorder may also have extraintestinal manifestations, including arthritis, uveitis, and skin lesions. The PillCam™SB capsule is an ingestible disposable video camera that transmits high quality images of the small intestinal mucosa. This enables the small intestine to be readily accessible to physicians investigating for the presence of small bowel disorders, such as Crohn’s disease. Four meta-analyses have demonstrated that capsule endoscopy identifies Crohn’s disease when other methods are not helpful. It should be noted that it is the best noninvasive procedure for assessing mucosal status, but is not superior to ileocolonoscopy, which remains the gold standard for assessment of ileocolonic disease. Mucosal healing along the small bowel can only be demonstrated by an endoscopic procedure such as capsule endoscopy. Achievement of long-term mucosal healing has been associated with a trend towards a decreased need for hospitalization and a decreased requirement for corticosteroid treatment in patients with Crohn’s disease. Recently, we have developed and validated the Capsule Endoscopy Crohn’s Disease Activity Index (also known as the Niv score) for Crohn’s disease of the small bowel. The next step is to expand our score to the colon, and to determine the role and benefit of a capsule endoscopy activity score in patients suffering from Crohn’s ileocolitis and/or colitis. This scoring system will also serve to improve our understanding of the impact of capsule endoscopy, and therefore treatment, on the immediate outcome of this disorder. As the best procedure available for assessing mucosal status, capsule endoscopy will provide important information about the course and outcome of Crohn’s disease. PMID:23818810

Mercury Capsule Retrorocket Test in the Altitude Wind Tunnel

NASA Image and Video Library

1960-09-21

A mechanic at the National Aeronautics and Space Administration (NASA) Lewis Research Center prepares the inverted base of a Mercury capsule for a test of its posigrade retrorockets inside the Altitude Wind Tunnel. In October 1959 NASA’s Space Task Group allocated several Project Mercury assignments to Lewis. The Altitude Wind Tunnel was modified to test the Atlas separation system, study the escape tower rocket plume, train astronauts to bring a spinning capsule under control, and calibrate the capsule’s retrorockets. The turning vanes, makeup air pipes, and cooling coils were removed from the wide western end of the tunnel to create a 51-foot diameter test chamber. The Mercury capsule had a six-rocket retro-package affixed to the bottom of the capsule. Three of these were posigrade rockets used to separate the capsule from the booster and three were retrograde rockets used to slow the capsule for reentry into the earth’s atmosphere. Performance of the retrorockets was vital since there was no backup system. Qualification tests of the retrorockets began in April 1960 on a retrograde thrust stand inside the southwest corner of the Altitude Wind Tunnel. These studies showed that a previous issue concerning the delayed ignition of the propellant had been resolved. Follow-up test runs verified reliability of the igniter’s attachment to the propellant. In addition, the capsule’s retrorockets were calibrated so they would not alter the capsule’s attitude when fired.

Mercury Capsule Construction at the NASA Lewis Research Center

NASA Image and Video Library

1959-08-21

A NASA mechanic secures the afterbody to a Mercury capsule in the hangar at the Lewis Research Center. The capsule was one of two built at Lewis for the “Big Joe” launches scheduled for September 1959. The initial phase of Project Mercury consisted of a series of unmanned launches using the Air Force’s Redstone and Atlas boosters and the Langley-designed Little Joe boosters. The first Atlas launch, referred to as “Big Joe”, was a single attempt early in Project Mercury to use a full-scale Atlas booster to simulate the reentry of a mock-up Mercury capsule without actually placing it in orbit. The overall design of Big Joe had been completed by December 1958, and soon thereafter project manager Aleck Bond assigned NASA Lewis the task of designing the electronic instrumentation and automatic stabilization system. Lewis also constructed the capsule’s lower section, which contained a pressurized area with the electronics and two nitrogen tanks for the retrorockets. Lewis technicians were responsible for assembling the entire capsule: the General Electric heatshield, NASA Langley afterbody and recovery canister, and Lewis electronics and control systems. On June 9, 1959, the capsule was loaded on an air force transport aircraft and flown to Cape Canaveral. A team of 45 test operations personnel from Lewis followed the capsule to Florida and spent the ensuing months preparing it for launch. The launch took place in the early morning hours of September 9, 1959.

Nifedipine capsules may provide a viable alternative to oral powders for paediatric patients.

PubMed

Helin-Tanninen, M; Naaranlahti, T; Kontra, K; Savolainen, K

2007-02-01

To compare content uniformities between different sizes of extemporaneously compounded nifedipine oral powders and capsules, in order to find out if capsules could be used instead of oral powders as paediatric medications. Actual content and content uniformity of extemporaneously compounded 1-mg nifedipine oral powders and capsules were evaluated by a high performance liquid chromatographic assay. Capsules and powders were prepared by triturating 10-mg nifedipine tablets with different amounts of lactose or microcrystalline cellulose with a mortar and pestle using a standard geometric dilution technique. Oral powders were weighed individually and capsules were filled by a hand-operated capsule-filling machine. Four different sizes of powders (500, 300, 100 and 50 mg) and three different sizes of capsules (numbers 1, 3 and 4) were prepared. Ten oral powders and 10 capsules from each batch were randomly selected and individually assayed for nifedipine amount. The extemporaneously prepared nifedipine oral powders and capsules were within acceptable limits for content uniformity, as defined by the European Pharmacopoeia, but the results indicate that the loss of nifedipine during the preparation process may be considerable for both preparations. The concentration on nifedipine decreased while the total mass of the oral powder decreased. These results demonstrate that nifedipine oral powders can be replaced by capsules, whose contents are emptied for use, in paediatric medications. Compounding small capsules, such as size number 3 or 4, is acceptable when considering the average drug content. The total weight of the oral powder should be at least 300 mg. The preparation of nifedipine in all studied capsule sizes was safe with either lactose monohydrate or microcrystalline cellulose as excipients. Thus, emptied capsules seem to be a good choice for delivering a paediatric medication. The loss of nifedipine was considerable in oral powders with low total weight.

Kinetic simulation of hydrodynamic equivalent capsule implosions

NASA Astrophysics Data System (ADS)

Kwan, Thomas; Le, Ari; Schmitt, Mark; Herrmann, Hans

2016-10-01

We have carried out simulations of direct-drive hydrodynamic equivalent capsule implosion experiments conducted on Omega laser facility at the Laboratory of Laser Energetics of the University of Rochester. The capsules had a glass shell (SiO2) 4.87 μm with an inner diameter of 1086 μm. One was filled with deuterium (D) and tritium (T) at 6.635 and 2.475 atmospheric pressure respectively. The other capsule with D, T, and He-3 at 2.475, 2.475, and 5.55 atmospheric pressure respectively. The capsules were imploded with 60 laser beams with a square pulse length of 0.6ns of total energy of 15.6 kJ. One-dimensional radiation hydrodynamic calculations with HYDRA and kinetic particle/hybrid simulations with LSP are carried out for the post-shot analysis. HYDRA outputs at 0.6ns are linked to LSP, in which the electrons are treated as a fluid while all the ion dynamics is simulated by the standard particle-in-cell technique. Additionally, simulations with the new photon package in LSP are initiated at the beginning of the implosion to include the implosion phase of the capsule. The simulation results of density, temperature, and velocity profiles of the electrons, D, T, He-3, and SiO2species are compared with HYDRA. Detail comparisons among the kinetic simulations, rad-hydro simulations, and experimental results of neutron yield, yield ratio, fusion burn histories, and shell convergence will be presented to assess plasma kinetic effects. Work performed under the auspices of the US DOE by the Los Alamos National Laboratory under Contract No. W7405-ENG-36.

Protective Role of the Capsule and Impact of Serotype 4 Switching on Streptococcus mitis

PubMed Central

Rukke, Håkon V.; Kalluru, Raja Sab; Repnik, Urska; Gerlini, Alice; José, Ricardo J.; Periselneris, Jimstan; Marshall, Helina; Griffiths, Gareth; Oggioni, Marco Rinaldo; Brown, Jeremy S.

2014-01-01

The polysaccharide capsule surrounding Streptococcus pneumoniae is essential for virulence. Recently, Streptococcus mitis, a human commensal and a close relative of S. pneumoniae, was also shown to have a capsule. In this study, the S. mitis type strain switched capsule by acquisition of the serotype 4 capsule locus of S. pneumoniae TIGR4, following induction of competence for natural transformation. Comparison of the wild type with the capsule-switching mutant and with a capsule deletion mutant showed that the capsule protected S. mitis against phagocytosis by RAW 264.7 macrophages. This effect was enhanced in the S. mitis strain expressing the S. pneumoniae capsule, which showed, in addition, increased resistance against early clearance in a mouse model of lung infection. Expression of both capsules also favored survival in human blood, and the effect was again more pronounced for the capsule-switching mutant. S. mitis survival in horse blood or in a mouse model of bacteremia was not significantly different between the wild type and the mutant strains. In all models, S. pneumoniae TIGR4 showed higher rates of survival than the S. mitis type strain or the capsule-switching mutant, except in the lung model, in which significant differences between S. pneumoniae TIGR4 and the capsule-switching mutant were not observed. Thus, we identified conditions that showed a protective function for the capsule in S. mitis. Under such conditions, S. mitis resistance to clearance could be enhanced by capsule switching to serotype 4, but it was enhanced to levels lower than those for the virulent strain S. pneumoniae TIGR4. PMID:24958712

Experimental investigation of a bioartificial capsule flowing in a narrow tube

NASA Astrophysics Data System (ADS)

Risso, Frédéric; Collé-Paillot, Fabienne; Zagzoule, Mokhtar

This work is an experimental study of the motion and deformation of a bioartificial capsule flowing in a tube of 4 mm diameter. The capsules, initially designed for medical applications, are droplets of salt water surrounded by a thin polymeric membrane. They are immersed in a very viscous Newtonian silicone oil that flows through a tube in the Stokes regime. The properties of the capsules were carefully determined. Two previous experimental papers were devoted to their characterization by osmotic swelling and compression between two plates. The present work also provides a series of tests that allows an accurate definition of the experimental model under investigation. The capsules are buoyant and initially quasi-spherical. Nevertheless, buoyancy and small departures from sphericity are shown to have no significant effects, provided the flowing velocity is large enough for the viscous stress to become predominant. The capsules are also initially slightly over-inflated, but there is no mass transfer through the membrane during the present experiments. Their volume therefore remains constant. The membrane can be described as an elastic two-dimensional material, the elastic moduli of which are independent of the deformation. Far from the tube ends, the capsule reaches a steady state that depends on two parameters: the capillary number, Ca; and the ratio of the radius of the capsule to that of the tube, a/R. The capillary number, which compares the hydrodynamic stresses to the elastic tensions in the membrane, was varied between 0 and 0.125. The radius ratio, which measures the magnitude of the confinement, was varied from 0.75 to 0.95. In the range investigated, the membrane material always remains in the elastic domain. At fixed a/R, the capsule is stretched in the axial direction when Ca is increased. The process of deformation involves two main stages. At small to moderate Ca, the lateral dimension of the capsule decreases whereas its axial length increases. The

Capsule Performance Optimization for the National Ignition Facility

NASA Astrophysics Data System (ADS)

Landen, Otto

2009-11-01

The overall goal of the capsule performance optimization campaign is to maximize the probability of ignition by experimentally correcting for likely residual uncertainties in the implosion and hohlraum physics used in our radiation-hydrodynamic computational models before proceeding to cryogenic-layered implosions and ignition attempts. This will be accomplished using a variety of targets that will set key laser, hohlraum and capsule parameters to maximize ignition capsule implosion velocity, while minimizing fuel adiabat, core shape asymmetry and ablator-fuel mix. The targets include high Z re-emission spheres setting foot symmetry through foot cone power balance [1], liquid Deuterium-filled ``keyhole'' targets setting shock speed and timing through the laser power profile [2], symmetry capsules setting peak cone power balance and hohlraum length [3], and streaked x-ray backlit imploding capsules setting ablator thickness [4]. We will show how results from successful tuning technique demonstration shots performed at the Omega facility under scaled hohlraum and capsule conditions relevant to the ignition design meet the required sensitivity and accuracy. We will also present estimates of all expected random and systematic uncertainties in setting the key ignition laser and target parameters due to residual measurement, calibration, cross-coupling, surrogacy, and scale-up errors, and show that these get reduced after a number of shots and iterations to meet an acceptable level of residual uncertainty. Finally, we will present results from upcoming tuning technique validation shots performed at NIF at near full-scale. Prepared by LLNL under Contract DE-AC52-07NA27344. [4pt] [1] E. Dewald, et. al. Rev. Sci. Instrum. 79 (2008) 10E903. [0pt] [2] T.R. Boehly, et. al., Phys. Plasmas 16 (2009) 056302. [0pt] [3] G. Kyrala, et. al., BAPS 53 (2008) 247. [0pt] [4] D. Hicks, et. al., BAPS 53 (2008) 2.

21 CFR 520.260 - n-Butyl chloride capsules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false n-Butyl chloride capsules. 520.260 Section 520.260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.260 n-Butyl chloride capsules...

On the anatomy of the temporomandibular joint and the muscles that act upon it: observations on the gray whale, Eschrichtius robustus.

PubMed

El Adli, Joseph J; Deméré, Thomas A

2015-04-01

The temporomandibular joint and its associated musculature are described in a neonate gray whale (Eschrichtius robustus) and serve as the basis for direct anatomical comparisons with the temporomandibular region in other clades of baleen whales (Mysticeti). Members of the right whale/bowhead whale clade (Balaenidae) are known to possess a synovial lower jaw joint, while members of the rorqual clade (Balaenopteridae) have a nonsynovial temporomandibular joint characterized by a highly flexible fibrocartilaginous pad and no joint capsule. In contrast, the gray whale possesses a modified temporomandibular joint (intermediate condition), with a vestigial joint cavity lacking a fibrous capsule, synovial membrane, and articular disk. In addition, the presence of a rudimentary fibrocartilaginous pad appears to be homologous to that seen in balaenopterid mysticetes. The intrinsic temporomandibular musculature in the gray whale was found to include a multibellied superficial masseter and a single-bellied deep masseter. The digastric and internal pterygoid muscles in E. robustus are enlarged relative to the condition documented in species of Balaenoptera. A relatively complex insertion of the temporalis muscle on the dentary is documented in the gray whale and the low, knob-like process on the gray whale dentary is determined to be homologous with the prominent coronoid process of rorquals. Comparison with the anatomy of the temporomandibular musculature in rorquals reveals an increased importance of alpha rotation of the dentary in the gray whale. This difference in muscular morphology and lines of muscle action is interpreted as representing adaptations for suction feeding. © 2015 Wiley Periodicals, Inc.

Sensory innervation of the temporomandibular joint in the mouse.

PubMed

Dreessen, D; Halata, Z; Strasmann, T

1990-01-01

The sensory innervation of the temporomandibular joints (TMJs) of 8 STR/IN mice was investigated by means of light and electron microscopy. Through the cutting of complete semithin sections in series it was possible to investigate the joints thoroughly. Additionally, one joint with its nerve supply was reconstructed three-dimensionally with a computerized three-dimensional programme. The reconstruction was based on one complete semithin section series. The joint's nerve supply originates from the nervus auriculotemporalis and additionally from motor branches of the n. mandibularis: n. massetericus, n. pterygoideus lateralis and the nn. temporales posteriores. The greatest number of nerve fibres and endings is located in the dorsolateral part of the joint capsule. They lie only in the stratum fibrosum and subsynovially. Neither the stratum synoviale nor the discus articularis contain any nerve fibres or endings, whereas the peri-articular loose connective tissue is richly innervated. The only type of nerve ending observed within the joint was the free nerve ending, which is assumed to serve not only as a nociceptor but also as a polymodal mechanoreceptor. Merely within the insertion of the musculus pterygoideus lateralis at the collum mandibulae single stretch receptors of the Ruffini type were observed. Ultrastructurally, they correspond to those described in the cat's knee joint. Neither lamellated nor nerve endings of the Golgi or Pacini type were observed in the joint or in the peri-articular connective tissue. The unexpected paucity of nerve fibres and endings in the TMJ itself of the mouse suggests that the afferent information from the joint is less important for position sense and movement than the afferent information from muscles, tendons and periodontal ligaments.

Stability of dronabinol capsules when stored frozen, refrigerated, or at room temperature.

PubMed

Wempe, Michael F; Oldland, Alan; Stolpman, Nancy; Kiser, Tyree H

2016-07-15

Results of a study to determine the 90-day stability of dronabinol capsules stored under various temperature conditions are reported. High-performance liquid chromatography (HPLC) with ultraviolet (UV) detection was used to assess the stability of dronabinol capsules (synthetic delta-9-tetrahydrocannabinol [Δ9-THC] mixed with high-grade sesame oil and other inactive ingredients and encapsulated as soft gelatin capsules) that were frozen, refrigerated, or kept at room temperature for three months. The dronabinol capsules remained in the original foil-sealed blister packs until preparation for HPLC-UV assessment. The primary endpoint was the percentage of the initial Δ9-THC concentration remaining at multiple designated time points. The secondary aim was to perform forced-degradation studies under acidic conditions to demonstrate that the HPLC-UV method used was stability indicating. The appearance of the dronabinol capsules remained unaltered during frozen, cold, or room-temperature storage. Regardless of storage condition, the percentage of the initial Δ9-THC content remaining was greater than 97% for all evaluated samples at all time points over the three-month study. These experimental data indicate that the product packaging and the sesame oil used to formulate dronabinol capsules efficiently protect Δ9-THC from oxidative degradation to cannabinol; this suggests that pharmacies can store dronabinol capsules in nonrefrigerated automated dispensing systems, with a capsule expiration date of 90 days after removal from the refrigerator. Dronabinol capsules may be stored at room temperature in their original packaging for up to three months without compromising capsule appearance and with minimal reduction in Δ9-THC concentration. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Therapeutic applications of radioactive (131)iodine: Procedures and incidents with capsules.

PubMed

Al Aamri, Marwa; Ravichandran, Ramamoorthy; Binukumar, John Pichy; Al Balushi, Naima

2016-01-01

Treatments for thyrotoxicosis and carcinoma thyroid are carried out by oral administration of radioactive iodine ((131)I) in the form of liquid or capsules. The liquid form of (131)I has higher risk factors such as vapourization, spillage and need for management of higher activity wastes. Use of (131)I in capsule form simplify procedures of handling compared to liquid form of (131)I. The guidelines of safe handling and quality assurance aspects for therapeutic use (131)I are well outlined by International Atomic Energy Agency (IAEA) reports. A few unusual incidents with I-131 capsules encountered in the past need to be highlighted from health physics point of view. In Royal Hospital, Oman, I-131 is imported in capsules, and the total activity handled/year steadily increased over 10 years. Discrete activities range from 185 MBq (5 mCi) up to 7.4 GBq (200 mCi). In four incidents deviations in standard operational procedures were recorded. Nature of incidents is described as follows: (1) After assay of activity, the capsule was directly put in the lead container with missing of inner cap. (2) Patient poured water in the Perspex tube, when the capsule was handed over to her, making an emergency situation. (3) In 3 high activity capsules (2 nos 2.96 GBq, 1 no. 4.26 GBq), observed sticky behavior in capsule holder on the 2(nd) day post receipt, which were in order on the 1(st) day. (4) A capsule could not be swallowed by a patient, which was taken back from the mouth. Monitoring of patient later did not show residual ingested activity. The report documents some of the unusual incidents for information to other centers engaged in such radioactive administrations.

PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activity.

PubMed

Pinchuk, Irina V; Saada, Jamal I; Beswick, Ellen J; Boya, Gushyalatha; Qiu, Sumin M; Mifflin, Randy C; Raju, Gottumukkala S; Reyes, Victor E; Powell, Don W

2008-10-01

A prominent role for inhibitory molecules PD-L1 and PD-L2 in peripheral tolerance has been proposed. However, the phenotype and function of PD-L-expressing cells in human gut remains unclear. Recent studies suggest that colonic myofibroblasts (CMFs) and fibroblasts are important in the switch from acute inflammation to adaptive immunity. In the normal human colon, CMFs represent a distinct population of major histocompatibility complex class II(+) cells involved in the regulation of mucosal CD4(+) T-cell responses. PD-L1 and PD-L2 expression on human CMFs was determined using Western blot, fluorescence-activated cell sorter analysis and confocal microscopy. Lymphoproliferation assays and cytokine enzyme-linked immunosorbent assays were used to evaluate the role of B7 costimulators expressed by CMFs with regard to the regulation of preactivated T-helper cell responses. We demonstrate here the expression of PD-L1/2 molecules by normal human CMF and fibroblasts in situ and in culture. Both molecules support suppressive functions of CMFs in the regulation of activated CD4(+) T-helper cell proliferative responses; blocking this interaction reverses the suppressive effect of CMFs on T-cell proliferation and leads to increased production of the major T-cell growth factor, interleukin (IL)-2. PD-L1/2-mediated CMF suppressive functions are mainly due to the inhibition of IL-2 production, because supplementation of the coculture media with exogenous IL-2 led to partial recovery of activated T-cell proliferation. Our data suggest that stromal myofibroblasts and fibroblasts may limit T-helper cell proliferative activity in the gut and, thus, might play a prominent role in mucosal intestinal tolerance.

Capsule Endoscopy in Patients with Implantable Electromedical Devices is Safe

PubMed Central

Harris, Lucinda A.; Hansel, Stephanie L.; Rajan, Elizabeth; Srivathsan, Komandoor; Rea, Robert; Crowell, Michael D.; Fleischer, David E.; Pasha, Shabana F.; Gurudu, Suryakanth R.; Heigh, Russell I.; Shiff, Arthur D.; Post, Janice K.; Leighton, Jonathan A.

2013-01-01

Background and Study Aims. The presence of an implantable electromechanical cardiac device (IED) has long been considered a relative contraindication to the performance of video capsule endoscopy (CE). The primary aim of this study was to evaluate the safety of CE in patients with IEDs. A secondary purpose was to determine whether IEDs have any impact on images captured by CE. Patients and Methods. A retrospective chart review of all patients who had a capsule endoscopy at Mayo Clinic in Scottsdale, AZ, USA, or Rochester, MN, USA, (January 2002 to June 2010) was performed to identify CE studies done on patients with IEDs. One hundred and eighteen capsule studies performed in 108 patients with IEDs were identified and reviewed for demographic data, method of preparation, and study data. Results. The most common indications for CE were obscure gastrointestinal bleeding (77%), anemia (14%), abdominal pain (5%), celiac disease (2%), diarrhea (1%), and Crohn's disease (1%). Postprocedure assessments did not reveal any detectable alteration on the function of the IED. One patient with an ICD had a 25-minute loss of capsule imaging due to recorder defect. Two patients with LVADs had interference with capsule image acquisition. Conclusions. CE did not interfere with IED function, including PM, ICD, and/or LVAD and thus appears safe. Additionally, PM and ICD do not appear to interfere with image acquisition but LVAD may interfere with capsule images and require that capsule leads be positioned as far away as possible from the IED to assure reliable image acquisition. PMID:23710168

Clinical usefulness of novel tag-less Agile patency capsule prior to capsule endoscopy for patients with suspected small bowel stenosis.

PubMed

Nakamura, Masanao; Hirooka, Yoshiki; Yamamura, Takeshi; Miyahara, Ryoji; Watanabe, Osamu; Ando, Takafumi; Ohmiya, Naoki; Goto, Hidemi

2015-01-01

The Agile patency capsule (PC; Given Imaging Ltd, Yoqneam, Israel) is used as a dummy prior to capsule endoscopy (CE) to avoid retention of the CE capsule. However, impaction of the PC's inner radio frequency identification (RFID) tag in a stricture could cause small-bowel ileus. Recently, the RFID tag-less PC was introduced into clinical practice. Herein, we aimed to retrospectively evaluate the usefulness of the tag-less PC. Of 154 patients who were scheduled to undergo CE, 100 consecutive patients (65%) who underwent PC evaluation were enrolled in the present study. Primary study end point was the retention rate of the CE capsule after successful passage of the PC. Secondary end point was analysis of the significant factors affecting the passage of the PC. In total, 87 patients (87%) had bowel patency confirmed by PC evaluation. There was no capsule retention in any of these 87 patients during CE. Abnormal findings were obtained from 60 CE, and 41 patients received new or modified treatment. Multivariate analysis of factors related to the confirmation of patency demonstrated that stenosis on imaging was the most influential factor (P = 0.002, odds ratio 16.387). The results confirmed that passage of the PC depends on stenosis on imaging. Use of the tag-less PC confirmed gastrointestinal tract patency for most of the patients who did not have stenosis on imaging and allowed estimation of the patency for patients who did have stenosis on imaging. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

Short article: Aspiration of capsule endoscopes: a comprehensive review of the existing literature.

PubMed

Yung, Diana E; Plevris, John N; Koulaouzidis, Anastasios

2017-04-01

Capsule endoscopy (CE) has an excellent safety profile. Although retention is the most cited complication, capsule aspiration is less frequent and is often reported only as isolated cases. This study represents a systematic effort to compile and scrutinize the available data on capsule aspiration to provide comprehensive and conclusive information on this CE complication. A systematic literature search was performed in PubMed, Embase and Chinese National Knowledge Infrastructure. The search terms used were 'capsule endoscopy' AND 'aspiration' (both terms searched as keyword and MeSH). We included case reports and/or series on capsule aspiration, as well as observational cohort studies that reported capsule aspiration among their complications/outcomes. Thirty-four case reports with 37 cases of capsule aspiration were identified. A further four observational studies reported aspiration as part of a cohort of patients undergoing CE. 94.6% of aspirations occurred in elderly men. 87.1% had significant comorbidities. 59.5% had symptoms on aspiration, with cough reported most frequently. The most common location of aspiration was the right main bronchus. Half of the patients required intervention for capsule retrieval; bronchoscopy was the most common management, with good effect. There was a single fatality following capsule aspiration, not directly related to the procedure, and one case of aspiration pneumonia. Outcomes were good for all other patients. The estimated overall aspiration rate is 0.1%. Although very rare and generally safely managed, capsule aspiration should be anticipated in certain patient groups and capsule administration should be approached with necessary precautions.

Associations Between Egg Capsule Morphology and Predation Among Populations of the Marine Gastropod, Nucella emarginata.

PubMed

Rawlings, T A

1990-12-01

Intraspecific variation in the morphology of egg capsules is ideal for assessing the costs and benefits of encapsulation, yet little is known about the extent of such variation among populations of a single species. In the present study, I compared capsule morphology among three populations of the intertidal gastropod, Nucella emarginata. Significant differences were found both in capsule wall thickness and capsule strength. Mean capsule wall thickness varied as much as 25% among populations, with the dry weight of capsular cases differing accordingly. Capsule strength, measured as resistance to puncturing and squeezing forces, also varied among populations, but did not directly reflect differences in capsule wall thickness. Despite extensive variation in capsule morphology within this species, the number and size of eggs contained within capsules of equal volume did not differ significantly among populations. I also compared the type of capsule-eating predators that were present at each site. Shore crabs, Hemigrapsus spp., were abundant at all three sites; however, the predatory isopods Idotea wosnesenskii were only present at sites containing relatively thick-walled capsules. Although Hemigrapsus and Idotea were able to chew through both thick- and thin-walled capsules, laboratory experiments revealed that Idotea preferentially opened thin-walled capsules. These results suggest that variation in capsule morphology among populations of N. emarginata may, at least in part, reflect selection for the protection of embryos against predation.

Radiation hydrodynamic effects in two beryllium plates with an idealized aluminum joint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belkov, S.A.; Mkhitarian, L.S.; Vinokurov, O.A.

A beryllium capsule formed from two hemispherical shells with a thin bond is one possible ignition target for the National Ignition Facility [J. A. Paisner {ital et al.}, Laser Focus World {bold 30}, 75 (1994)] Nonuniformities in density, opacity, and interface position at the joint between these hemishells will initiate two-dimensional (2-D) perturbations of the shock wave and material behind the shock as the shock passes through the shell perpendicular to the joint width. Rarefaction of material flow behind the shock front can cause the interface between the shell and joint material to oscillate in position. The amplitude of thesemore » oscillations may be comparable to the joint width. The evolution of these perturbations is studied by numerically simulating shock passage through flat beryllium plates containing aluminum joints. Using the MIMOSA-ND code [D. Sofronov {ital et al.}, Vopr. At. Nauki Tekh., Ser: Mat. modelirovanie fizicheskih processov {bold 2}, 3 (1990)] two different cases are calculated{emdash}a wide (10 {mu}m) and a narrow (1 {mu}m) joint of aluminum between two 150 {mu}m long semiinfinite beryllium plates. Both cases showed good agreement with an analytic representation of the oscillation behavior. For the narrow joint, a special technique allows the calculation of mixing between the joint and surrounding material caused by the Kelvin{endash}Helmholtz instability. {copyright} {ital 1999 American Institute of Physics.}« less

First beryllium capsule implosions on the National Ignition Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kline, J. L.; Yi, S. A.; Simakov, A. N.

2016-05-15

The first indirect drive implosion experiments using Beryllium (Be) capsules at the National Ignition Facility confirm the superior ablation properties and elucidate possible Be-ablator issues such as hohlraum filling by ablator material. Since the 1990s, Be has been the preferred Inertial Confinement Fusion (ICF) ablator because of its higher mass ablation rate compared to that of carbon-based ablators. This enables ICF target designs with higher implosion velocities at lower radiation temperatures and improved hydrodynamic stability through greater ablative stabilization. Recent experiments to demonstrate the viability of Be ablator target designs measured the backscattered laser energy, capsule implosion velocity, core implosionmore » shape from self-emission, and in-flight capsule shape from backlit imaging. The laser backscatter is similar to that from comparable plastic (CH) targets under the same hohlraum conditions. Implosion velocity measurements from backlit streaked radiography show that laser energy coupling to the hohlraum wall is comparable to plastic ablators. The measured implosion shape indicates no significant reduction of laser energy from the inner laser cone beams reaching the hohlraum wall as compared with plastic and high-density carbon ablators. These results indicate that the high mass ablation rate for beryllium capsules does not significantly alter hohlraum energetics. In addition, these data, together with data for low fill-density hohlraum performance, indicate that laser power multipliers, required to reconcile simulations with experimental observations, are likely due to our limited understanding of the hohlraum rather than the capsule physics since similar multipliers are needed for both Be and CH capsules as seen in experiments.« less

First beryllium capsule implosions on the National Ignition Facility

DOE PAGES

Kline, J. L.; Yi, S. A.; Simakov, A. N.; ...

2016-05-01

The first indirect drive implosion experiments using Beryllium (Be) capsules at the National Ignition Facility confirm the superior ablation properties and elucidate possible Be-ablator issues such as hohlraum filling by ablator material. Since the 1990s, Be has been the preferred Inertial Confinement Fusion (ICF) ablator because of its higher mass ablation rate compared to that of carbon-based ablators. This enables ICF target designs with higher implosion velocities at lower radiation temperatures and improved hydrodynamic stability through greater ablative stabilization. Recent experiments to demonstrate the viability of Be ablator target designs measured the backscattered laser energy, capsule implosion velocity, core implosionmore » shape from self-emission, and in-flight capsule shape from backlit imaging. The laser backscatter is similar to that from comparable plastic (CH) targets under the same hohlraum conditions. Implosion velocity measurements from backlit streaked radiography show that laser energy coupling to the hohlraum wall is comparable to plastic ablators. The measured implosion shape indicates no significant reduction of laser energy from the inner laser cone beams reaching the hohlraum wall as compared with plastic and high-density carbon ablators. These results indicate that the high mass ablation rate for beryllium capsules does not significantly alter hohlraum energetics. In addition, these data, together with data for low fill-density hohlraum performance, indicate that laser power multipliers, required to reconcile simulations with experimental observations, are likely due to our limited understanding of the hohlraum rather than the capsule physics since similar multipliers are needed for both Be and CH capsules as seen in experiments.« less

Synergistic role of HSP90α and HSP90β to promote myofibroblast persistence in lung fibrosis.

PubMed

Bellaye, Pierre-Simon; Shimbori, Chiko; Yanagihara, Toyoshi; Carlson, David A; Hughes, Philip; Upagupta, Chandak; Sato, Seidai; Wheildon, Nolan; Haystead, Timothy; Ask, Kjetil; Kolb, Martin

2018-02-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung parenchyma, causing significant morbidity through worsening dyspnoea and overall functional decline. IPF is characterised by apoptosis-resistant myofibroblasts, which are a major source for the excessive production of extracellular matrix (ECM) overtaking normal lung tissue. We sought to study the role of heat shock protein (HSP) isoforms HSP90α and HSP90β, whose distinct roles in lung fibrogenesis remain elusive.We determined the level of circulating HSP90α in IPF patients (n=31) and age-matched healthy controls (n=9) by ELISA. The release of HSP90α and HSP90β was evaluated in vitro in primary IPF and control lung fibroblasts and ex vivo after mechanical stretch on fibrotic lung slices from rats receiving adenovector-mediated transforming growth factor-β1.We demonstrate that circulating HSP90α is upregulated in IPF patients in correlation with disease severity. The release of HSP90α is enhanced by the increase in mechanical stress of the fibrotic ECM. This increase in extracellular HSP90α signals through low-density lipoprotein receptor-related protein 1 (LRP1) to promote myofibroblast differentiation and persistence. In parallel, we demonstrate that the intracellular form of HSP90β stabilises LRP1, thus amplifying HSP90α extracellular action.We believe that the specific inhibition of extracellular HSP90α is a promising therapeutic strategy to reduce pro-fibrotic signalling in IPF. Copyright ©ERS 2018.

Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions

PubMed Central

Krieg, Thomas; Abraham, David; Lafyatis, Robert

2007-01-01

Fibrosis, characterized by excessive extracellular matrix accumulation, is a common feature of many connective tissue diseases, notably scleroderma (systemic sclerosis). Experimental studies suggest that a complex network of intercellular interactions involving endothelial cells, epithelial cells, fibroblasts and immune cells, using an array of molecular mediators, drives the pathogenic events that lead to fibrosis. Transforming growth factor-β and endothelin-1, which are part of a cytokine hierarchy with connective tissue growth factor, are key mediators of fibrogenesis and are primarily responsible for the differentiation of fibroblasts toward a myofibroblast phenotype. The tight skin mouse (Tsk-1) model of cutaneous fibrosis suggests that numerous other genes may also be important. PMID:17767742

Capsule endoscopy of the future: What’s on the horizon?

PubMed Central

Slawinski, Piotr R; Obstein, Keith L; Valdastri, Pietro

2015-01-01

Capsule endoscopes have evolved from passively moving diagnostic devices to actively moving systems with potential therapeutic capability. In this review, we will discuss the state of the art, define the current shortcomings of capsule endoscopy, and address research areas that aim to overcome said shortcomings. Developments in capsule mobility schemes are emphasized in this text, with magnetic actuation being the most promising endeavor. Research groups are working to integrate sensor data and fuse it with robotic control to outperform today’s standard invasive procedures, but in a less intrusive manner. With recent advances in areas such as mobility, drug delivery, and therapeutics, we foresee a translation of interventional capsule technology from the bench-top to the clinical setting within the next 10 years. PMID:26457013

The proposal of the locomotive system for capsule endoscopes.

PubMed

Watada, Masaya; Ozawa, Ken-ichi

2008-01-01

The capsule endoscope authorized in some countries in late years has the advantage of preparing the observation in difficult small intestines in a past endoscope. However, because the promotion mechanism of a capsule endoscope depends only on the peristaltic motion of a digestive organ, the oversight of change to a morbid state is feared. Authors aim at the achievement of a free movement and remote diagnoses in small intestines, and are developing a locomotive system for capsule endoscopes. This paper describes the proposal of the locomotive system with an electromagnetic actuator, and examination of a simulation model for this locomotive system.

Biocatalytic response of multi-layer assembled collagen/hyaluronic acid nanoengineered capsules.

PubMed

Sousa, Fernanda; Kreft, Oliver; Sukhorukov, Gleb B; Möhwald, Helmuth; Kokol, Vanja

2014-01-01

Biodegradable hollow capsules filled with fluorescently labelled bovine serum albumin (BSA) as a model drug were prepared via layer-by-layer (LbL) self-assembly of type-I collagen (COL) and hyaluronic acid (HA) using calcium carbonate micro-particles and co-precipitation method. Capsules loaded with fluorescein isothiocyanate (FITC)-BSA, tetramethylrhodamin isothiocyanate (TRITC)-BSA or Alex-Fluor-488-BSA, respectively, were characterised before and after core removal using Confocal Laser Scanning Microscopy (CLSM), whilst the morphologies of individual hollow capsules were assessed using Atomic Force Microscopy (AFM). The sustained release of the encapsulated FITC-BSA protein was attained using enzymatic degradation of the capsule shells by collagenase. The released profile of the fluorescently-labelled BSA indicated that it could be successfully controlled by modulating the number of layers and/or by collagen crosslinking either before or after the capsule's assembly.

Comparative study of antibiotic-containing polymethylmetacrylate capsules and beads.

PubMed

Borzsei, László; Mintál, Tibor; Horváth, Aranka; Koós, Zoltán; Kocsis, Béla; Nyárády, József

2006-01-01

This study aimed at making local antibiotic therapy wider in cases of chronic suppurations by administering antibiotics which previously could not be given in this way through the conventional polymethylmetacrylate (PMMA) carrier techniques. Capsules from this material were produced with a pressing machine designed and laid out by us. The characteristics of antibiotic penetration from this novel carrier were compared to those of PMMA beads. The time-dependent outflow of amikacin, clindamycin, pefloxacin, piperacillin + tazobactam, amoxicillin + clavulanic acid and cefotaxime was examined from the capsules and the beads with standard microbiological techniques using the Micrococcus luteus ATCC9341 test strain. The diameter of the inhibitory zones was measured after 24 h incubation at 37 degrees C and converted to mug/ml antibiotic concentrations. Our results revealed that all antibiotics showed longer-lasting and higher concentration outflow from the PMMA capsules than from the beads. Therefore, these capsules can provide a more promising new opportunity for specific local antimicrobial treatment in cases of chronic suppurative bone and soft tissue injuries. In these cases the polymerization has already been completed and the heat does not influence the structure of the antibiotics; therefore, it can be inserted into the capsules in powder or solution form. Copyright 2006 S. Karger AG, Basel.

Effect of Counterflow Jet on a Supersonic Reentry Capsule

NASA Technical Reports Server (NTRS)

Chang, Chau-Lyan; Venkatachari, Balaji Shankar; Cheng, Gary C.

2006-01-01

Recent NASA initiatives for space exploration have reinvigorated research on Apollo-like capsule vehicles. Aerothermodynamic characteristics of these capsule configurations during reentry play a crucial role in the performance and safety of the planetary entry probes and the crew exploration vehicles. At issue are the forebody thermal shield protection and afterbody aeroheating predictions. Due to the lack of flight or wind tunnel measurements at hypersonic speed, design decisions on such vehicles would rely heavily on computational results. Validation of current computational tools against experimental measurement thus becomes one of the most important tasks for general hypersonic research. This paper is focused on time-accurate numerical computations of hypersonic flows over a set of capsule configurations, which employ a counterflow jet to offset the detached bow shock. The accompanying increased shock stand-off distance and modified heat transfer characteristics associated with the counterflow jet may provide guidance for future design of hypersonic reentry capsules. The newly emerged space-time conservation element solution element (CESE) method is used to perform time-accurate, unstructured mesh Navier-Stokes computations for all cases investigated. The results show good agreement between experimental and numerical Schlieren pictures. Surface heat flux and aerodynamic force predictions of the capsule configurations are discussed in detail.

Comparative Bioavailability of Sulindac in Capsule and Tablet Formulations

PubMed Central

Reid, Joel M.; Mandrekar, Sumithra J.; Carlson, Elsa C.; Harmsen, W. Scott; Green, Erin M.; McGovern, Renee M.; Szabo, Eva; Ames, Matthew M.; Boring, Daniel; Limburg, Paul J.

2008-01-01

The cyclooxygenase-2 (COX-2) enzyme appears to be an important target for cancer chemoprevention. Given the recent emergence of potentially serious cardiovascular toxicity associated with selective COX-2 inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), which inhibit both COX-1 and COX-2, have received renewed attention as candidate chemoprevention agents. Sulindac has demonstrated consistent chemopreventive potential in preclinical studies, as well as in a limited number of clinical trials reported to date. For the current pharmacokinetic study, sulindac capsules were prepared to facilitate ample agent supplies for future intervention studies. Encapsulation of the parent compound (sulindac sulfoxide) can be readily accomplished, but the effects of alternate formulations on bioavailability have not been rigorously examined. In the present single-dose, two-period crossover trial, we conducted pharmacokinetic analyses of sulindac in capsule (test) versus tablet (reference) formulations. Overall, bioavailability appeared to be higher for the capsule compared to the tablet formulation, based on test-to-reference pharmacokinetic parameter ratios for the parent compound. However, additional analyses based on the sulfide and sulfone metabolites of sulindac with the same pharmacokinetic parameters indicated similar chemopreventive exposures between the capsule and tablet formulations. These data support the use of sulindac capsules, which can be readily prepared with matching placebos, in future blinded chemoprevention trials. PMID:18349286

Spacecraft Escape Capsule

NASA Technical Reports Server (NTRS)

Robertson, Edward A.; Charles, Dingell W.; Bufkin, Ann L.; Rodriggs, Liana M.; Peterson, Wayne; Cuthbert, Peter; Lee, David E.; Westhelle, Carlos

2006-01-01

A report discusses the Gumdrop capsule a conceptual spacecraft that would enable the crew to escape safely in the event of a major equipment failure at any time from launch through atmospheric re-entry. The scaleable Gumdrop capsule would comprise a command module (CM), a service module (SM), and a crew escape system (CES). The CM would contain a pressurized crew environment that would include avionic, life-support, thermal control, propulsive attitude control, and recovery systems. The SM would provide the primary propulsion and would also supply electrical power, life-support resources, and active thermal control to the CM. The CES would include a solid rocket motor, embedded within the SM, for pushing the CM away from the SM in the event of a critical thermal-protection-system failure or loss of control. The CM and SM would normally remain integrated with each other from launch through recovery, but could be separated using the CES, if necessary, to enable the safe recovery of the crew in the CM. The crew escape motor could be used, alternatively, as a redundant means of de-orbit propulsion for the CM in the event of a major system failure in the SM.

Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres.

PubMed

Falke, Lucas L; van Vuuren, Stefan H; Kazazi-Hyseni, Filis; Ramazani, Farshad; Nguyen, Tri Q; Veldhuis, Gert J; Maarseveen, Erik M; Zandstra, Jurjen; Zuidema, Johan; Duque, Luisa F; Steendam, Rob; Popa, Eliane R; Kok, Robbert Jan; Goldschmeding, Roel

2015-02-01

Kidney injury triggers fibrosis, the final common pathway of chronic kidney disease (CKD). The increase of CKD prevalence worldwide urgently calls for new therapies. Available systemic treatment such as rapamycin are associated with serious side effects. To study the potential of local antifibrotic therapy, we administered rapamycin-loaded microspheres under the kidney capsule of ureter-obstructed rats and assessed the local antifibrotic effects and systemic side effects of rapamycin. After 7 days, microsphere depots were easily identifiable under the kidney capsule. Both systemic and local rapamycin treatment reduced intrarenal mTOR activity, myofibroblast accumulation, expression of fibrotic genes, and T-lymphocyte infiltration. Upon local treatment, inhibition of mTOR activity and reduction of myofibroblast accumulation were limited to the immediate vicinity of the subcapsular pocket, while reduction of T-cell infiltration was widespread. In contrast to systemically administered rapamycin, local treatment did not induce off target effects such as weight loss. Thus subcapsular delivery of rapamycin-loaded microspheres successfully inhibited local fibrotic response in UUO with less systemic effects. Therapeutic effect of released rapamycin was most prominent in close vicinity to the implanted microspheres. Copyright © 2014 Elsevier Ltd. All rights reserved.

Shape memory alloy-based biopsy device for active locomotive intestinal capsule endoscope.

PubMed

Le, Viet Ha; Hernando, Leon-Rodriguez; Lee, Cheong; Choi, Hyunchul; Jin, Zhen; Nguyen, Kim Tien; Go, Gwangjun; Ko, Seong-Young; Park, Jong-Oh; Park, Sukho

2015-03-01

Recently, capsule endoscopes have been used for diagnosis in digestive organs. However, because a capsule endoscope does not have a locomotive function, its use has been limited to small tubular digestive organs, such as small intestine and esophagus. To address this problem, researchers have begun studying an active locomotive intestine capsule endoscope as a medical instrument for the whole gastrointestinal tract. We have developed a capsule endoscope with a small permanent magnet that is actuated by an electromagnetic actuation system, allowing active and flexible movement in the patient's gut environment. In addition, researchers have noted the need for a biopsy function in capsule endoscope for the definitive diagnosis of digestive diseases. Therefore, this paper proposes a novel robotic biopsy device for active locomotive intestine capsule endoscope. The proposed biopsy device has a sharp blade connected with a shape memory alloy actuator. The biopsy device measuring 12 mm in diameter and 3 mm in length was integrated into our capsule endoscope prototype, where the device's sharp blade was activated and exposed by the shape memory alloy actuator. Then the electromagnetic actuation system generated a specific motion of the capsule endoscope to extract the tissue sample from the intestines. The final biopsy sample tissue had a volume of about 6 mm(3), which is a sufficient amount for a histological analysis. Consequently, we proposed the working principle of the biopsy device and conducted an in-vitro biopsy test to verify the feasibility of the biopsy device integrated into the capsule endoscope prototype using the electro-magnetic actuation system. © IMechE 2015.

Ganglion cyst arising from the composite occipito-atlanto-axial joint cavity in a cat.

PubMed

Aikawa, T; Sadahiro, S; Nishimura, M; Miyazaki, Y; Shibata, M

2014-01-01

A four-year-old, female spayed Domestic Longhaired cat was referred for evaluation with a two month history of initial inability to jump progressing to ambulatory tetraparesis. Magnetic resonance imaging studies demonstrated a cystic lesion arising from the composite occipito-atlanto-axial joint cavity and extending to the region of the occipital bone and the axis. The lesion surrounded the spinal canal, causing moderate dorsal spinal cord compression at the atlanto-occipital joint. A dynamic myelographic study demonstrated attenuation of the dorsal contrast column at the atlanto-occipital joint when the cervical spine was positioned in extension. Partial excision of the cyst capsule by a ventral approach resulted in long-term (64 months) resolution of clinical signs. Histological evaluation was consistent with a ganglion cyst. An intra-spinal ganglion cyst arising from the composite occipito-atlanto-axial joint cavity may be considered as an uncommon differential diagnosis for cats with cervical myelopathy.

21 CFR 520.1920 - Prochlorperazine, isopropamide sustained release capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prochlorperazine, isopropamide sustained release capsules. 520.1920 Section 520.1920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... dogs in which gastrointestinal disturbances are associated with emotional stress. (2)(i) Capsules...

Simulating Space Capsule Water Landing with Explicit Finite Element Method

NASA Technical Reports Server (NTRS)

Wang, John T.; Lyle, Karen H.

2007-01-01

A study of using an explicit nonlinear dynamic finite element code for simulating the water landing of a space capsule was performed. The finite element model contains Lagrangian shell elements for the space capsule and Eulerian solid elements for the water and air. An Arbitrary Lagrangian Eulerian (ALE) solver and a penalty coupling method were used for predicting the fluid and structure interaction forces. The space capsule was first assumed to be rigid, so the numerical results could be correlated with closed form solutions. The water and air meshes were continuously refined until the solution was converged. The converged maximum deceleration predicted is bounded by the classical von Karman and Wagner solutions and is considered to be an adequate solution. The refined water and air meshes were then used in the models for simulating the water landing of a capsule model that has a flexible bottom. For small pitch angle cases, the maximum deceleration from the flexible capsule model was found to be significantly greater than the maximum deceleration obtained from the corresponding rigid model. For large pitch angle cases, the difference between the maximum deceleration of the flexible model and that of its corresponding rigid model is smaller. Test data of Apollo space capsules with a flexible heat shield qualitatively support the findings presented in this paper.

Loss of iron to gold capsules in rock-melting experiments

USGS Publications Warehouse

Ratajeski, K.; Sisson, T.W.

1999-01-01

Gold is used widely for capsules in high-temperature rock-melting studies because it is generally thought to absorb negligible Fe from silicate samples. However, we observed significant losses of Fe from fluid-absent melting experiments on hornblende gabbros at 800-975 ??C and 8 kbar, using standard piston-cylinder techniques. The extent of Fe loss from the sample is dependent on the relative masses of the sample and the capsule. Low sample to capsule mass ratios (~0.04) lead to the highest Fe losses (32-49% relative). Concentrations of Fe in silicate melt and used gold capsules define an apparent equilibrium constant (K') that follows a linear 1n K' vs. 1/T relation (at an estimated log f(O)(2) of QFM-1). The apparent equilibrium constant is used to make limiting upper estimates on the amount of Fe that could be lost during rock-melting experiments for a range of f(O)(2) and sample to capsule mass ratios. At high f(O)(2) (NNO + 2), loss of Fe to gold is negligible (<2% relative) for a wide range of sample to capsule mass ratios. At an f(O)(2) of NNO, Fe loss can be kept to <10% relative by using a sample to capsule mass ratio of 0.2 or greater. At low f(O)(2) (QFM-1), presaturating the Au with Fe would be necessary to ensure that Fe losses remained <10% relative. Fe loss can compromise experimental results for small samples run at low f(O)(2) conditions, be they buffered, imposed by the pressure media, or produced by intrinsically reduced (graphitic) starting materials.

Noncontact optical measurement of lens capsule thickness ex vivo

NASA Astrophysics Data System (ADS)

Ziebarth, Noel M.; Manns, Fabrice; Uhlhorn, Stephen; Parel, Jean-Marie

2004-07-01

Purpose: To design a non-contact optical system to measure lens capsule thickness in cadaver eyes. Methods: The optical system uses a 670nm laser beam delivered to a single-mode fiber coupler. The output of the fiber coupler is focused onto the tissue using an aspheric lens (NA=0.68) mounted on a motorized translation stage. Light reflected from the sample is collected by the fiber coupler and sent to a silicon photodiode connected to a power meter. Peaks in the power signal are detected when the focal point of the aspheric lens coincides with the capsule boundaries. The capsule thickness is proportional to the distance between successive peaks. Anterior and posterior lens capsule thickness measurements were performed on 13 human, 10 monkey, and 34 New Zealand white rabbit lenses. The cadaver eyes were prepared for optical measurements by bonding a PMMA ring on the sclera. The posterior pole was sectioned, excess vitreous was removed, and the eye was placed on a Teflon slide. The cornea and iris were then sectioned. After the experiments, the lenses were excised, placed in 10% buffered formalin, and prepared for histology. Results: Central anterior lens capsule thickness was 9.4+/-2.9μm (human), 11.2+/-6.6μm (monkey), and 10.3+/-3.6μm (rabbit) optically and 14.9+/-1.6μm (human), 17.7+/-4.9μm (monkey), and 12.6+/-2.3μm (rabbit) histologically. The values for the central posterior capsule were 9.4+/-2.9μm (human), 6.6+/-2.5μm (monkey), and 7.9+/-2.3μm (rabbit) optically and 4.6+/-1.4μm (human), 4.5+/-1.2μm (monkey), and 5.7+/-1.7μm (rabbit) histologically. Conclusions: This study demonstrates that a non-contact optical system can successfully measure lens capsule thickness in cadaver eyes.

Measurement of motion detection of wireless capsule endoscope inside large intestine.

PubMed

Zhou, Mingda; Bao, Guanqun; Pahlavan, Kaveh

2014-01-01

Wireless Capsule Endoscope (WCE) provides a noninvasive way to inspect the entire Gastrointestinal (GI) tract, including large intestine, where intestinal diseases most likely occur. As a critical component of capsule endoscopic examination, physicians need to know the precise position of the endoscopic capsule in order to identify the position of detected intestinal diseases. Knowing how the capsule moves inside the large intestine would greatly complement the existing wireless localization systems by providing the motion information. Since the most recently released WCE can take up to 6 frames per second, it's possible to estimate the movement of the capsule by processing the successive image sequence. In this paper, a computer vision based approach without utilizing any external device is proposed to estimate the motion of WCE inside the large intestine. The proposed approach estimate the displacement and rotation of the capsule by calculating entropy and mutual information between frames using Fibonacci method. The obtained results of this approach show its stability and better performance over other existing approaches of motion measurements. Meanwhile, findings of this paper lay a foundation for motion pattern of WCEs inside the large intestine, which will benefit other medical applications.

Anterior Lens Capsule and Iris Thicknesses in Pseudoexfoliation Syndrome.

PubMed

Batur, Muhammed; Seven, Erbil; Tekin, Serek; Yasar, Tekin

2017-11-01

The aim of this study was to evaluate anatomic properties of the lens capsule and iris by anterior segment optical coherence tomography (AS-OCT) in patients with pseudoexfoliation (PEX). This prospective study included 62 eyes of 62 patients with PEX syndrome and 43 eyes of 43 age- and gender-matched controls. All subjects underwent full ophthalmologic examinations including AS-OCT. Pupillary diameter, midperipheral stromal iris thickness, central and temporal lens capsule thicknesses, and peripheral pseudoexfoliation material thickness on the anterior lens capsule surface were measured and recorded. Mean age was 66.8 ± 9.3 years in the PEX group and 65.5 ± 8.9 years in the control group (p = 0.44). The PEX group consisted of 62 patients: 38 men (61.3%) and 24 women (38.7%); the control group included 43 subjects: 25 men (58.1%) and 18 women (41.9%). Pupillary diameter after pharmacologic mydriasis was 21% smaller in the PEX group than controls. Mean midperipheral iris thickness was 36 ± 7.2 μm (7.8%) thinner in the PEX group than that of control group (p = 0.047). The central anterior capsule was a mean of 3.40 ± 0.51 μm (18%) thicker in the PEX group compared to the control group (p = 0.0001). The temporal anterior lens capsule was a mean of 0.17 ± 0.15 μm thicker in the PEX group compared to the control group (p = 0.81). With high-resolution OCT imaging, it has become possible to evaluate the anterior lens capsule without histologic examination and demonstrate that it is thicker than normal in PEX patients.

Internalization of Red Blood Cell-Mimicking Hydrogel Capsules with pH-Triggered Shape Responses

PubMed Central

2015-01-01

We report on naturally inspired hydrogel capsules with pH-induced transitions from discoids to oblate ellipsoids and their interactions with cells. We integrate characteristics of erythrocytes such as discoidal shape, hollow structure, and elasticity with reversible pH-responsiveness of poly(methacrylic acid) (PMAA) to design a new type of drug delivery carrier to be potentially triggered by chemical stimuli in the tumor lesion. The capsules are fabricated from cross-linked PMAA multilayers using sacrificial discoid silicon templates. The degree of capsule shape transition is controlled by the pH-tuned volume change, which in turn is regulated by the capsule wall composition. The (PMAA)15 capsules undergo a dramatic 24-fold volume change, while a moderate 2.3-fold volume variation is observed for more rigid PMAA–(poly(N-vinylpyrrolidone) (PMAA–PVPON)5 capsules when solution pH is varied between 7.4 and 4. Despite that both types of capsules exhibit discoid-to-oblate ellipsoid transitions, a 3-fold greater swelling in radial dimensions is found for one-component systems due to a greater degree of the circular face bulging. We also show that (PMAA–PVPON)5 discoidal capsules interact differently with J774A.1 macrophages, HMVEC endothelial cells, and 4T1 breast cancer cells. The discoidal capsules show 60% lower internalization as compared to spherical capsules. Finally, hydrogel capsules demonstrate a 2-fold decrease in size upon internalization. These capsules represent a unique example of elastic hydrogel discoids capable of pH-induced drastic and reversible variations in aspect ratios. Considering the RBC-mimicking shape, their dimensions, and their capability to undergo pH-triggered intracellular responses, the hydrogel capsules demonstrate considerable potential as novel carriers in shape-regulated transport and cellular uptake. PMID:24848786

Capsulitis of the Second Toe

MedlinePlus

... second toe is a result of abnormal foot mechanics, where the ball of the foot beneath the ... options for early treatment of capsulitis: Rest and ice. Staying off the foot and applying ice packs ...

Reactor for making uniform capsules

NASA Technical Reports Server (NTRS)

Wang, Taylor G. (Inventor); Anikumar, Amrutur V. (Inventor); Lacik, Igor (Inventor)

1999-01-01

The present invention provides a novel reactor for making capsules with uniform membrane. The reactor includes a source for providing a continuous flow of a first liquid through the reactor; a source for delivering a steady stream of drops of a second liquid to the entrance of the reactor; a main tube portion having at least one loop, and an exit opening, where the exit opening is at a height substantially equal to the entrance. In addition, a method for using the novel reactor is provided. This method involves providing a continuous stream of a first liquid; introducing uniformly-sized drops of the second liquid into the stream of the first liquid; allowing the drops to react in the stream for a pre-determined period of time; and collecting the capsules.

Capsule Performance Optimization in the National Ignition Campaign

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landen, O L; MacGowan, B J; Haan, S W

2009-10-13

A capsule performance optimization campaign will be conducted at the National Ignition Facility to substantially increase the probability of ignition. The campaign will experimentally correct for residual uncertainties in the implosion and hohlraum physics used in our radiation-hydrodynamic computational models before proceeding to cryogenic-layered implosions and ignition attempts. The required tuning techniques using a variety of ignition capsule surrogates have been demonstrated at the Omega facility under scaled hohlraum and capsule conditions relevant to the ignition design and shown to meet the required sensitivity and accuracy. In addition, a roll-up of all expected random and systematic uncertainties in setting themore » key ignition laser and target parameters due to residual measurement, calibration, cross-coupling, surrogacy, and scale-up errors has been derived that meets the required budget.« less

Capsule performance optimization in the national ignition campaign

NASA Astrophysics Data System (ADS)

Landen, O. L.; MacGowan, B. J.; Haan, S. W.; Edwards, J.

2010-08-01

A capsule performance optimization campaign will be conducted at the National Ignition Facility [1] to substantially increase the probability of ignition. The campaign will experimentally correct for residual uncertainties in the implosion and hohlraum physics used in our radiation-hydrodynamic computational models before proceeding to cryogenic-layered implosions and ignition attempts. The required tuning techniques using a variety of ignition capsule surrogates have been demonstrated at the Omega facility under scaled hohlraum and capsule conditions relevant to the ignition design and shown to meet the required sensitivity and accuracy. In addition, a roll-up of all expected random and systematic uncertainties in setting the key ignition laser and target parameters due to residual measurement, calibration, cross-coupling, surrogacy, and scale-up errors has been derived that meets the required budget.

Arthroscopy of the fetlock joint of the dromedary camel.

PubMed

Ali, M M; Abd-Elnaeim, M

2012-01-01

To describe a technique for arthroscopy of the fetlock joint of the dromedary camel, and the problems that could occur during and after arthroscopy. Seven animals (4 cadaveric limbs and 3 living camels) were used in this study. Two dorsal arthroscopic portals (lateral and medial) and one palmaro-lateral portal were used. Distension of the joint capsule was effected by injecting Ringer´s lactate solution into the joint cavity. Landmarks for the dorsal arthroscopic portals were located at the centre of the groove bounded by the lateral branch of the suspensory ligament and the large metacarpus at a point 1 cm proximal to the joint. The palmaro-lateral portal was located in a triangular area between the branch of the suspensory ligament, the large metacarpus, and the sesamoid bone, with insertion of the arthroscope in a 45° joint flexion angle. Arthroscopy of the fetlock joint via the dorso-lateral portal allowed examination of the distal end of the large metacarpus and the proximal end of the first phalanx of the fourth digit. Arthroscopy via a dorso-medial approach allowed examination of the distal end of the large metacarpus and the proximal end of the first phalanx and the distal end of the third digit. The palmaro-lateral portal allowed examination of the sesamoid bones, the synovial membrane, and the synovial villi. The main complications recorded during arthroscopy were iatrogenic articular surface injury as well as obstruction of vision with the synovial villi. This is the first work to describe the normal arthroscopy of the fetlock joint in the dromedary camel, the arthroscopic portals, and the complications that could occur during and after arthroscopy. Further studies are required for diagnosis of pathological changes in the fetlock joint of the dromedary camel and for arthroscopy of other joints in the dromedary camel.

The Anterolateral Capsule of the Knee Behaves Like a Sheet of Fibrous Tissue.

PubMed

Guenther, Daniel; Rahnemai-Azar, Amir A; Bell, Kevin M; Irarrázaval, Sebastián; Fu, Freddie H; Musahl, Volker; Debski, Richard E

2017-03-01

The function of the anterolateral capsule of the knee has not been clearly defined. However, the contribution of this region of the capsule to knee stability in comparison with other anterolateral structures can be determined by the relative force that each structure carries during loading of the knee. Purpose/Hypothesis: The purpose of this study was to determine the forces in the anterolateral structures of the intact and anterior cruciate ligament (ACL)-deficient knee in response to an anterior tibial load and internal tibial torque. It was hypothesized that the anterolateral capsule would not function like a traditional ligament (ie, transmitting forces only along its longitudinal axis). Controlled laboratory study. Loads (134-N anterior tibial load and 7-N·m internal tibial torque) were applied continuously during flexion to 7 fresh-frozen cadaveric knees in the intact and ACL-deficient state using a robotic testing system. The lateral collateral ligament (LCL) and the anterolateral capsule were separated from the surrounding tissue and from each other. This was done by performing 3 vertical incisions: lateral to the LCL, medial to the LCL, and lateral to the Gerdy tubercle. Attachments of the LCL and anterolateral capsule were detached from the underlying tissue (ie, meniscus), leaving the insertions and origins intact. The force distribution in the anterolateral capsule, ACL, and LCL was then determined at 30°, 60°, and 90° of knee flexion using the principle of superposition. In the intact knee, the force in the ACL in response to an anterior tibial load was greater than that in the other structures ( P < .001). However, in response to an internal tibial torque, no significant differences were found between the ACL, LCL, and forces transmitted between each region of the anterolateral capsule after capsule separation. The anterolateral capsule experienced smaller forces (~50% less) compared with the other structures ( P = .048). For the ACL

Capsule endoscopy: impact on clinical decision making in patients with suspected small bowel bleeding.

PubMed

Gubler, C; Fox, M; Hengstler, P; Abraham, D; Eigenmann, F; Bauerfeind, P

2007-12-01

Capsule endoscopy is widely used for diagnosis of small-bowel disease; however, the impact of capsule endoscopy on clinical management remains uncertain. We conducted a prospective study of the impact capsule endoscopy on clinical management decisions in 128 patients with suspected small-bowel pathology. Prior to performing each procedure the gastroenterologist predicted the findings of capsule endoscopy and further management based on the clinical history and previous investigations. This prediction was compared with the actual results of capsule endoscopy and the following investigative and therapeutic management. The actual findings of capsule endoscopy and the further management were consistent with clinical prediction in 93/128 patients (73 %) and, irrespective of capsule endoscopy findings, no further procedures were required in 80 % of these patients. In 13 patients (10 %), gastric or colonic pathology was discovered that had not been detected on prior gastroscopy or colonoscopy. Thus, capsule endoscopy findings in the small bowel changed clinical management in 22 patients (17 %). In 4 patients, positive findings on capsule endoscopy that had not been predicted by the examiner prompted referral for abdominal surgery. Conversely, planned surgery was canceled in four other patients. In this series of patients referred for capsule endoscopy, small-bowel findings and appropriate clinical management were predicted on clinical grounds alone in approximately three-quarters of patients. Repetition of standard upper and lower endoscopy may be useful in many patients prior to small-bowel imaging. Referral for capsule endoscopy should take into account whether the findings will impact on clinical management; however, capsule endoscopy is mandatory in patients in whom surgery for small-bowel bleeding is intended.