Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

Energy Technology Data Exchange (ETDEWEB)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

Integrating physiological regulation with stem cell and tissue homeostasis

Science.gov (United States)

Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

2015-01-01

Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

Increased tissue oxygenation explains the attenuation of hyperemia upon repetitive pneumatic compression of the lower leg.

Science.gov (United States)

Messere, Alessandro; Ceravolo, Gianluca; Franco, Walter; Maffiodo, Daniela; Ferraresi, Carlo; Roatta, Silvestro

2017-12-01

The rapid hyperemia evoked by muscle compression is short lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation, which include local metabolic mechanisms, desensitization of mechanosensitive pathways, and reduced efficacy of the muscle pump. In 10 healthy subjects, short sequences of mechanical compressions ( n = 3-6; 150 mmHg) of the lower leg were delivered at different interstimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near-infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, and simultaneous echo-Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. The results indicate that 1 ) a long-lasting (>100 s) increase in local tissue oxygenation follows compression-induced hyperemia, 2 ) compression-induced hyperemia exhibits different patterns of attenuation depending on the interstimulus interval, 3 ) the amplitude of the hyperemia is not correlated with the amount of blood volume displaced by the compression, and 4 ) the extent of attenuation negatively correlates with tissue oxygenation ( r  = -0,78, P < 0.05). Increased tissue oxygenation appears to be the key factor for the attenuation of hyperemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. NEW & NOTEWORTHY This study shows that 1 ) the hyperemia induced by muscle compression produces a long-lasting increase in tissue oxygenation, 2 ) the hyperemia produced by subsequent muscle compressions exhibits different patterns of attenuation at different interstimulus intervals, and 3 ) the extent of attenuation of the compression-induced hyperemia is proportional to the level of

Ontology-based, Tissue MicroArray oriented, image centered tissue bank

Directory of Open Access Journals (Sweden)

Viti Federica

2008-04-01

Full Text Available Abstract Background Tissue MicroArray technique is becoming increasingly important in pathology for the validation of experimental data from transcriptomic analysis. This approach produces many images which need to be properly managed, if possible with an infrastructure able to support tissue sharing between institutes. Moreover, the available frameworks oriented to Tissue MicroArray provide good storage for clinical patient, sample treatment and block construction information, but their utility is limited by the lack of data integration with biomolecular information. Results In this work we propose a Tissue MicroArray web oriented system to support researchers in managing bio-samples and, through the use of ontologies, enables tissue sharing aimed at the design of Tissue MicroArray experiments and results evaluation. Indeed, our system provides ontological description both for pre-analysis tissue images and for post-process analysis image results, which is crucial for information exchange. Moreover, working on well-defined terms it is then possible to query web resources for literature articles to integrate both pathology and bioinformatics data. Conclusions Using this system, users associate an ontology-based description to each image uploaded into the database and also integrate results with the ontological description of biosequences identified in every tissue. Moreover, it is possible to integrate the ontological description provided by the user with a full compliant gene ontology definition, enabling statistical studies about correlation between the analyzed pathology and the most commonly related biological processes.

Simultaneous inference of phenotype-associated genes and relevant tissues from GWAS data via Bayesian integration of multiple tissue-specific gene networks.

Science.gov (United States)

Wu, Mengmeng; Lin, Zhixiang; Ma, Shining; Chen, Ting; Jiang, Rui; Wong, Wing Hung

2017-12-01

Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the advanced analysis of the vast volume of existing and anticipated genetic data. Towards this goal, gene-level integrative GWAS analysis with the assumption that genes associated with a phenotype tend to be enriched in biological gene sets or gene networks has recently attracted much attention, due to such advantages as straightforward interpretation, less multiple testing burdens, and robustness across studies. However, existing methods in this category usually exploit non-tissue-specific gene networks and thus lack the ability to utilize informative tissue-specific characteristics. To overcome this limitation, we proposed a Bayesian approach called SIGNET (Simultaneously Inference of GeNEs and Tissues) to integrate GWAS data and multiple tissue-specific gene networks for the simultaneous inference of phenotype-associated genes and relevant tissues. Through extensive simulation studies, we showed the effectiveness of our method in finding both associated genes and relevant tissues for a phenotype. In applications to real GWAS data of 14 complex phenotypes, we demonstrated the power of our method in both deciphering genetic basis and discovering biological insights of a phenotype. With this understanding, we expect to see SIGNET as a valuable tool for integrative GWAS analysis, thereby boosting the prevention, diagnosis, and treatment of human inherited diseases and eventually facilitating precision medicine.

Tissue integration of polyacrylamide hydrogel: an experimental study of periurethral, perivesical, and mammary gland tissue in the pig

DEFF Research Database (Denmark)

Christensen, Lise H; Nielsen, John B; Mouritsen, Lone

2008-01-01

BACKGROUND Polyacrylamide hydrogel (PAAG) is a nondegradable water-based polymer with high viscoelasticity. The gel is used as a tissue filler, the only risk being prolonged infection with anaerobic, contaminating microorganisms if not treated early with broad-spectrum antibiotics. OBJECTIVE...... With silicone gel as reference, PAAG tissue integration and migration was studied in a longitudinal study of the pig. MATERIALS AND METHODS Forty-one pigs were used. PAAG and silicone gel were injected into mammary tissue, and PAAG was injected into urethral or bladder wall or the anal canal. Tissues...... and regional lymph nodes were examined at 1, 1 1/2, 3, 3 1/2, 6, 12, and 14 months, and other lymph nodes and organs were examined at 1, 6, 12, and 14 months. RESULTS PAAG was invaded by macrophages and giant cells that were gradually replaced by a network of fibrous tissue. Silicone gel was seen inside...

Advancing Tissue Engineering: A Tale of Nano-, Micro-, and Macroscale Integration

NARCIS (Netherlands)

Leijten, Jeroen Christianus Hermanus; Rouwkema, Jeroen; Zhang, Y.S.; Nasajpour, A.; Dokmeci, M.R.; Khademhosseini, A.

2016-01-01

Tissue engineering has the potential to revolutionize the health care industry. Delivering on this promise requires the generation of efficient, controllable and predictable implants. The integration of nano- and microtechnologies into macroscale regenerative biomaterials plays an essential role in

Optical Characterization of Tissue Phantoms Using a Silicon Integrated fdNIRS System on Chip.

Science.gov (United States)

Sthalekar, Chirag C; Miao, Yun; Koomson, Valencia Joyner

2017-04-01

An interface circuit with signal processing and digitizing circuits for a high frequency, large area avalanche photodiode (APD) has been integrated in a 130 nm BiCMOS chip. The system enables the absolute oximetry of tissue using frequency domain Near Infrared Spectroscopy (fdNIRS). The system measures the light absorbed and scattered by the tissue by measuring the reduction in the amplitude of signal and phase shift introduced between the light source and detector which are placed a finite distance away from each other. The received 80 MHz RF signal is downconverted to a low frequency and amplified using a heterodyning scheme. The front-end transimpedance amplifier has a 3-level programmable gain that increases the dynamic range to 60 dB. The phase difference between an identical reference channel and the optical channel is measured with a 0.5° accuracy. The detectable current range is [Formula: see text] and with a 40 A/W reponsivity using the APD, power levels as low as 500 pW can be detected. Measurements of the absorption and reduced scattering coefficients of solid tissue phantoms using this system are compared with those using a commercial instrument with differences within 30%. Measurement of a milk based liquid tissue phantom show an increase in absorption coefficient with addition of black ink. The miniaturized circuit serves as an efficiently scalable system for multi-site detection for applications in neonatal cerebral oximetry and optical mammography.

The effects of frozen tissue storage conditions on the integrity of RNA and protein.

Science.gov (United States)

Auer, H; Mobley, J A; Ayers, L W; Bowen, J; Chuaqui, R F; Johnson, L A; Livolsi, V A; Lubensky, I A; McGarvey, D; Monovich, L C; Moskaluk, C A; Rumpel, C A; Sexton, K C; Washington, M K; Wiles, K R; Grizzle, W E; Ramirez, N C

2014-10-01

Unfixed tissue specimens most frequently are stored for long term research uses at either -80° C or in vapor phase liquid nitrogen (VPLN). There is little information concerning the effects such long term storage on tissue RNA or protein available for extraction. Aliquots of 49 specimens were stored for 5-12 years at -80° C or in VPLN. Twelve additional paired specimens were stored for 1 year under identical conditions. RNA was isolated from all tissues and assessed for RNA yield, total RNA integrity and mRNA integrity. Protein stability was analyzed by surface-enhanced or matrix-assisted laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS, MALDI-TOF-MS) and nano-liquid chromatography electrospray ionization tandem mass spectrometry (nLC-ESI-MS/MS). RNA yield and total RNA integrity showed significantly better results for -80° C storage compared to VPLN storage; the transcripts that were preferentially degraded during VPLN storage were these involved in antigen presentation and processing. No consistent differences were found in the SELDI-TOF-MS, MALDI-TOF-MS or nLC-ESI-MS/MS analyses of specimens stored for more than 8 years at -80° C compared to those stored in VPLN. Long term storage of human research tissues at -80° C provides at least the same quality of RNA and protein as storage in VPLN.

Increased PDGFRα Activation Disrupts Connective Tissue Development and Drives Systemic Fibrosis

OpenAIRE

Olson, Lorin E.; Soriano, Philippe

2009-01-01

PDGF signaling regulates the development of mesenchymal cell types in the embryo and in the adult, but the role of receptor activation in tissue homeostasis has not been investigated. We have generated conditional knockin mice with mutations in PDGFRα that drive increased kinase activity under the control of the endogenous PDGFRα promoter. In embryos, increased PDGFRα signaling leads to hyperplasia of stromal fibroblasts that disturbs normal smooth muscle tissue in radially patterned organs. ...

Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative.

Directory of Open Access Journals (Sweden)

Martina Loibner

Full Text Available Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene, was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples.Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV. Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays.All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity.PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment.

Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative.

Science.gov (United States)

Loibner, Martina; Buzina, Walter; Viertler, Christian; Groelz, Daniel; Hausleitner, Anja; Siaulyte, Gintare; Kufferath, Iris; Kölli, Bettina; Zatloukal, Kurt

2016-01-01

Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene), was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples. Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV). Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays. All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity. PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment.

Tissue engineering and cell-based therapy toward integrated strategy with artificial organs.

Science.gov (United States)

Gojo, Satoshi; Toyoda, Masashi; Umezawa, Akihiro

2011-09-01

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.

Endoplasmic reticulum stress is increased in adipose tissue of women with gestational diabetes.

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Stella Liong

Full Text Available Maternal obesity and gestational diabetes mellitus (GDM are two increasingly common and important obstetric complications that are associated with severe long-term health risks to mothers and babies. IL-1β, which is increased in obese and GDM pregnancies, plays an important role in the pathophysiology of these two pregnancy complications. In non-pregnant tissues, endoplasmic (ER stress is increased in diabetes and can induce IL-1β via inflammasome activation. The aim of this study was to determine whether ER stress is increased in omental adipose tissue of women with GDM, and if ER stress can also upregulate inflammasome-dependent secretion of IL-1β. ER stress markers IRE1α, GRP78 and XBP-1s were significantly increased in adipose tissue of obese compared to lean pregnant women. ER stress was also increased in adipose tissue of women with GDM compared to BMI-matched normal glucose tolerant (NGT women. Thapsigargin, an ER stress activator, induced upregulated secretion of mature IL-1α and IL-1β in human omental adipose tissue explants primed with bacterial endotoxin LPS, the viral dsRNA analogue poly(I:C or the pro-inflammatory cytokine TNF-α. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1α and IL-1β secretion, whereas inhibition of pannexin-1 with carbenoxolone suppressed IL-1β secretion only. Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1α and IL-1β secretion in infection and cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER stress to activate the inflammasome in pregnant adipose tissue. Therefore, increased ER stress may contribute towards the pathophysiology of obesity in pregnancy and GDM.

Connective tissue integrity is lost in vitamin B-6-deficient chicks

Science.gov (United States)

Masse, P. G.; Yamauchi, M.; Mahuren, J. D.; Coburn, S. P.; Muniz, O. E.; Howell, D. S.

1995-01-01

The objective of the present investigation was to characterize further the connective tissue disorder produced by pyridoxine (vitamin B-6) deficiency, as previously evidenced by electron microscopy. Following the second post-natal week, fast growing male chicks were deprived of pyridoxine for a 1-mo period. Six weeks post-natally, blood concentrations in the experimental deficiency group had declined to deficiency levels as registered by low concentrations of pyridoxal phosphate (coenzyme form) in erythrocytes, but did not reach levels associated with neurological symptoms. Light microscopic study showed abnormalities in the extracellular matrix of the connective tissues. Collagen cross-links and the aldehyde contents were not significantly lower in cartilage and tendon collagens of vitamin B-6-deficient animals than in age-matched controls; also, their proteoglycan degrading protease and collagenase activities measured in articular cartilages were not greater. Thus, proteolysis was an unlikely alternative mechanism to account for the loss of connective tissue integrity. These results point to the need for further investigation into adhesive properties of collagen associated proteoglycans or other proteins in vitamin B-6-deficient connective tissue.

Integration of 3D Printed and Micropatterned Polycaprolactone Scaffolds for Guidance of Oriented Collagenous Tissue Formation In Vivo.

Science.gov (United States)

Pilipchuk, Sophia P; Monje, Alberto; Jiao, Yizu; Hao, Jie; Kruger, Laura; Flanagan, Colleen L; Hollister, Scott J; Giannobile, William V

2016-03-01

Scaffold design incorporating multiscale cues for clinically relevant, aligned tissue regeneration has potential to improve structural and functional integrity of multitissue interfaces. The objective of this preclinical study is to develop poly(ε-caprolactone) (PCL) scaffolds with mesoscale and microscale architectural cues specific to human ligament progenitor cells and assess their ability to form aligned bone-ligament-cementum complexes in vivo. PCL scaffolds are designed to integrate a 3D printed bone region with a micropatterned PCL thin film consisting of grooved pillars. The patterned film region is seeded with human ligament cells, fibroblasts transduced with bone morphogenetic protein-7 genes seeded within the bone region, and a tooth dentin segment positioned on the ligament region prior to subcutaneous implantation into a murine model. Results indicate increased tissue alignment in vivo using micropatterned PCL films, compared to random-porous PCL. At week 6, 30 μm groove depth significantly enhances oriented collagen fiber thickness, overall cell alignment, and nuclear elongation relative to 10 μm groove depth. This study demonstrates for the first time that scaffolds with combined hierarchical mesoscale and microscale features can align cells in vivo for oral tissue repair with potential for improving the regenerative response of other bone-ligament complexes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association between increased epicardial adipose tissue volume and coronary plaque composition.

Science.gov (United States)

Yamashita, Kennosuke; Yamamoto, Myong Hwa; Ebara, Seitarou; Okabe, Toshitaka; Saito, Shigeo; Hoshimoto, Koichi; Yakushiji, Tadayuki; Isomura, Naoei; Araki, Hiroshi; Obara, Chiaki; Ochiai, Masahiko

2014-09-01

To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or calcified tissue, based on the radiofrequency spectrum. Epicardial adipose tissue was measured as the tissue ranging from -190 to -30 Hounsfield units. EATV, calculated as the sum of the fat areas on short-axis images, was 85.0 ± 34.0 cm(3). There was a positive correlation between EATV and the percentage of necrotic plaque tissue (R (2) = 0.34, P EATV and the percentage of fibrous tissue (R (2) = 0.24, P EATV (β = 0.14, P = 0.02) were independently associated with the percentage of necrotic plaque tissue. An increase in EATV was associated with the development of coronary atherosclerosis and, potentially, with the most dangerous type of plaque.

Study of the optical properties of solid tissue phantoms using single and double integrating sphere systems

CSIR Research Space (South Africa)

Monem, S

2015-12-01

Full Text Available light propagation mechanisms inside the tissues. In this work, two calibration models based on measurements adopting integrating sphere systems have been used to determine the optical properties of the studied solid phantoms. Integrating sphere...

Integrated engineering increases flexibility

International Nuclear Information System (INIS)

Smith, Ray

1991-01-01

Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author)

Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice

International Nuclear Information System (INIS)

Andersson, C.; Iresjoe, B.M.L.; Lundholm, K.

1991-01-01

Plasma albumin concentration declines in both experimental and clinical cancer. Previous investigations have demonstrated that this is partly explained by increased breakdown of albumin. The present study has identified the tissue sites for increased albumin degradation in a nonmetastasizing sarcoma mouse (C57/BL6J) model. Results have been compared to nontumor-bearing animals either freely fed or food restricted (pair-weighed) so that their body composition was similar to tumor-bearing animals. Tumor-bearing mice had increased albumin degradation (0.13 +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair-weighed control animals (0.05 +/- 0.008). Radioactivity from circulating [3H]raffine aldehyde labeled albumin appeared with maximum peak values in lysosomes isolated from both tumor and nontumor tissues at 48 hr following iv injection. The intralysosomal accumulation of radioactivity was two- to threefold higher in tumor tissue compared to liver tissue, although the specific activity of protease(s) for albumin degradation measured in vitro was not higher in tumor tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/- 1.7). Accounting for the entire tumor the proteolytic capacity for albumin breakdown was however much larger in the tumor (161.6 +/- 32.6 mg/organ) compared to both normal liver (37.5 +/- 2.3) and tumor-host liver (56.4 +/- 2.8). Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the tumor measured by 125I-labeled undenatured mouse albumin as the substrate. Leupeptin inhibited 49 +/- 6%. There was a significantly decreased breakdown of albumin in both skeletal muscles and the gastrointestinal tract from tumor-bearing animals

Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane.

Science.gov (United States)

Nap, Annemiek W; Groothuis, Patrick G; Demir, Ayse Y; Maas, Jacques W M; Dunselman, Gerard A J; de Goeij, Anton F P M; Evers, Johannes L H

2003-01-01

Not all women with patent tubes develop clinically manifest endometriosis. Quality and quantity of endometrium in retrograde menstruation may be the determining factor in the development of the disease. We hypothesize that retrograde shedding of endometrial fragments with preserved integrity facilitates implantation of endometrium in ectopic locations, resulting in endometriotic lesion development. We evaluate the impact of tissue integrity on the success of endometriosis-like lesion development in the chicken embryo chorioallantoic membrane (CAM) model. Menstrual and non-menstrual (cyclic) endometrium were collected by biopsy, and either minced or enzymatically dispersed. Spontaneously shed menstrual effluent was collected by a menstrual cup, and cells and tissue were isolated. We evaluated whether infiltration or lesion formation in the CAM occurred after transplantation of endometrium onto the CAM. Transplantation of biopsied menstrual and cyclic endometrium fragments, and of endometrium fragments >1 mm(3) isolated from menstrual effluent, resulted in lesion formation. Transplantation of endometrial cells isolated from menstrual effluent did not lead to lesion formation. After transplantation of digested biopsied cyclic endometrium, infiltration in the CAM but no lesions were observed. In the CAM assay, integrity of tissue architecture determines success of implantation of human endometrium in ectopic locations.

An integrated finite-element approach to mechanics, transport and biosynthesis in tissue engineering

NARCIS (Netherlands)

Sengers, B.G.; Oomens, C.W.J.; Baaijens, F.P.T.

2004-01-01

A finite-element approach was formulated, aimed at enabling an integrated study of mechanical and biochemical factors that control the functional development of tissue engineered constructs. A nonlinear biphasic displacement-velocity-pressure description was combined with adjective and diffusive

Tissue banking in a regional hospital: a promising future concept? First report on fresh frozen tissue banking in a hospital without an integrated institute of pathology.

Science.gov (United States)

von Strauss und Torney, Marco; Güller, Ulrich; Rezaeian, Farid; Brosi, Philippe; Terracciano, Luigi; Zuber, Markus

2012-10-01

Vital tissue provided by fresh frozen tissue banking is often required for genetic tumor profiling and tailored therapies. However, the potential patient benefits of fresh frozen tissue banking are currently limited to university hospitals. The objective of the present pilot study--the first one in the literature--was to evaluate whether fresh frozen tissue banking is feasible in a regional hospital without an integrated institute of pathology. Patients with resectable breast and colon cancer were included in this prospective study. Both malignant and healthy tissue were sampled using isopentan-based snap-freezing 1 h after tumor resection and stored at -80 °C before transfer to the main tissue bank of a University institute of pathology. The initial costs to set up tissue banking were 35,662 US$. Furthermore, the running costs are 1,250 US$ yearly. During the first 13 months, 43 samples (nine samples of breast cancer and 34 samples of colon cancer) were collected from 41 patients. Based on the pathology reports, there was no interference with standard histopathologic analyses due to the sample collection. This is the first report in the literature providing evidence that tissue banking in a regional hospital without an integrated institute of pathology is feasible. The interesting findings of the present pilot study must be confirmed by larger investigations.

Integrated outages increase Surry's availability

International Nuclear Information System (INIS)

Harms, S.R.; Downs, J.L.

1995-01-01

This article describes how, through Virginia Power's and Westinghouse's goal-oriented planning philosophy, teamwork and commitment, average outage duration has decreased significantly. During the past 10 years Virginia Power and its nuclear steam supply system (NSSS) services vendor, Westinghouse Electric Corp., have developed a working partnership with one goal in mind: increasing the availability and capacity factors of the North Anna and Surry nuclear power stations while driving down the operating costs of the plants. The outage integration program, steam generator maintenance agreement (SGMA), and integrated radiological services program form the core of this relationship and helped Virginia Power complete one of the most successful outages in Surry Power Station's operating history

A Trifunctional, Modular Biomaterial Coating : Nonadhesive to Bacteria, Chlorhexidine-Releasing and Tissue-Integrating

NARCIS (Netherlands)

Sjollema, Jelmer; Keul, Heidrun; van der Mei, Henny; Dijkstra, Rene; Rustema-Abbing, Minie; de Vries, Joop; Loontjens, Ton; Dirks, Ton; Busscher, Henk

Various potential anti-infection strategies can be thought of for biomaterial implants and devices. Permanent, tissue-integrated implants such as artificial joint prostheses require a different anti-infection strategy than, for instance, removable urinary catheters. The different requirements set to

Nanotechnology and picotechnology to increase tissue growth: a summary of in vivo studies

Directory of Open Access Journals (Sweden)

Alpaslan E

2014-05-01

Full Text Available Ece Alpaslan,1 Thomas J Webster1,21Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi ArabiaAbstract: The aim of tissue engineering is to develop functional substitutes for damaged tissues or malfunctioning organs. Since only nanomaterials can mimic the surface properties (ie, roughness of natural tissues and have tunable properties (such as mechanical, magnetic, electrical, optical, and other properties, they are good candidates for increasing tissue growth, minimizing inflammation, and inhibiting infection. Recently, the use of nanomaterials in various tissue engineering applications has demonstrated improved tissue growth compared to what has been achieved until today with our conventional micron structured materials. This short report paper will summarize some of the more relevant advancements nanomaterials have made in regenerative medicine, specifically improving bone and bladder tissue growth. Moreover, this short report paper will also address the continued potential risks and toxicity concerns, which need to be accurately addressed by the use of nanomaterials. Lastly, this paper will emphasize a new field, picotechnology, in which researchers are altering electron distributions around atoms to promote surface energy to achieve similar increased tissue growth, decreased inflammation, and inhibited infection without potential nanomaterial toxicity concerns.Keywords: nanomaterials, tissue engineering, toxicity

Noninvasive computerized scanning method for the correlation between the facial soft and hard tissues for an integrated three-dimensional anthropometry and cephalometry.

Science.gov (United States)

Galantucci, Luigi Maria; Percoco, Gianluca; Lavecchia, Fulvio; Di Gioia, Eliana

2013-05-01

The article describes a new methodology to scan and integrate facial soft tissue surface with dental hard tissue models in a three-dimensional (3D) virtual environment, for a novel diagnostic approach.The facial and the dental scans can be acquired using any optical scanning systems: the models are then aligned and integrated to obtain a full virtual navigable representation of the head of the patient. In this article, we report in detail and further implemented a method for integrating 3D digital cast models into a 3D facial image, to visualize the anatomic position of the dentition. This system uses several 3D technologies to scan and digitize, integrating them with traditional dentistry records. The acquisitions were mainly performed using photogrammetric scanners, suitable for clinics or hospitals, able to obtain high mesh resolution and optimal surface texture for the photorealistic rendering of the face. To increase the quality and the resolution of the photogrammetric scanning of the dental elements, the authors propose a new technique to enhance the texture of the dental surface. Three examples of the application of the proposed procedure are reported in this article, using first laser scanning and photogrammetry and then only photogrammetry. Using cheek retractors, it is possible to scan directly a great number of dental elements. The final results are good navigable 3D models that integrate facial soft tissue and dental hard tissues. The method is characterized by the complete absence of ionizing radiation, portability and simplicity, fast acquisition, easy alignment of the 3D models, and wide angle of view of the scanner. This method is completely noninvasive and can be repeated any time the physician needs new clinical records. The 3D virtual model is a precise representation both of the soft and the hard tissue scanned, and it is possible to make any dimensional measure directly in the virtual space, for a full integrated 3D anthropometry and

Multifunctional Hydrogel with Good Structure Integrity, Self-Healing, and Tissue-Adhesive Property Formed by Combining Diels-Alder Click Reaction and Acylhydrazone Bond.

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Yu, Feng; Cao, Xiaodong; Du, Jie; Wang, Gang; Chen, Xiaofeng

2015-11-04

Hydrogel, as a good cartilage tissue-engineered scaffold, not only has to possess robust mechanical property but also has to have an intrinsic self-healing property to integrate itself or the surrounding host cartilage. In this work a double cross-linked network (DN) was designed and prepared by combining Diels-Alder click reaction and acylhydrazone bond. The DA reaction maintained the hydrogel's structural integrity and mechanical strength in physiological environment, while the dynamic covalent acylhydrazone bond resulted in hydrogel's self-healing property and controlled the on-off switch of network cross-link density. At the same time, the aldehyde groups contained in hydrogel further promote good integration of the hydrogel to surrounding tissue based on aldehyde-amine Schiff-base reaction. This kind of hydrogel has good structural integrity, autonomous self-healing, and tissue-adhesive property and simultaneously will have a good application in tissue engineering and tissue repair field.

Fit for purpose frozen tissue collections by RNA integrity number-based quality control assurance at the Erasmus MC tissue bank.

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Kap, Marcel; Oomen, Monique; Arshad, Shazia; de Jong, Bas; Riegman, Peter

2014-04-01

About 5000 frozen tissue samples are collected each year by the Erasmus Medical Center tissue bank. Two percent of these samples are randomly selected annually for RNA isolation and RNA Integrity Number (RIN) measurement. A similar quality assessment was conducted during centralization of a 20-year-old tissue collection from the cancer institute, a 15-year-old liver sample archive (-80°C), and a 13-year-old clinical pathology frozen biopsy archive (Liquid Nitrogen). Samples were divided into either high-quality (RIN ≥6.5) or low-quality overall categories, or into four "fit-for-purpose" quality groups: RIN procurement protocols used for these samples needed immediate evaluation. When the distribution of RIN values of the different collections were compared, no significant differences were found, despite differences in average storage time and temperature. According to the principle of "fit-for-purpose" distribution, the vast majority of samples are considered good enough for most downstream techniques. In conclusion, an annual tissue bank quality control procedure provides useful information on tissue sample quality and sheds light on where and if improvements need to be made.

Design of a miniaturized integrated spectrometer for spectral tissue sensing

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Belay, Gebirie Yizengaw; Hoving, Willem; Ottevaere, Heidi; van der Put, Arthur; Weltjens, Wim; Thienpont, Hugo

2016-04-01

Minimally-invasive image-guided procedures become increasingly used by physicians to obtain real-time characterization feedback from the tissue at the tip of their interventional device (needle, catheter, endoscopic or laparoscopic probes, etc…) which can significantly improve the outcome of diagnosis and treatment, and ultimately reduce cost of the medical treatment. Spectral tissue sensing using compact photonic probes has the potential to be a valuable tool for screening and diagnostic purposes, e.g. for discriminating between healthy and tumorous tissue. However, this technique requires a low-cost broadband miniature spectrometer so that it is commercially viable for screening at point-of-care locations such as physicians' offices and outpatient centers. Our goal is therefore to develop a miniaturized spectrometer based on diffractive optics that combines the functionalities of a visible/near-infrared (VIS/NIR) and shortwave-infrared (SWIR) spectrometer in one very compact housing. A second goal is that the hardware can be produced in high volume at low cost without expensive time consuming alignment and calibration steps. We have designed a miniaturized spectrometer which operates both in the visible/near-infrared and shortwave-infrared wavelength regions ranging from 400 nm to 1700 nm. The visible/near-infrared part of the spectrometer is designed for wavelengths from 400 nm to 800 nm whereas the shortwave-infrared segment ranges from 850 nm to 1700 nm. The spectrometer has a resolution of 6 nm in the visible/near-infrared wavelength region and 10 nm in the shortwave-infrared. The minimum SNR of the spectrometer for the intended application is about 151 in the VIS/NIR range and 6000 for SWIR. In this paper, the modelling and design, and power budget analysis of the miniaturized spectrometer are presented. Our work opens a door for future affordable micro- spectrometers which can be integrated with smartphones and tablets, and used for point

Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

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Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

2014-01-01

Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, Pkale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone. PMID:25084454

Tissue-based map of the human proteome

DEFF Research Database (Denmark)

Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.

2015-01-01

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transc...

Various Techniques to Increase Keratinized Tissue for Implant Supported Overdentures: Retrospective Case Series

Directory of Open Access Journals (Sweden)

Ahmed Elkhaweldi

2015-01-01

Full Text Available Purpose. The purpose of this retrospective case series is to describe and compare different surgical techniques that can be utilized to augment the keratinized soft tissue around implant-supported overdentures. Materials and Methods. The data set was extracted as deidentified information from the routine treatment of patients at the Ashman Department of Periodontology and Implant Dentistry at New York University College of Dentistry. Eight edentulous patients were selected to be included in this study. Patients were treated for lack of keratinized tissue prior to implant placement, during the second stage surgery, and after delivery of the final prosthesis. Results. All 8 patients in this study were wearing a complete maxillary and/or mandibular denture for at least a year before the time of the surgery. One of the following surgical techniques was utilized to increase the amount of keratinized tissue: apically positioned flap (APF, pedicle graft (PG, connective tissue graft (CTG, or free gingival graft (FGG. Conclusions. The amount of keratinized tissue should be taken into consideration when planning for implant-supported overdentures. The apical repositioning flap is an effective approach to increase the width of keratinized tissue prior to the implant placement.

Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues

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Faber, James E.; Zhang, Hua; Lassance-Soares, Roberta M.; Prabhakar, Pranay; Najafi, Amir H.; Burnett, Mary Susan; Epstein, Stephen E.

2011-01-01

Objective Aging is a major risk factor for increased ischemic tissue injury. Whether collateral rarefaction and impaired remodeling contribute to this is unknown. We quantified the number and diameter of native collaterals, and their remodeling in 3-, 16-, 24-, and 31-months-old mice. Methods and Results Aging caused an “age-dose-dependent” greater drop in perfusion immediately after femoral artery ligation, followed by a diminished recovery of flow and increase in tissue injury. These effects were associated with a decline in collateral number, diameter and remodeling. Angiogenesis was also impaired. Mechanistically, these changes were not accompanied by reduced recruitment of T-cells or macrophages to remodeling collaterals. However, eNOS signaling was dysfunctional, as indicated by increased protein nitrosylation and less phosphorylated eNOS and VASP in collateral wall cells. The cerebral circulation exhibited a similar age-dose-dependent loss of collateral number and diameter and increased tortuosity, resulting in an increase in collateral resistance and infarct volume (e.g., 6- and 3-fold, respectively, in 24-months-old mice) after artery occlusion. This was not associated with rarefaction of similarly-sized arterioles. Collateral remodeling was also reduced. Conclusions Our findings demonstrate that aging causes rarefaction and insufficiency of the collateral circulation in multiple tissues, resulting in more severe ischemic tissue injury. PMID:21617137

Increased activities of mitochondrial enzymes in white adipose tissue in trained rats

DEFF Research Database (Denmark)

Stallknecht, B; Vinten, J; Ploug, T

1991-01-01

of 8-12 rats were swim trained for 10 wk or served as either sedentary, sham swim-trained, or cold-stressed controls. White adipose tissue was removed, and the activities of the respiratory chain enzyme cytochrome-c oxidase (CCO) and of the enzyme malate dehydrogenase (MDH), which participates...... 0.05). In female rats the CCO activity expressed per milligram protein was increased 4.5-fold in the trained compared with the sedentary control rats (P less than 0.01). Neither cold stress nor sham swim training increased CCO or MDH activities in white adipose tissue (P greater than 0...

Age-associated increase in heterochromatic marks in murine and primate tissues.

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Kreiling, Jill A; Tamamori-Adachi, Mimi; Sexton, Alec N; Jeyapalan, Jessie C; Munoz-Najar, Ursula; Peterson, Abigail L; Manivannan, Jayameenakshi; Rogers, Elizabeth S; Pchelintsev, Nikolay A; Adams, Peter D; Sedivy, John M

2011-04-01

Chromatin is highly dynamic and subject to extensive remodeling under many physiologic conditions. Changes in chromatin that occur during the aging process are poorly documented and understood in higher organisms, such as mammals. We developed an immunofluorescence assay to quantitatively detect, at the single cell level, changes in the nuclear content of chromatin-associated proteins. We found increased levels of the heterochromatin-associated proteins histone macro H2A (mH2A) and heterochromatin protein 1 beta (HP1β) in human fibroblasts during replicative senescence in culture, and for the first time, an age-associated increase in these heterochromatin marks in several tissues of mice and primates. Mouse lung was characterized by monophasic mH2A expression histograms at both ages, and an increase in mean staining intensity at old age. In the mouse liver, we observed increased age-associated localization of mH2A to regions of pericentromeric heterochromatin. In the skeletal muscle, we found two populations of cells with either low or high mH2A levels. This pattern of expression was similar in mouse and baboon, and showed a clear increase in the proportion of nuclei with high mH2A levels in older animals. The frequencies of cells displaying evidence of increased heterochromatinization are too high to be readily accounted for by replicative or oncogene-induced cellular senescence, and are prominently found in terminally differentiated, postmitotic tissues that are not conventionally thought to be susceptible to senescence. Our findings distinguish specific chromatin states in individual cells of mammalian tissues, and provide a foundation to investigate further the progressive epigenetic changes that occur during aging. © 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

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Fedorov, I. V.; Chernyy, A. V.; Fedorov, A. I.

1978-01-01

During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

Products of neutrophils and eosinophils increase the responsiveness of human isolated bronchial tissue.

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Hallahan, A R; Armour, C L; Black, J L

1990-05-01

This study examines the possibility that products of neutrophils and eosinophils could increase the responsiveness of human isolated bronchial tissue. Neutrophils and eosinophils were isolated from the peripheral blood of healthy volunteers. The cells were incubated with 1 microM calcium ionophore A23187 for 10-15 min then centrifuged, the supernatant collected and stored at -70 degrees C. Human bronchial rings (2-3 mm diameter, 3-4 mm long) were prepared from specimens resected at thoracotomy. The tissues were suspended in organ baths under a 1 g load and changes in tension measured isometrically. Stable contractions to bolus doses of histamine (0.1-10 microM) or to electrical field stimulation (40-100 V, 4-16 Hz, 1 ms for 20 s) were established. Supernatant from 106 neutrophils or 105 eosinophils was then added and tissue responsiveness reassessed. Neutrophil supernatant increased tissue responsiveness to histamine and electrical field stimulation by 54 +/- 17% (n = 5, p less than 0.05) and 18 +/- 7% (n = 6, p less than 0.05), respectively. Eosinophil supernatant increased the histamine response by 60 +/- 23% (n = 8, p less than 0.05) while tissue responsiveness to electrical field stimulation was unchanged (n = 3). Thus, as neutrophils and eosinophils can change the responsiveness of human bronchus in vitro it is possible that they do this in vivo and may not simply be temporally related to the development of bronchial hyperresponsiveness.

A low-protein, high-carbohydrate diet increases browning in perirenal adipose tissue but not in inguinal adipose tissue.

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Pereira, Mayara P; Ferreira, Laís A A; da Silva, Flávia H S; Christoffolete, Marcelo A; Metsios, George S; Chaves, Valéria E; de França, Suélem A; Damazo, Amílcar S; Flouris, Andreas D; Kawashita, Nair H

2017-10-01

The aim of this study was to evaluate the browning and origin of fatty acids (FAs) in the maintenance of triacylglycerol (TG) storage and/or as fuel for thermogenesis in perirenal adipose tissue (periWAT) and inguinal adipose tissue (ingWAT) of rats fed a low-protein, high-carbohydrate (LPHC) diet. LPHC (6% protein, 74% carbohydrate) or control (C; 17% protein, 63% carbohydrate) diets were administered to rats for 15 d. The tissues were stained with hematoxylin and eosin for histologic analysis. The content of uncoupling protein 1 (UCP1) was determined by immunofluorescence. Levels of T-box transcription factor (TBX1), PR domain containing 16 (PRDM16), adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase, lipoprotein lipase (LPL), glycerokinase, phosphoenolpyruvate carboxykinase (PEPCK), glucose transporter 4, β 3 -adrenergic receptor (AR), β 1 -AR, protein kinase A (PKA), adenosine-monophosphate-activated protein kinase (AMPK), and phospho-AMPK were determined by immunoblotting. Serum fibroblast growth factor 21 (FGF21) was measured using a commercial kit (Student's t tests, P diet increased FGF21 levels by 150-fold. The presence of multilocular adipocytes, combined with the increased contents of UCP1, TBX1, and PRDM16 in periWAT of LPHC-fed rats, suggested the occurrence of browning. The contents of β 1 -AR and LPL were increased in the periWAT. The ingWAT showed higher ATGL and PEPCK levels, phospho-AMPK/AMPK ratio, and reduced β 3 -AR and PKA levels. These findings suggest that browning occurred only in the periWAT and that higher utilization of FAs from blood lipoproteins acted as fuel for thermogenesis. Increased glycerol 3-phosphate generation by glyceroneogenesis increased FAs reesterification from lipolysis, explaining the increased TG storage in the ingWAT. Copyright © 2017 Elsevier Inc. All rights reserved.

ISSLS prize winner: integrating theoretical and experimental methods for functional tissue engineering of the annulus fibrosus.

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Nerurkar, Nandan L; Mauck, Robert L; Elliott, Dawn M

2008-12-01

Integrating theoretical and experimental approaches for annulus fibrosus (AF) functional tissue engineering. Apply a hyperelastic constitutive model to characterize the evolution of engineered AF via scalar model parameters. Validate the model and predict the response of engineered constructs to physiologic loading scenarios. There is need for a tissue engineered replacement for degenerate AF. When evaluating engineered replacements for load-bearing tissues, it is necessary to evaluate mechanical function with respect to the native tissue, including nonlinearity and anisotropy. Aligned nanofibrous poly-epsilon-caprolactone scaffolds with prescribed fiber angles were seeded with bovine AF cells and analyzed over 8 weeks, using experimental (mechanical testing, biochemistry, histology) and theoretical methods (a hyperelastic fiber-reinforced constitutive model). The linear region modulus for phi = 0 degrees constructs increased by approximately 25 MPa, and for phi = 90 degrees by approximately 2 MPa from 1 day to 8 weeks in culture. Infiltration and proliferation of AF cells into the scaffold and abundant deposition of s-GAG and aligned collagen was observed. The constitutive model had excellent fits to experimental data to yield matrix and fiber parameters that increased with time in culture. Correlations were observed between biochemical measures and model parameters. The model was successfully validated and used to simulate time-varying responses of engineered AF under shear and biaxial loading. AF cells seeded on nanofibrous scaffolds elaborated an organized, anisotropic AF-like extracellular matrix, resulting in improved mechanical properties. A hyperelastic fiber-reinforced constitutive model characterized the functional evolution of engineered AF constructs, and was used to simulate physiologically relevant loading configurations. Model predictions demonstrated that fibers resist shear even when the shearing direction does not coincide with the fiber direction

Increasing self-other integration through divergent thinking.

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Colzato, Lorenza S; van den Wildenberg, Wery P M; Hommel, Bernhard

2013-10-01

Increasing evidence suggests that people may cognitively represent themselves and others just like any other, nonsocial event. Here, we provide evidence that the degree of self-other integration (as reflected by the joint Simon effect; JSE) is systematically affected by the control characteristics of temporally overlapping but unrelated and nonsocial creativity tasks. In particular, the JSE was found to be larger in the context of a divergent-thinking task (alternate uses task) than in the context of a convergent-thinking task (remote association task). This suggests that self-other integration and action corepresentation are controlled by domain-general cognitive-control parameters that regulate the integrativeness (strong vs. weak top-down control and a resulting narrow vs. broad attentional focus) of information processing irrespective of its social implications.

Integrated and convenient procedure for protein extraction from formalin-fixed, paraffin-embedded tissues for LC-MS/MS analysis.

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Lai, Xianyin; Schneider, Bryan P

2014-11-01

Because fresh-frozen tissue samples associated with long-term clinical data and of rare diseases are often unobtainable at the present time, formalin-fixed paraffin-embedded (FFPE) tissue samples are considered a highly valuable resource for researchers. However, protein extraction from FFPE tissues faces challenges of deparaffinization and cross-link reversion. Current procedures for protein extraction from FFPE tissue require separate steps and toxic solvents, resulting in inconvenience in protein extraction. To overcome these limitations, an integrated method was developed using nontoxic solvents in four types of FFPE tissues. The average amount of proteins from three replicates of bladder, kidney, liver, and lung FFPE tissues were 442.6, 728.9, 736.4, and 694.7 μg with CVs of 7.5, 5.8, 2.4, and 4.5%, respectively. Proteomic analysis showed that 348, 417, 607, and 304 unique proteins were identified and quantified without specification of isoform by a least two peptides from bladder, kidney, liver, and lung FFPE tissue samples, respectively. The analysis of individual protein CV demonstrated that 97-99% of the proteins were quantified with a CV ≤ 30%, verifying the reproducibility of the integrated protein extraction method. In summary, the developed method is high-yield, reproducible, convenient, simple, low cost, nonvolatile, nonflammable, and nontoxic. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice.

Directory of Open Access Journals (Sweden)

Desiree Wanders

Full Text Available To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity.Male C57BL/6 mice were placed on a control or high-fat diet (HFD and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/- (niacin receptor(-/- mice.Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/- mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARγ C/EBPα or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lα, or DsbA-L (key ER chaperones involved in adiponectin production and secretion. However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1β in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice.Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.

Increased fibrosis: A novel means by which GH influences white adipose tissue function.

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Householder, Lara A; Comisford, Ross; Duran-Ortiz, Silvana; Lee, Kevin; Troike, Katie; Wilson, Cody; Jara, Adam; Harberson, Mitchell; List, Edward O; Kopchick, John J; Berryman, Darlene E

2018-04-01

White adipose tissue (WAT) fibrosis - the buildup of extracellular matrix (ECM) proteins, primarily collagen - is now a recognized hallmark of tissue dysfunction and is increased with obesity and lipodystrophy. While growth hormone (GH) is known to increase collagen in several tissues, no previous research has addressed its effect on ECM in WAT. Thus, the purpose of this study is to determine if GH influences WAT fibrosis. This study examined WAT from four distinct strains of GH-altered mice (bGH and GHA transgenic mice as well as two tissue specific GH receptor gene disrupted lines, fat growth hormone receptor knockout or FaGHRKO and liver growth hormone receptor knockout or LiGHRKO mice). Collagen content and adipocyte size were studied in all cohorts and compared to littermate controls. In addition, mRNA expression of fibrosis-associated genes was assessed in one cohort (6month old male bovine GH transgenic and WT mice) and cultured 3T3-L1 adipocytes treated with GH. Collagen stained area was increased in WAT from bGH mice, was depot-dependent, and increased with age. Furthermore, increased collagen content was associated with decreased adipocyte size in all depots but more dramatic changes in the subcutaneous fat pad. Notably, the increase in collagen was not associated with an increase in collagen gene expression or other genes known to promote fibrosis in WAT, but collagen gene expression was increased with acute GH administration in 3T3-LI cells. In contrast, evaluation of 6month old GH antagonist (GHA) male mice showed significantly decreased collagen in the subcutaneous depot. Lastly, to assess if GH induced collagen deposition directly or indirectly (via IGF-1), fat (Fa) and liver (Li) specific GHRKO mice were evaluated. Decreased fibrosis in FaGHRKO and increased fibrosis in LiGHRKO mice suggest GH is primarily responsible for the alterations in collagen. Our results show that GH action is positively associated with an increase in WAT collagen content as

Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications.

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Attalla, R; Ling, C; Selvaganapathy, P

2016-02-01

The lack of a simple and effective method to integrate vascular network with engineered scaffolds and tissue constructs remains one of the biggest challenges in true 3D tissue engineering. Here, we detail the use of a commercially available, low-cost, open-source 3D printer modified with a microfluidic print-head in order to develop a method for the generation of instantly perfusable vascular network integrated with gel scaffolds seeded with cells. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can be easily patterned using 3D printing techniques. The diameter of the hollow channel can be precisely controlled and varied between 500 μm - 2 mm by changing applied flow rates or print-head speed. These channels are integrated into gel layers with a thickness of 800 μm - 2.5 mm. The structural rigidity of these constructs allows the fabrication of multi-layered structures without causing the collapse of hollow channels in lower layers. The 3D printing method was fully characterized at a range of operating speeds (0-40 m/min) and corresponding flow rates (1-30 mL/min) were identified to produce precise definition. This microfluidic design also allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. Media perfusion of the channels causes a significant viability increase in the bulk of cell-laden structures over the long-term. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.

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da Costa, Rafael M; da Silva, Josiane F; Alves, Juliano V; Dias, Thiago B; Rassi, Diane M; Garcia, Luis V; Lobato, Núbia de Souza; Tostes, Rita C

2018-01-01

Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility. This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia. The O -linked β-N-acetylglucosamine ( O -GlcNAc) modification of proteins ( O -GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity. Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O -GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions. We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O -GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects. Therefore, the current study was devised to determine whether a high-sugar diet increases O -GlcNAcylation in the PVAT and how increased O -GlcNAc interferes with PVAT vasorelaxant function. To assess molecular mechanisms by which O -GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks. Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O -GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect. PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O -GlcNAcylation of eNOS. High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT. Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O -GlcNAc-modified proteins, increased ROS

Increased in vivo glucose utilization in 30-day-old obese Zucker rat: Role of white adipose tissue

International Nuclear Information System (INIS)

Krief, S.; Bazin, R.; Dupuy, F.; Lavau, M.

1988-01-01

In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3- 3 H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia. In obese compared with lean rats, tissue glucose uptake was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart in proximal intestine, and in total muscular mass of limbs. The data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake

Heparin functionalization increases retention of TGF-β2 and GDF5 on biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering.

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Font Tellado, Sònia; Chiera, Silvia; Bonani, Walter; Poh, Patrina S P; Migliaresi, Claudio; Motta, Antonella; Balmayor, Elizabeth R; van Griensven, Martijn

2018-05-01

The tendon/ligament-to-bone transition (enthesis) is a highly specialized interphase tissue with structural gradients of extracellular matrix composition, collagen molecule alignment and mineralization. These structural features are essential for enthesis function, but are often not regenerated after injury. Tissue engineering is a promising strategy for enthesis repair. Engineering of complex tissue interphases such as the enthesis is likely to require a combination of biophysical, biological and chemical cues to achieve functional tissue regeneration. In this study, we cultured human primary adipose-derived mesenchymal stem cells (AdMCs) on biphasic silk fibroin scaffolds with integrated anisotropic (tendon/ligament-like) and isotropic (bone/cartilage like) pore alignment. We functionalized those scaffolds with heparin and explored their ability to deliver transforming growth factor β2 (TGF-β2) and growth/differentiation factor 5 (GDF5). Heparin functionalization increased the amount of TGF-β2 and GDF5 remaining attached to the scaffold matrix and resulted in biological effects at low growth factor doses. We analyzed the combined impact of pore alignment and growth factors on AdMSCs. TGF-β2 and pore anisotropy synergistically increased the expression of tendon/ligament markers and collagen I protein content. In addition, the combined delivery of TGF-β2 and GDF5 enhanced the expression of cartilage markers and collagen II protein content on substrates with isotropic porosity, whereas enthesis markers were enhanced in areas of mixed anisotropic/isotropic porosity. Altogether, the data obtained in this study improves current understanding on the combined effects of biological and structural cues on stem cell fate and presents a promising strategy for tendon/ligament-to-bone regeneration. Regeneration of the tendon/ligament-to-bone interphase (enthesis) is of significance in the repair of ruptured tendons/ligaments to bone to improve implant integration and

Application of electrical stimulation for functional tissue engineering in vitro and in vivo

Science.gov (United States)

Park, Hyoungshin (Inventor); Freed, Lisa (Inventor); Vunjak-Novakovic, Gordana (Inventor); Langer, Robert (Inventor); Radisic, Milica (Inventor)

2013-01-01

The present invention provides new methods for the in vitro preparation of bioartificial tissue equivalents and their enhanced integration after implantation in vivo. These methods include submitting a tissue construct to a biomimetic electrical stimulation during cultivation in vitro to improve its structural and functional properties, and/or in vivo, after implantation of the construct, to enhance its integration with host tissue and increase cell survival and functionality. The inventive methods are particularly useful for the production of bioartificial equivalents and/or the repair and replacement of native tissues that contain electrically excitable cells and are subject to electrical stimulation in vivo, such as, for example, cardiac muscle tissue, striated skeletal muscle tissue, smooth muscle tissue, bone, vasculature, and nerve tissue.

Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

Science.gov (United States)

Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

2015-12-01

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhancing tissue integration and angiogenesis of a novel nanocomposite polymer using plasma surface polymerisation, an in vitro and in vivo study.

Science.gov (United States)

Griffin, Michelle F; Palgrave, Robert G; Seifalian, Alexander M; Butler, Peter E; Kalaskar, Deepak M

2016-01-01

Current surgical reconstruction of facial defects including nose or ear involves harvesting patient's own autologous tissue, causing donor site morbidity and is limited by tissue availability. The use of alternative synthetic materials is also limited due to complications related to poor tissue integration and angiogenesis, which lead to extrusion of implants and infection. We intend to meet this clinical challenge by using a novel nanocomposite called polyhedral oligomeric silsesquioxane poly(carbonate-urea)urethane (POSS-PCU), which has already been successfully taken to the clinical bench-side as a replacement for trachea, tear duct and vascular by-pass graft. In this study, we aimed to enhance tissue integration and angiogenesis of POSS-PCU using an established surface treatment technique, plasma surface polymerisation (PSP), functionalising the surface using NH2 and COOH chemical groups. Physical characterisation of scaffolds was achieved by using a number of techniques, including water contact angle, SEM, AFM and XPS to study the effects of PSM modification on the POSS-PCU nanocomposite in detail, which has not been previously documented. Wettability evaluation confirmed that scaffolds become hydrophilic and AFM analysis confirmed that nano topographical alterations resulted as a consequence of PSP treatment. Chemical functionalisation was confirmed using XPS, which suggested the presence of NH2 and COOH functional groups on the scaffolds. The modified scaffolds were then tested both in vitro and in vivo to investigate the potential of PSP modified POSS-PCU scaffolds on tissue integration and angiogenesis. In vitro analysis confirmed that PSM modification resulted in higher cellular growth, proliferation and ECM production as assessed by biochemical assays and immunofluorescence. Subcutaneous implantation of modified POSS-PCU scaffolds was then carried out over 12-weeks, resulting in enhanced tissue integration and angiogenesis (p < 0.05). This study

Integrity of the oral tissues in patients with solid-organ transplants.

Science.gov (United States)

Rojas, Gonzalo; Bravo, Loreto; Cordero, Karina; Sepúlveda, Luis; Elgueta, Leticia; Díaz, Juan Carlos; Urzúa, Blanca; Morales, Irene

2012-01-01

The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE), decayed, missing, filled teeth (DMFT) index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%). Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

Integrity of the Oral Tissues in Patients with Solid-Organ Transplants

Directory of Open Access Journals (Sweden)

Gonzalo Rojas

2012-01-01

Full Text Available The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE, decayed, missing, filled teeth (DMFT index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%. Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

Creation of Cardiac Tissue Exhibiting Mechanical Integration of Spheroids Using 3D Bioprinting.

Science.gov (United States)

Ong, Chin Siang; Fukunishi, Takuma; Nashed, Andrew; Blazeski, Adriana; Zhang, Huaitao; Hardy, Samantha; DiSilvestre, Deborah; Vricella, Luca; Conte, John; Tung, Leslie; Tomaselli, Gordon; Hibino, Narutoshi

2017-07-02

This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array. Three days after 3D bioprinting, the spheroids are removed as an intact patch, which is already spontaneously beating. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.

Integrated engineering increases flexibility. [At BNFL

Energy Technology Data Exchange (ETDEWEB)

Smith, Ray [British Nuclear Fuels plc, London (UK)

1991-05-01

Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author).

Investigation of landfill leachate toxic potency: An integrated approach with the use of stress indices in tissues of mussels

Energy Technology Data Exchange (ETDEWEB)

Tsarpali, Vasiliki [Section of Animal Biology, Department of Biology, Faculty of Sciences, University of Patras, 26500 Patras (Greece); Dailianis, Stefanos, E-mail: sdailianis@upatras.gr [Section of Animal Biology, Department of Biology, Faculty of Sciences, University of Patras, 26500 Patras (Greece)

2012-11-15

Highlights: Black-Right-Pointing-Pointer Leachate induces mortality of mussels and their cell death at very low doses. Black-Right-Pointing-Pointer Prepathological alterations occur in tissues of leachate-exposed mussels. Black-Right-Pointing-Pointer Alterations of stress indices reveal neurotoxic and genotoxic potency of leachate. Black-Right-Pointing-Pointer Leachate could induce oxidative damage in tissues of leachate-exposed mussels. - Abstract: The present study investigates the harmful impacts of landfill leachate release and/or disposal into the marine environment, as well as its ability to induce lethal and pre-pathological alterations in marine organisms, such as the mussel Mytilus galloprovincialis. In specific, mortality test (96 h), performed first in order to estimate leachate lethal endpoints, showed increased levels of mussel mortality after exposure to leachate higher than 0.5%, v/v (96 h LC{sub 50} = 0.526%, v/v), while the exposure to 0.01 and 0.1% (v/v) of leachate showed negligible levels of mortality (96 h LC{sub 10} = 0.167%, v/v). Furthermore, the estimation of lysosomal membrane integrity in hemocytes of exposed mussels (Neutral Red Retention Time assay) showed increased levels of lysosomal destabilization in cells of mussels exposed to sub-lethal concentrations of leachate (0.01, 0.1 and 0.5%, v/v) for 4 days. In order to exclude parameters, such as mussel mortality and cell death, which could interfere with the obtained results, leachate at final concentrations of 0.01 and 0.1% (v/v) were finally used for the estimation of a battery of stress indices in target tissues of mussels, such as hemolymph, gills and digestive gland. According to the results, leachate-exposed mussels showed a significant inhibition of acetylcholinesterase activity, increased levels of nuclear abnormalities, as well as increased levels of metallothionein, superoxide anion and lipid peroxides (in terms of malondialdehyde equivalents) in each tissue tested. The

Increased Dapivirine tissue accumulation through vaginal film codelivery of dapivirine and Tenofovir.

Science.gov (United States)

Akil, Ayman; Devlin, Brid; Cost, Marilyn; Rohan, Lisa Cencia

2014-05-05

The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising drug candidates being used in topical microbicide products for prevention of HIV-1 sexual transmission. To be able to block HIV-1 replication, DPV must have access to the viral reverse transcriptase enzyme. The window for DPV to access the enzyme happens during the HIV-1 cellular infection cycle. Thus, in order for DPV to exert its anti-HIV activity, it must be present in the mucosal tissue or cells where HIV-1 infection occurs. A dosage form containing DPV must be able to deliver the drug to the tissue site of action. Polymeric films are solid dosage forms that dissolve and release their payload upon contact with fluids. Films have been used as vaginal delivery systems of topical microbicide drug candidates including DPV. For use in topical microbicide products containing DPV, polymeric films must prove their ability to deliver DPV to the target tissue site of action. Ex vivo exposure studies of human ectocervical tissue to DPV film revealed that DPV was released from the film and did diffuse into the tissue in a concentration dependent manner indicating a process of passive diffusion. Analysis of drug distribution in the tissue revealed that DPV accumulated mostly at the basal layer of the epithelium infiltrating the upper part of the stroma. Furthermore, as a combination microbicide product, codelivery of DPV and TFV from a polymeric film resulted in a significant increase in DPV tissue concentration [14.21 (single entity film) and 31.03 μg/g (combination film)], whereas no impact on TFV tissue concentration was found. In vitro release experiments showed that this observation was due to a more rapid DPV release from the combination film as compared to the single entity film. In conclusion, the findings of this study confirm the ability of polymeric films to deliver DPV and TFV to human ectocervical tissue and show that codelivery of the two agents has a significant impact on DPV

Three-dimensional CaP/gelatin lattice scaffolds with integrated osteoinductive surface topographies for bone tissue engineering

International Nuclear Information System (INIS)

Nadeem, Danish; Su, Bo; Smith, Carol-Anne; Dalby, Matthew J; Dominic Meek, R M; Lin, Sien; Li, Gang

2015-01-01

Surface topography is known to influence stem cells and has been widely used as physical stimuli to modulate cellular behaviour including adhesion, proliferation and differentiation on 2D surfaces. Integration of well-defined surface topography into three-dimensional (3D) scaffolds for tissue engineering would be useful to direct the cell fate for intended applications. Technical challenges are remaining as how to fabricate such 3D scaffolds with controlled surface topography from a range of biodegradable and biocompatible materials. In this paper, a novel fabrication process using computer numerically controlled machining and lamination is reported to make 3D calcium phosphate/gelatin composite scaffolds with integrated surface micropatterns that are introduced by embossing prior to machining. Geometric analysis shows that this method is versatile and can be used to make a wide range of lattices with porosities that meet the basic requirements for bone tissue engineering. Both in vitro and in vivo studies show that micropatterned composite scaffolds with surfaces comprising 40 μm pits and 50 μm grooves were optimal for improved osteogenesis. The results have demonstrated the potential of a novel fabrication process for producing cell-instructive scaffolds with designed surface topographies to induce specific tissue regeneration. (paper)

Design and characterization of microcapsules-integrated collagen matrixes as multifunctional three-dimensional scaffolds for soft tissue engineering.

Science.gov (United States)

Del Mercato, Loretta L; Passione, Laura Gioia; Izzo, Daniela; Rinaldi, Rosaria; Sannino, Alessandro; Gervaso, Francesca

2016-09-01

Three-dimensional (3D) porous scaffolds based on collagen are promising candidates for soft tissue engineering applications. The addition of stimuli-responsive carriers (nano- and microparticles) in the current approaches to tissue reconstruction and repair brings about novel challenges in the design and conception of carrier-integrated polymer scaffolds. In this study, a facile method was developed to functionalize 3D collagen porous scaffolds with biodegradable multilayer microcapsules. The effects of the capsule charge as well as the influence of the functionalization methods on the binding efficiency to the scaffolds were studied. It was found that the binding of cationic microcapsules was higher than that of anionic ones, and application of vacuum during scaffolds functionalization significantly hindered the attachment of the microcapsules to the collagen matrix. The physical properties of microcapsules-integrated scaffolds were compared to pristine scaffolds. The modified scaffolds showed swelling ratios, weight losses and mechanical properties similar to those of unmodified scaffolds. Finally, in vitro diffusional tests proved that the collagen scaffolds could stably retain the microcapsules over long incubation time in Tris-HCl buffer at 37°C without undergoing morphological changes, thus confirming their suitability for tissue engineering applications. The obtained results indicate that by tuning the charge of the microcapsules and by varying the fabrication conditions, collagen scaffolds patterned with high or low number of microcapsules can be obtained, and that the microcapsules-integrated scaffolds fully retain their original physical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integration of soft tissue model and open haptic device for medical training simulator

Science.gov (United States)

Akasum, G. F.; Ramdhania, L. N.; Suprijanto; Widyotriatmo, A.

2016-03-01

Minimally Invasive Surgery (MIS) has been widely used to perform any surgical procedures nowadays. Currently, MIS has been applied in some cases in Indonesia. Needle insertion is one of simple MIS procedure that can be used for some purposes. Before the needle insertion technique used in the real situation, it essential to train this type of medical student skills. The research has developed an open platform of needle insertion simulator with haptic feedback that providing the medical student a realistic feel encountered during the actual procedures. There are three main steps in build the training simulator, which are configure hardware system, develop a program to create soft tissue model and the integration of hardware and software. For evaluating its performance, haptic simulator was tested by 24 volunteers on a scenario of soft tissue model. Each volunteer must insert the needle on simulator until rearch the target point with visual feedback that visualized on the monitor. From the result it can concluded that the soft tissue model can bring the sensation of touch through the perceived force feedback on haptic actuator by looking at the different force in accordance with different stiffness in each layer.

[The increasing importance of tumor and tissue banks in the light of genomic and proteomic research].

Science.gov (United States)

Tschulik, A; Zatloukal, K

2001-09-01

Recent technological advances in genome and proteome research offer new perspectives for diagnosis and therapy. The DNA chip technology as well as high-resolution two-dimensional gel electrophoresis in combination with mass spectrometry is able to provide comprehensive information on gene and protein expression patterns, which allow insights into the dynamic and functional aspects of diseases. The application of these techniques depends on the availability of unfixed fresh or cryopreserved tissue with short ischaemia time. For this reason tissue banks are of increasing importance. The pathologist with his expertise and responsibility for histopathological diagnosis, plays a central role in the collection of the human tissues, in accordance with medical, legal and ethical standards, not only for diagnostic purposes, but also for research. The scientific value of a tissue bank is markedly increased if tissue samples are accompanied by detailed patient data as well as blood samples. Informed consent given by the patient is an essential requirement for the use of human tissue banks in biomedical research. The informed consent should not be restricted to scientific investigations but also include the potential commercial use of the data generated.

Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects

DEFF Research Database (Denmark)

Højbjerre, Lise; Rosenzweig, Mary; Dela, Flemming

2007-01-01

-) plasma concentration did not change during exercise in any of the groups, but SCAAT TNF- mRNA increased after exercise in both groups. Furthermore, exercise decreased SCAAT leptin mRNA with no change in resistin mRNA. CONCLUSIONS: Acute exercise increases adipose tissue interstitial adiponectin...

Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism

DEFF Research Database (Denmark)

Vagn Nielsen, H; Hasselström, K; Feldt-Rasmussen, U

1987-01-01

vasoconstriction normally seen after lowering the forearm 40 cm below heart level was absent since SBF only decreased by 4% (+/- 7%, P greater than 0.1) during these conditions. In head-up vertical position we noticed a diminished baroreceptor response as SBF at heart level was reduced by 11% (+/- 7%, P greater...... than 0.1) compared to supine position. After proximal local anaesthesia SBF increased by 351% (+/- 81%, P less than 0.01) and disclosed a normal vasoconstrictor response as SBF was reduced by 53% (+/- 5%, P less than 0.01) during arm lowering. Five of the treated patients were restudied.......02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment....

Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

DEFF Research Database (Denmark)

Langberg, H; Bjørn, C; Boushel, Robert Christopher

2002-01-01

been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years...... increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P increases the interstitial concentrations......Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet...

Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

Directory of Open Access Journals (Sweden)

Therése Andersson

Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Gauss-Kronrod-Trapezoidal Integration Scheme for Modeling Biological Tissues with Continuous Fiber Distributions

Science.gov (United States)

Hou, Chieh; Ateshian, Gerard A.

2015-01-01

Fibrous biological tissues may be modeled using a continuous fiber distribution (CFD) to capture tension-compression nonlinearity, anisotropic fiber distributions, and load-induced anisotropy. The CFD framework requires spherical integration of weighted individual fiber responses, with fibers contributing to the stress response only when they are in tension. The common method for performing this integration employs the discretization of the unit sphere into a polyhedron with nearly uniform triangular faces (finite element integration or FEI scheme). Although FEI has proven to be more accurate and efficient than integration using spherical coordinates, it presents three major drawbacks: First, the number of elements on the unit sphere needed to achieve satisfactory accuracy becomes a significant computational cost in a finite element analysis. Second, fibers may not be in tension in some regions on the unit sphere, where the integration becomes a waste. Third, if tensed fiber bundles span a small region compared to the area of the elements on the sphere, a significant discretization error arises. This study presents an integration scheme specialized to the CFD framework, which significantly mitigates the first drawback of the FEI scheme, while eliminating the second and third completely. Here, integration is performed only over the regions of the unit sphere where fibers are in tension. Gauss-Kronrod quadrature is used across latitudes and the trapezoidal scheme across longitudes. Over a wide range of strain states, fiber material properties, and fiber angular distributions, results demonstrate that this new scheme always outperforms FEI, sometimes by orders of magnitude in the number of computational steps and relative accuracy of the stress calculation. PMID:26291492

Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn.

Directory of Open Access Journals (Sweden)

Yongbin Dong

Full Text Available The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize.

A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

Science.gov (United States)

Rosca, Florin

2012-06-01

To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E+IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. The normal tissue integral dose was lowered by about 20% by the E+IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E+IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E+IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning

Sensing of EGTA Mediated Barrier Tissue Disruption with an Organic Transistor

Directory of Open Access Journals (Sweden)

Scherrine Tria

2013-01-01

Full Text Available Barrier tissue protects the body against external factors by restricting the passage of molecules. The gastrointestinal epithelium is an example of barrier tissue with the primary purpose of allowing the passage of ions and nutrients, while restricting the passage of pathogens and toxins. It is well known that the loss of barrier function can be instigated by a decrease in extracellular calcium levels, leading to changes in protein conformation and an increase in paracellular transport. In this study, ethylene glycol-bis(beta-aminoethyl ether-N,N,N',N'-tetra acetic acid (EGTA, a calcium chelator, was used to disrupt the gastrointestinal epithelial barrier. The effect of EGTA on barrier tissue was monitored by a novel label-free method based on an organic electrochemical transistor (OECT integrated with living cells and validated against conventional methods for measuring barrier tissue integrity. We demonstrate that the OECT can detect breaches in barrier tissue upon exposure to EGTA with the same sensitivity as existing methods but with increased temporal resolution. Due to the potential of low cost processing techniques and the flexibility in design associated with organic electronics, the OECT has great potential for high-throughput, disposable sensing and diagnostics.

The Chernobyl Tissue Bank — A Repository for Biomaterial and Data Used in Integrative and Systems Biology Modeling the Human Response to Radiation

Science.gov (United States)

Thomas, Geraldine; Unger, Kristian; Krznaric, Marko; Galpine, Angela; Bethel, Jackie; Tomlinson, Christopher; Woodbridge, Mark; Butcher, Sarah

2012-01-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer post Chernobyl, the Chernobyl Tissue Bank (CTB: www.chernobyltissuebank.com) was established in 1998. Thus far it is has collected biological samples from 3,861 individuals, and provided 27 research projects with 11,254 samples. The CTB was designed from its outset as a resource to promote the integration of research and clinical data to facilitate a systems biology approach to radiation related thyroid cancer. The project has therefore developed as a multidisciplinary collaboration between clinicians, dosimetrists, molecular biologists and bioinformaticians and serves as a paradigm for tissue banking in the omics era. PMID:24704918

Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country.

Science.gov (United States)

Backer, Vibeke; Baines, Katherine J; Powell, Heather; Porsbjerg, Celeste; Gibson, Peter G

2016-02-01

An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue inflammation can be modified by migration and diet. To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). Of the 1059 Greenlandic Inuit participants, 556 were living in Greenland and 6.4% had asthma. Asthma was increased in Denmark (9%) compared to Greenland (3.6%, p Inuit (p Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased PADI4 expression in blood and tissues of patients with malignant tumors

Directory of Open Access Journals (Sweden)

Zhao Yan

2009-01-01

Full Text Available Abstract Background Peptidylarginine deiminase type 4 (PAD4/PADI4 post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Methods Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673 as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT were investigated in the blood of patients with various tumors by ELISA (n = 1121. Results Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with

Increased PADI4 expression in blood and tissues of patients with malignant tumors

International Nuclear Information System (INIS)

Chang, Xiaotian; Han, Jinxiang; Pang, Li; Zhao, Yan; Yang, Yi; Shen, Zhonglin

2009-01-01

Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors compared to those in patients

Trans-activation function of a 3' truncated X gene-cell fusion product from integrated hepatitis B virus DNA in chronic hepatitis tissues

International Nuclear Information System (INIS)

Takada, Shinako; Koike, Katsuro

1990-01-01

To investigate the expression and transactivation function of the X gene in integrated hepatitis B virus (HBV) DNA from chronic hepatitis tissues, a series of transfectants containing cloned integrated HBV DNAs was made and analyzed for X mRNA expression and trans-activation activity by using a chloramphenicol acetyltransferase assay. Most of the integrated HBV DNAs expressed X mRNA and encoded a product with trans-activation activity in spite of the loss of the 3' end region of the X gene due to integration. From cDNA cloning and sequence analysis of X mRNA transcribed from native or integrated HBV DNA, the X protein was found to be translated from the X open reading frame without splicing. For integrated HBV DNA, transcription was extended to a cellular flanking DNA and an X gene-cell fusion transcript was terminated by using a cellular poly(A) signal. The amino acid sequence deduced from an X-cell fusion transcript indicated truncation of the carboxyl-terminal five amino acids, but the upstream region of seven amino acids conserved among hepadnaviruses was retained in the integrated HBV DNA, suggesting that this conserved region is essential for the transactivation function of the X protein. These findings support the following explanation for hepatocarcinogenesis by HBV DNA integration: the expression of a cellular oncogene(s) is transactivated at the time of chronic infection by the increasing amounts of the integrated HBV gene product(s), such as the X-cell fusion product

Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

Directory of Open Access Journals (Sweden)

Ryan C. Bates

2015-08-01

Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

In vitro double-integrating-sphere optical properties of tissues between 630 and 1064 nm

Science.gov (United States)

Beek, J. F.; Blokland, P.; Posthumus, P.; Aalders, M.; Pickering, J. W.; Sterenborg, H. J. C. M.; van Gemert, M. J. C.

1997-11-01

The optical properties (absorption and scattering coefficients and the scattering anisotropy factor) were measured in vitro for cartilage, liver, lung, muscle, myocardium, skin, and tumour (colon adenocarcinoma CC 531) at 630, 632.8, 790, 850 and 1064 nm. Rabbits, rats, piglets, goats, and dogs were used to obtain the tissues. A double-integrating-sphere setup with an intervening sample was used to determine the reflectance, and the diffuse and collimated transmittances of the sample. The inverse adding - doubling algorithm was used to determine the optical properties from the measurements. The overall results were comparable to those available in the literature, although only limited data are available at 790 - 850 nm. The results were reproducible for a specific sample at a specific wavelength. However, when comparing the results of different samples of the same tissue or different lasers with approximately the same wavelength (e.g. argon dye laser at 630 nm and HeNe laser at 632.8 nm) variations are large. We believe these variations in optical properties should be explained by biological variations of the tissues. In conclusion, we report on an extensive set of in vitro absorption and scattering properties of tissues measured with the same equipment and software, and by the same group. Although the accuracy of the method requires further improvement, it is highly likely that the other existing data in the literature have a similar level of accuracy.

Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

Science.gov (United States)

Boominathan, Vijay P; Ferreira, Tracie L

2012-12-01

Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise.

Meat Science and Muscle Biology Symposium: manipulating meat tenderness by increasing the turnover of intramuscular connective tissue.

Science.gov (United States)

Purslow, P P; Archile-Contreras, A C; Cha, M C

2012-03-01

Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the

Biomaterials in co-culture systems: towards optimizing tissue integration and cell signaling within scaffolds.

Science.gov (United States)

Battiston, Kyle G; Cheung, Jane W C; Jain, Devika; Santerre, J Paul

2014-05-01

Most natural tissues consist of multi-cellular systems made up of two or more cell types. However, some of these tissues may not regenerate themselves following tissue injury or disease without some form of intervention, such as from the use of tissue engineered constructs. Recent studies have increasingly used co-cultures in tissue engineering applications as these systems better model the natural tissues, both physically and biologically. This review aims to identify the challenges of using co-culture systems and to highlight different approaches with respect to the use of biomaterials in the use of such systems. The application of co-culture systems to stimulate a desired biological response and examples of studies within particular tissue engineering disciplines are summarized. A description of different analytical co-culture systems is also discussed and the role of biomaterials in the future of co-culture research are elaborated on. Understanding the complex cell-cell and cell-biomaterial interactions involved in co-culture systems will ultimately lead the field towards biomaterial concepts and designs with specific biochemical, electrical, and mechanical characteristics that are tailored towards the needs of distinct co-culture systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

Applying the Health Belief Model and an Integrated Behavioral Model to Promote Breast Tissue Donation Among Asian Americans.

Science.gov (United States)

Shafer, Autumn; Kaufhold, Kelly; Luo, Yunjuan

2018-07-01

An important part in the effort to prevent, treat, and cure breast cancer is research done with healthy breast tissue. The Susan G. Komen for the Cure Tissue Bank at Indiana University Simon Cancer Center (KTB) encourages women to donate a small amount of healthy breast tissue and then provides that tissue to researchers studying breast cancer. Although KTB has a large donor base, the volume of tissue samples from Asian women is low despite prior marketing efforts to encourage donation among this population. This study builds on prior work promoting breast cancer screenings among Asian women by applying constructs from the Health Belief Model (HBM) and the Integrated Behavioral Model (IBM) to investigate why Asian-American women are less inclined to donate their healthy breast tissue than non-Asian women and how this population may be motivated to donate in the future. A national online survey (N = 1,317) found Asian women had significantly lower perceived severity, some lower perceived benefits, and higher perceived barriers to tissue donation than non-Asian women under HBM and significantly lower injunctive norms supporting breast tissue donation, lower perceived behavioral control, and lower intentions to donate under IBM. This study also compares and discusses similarities and differences among East, Southeast, and South Asian women on these same constructs.

A Gauss-Kronrod-Trapezoidal integration scheme for modeling biological tissues with continuous fiber distributions.

Science.gov (United States)

Hou, Chieh; Ateshian, Gerard A

2016-01-01

Fibrous biological tissues may be modeled using a continuous fiber distribution (CFD) to capture tension-compression nonlinearity, anisotropic fiber distributions, and load-induced anisotropy. The CFD framework requires spherical integration of weighted individual fiber responses, with fibers contributing to the stress response only when they are in tension. The common method for performing this integration employs the discretization of the unit sphere into a polyhedron with nearly uniform triangular faces (finite element integration or FEI scheme). Although FEI has proven to be more accurate and efficient than integration using spherical coordinates, it presents three major drawbacks: First, the number of elements on the unit sphere needed to achieve satisfactory accuracy becomes a significant computational cost in a finite element (FE) analysis. Second, fibers may not be in tension in some regions on the unit sphere, where the integration becomes a waste. Third, if tensed fiber bundles span a small region compared to the area of the elements on the sphere, a significant discretization error arises. This study presents an integration scheme specialized to the CFD framework, which significantly mitigates the first drawback of the FEI scheme, while eliminating the second and third completely. Here, integration is performed only over the regions of the unit sphere where fibers are in tension. Gauss-Kronrod quadrature is used across latitudes and the trapezoidal scheme across longitudes. Over a wide range of strain states, fiber material properties, and fiber angular distributions, results demonstrate that this new scheme always outperforms FEI, sometimes by orders of magnitude in the number of computational steps and relative accuracy of the stress calculation.

Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages

Science.gov (United States)

Waqas, Syed F. Hassnain; Hoang, Anh Cuong; Ampem, Grace; Azegrouz, Hind; Balogh, Lajos; Thuróczy, Julianna; Gerling, Ivan C.; Nam, Sorim; Lim, Jong-Seok; Martinez-Ibañez, Juncal; Real, José T.; Paschke, Stephan; Quillet, Raphaëlle; Ayachi, Safia; Simonin, Frédéric; Schneider, E. Marion; Brinkman, Jacqueline A.; Seroogy, Christine M.

2017-01-01

The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet–fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage–associated genes IL-4 receptor α (Il4ra), arginase 1 (Arg1), IL-10 (Il10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs. PMID:28581443

Conditioning Influences Audio-Visual Integration by Increasing Sound Saliency

Directory of Open Access Journals (Sweden)

Fabrizio Leo

2011-10-01

Full Text Available We investigated the effect of prior conditioning of an auditory stimulus on audiovisual integration in a series of four psychophysical experiments. The experiments factorially manipulated the conditioning procedure (picture vs monetary conditioning and multisensory paradigm (2AFC visual detection vs redundant target paradigm. In the conditioning sessions, subjects were presented with three pure tones (= conditioned stimulus, CS that were paired with neutral, positive, or negative unconditioned stimuli (US, monetary: +50 euro cents,.–50 cents, 0 cents; pictures: highly pleasant, unpleasant, and neutral IAPS. In a 2AFC visual selective attention paradigm, detection of near-threshold Gabors was improved by concurrent sounds that had previously been paired with a positive (monetary or negative (picture outcome relative to neutral sounds. In the redundant target paradigm, sounds previously paired with positive (monetary or negative (picture outcomes increased response speed to both auditory and audiovisual targets similarly. Importantly, prior conditioning did not increase the multisensory response facilitation (ie, (A + V/2 – AV or the race model violation. Collectively, our results suggest that prior conditioning primarily increases the saliency of the auditory stimulus per se rather than influencing audiovisual integration directly. In turn, conditioned sounds are rendered more potent for increasing response accuracy or speed in detection of visual targets.

Ethical tissue: a not-for-profit model for human tissue supply.

Science.gov (United States)

Adams, Kevin; Martin, Sandie

2011-02-01

Following legislative changes in 2004 and the establishment of the Human Tissue Authority, access to human tissues for biomedical research became a more onerous and tightly regulated process. Ethical Tissue was established to meet the growing demand for human tissues, using a process that provided ease of access by researchers whilst maintaining the highest ethical and regulatory standards. The establishment of a licensed research tissue bank entailed several key criteria covering ethical, legal, financial and logistical issues being met. A wide range of stakeholders, including the HTA, University of Bradford, flagged LREC, hospital trusts and clinical groups were also integral to the process.

Characterisation of connective tissue from the hypertrophic skeletal muscle of myostatin null mice.

Science.gov (United States)

Elashry, Mohamed I; Collins-Hooper, Henry; Vaiyapuri, Sakthivel; Patel, Ketan

2012-06-01

Myostatin is a potent inhibitor of muscle development. Genetic deletion of myostatin in mice results in muscle mass increase, with muscles often weighing three times their normal values. Contracting muscle transfers tension to skeletal elements through an elaborate connective tissue network. Therefore, the connective tissue of skeletal muscle is an integral component of the contractile apparatus. Here we examine the connective tissue architecture in myostatin null muscle. We show that the hypertrophic muscle has decreased connective tissue content compared with wild-type muscle. Secondly, we show that the hypertrophic muscle fails to show the normal increase in muscle connective tissue content during ageing. Therefore, genetic deletion of myostatin results in an increase in contractile elements but a decrease in connective tissue content. We propose a model based on the contractile profile of muscle fibres that reconciles this apparent incompatible tissue composition phenotype. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.

Science.gov (United States)

Andrews, Shan V; Ellis, Shannon E; Bakulski, Kelly M; Sheppard, Brooke; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Feinberg, Andrew P; Arking, Dan E; Ladd-Acosta, Christine; Fallin, M Daniele

2017-10-24

Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.

Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis.

Science.gov (United States)

Mize, T W; Sundararaj, K P; Leite, R S; Huang, Y

2015-06-01

Both gingival tissue destruction and regeneration are associated with chronic periodontitis, although the former overwhelms the latter. Studies have shown that transforming growth factor beta 1 (TGF-β1), a growth factor largely involved in tissue regeneration and remodeling, is upregulated in chronic periodontitis. However, the gingival expression of connective tissue growth factor (CTGF or CCN2), a TGF-β1-upregulated gene, in patients with periodontitis remains undetermined. Although both CTGF/CCN2 and TGF-b1 increase the production of extracellular matrix, they have many different biological functions. Therefore, it is important to delineate the impact of periodontitis on gingival CTGF/CCN2 expression. Periodontal tissue specimens were collected from seven individuals without periodontitis (group 1) and from 14 with periodontitis (group 2). The expression of CTGF and TGFβ1 mRNAs were quantified using real-time PCR. Analysis using the nonparametric Mann-Whitney U-test showed that the levels of expression of both CTGF/CCN2 and TGFβ1 mRNAs were significantly increased in individuals with periodontitis compared with individuals without periodontitis. Furthermore, analysis using a nonparametric correlation (Spearman r) test showed a positive correlation between TGFβ1 and CTGF/CCN2 mRNAs. The gingival expression levels of CTGF/CCN2 and TGFβ1 mRNAs in individuals with periodontitis are upregulated and correlated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increasing efficiency through integrated energy data management

International Nuclear Information System (INIS)

Brack, M.

2002-01-01

This article discusses how improved management of energy data can bring about the increase in efficiency that is necessary for an electricity enterprise operating in a liberalised electricity market. The relevant technical and business processes involved for a typical power distribution utility are described. The present situation is reviewed and the various physical, data-logistics and commercial 'domains' involved are examined. Possible solutions for energy data logistics and integrated data management are discussed from the points of view of the operating utility, the power supplier and those responsible for balancing out supply and demand

Engineering complex orthopaedic tissues via strategic biomimicry.

Science.gov (United States)

Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

2015-03-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

Science.gov (United States)

Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

2014-01-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells

OpenAIRE

Eirin, Alfonso; Zhu, Xiang-Yang; Puranik, Amrutesh S.; Woollard, John R.; Tang, Hui; Dasari, Surendra; Lerman, Amir; van Wijnen, Andre J.; Lerman, Lilach O.

2017-01-01

Background Mesenchymal stromal/stem cell (MSC) transplantation is a promising therapy for tissue regeneration. Extracellular vesicles (EVs) released by MSCs act as their paracrine effectors by delivering proteins and genetic material to recipient cells. To assess how their cargo mediates biological processes that drive their therapeutic effects, we integrated miRNA, mRNA, and protein expression data of EVs from porcine adipose tissue-derived MSCs. Methods Simultaneous expression profiles of m...

AAV vector encoding human VEGF165-transduced pectineus muscular flaps increase the formation of new tissue through induction of angiogenesis in an in vivo chamber for tissue engineering: A technique to enhance tissue and vessels in microsurgically engineered tissue.

Science.gov (United States)

Moimas, Silvia; Manasseri, Benedetto; Cuccia, Giuseppe; Stagno d'Alcontres, Francesco; Geuna, Stefano; Pattarini, Lucia; Zentilin, Lorena; Giacca, Mauro; Colonna, Michele R

2015-01-01

In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen-glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene β-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine.

Post-processing of polymer foam tissue scaffolds with high power ultrasound: A route to increased pore interconnectivity, pore size and fluid transport

International Nuclear Information System (INIS)

Watson, N.J.; Johal, R.K.; Glover, Z.; Reinwald, Y.; White, L.J.; Ghaemmaghami, A.M.; Morgan, S.P.; Rose, F.R.A.J.; Povey, M.J.W.; Parker, N.G.

2013-01-01

The aim of this work is to demonstrate that the structural and fluidic properties of polymer foam tissue scaffolds, post-fabrication but prior to the introduction of cells, can be engineered via exposure to high power ultrasound. Our analysis is supported by measurements of fluid uptake during insonification and imaging of the scaffold microstructure via X-ray computed tomography, scanning electron microscopy and acoustic microscopy. The ultrasonic treatment is performed with a frequency of 30 kHz, average intensities up to 80,000 Wm −2 and exposure times up to 20 h. The treatment is found to increase the mean pore size by over 10%. More striking is the improvement in fluid uptake: for scaffolds with only 40% water uptake via standard immersion techniques, we can routinely achieve full saturation of the scaffold over approximately one hour of exposure. These desirable modifications occur with negligible loss of scaffold integrity and mass, and are optimized when the ultrasound treatment is coupled to a pre-wetting stage with ethanol. Our findings suggest that high power ultrasound is highly targeted towards flow obstructions in the scaffold architecture, thereby providing an efficient means to promote pore interconnectivity and fluid transport in thick foam tissue scaffolds. - Highlights: • We expose thick PLA foam tissue scaffolds to high power ultrasound. • This treatment both accelerates and enhances the uptake of fluid into the scaffold. • It leads to significant increases in the mean pore size, pore interconnectivity and porosity. • The ultrasonic treatment is most effective when the scaffold is pre-wet with ethanol. • We demonstrate the use of acoustic microscopy to characterize the scaffold microstructure

The interplay between tissue growth and scaffold degradation in engineered tissue constructs

KAUST Repository

O’Dea, R. D.

2012-09-18

In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of

Ruminant Metabolic Systems Biology: Reconstruction and Integration of Transcriptome Dynamics Underlying Functional Responses of Tissues to Nutrition and Physiological Statea

Science.gov (United States)

Bionaz, Massimo; Loor, Juan J.

2012-01-01

High-throughput ‘omics’ data analysis via bioinformatics is one key component of the systems biology approach. The systems approach is particularly well-suited for the study of the interactions between nutrition and physiological state with tissue metabolism and functions during key life stages of organisms such as the transition from pregnancy to lactation in mammals, ie, the peripartal period. In modern dairy cows with an unprecedented genetic potential for milk synthesis, the nature of the physiologic and metabolic adaptations during the peripartal period is multifaceted and involves key tissues such as liver, adipose, and mammary. In order to understand such adaptation, we have reviewed several works performed in our and other labs. In addition, we have used a novel bioinformatics approach, Dynamic Impact Approach (DIA), in combination with partly previously published data to help interpret longitudinal biological adaptations of bovine liver, adipose, and mammary tissue to lactation using transcriptomics datasets. Use of DIA with transcriptomic data from those tissues during normal physiological adaptations and in animals fed different levels of energy prepartum allowed visualization and integration of most-impacted metabolic pathways around the time of parturition. The DIA is a suitable tool for applying the integrative systems biology approach. The ultimate goal is to visualize the complexity of the systems at study and uncover key molecular players involved in the tissue’s adaptations to physiological state or nutrition. PMID:22807626

Virtual Plant Tissue: Building Blocks for Next-Generation Plant Growth Simulation

Directory of Open Access Journals (Sweden)

Dirk De Vos

2017-05-01

Full Text Available Motivation: Computational modeling of plant developmental processes is becoming increasingly important. Cellular resolution plant tissue simulators have been developed, yet they are typically describing physiological processes in an isolated way, strongly delimited in space and time.Results: With plant systems biology moving toward an integrative perspective on development we have built the Virtual Plant Tissue (VPTissue package to couple functional modules or models in the same framework and across different frameworks. Multiple levels of model integration and coordination enable combining existing and new models from different sources, with diverse options in terms of input/output. Besides the core simulator the toolset also comprises a tissue editor for manipulating tissue geometry and cell, wall, and node attributes in an interactive manner. A parameter exploration tool is available to study parameter dependence of simulation results by distributing calculations over multiple systems.Availability: Virtual Plant Tissue is available as open source (EUPL license on Bitbucket (https://bitbucket.org/vptissue/vptissue. The project has a website https://vptissue.bitbucket.io.

DUOX2 Expression Is Increased in Barrett Esophagus and Cancerous Tissues of Stomach and Colon

Directory of Open Access Journals (Sweden)

Ran Qi

2016-01-01

Full Text Available Aim. To detect the expression of dual oxidase (DUOX 2 in Barrett esophagus, gastric cancer, and colorectal cancer (CRC. Materials and Methods. The endoscopic biopsies were collected from patients with Barrett esophagus, while the curative resection tissues were obtained from patients with gastric cancer, CRC, or hepatic carcinoma. The DUOX2 protein and mRNA levels were detected with immunohistochemistry (IHC and real-time quantitative PCR (qPCR. The correlation of DUOX2 expression with clinicopathological parameters of tumors was identified. Results. Low levels of DUOX2 mRNA were detected in Barrett esophagus and the adjacent normal tissues, and there was no difference between these two groups. DUOX2 protein was found in Barrett esophagus and undetectable in the normal epithelium. The DUOX2 mRNA and protein levels in the gastric cancer and CRC were increased compared to the adjacent nonmalignant tissues. The elevated DUOX2 in the gastric cancer was significantly associated with smoking history. In CRC tissues, the DUOX2 protein expression level in stages II–IV was significantly higher than that in stage I. In both hepatic carcinoma and the adjacent nonmalignant tissue, the DUOX2 was virtually undetectable. Conclusion. DUOX2 in Barrett esophagus, gastric cancer, and CRC may be involved in the tumorigenesis of these tissues.

Increased demand-side flexibility: market effects and impacts on variable renewable energy integration

Directory of Open Access Journals (Sweden)

Åsa Grytli Tveten

2016-12-01

Full Text Available This paper investigates the effect of increased demand-side flexibility (DSF on integration and market value of variable renewable energy sources (VRE. Using assumed potentials, system-optimal within-day shifts in demand are investigated for the Northern European power markets in 2030, applying a comprehensive partial equilibrium model with high temporal and spatial resolution. Increased DSF is found to cause only a minor (less than 3% reduction in consumers’ cost of electricity. VRE revenues are found to increase (up to 5% and 2% for wind and solar power, respectively, and total VRE curtailment decreases by up to 7.2 TWh. Increased DSF causes only limited reductions in GHG emissions. The emission reduction is, however, sensitive to underlying assumptions. We conclude that increased DSF is a promising measure for improving VRE integration. However, low consumers’ savings imply that policies stimulating DFS will be needed to fully use the potential benefits of DSF for VRE integration

"Project ACTS": An Intervention to Increase Organ and Tissue Donation Intentions among African Americans

Science.gov (United States)

Arriola, Kimberly; Robinson, Dana H.; Thompson, Nancy J.; Perryman, Jennie P.

2010-01-01

This study sought to evaluate the effectiveness of "Project ACTS: About Choices in Transplantation and Sharing," which was developed to increase readiness for organ and tissue donation among African American adults. Nine churches (N = 425 participants) were randomly assigned to receive donation education materials currently available to consumers…

AAV vector encoding human VEGF165–transduced pectineus muscular flaps increase the formation of new tissue through induction of angiogenesis in an in vivo chamber for tissue engineering: A technique to enhance tissue and vessels in microsurgically engineered tissue

Directory of Open Access Journals (Sweden)

Silvia Moimas

2015-12-01

Full Text Available In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen–glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene β-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine.

Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

Science.gov (United States)

LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

2016-02-01

The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country

DEFF Research Database (Denmark)

Backer, Vibeke; Baines, Katherine J; Powell, Heather

2016-01-01

inflammation can be modified by migration and diet. OBJECTIVE: To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. METHODS: Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed...... of mast cell markers in adipose tissue and asthma. Among Greenlandic Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes....... by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). RESULTS: Of the 1059 Greenlandic Inuit...

Imagenology of the bio integration of polymers synthesized by plasma in pith tissue; Imagenologia de la biointegracion de polimeros sintetizados por plasma en tejido de medula espinal

Energy Technology Data Exchange (ETDEWEB)

Morales, J.; Olayo, R. [Departamento de Fisica, Universidad Autonoma Metropolitana Iztapalapa. 09340 Mexico D.F. (Mexico); Escalona, A.; Morales, A.; Mondragon, R. [Departamento de Ingeniera Electrica, Universidad Autonoma Metropolitana Iztapalapa. 09340 Mexico D.F. (Mexico); Diaz, A.; Rios, C. [Departamento de Neuroquimica, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez S.S.A., Mexico D.F. (Mexico); Salgado, H. [Unidad de Investigacion Medica en Enfermedades Neurologicas, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Mexico D.F. (Mexico); Cruz, G.; Olayo, M.G. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)]. e-mail: jmor@xanum.uam.mx

2007-07-01

The general characteristics of the bio integration of pyrrole derived polymers in spinal marrows with traumatic lesions are evaluated by visual mediums. Histological images of spinal marrow tinted by the Eosin/Hematoxyline technique are used and images obtained by computerized axial tomography and nuclear magnetic resonance with those that are carried out some three-dimensional reconstructions of the injured area. It intends an algorithm that relates the area of the bottom-tissue relationship with the sum of the tissue areas and of the implanted polymer. Some computational procedures for segmentation of spinal marrow on the integration of the polymer to the tissue of the injured marrow are presented. (Author)

Engineered Muscle Actuators: Cells and Tissues

National Research Council Canada - National Science Library

Dennis, Robert G; Herr, Hugh; Parker, Kevin K; Larkin, Lisa; Arruda, Ellen; Baar, Keith

2007-01-01

.... Our primary objectives were to engineer living skeletal muscle actuators in culture using integrated bioreactors to guide tissue development and to maintain tissue contractility, to achieve 50...

Combined Monte Carlo and path-integral method for simulated library of time-resolved reflectance curves from layered tissue models

Science.gov (United States)

Wilson, Robert H.; Vishwanath, Karthik; Mycek, Mary-Ann

2009-02-01

Monte Carlo (MC) simulations are considered the "gold standard" for mathematical description of photon transport in tissue, but they can require large computation times. Therefore, it is important to develop simple and efficient methods for accelerating MC simulations, especially when a large "library" of related simulations is needed. A semi-analytical method involving MC simulations and a path-integral (PI) based scaling technique generated time-resolved reflectance curves from layered tissue models. First, a zero-absorption MC simulation was run for a tissue model with fixed scattering properties in each layer. Then, a closed-form expression for the average classical path of a photon in tissue was used to determine the percentage of time that the photon spent in each layer, to create a weighted Beer-Lambert factor to scale the time-resolved reflectance of the simulated zero-absorption tissue model. This method is a unique alternative to other scaling techniques in that it does not require the path length or number of collisions of each photon to be stored during the initial simulation. Effects of various layer thicknesses and absorption and scattering coefficients on the accuracy of the method will be discussed.

Increased adsorption of histidine-tagged proteins onto tissue culture polystyrene

DEFF Research Database (Denmark)

Holmberg, Maria; Hansen, Thomas Steen; Lind, Johan Ulrik

2012-01-01

and ethylenediaminetetraacetic acid (EDTA), as well as adsorption performed at different pH and ionic strength indicates that the high adsorption is caused by electrostatic interaction between negatively charged carboxylate groups on the TCPS surface and positively charged histidine residues in the proteins. Pre......In this study we compare histidine-tagged and native proteins with regards to adsorption properties. We observe significantly increased adsorption of proteins with an incorporated polyhistidine amino acid motif (HIS-tag) onto tissue culture polystyrene (TCPS) compared to similar proteins without...... a HIS-tag. The effect is not observed on polystyrene (PS). Adsorption experiments have been performed at physiological pH (7.4) and the effect was only observed for the investigated proteins that have pI values below or around 7.4. Competitive adsorption experiments with imidazole...

Vertical leaf mass per area gradient of mature sugar maple reflects both height-driven increases in vascular tissue and light-driven increases in palisade layer thickness.

Science.gov (United States)

Coble, Adam P; Cavaleri, Molly A

2017-10-01

A key trait used in canopy and ecosystem function modeling, leaf mass per area (LMA), is influenced by changes in both leaf thickness and leaf density (LMA = Thickness × Density). In tall trees, LMA is understood to increase with height through two primary mechanisms: (i) increasing palisade layer thickness (and thus leaf thickness) in response to light and/or (ii) reduced cell expansion and intercellular air space in response to hydrostatic constraints, leading to increased leaf density. Our objective was to investigate within-canopy gradients in leaf anatomical traits in order to understand environmental factors that influence leaf morphology in a sugar maple (Acer saccharum Marshall) forest canopy. We teased apart the effects of light and height on anatomical traits by sampling at exposed and closed canopies that had different light conditions at similar heights. As expected, palisade layer thickness responded strongly to cumulative light exposure. Mesophyll porosity, however, was weakly and negatively correlated with light and height (i.e., hydrostatic gradients). Reduced mesophyll porosity was not likely caused by limitations on cell expansion; in fact, epidermal cell width increased with height. Palisade layer thickness was better related to LMA, leaf density and leaf thickness than was mesophyll porosity. Vein diameter and fraction of vascular tissue also increased with height and LMA, density and thickness, revealing that greater investment in vascular and support tissue may be a third mechanism for increased LMA with height. Overall, decreasing mesophyll porosity with height was likely due to palisade cells expanding into the available air space and also greater investments in vascular and support tissue, rather than a reduction of cell expansion due to hydrostatic constraints. Our results provide evidence that light influences both palisade layer thickness and mesophyll porosity and indicate that hydrostatic gradients influence leaf vascular and support

Integrating research on thyroid cancer after Chernobyl--the Chernobyl Tissue Bank.

Science.gov (United States)

Thomas, G A; Bethel, J A; Galpine, A; Mathieson, W; Krznaric, M; Unger, K

2011-05-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer after Chernobyl, the Chernobyl Tissue Bank was established. The project is supported by the governments of Ukraine and Russia, and financially supported (in total around US$3 million) by the European Commission, the National Cancer Institute of the USA and the Sasakawa Memorial Health Foundation of Japan. The project began collecting a variety of biological samples from patients on 1 October 1988, and has supplied material to 21 research projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue Bank has facilitated co-operation between these research projects and the combination of clinical and research data provides a paradigm for cancer research in the molecular biological age. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Altered tissue mineralization, increased hepatic lipid and inhibited ...

African Journals Online (AJOL)

Mineral homeostasis is often disrupted in intrauterine growth retardation (IUGR) infants. Most studies focus on calcium or phosphorus metabolism of IUGR infants via determining serum mineral concentrations instead of tissues. This study was conducted to investigate the effects of IUGR on the mineralization and ...

Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

Science.gov (United States)

Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

2011-05-01

Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

Increased epidermal laser fluence through simultaneous ultrasonic microporation

Science.gov (United States)

Whiteside, Paul J. D.; Chininis, Jeff A.; Schellenberg, Mason W.; Qian, Chenxi; Hunt, Heather K.

2016-03-01

Lasers have demonstrated widespread applicability in clinical dermatology as minimally invasive instruments that achieve photogenerated responses within tissue. However, before reaching its target, the incident light must first transmit through the surface layer of tissue, which is interspersed with chromophores (e.g. melanin) that preferentially absorb the light and may also generate negative tissue responses. These optical absorbers decrease the efficacy of the procedures. In order to ensure that the target receives a clinically relevant dose, most procedures simply increase the incident energy; however, this tends to exacerbate the negative complications of melanin absorption. Here, we present an alternative solution aimed at increasing epidermal energy uence while mitigating excess absorption by unintended targets. Our technique involves the combination of a waveguide-based contact transmission modality with simultaneous high-frequency ultrasonic pulsation, which alters the optical properties of the tissue through the agglomeration of dissolved gasses into micro-bubbles within the tissue. Doing so effectively creates optically transparent pathways for the light to transmit unobstructed through the tissue, resulting in an increase in forward scattering and a decrease in absorption. To demonstrate this, Q-switched nanosecond-pulsed laser light at 532nm was delivered into pig skin samples using custom glass waveguides clad in titanium and silver. Light transmission through the tissue was measured with a photodiode and integrating sphere for tissue with and without continuous ultrasonic pulsation at 510 kHz. The combination of these techniques has the potential to improve the efficiency of laser procedures while mitigating negative tissue effects caused by undesirable absorption.

Three-dimensional visualization of functional brain tissue and functional magnetic resonance imaging-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex

International Nuclear Information System (INIS)

Han Tong; Cui Shimin; Tong Xiaoguang; Liu Li; Xue Kai; Liu Meili; Liang Siquan; Zhang Yunting; Zhi Dashi

2011-01-01

Objective: To assess the value of three -dimensional visualization of functional brain tissue and the functional magnetic resonance imaging (fMRI)-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex. Method: Sixty patients with tumor located in the central sulcus were enrolled. Thirty patients were randomly assigned to function group and 30 to control group. Patients in function group underwent fMRI to localize the functional brain tissues. Then the function information was transferred to the neurosurgical navigator. The patients in control group underwent surgery with navigation without function information. The therapeutic effect, excision rate. improvement of motor function, and survival quality during follow-up were analyzed. Result: All patients in function group were accomplished visualization of functional brain tissues and fMRI-integrated neuronavigation. The locations of tumors, central sulcus and motor cortex were marked during the operation. The fMRI -integrated information played a great role in both pre- and post-operation. Pre-operation: designing the location of the skin flap and window bone, determining the relationship between the tumor and motor cortex, and designing the pathway for the resection. Post- operation: real-time navigation of relationship between the tumor and motor cortex, assisting to localize the motor cortex using interoperation ultra-sound for correcting the displacement by the CSF outflow and collapsing tumor. The patients in the function group had better results than the patients in the control group in therapeutic effect (u=2.646, P=0.008), excision rate (χ = 7.200, P<0.01), improvement of motor function (u=2.231, P=0.026), and survival quality (KPS u c = 2.664, P=0.008; Zubrod -ECOG -WHO u c =2.135, P=0.033). Conclusions: Using preoperative three -dimensional visualization of cerebral function tissue and the fMRI-integrated neuronavigation technology, combining intraoperative accurate

Maintaining Breast Cancer Specimen Integrity and Individual or Simultaneous Extraction of Quality DNA, RNA, and Proteins from Allprotect-Stabilized and Nonstabilized Tissue Samples

LENUS (Irish Health Repository)

Mee, Blanaid C.

2011-12-29

The Saint James\\'s Hospital Biobank was established in 2008, to develop a high-quality breast tissue BioResource, as a part of the breast cancer clinical care pathway. The aims of this work were: (1) to ascertain the quality of RNA, DNA, and protein in biobanked carcinomas and normal breast tissues, (2) to assess the efficacy of AllPrep® (Qiagen) in isolating RNA, DNA, and protein simultaneously, (3) to compare AllPrep with RNEasy® and QIAamp® (both Qiagen), and (4) to examine the effectiveness of Allprotect® (Qiagen), a new tissue stabilization medium in preserving DNA, RNA, and proteins. One hundred eleven frozen samples of carcinoma and normal breast tissue were analyzed. Tumor and normal tissue morphology were confirmed by frozen sections. Tissue type, tissue treatment (Allprotect vs. no Allprotect), extraction kit, and nucleic acid quantification were analyzed by utilizing a 4 factorial design (SPSS PASW 18 Statistics Software®). QIAamp (DNA isolation), AllPrep (DNA, RNA, and Protein isolation), and RNeasy (RNA isolation) kits were assessed and compared. Mean DNA yield and A260\\/280 values using QIAamp were 33.2 ng\\/μL and 1.86, respectively, and using AllPrep were 23.2 ng\\/μL and 1.94. Mean RNA yield and RNA Integrity Number (RIN) values with RNeasy were 73.4 ng\\/μL and 8.16, respectively, and with AllPrep were 74.8 ng\\/μL and 7.92. Allprotect-treated tissues produced higher RIN values of borderline significance (P=0.055). No discernible loss of RNA stability was detected after 6 h incubation of stabilized or nonstabilized tissues at room temperature or 4°C or in 9 freeze-thaw cycles. Allprotect requires further detailed evaluation, but we consider AllPrep to be an excellent option for the simultaneous extraction of RNA, DNA, and protein from tumor and normal breast tissues. The essential presampling procedures that maintain the diagnostic integrity of pathology specimens do not appear to compromise the quality of molecular isolates.

An integrated sample preparation to determine coccidiostats and emerging Fusarium-mycotoxins in various poultry tissues with LC-MS/MS.

Science.gov (United States)

Jestoi, Marika; Rokka, Mervi; Peltonen, Kimmo

2007-05-01

The usefulness of an existing sample preparation technique used for ionophoric coccidiostats (lasalocid, monensin, salinomycin and narasin) was applied in the analysis of emerging Fusarium-mycotoxins beauvericin (BEA) and enniatins (ENNs) in poultry tissues (liver and meat). Also, maduramicin and liver as a new sample matrix was introduced. The developed methods were validated and applied for the determination of coccidiostats and BEA/ENNs in Finnish poultry tissues in 2004-2005. The validation parameters demonstrated that the integrated sample preparation technique is applicable to the parallel determination of these contaminants in poultry tissues. Of the samples analysed (276 meat and 43 liver), only trace levels of LAS, MON, SAL, NAR and MAD were detected in 7, 3, 5, 6 and 4% of the samples, respectively. Interestingly, for the first time, traces of BEA and ENNs could also be detected in animal tissues. BEA and ENNs A, A1, B and B1 were found in 2, 0.3, 0.6, 4 and 3% of the samples, respectively. The simultaneous presence of coccidiostats and mycotoxins was detected in three turkey samples in 2004.

Increased expression of resistin in ectopic endometrial tissue of women with endometriosis.

Science.gov (United States)

Oh, Yoon Kyung; Ha, Young Ran; Yi, Kyong Wook; Park, Hyun Tae; Shin, Jung-Ho; Kim, Tak; Hur, Jun-Young

2017-11-01

Inflammation is a key process in the establishment and progression of endometriosis. Resistin, an adipocytokine, has biological properties linked to immunologic functions, but its role in endometriosis is unclear. Resistin gene expression was examined in eutopic and ectopic endometrial tissues from women with (n=25) or without (n=25) endometriosis. Resistin mRNA and protein levels were determined in endometrial tissue using quantitative real-time reverse transcription PCR and Western blotting, following adipokine profiling arrays. Resistin protein was detected in human endometrial tissues using an adipokine array test. Resistin mRNA and protein levels were significantly higher in ectopic endometrial tissue of patients with endometriosis than in normal eutopic endometrial tissue. Our results indicate that resistin is differentially expressed in endometrial tissues from women with endometriosis and imply a role for resistin in endometriosis-associated pelvic inflammation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues.

Science.gov (United States)

Coutinho, Eulalia A; Okamoto, Shiki; Ishikawa, Ayako Wendy; Yokota, Shigefumi; Wada, Nobuhiro; Hirabayashi, Takahiro; Saito, Kumiko; Sato, Tatsuya; Takagi, Kazuyo; Wang, Chen-Chi; Kobayashi, Kenta; Ogawa, Yoshihiro; Shioda, Seiji; Yoshimura, Yumiko; Minokoshi, Yasuhiko

2017-09-01

The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine- N -oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues. © 2017 by the American Diabetes Association.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering

OpenAIRE

Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

2010-01-01

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-s...

Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS).

Science.gov (United States)

Borruel, Susana; Fernández-Durán, Elena; Alpañés, Macarena; Martí, David; Alvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2013-03-01

Sexual dimorphism suggests a role for androgens in body fat distribution. Women with polycystic ovary syndrome (PCOS), a mainly androgen excess disorder, often present with abdominal obesity and visceral adiposity. We hypothesized that women with PCOS have a masculinized body fat distribution favoring the deposition of fat in visceral and organ-specific adipose tissue depots. This was a case-control study. The study was conducted at an academic hospital. Women with PCOS (n = 55), women without androgen excess (n = 25), and men (n = 26) presenting with similar body mass index participated in the study. There were no interventions. Ultrasound measurements of adipose tissue depots including sc (minimum and maximum), preperitoneal, ip, mesenteric, epicardial, and perirenal fat thickness were obtained and total body fat mass was estimated using a body fat monitor. Men and patients with PCOS had increased amounts of total body fat compared with control women. Men had increased thickness of intraabdominal adipose tissue depots compared with the control women, with the women with PCOS showing intermediate values that were also higher than those of control women in the case of ip and mesenteric fat thickness and was close to reaching statistical significance in the case of epicardial fat thickness. Women with PCOS also showed increased minimum sc fat thickness compared with the control women. Obesity increased the thickness of all of the adipose tissue depots in the 3 groups of subjects. Women with PCOS have higher global adiposity and increased amounts of visceral adipose tissue compared with control women, especially in the ip and mesenteric depots.

Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling.

Science.gov (United States)

Vlot, Anna H C; de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; van Westen, Gerard J P; de Lange, Elizabeth C M

2017-12-04

Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of the underlying (pharmacological) mechanisms and availability of directly applicable predictive methods complicates the prediction of selectivity. We explore the value of combining physiologically based pharmacokinetic (PBPK) modeling with quantitative structure-activity relationship (QSAR) modeling to predict the influence of the target dissociation constant (K D ) and the target dissociation rate constant on target and tissue selectivity. The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). Of these CB1 ligands, rimonabant, CP-55940, and Δ 8 -tetrahydrocanabinol, one of the active ingredients of cannabis, were selected for simulations of target occupancy for CB1, TRPV1, mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the combined PBPK-QSAR modeling. Our combined PBPK and target binding modeling demonstrated that the optimal values of the K D and k off for target and tissue selectivity were dependent on target concentration and tissue distribution kinetics. Interestingly, if the target concentration is high and the perfusion of the target site is low, the optimal K D value is often not the lowest K D value, suggesting that optimization towards high drug-target affinity can decrease the benefit-risk ratio. The presented integrative structure-pharmacokinetic-pharmacodynamic modeling provides an improved understanding of tissue and target selectivity.

Integrated approaches to spatiotemporally directing angiogenesis in host and engineered tissues.

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Kant, Rajeev J; Coulombe, Kareen L K

2018-03-15

The field of tissue engineering has turned towards biomimicry to solve the problem of tissue oxygenation and nutrient/waste exchange through the development of vasculature. Induction of angiogenesis and subsequent development of a vascular bed in engineered tissues is actively being pursued through combinations of physical and chemical cues, notably through the presentation of topographies and growth factors. Presenting angiogenic signals in a spatiotemporal fashion is beginning to generate improved vascular networks, which will allow for the creation of large and dense engineered tissues. This review provides a brief background on the cells, mechanisms, and molecules driving vascular development (including angiogenesis), followed by how biomaterials and growth factors can be used to direct vessel formation and maturation. Techniques to accomplish spatiotemporal control of vascularization include incorporation or encapsulation of growth factors, topographical engineering, and 3D bioprinting. The vascularization of engineered tissues and their application in angiogenic therapy in vivo is reviewed herein with an emphasis on the most densely vascularized tissue of the human body - the heart. Vascularization is vital to wound healing and tissue regeneration, and development of hierarchical networks enables efficient nutrient transfer. In tissue engineering, vascularization is necessary to support physiologically dense engineered tissues, and thus the field seeks to induce vascular formation using biomaterials and chemical signals to provide appropriate, pro-angiogenic signals for cells. This review critically examines the materials and techniques used to generate scaffolds with spatiotemporal cues to direct vascularization in engineered and host tissues in vitro and in vivo. Assessment of the field's progress is intended to inspire vascular applications across all forms of tissue engineering with a specific focus on highlighting the nuances of cardiac tissue

Silk fibroin in tissue engineering.

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Kasoju, Naresh; Bora, Utpal

2012-07-01

Tissue engineering (TE) is a multidisciplinary field that aims at the in vitro engineering of tissues and organs by integrating science and technology of cells, materials and biochemical factors. Mimicking the natural extracellular matrix is one of the critical and challenging technological barriers, for which scaffold engineering has become a prime focus of research within the field of TE. Amongst the variety of materials tested, silk fibroin (SF) is increasingly being recognized as a promising material for scaffold fabrication. Ease of processing, excellent biocompatibility, remarkable mechanical properties and tailorable degradability of SF has been explored for fabrication of various articles such as films, porous matrices, hydrogels, nonwoven mats, etc., and has been investigated for use in various TE applications, including bone, tendon, ligament, cartilage, skin, liver, trachea, nerve, cornea, eardrum, dental, bladder, etc. The current review extensively covers the progress made in the SF-based in vitro engineering and regeneration of various human tissues and identifies opportunities for further development of this field. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomaterials for Tissue Engineering

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Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

2013-01-01

Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties. Despite these differences, both meet at the osteochondral interface. This article presents an overview of current biomaterials employed in bone and cartilage applications, discusses some design considerations, and alludes to future prospects within this field of research. PMID:23820768

Polyploidization of glia in neural development links tissue growth to blood-brain barrier integrity.

Science.gov (United States)

Unhavaithaya, Yingdee; Orr-Weaver, Terry L

2012-01-01

Proper development requires coordination in growth of the cell types composing an organ. Many plant and animal cells are polyploid, but how these polyploid tissues contribute to organ growth is not well understood. We found the Drosophila melanogaster subperineurial glia (SPG) to be polyploid, and ploidy is coordinated with brain mass. Inhibition of SPG polyploidy caused rupture of the septate junctions necessary for the blood-brain barrier. Thus, the increased SPG cell size resulting from polyploidization is required to maintain the SPG envelope surrounding the growing brain. Polyploidization likely is a conserved strategy to coordinate tissue growth during organogenesis, with potential vertebrate examples.

Biomaterials for tissue engineering applications.

Science.gov (United States)

Keane, Timothy J; Badylak, Stephen F

2014-06-01

With advancements in biological and engineering sciences, the definition of an ideal biomaterial has evolved over the past 50 years from a substance that is inert to one that has select bioinductive properties and integrates well with adjacent host tissue. Biomaterials are a fundamental component of tissue engineering, which aims to replace diseased, damaged, or missing tissue with reconstructed functional tissue. Most biomaterials are less than satisfactory for pediatric patients because the scaffold must adapt to the growth and development of the surrounding tissues and organs over time. The pediatric community, therefore, provides a distinct challenge for the tissue engineering community. Copyright © 2014. Published by Elsevier Inc.

Colonization and effector functions of innate lymphoid cells in mucosal tissues

Science.gov (United States)

Kim, Myunghoo; Kim, Chang H.

2016-01-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

Automatic registration of multi-modal microscopy images for integrative analysis of prostate tissue sections

International Nuclear Information System (INIS)

Lippolis, Giuseppe; Edsjö, Anders; Helczynski, Leszek; Bjartell, Anders; Overgaard, Niels Chr

2013-01-01

Prostate cancer is one of the leading causes of cancer related deaths. For diagnosis, predicting the outcome of the disease, and for assessing potential new biomarkers, pathologists and researchers routinely analyze histological samples. Morphological and molecular information may be integrated by aligning microscopic histological images in a multiplex fashion. This process is usually time-consuming and results in intra- and inter-user variability. The aim of this study is to investigate the feasibility of using modern image analysis methods for automated alignment of microscopic images from differently stained adjacent paraffin sections from prostatic tissue specimens. Tissue samples, obtained from biopsy or radical prostatectomy, were sectioned and stained with either hematoxylin & eosin (H&E), immunohistochemistry for p63 and AMACR or Time Resolved Fluorescence (TRF) for androgen receptor (AR). Image pairs were aligned allowing for translation, rotation and scaling. The registration was performed automatically by first detecting landmarks in both images, using the scale invariant image transform (SIFT), followed by the well-known RANSAC protocol for finding point correspondences and finally aligned by Procrustes fit. The Registration results were evaluated using both visual and quantitative criteria as defined in the text. Three experiments were carried out. First, images of consecutive tissue sections stained with H&E and p63/AMACR were successfully aligned in 85 of 88 cases (96.6%). The failures occurred in 3 out of 13 cores with highly aggressive cancer (Gleason score ≥ 8). Second, TRF and H&E image pairs were aligned correctly in 103 out of 106 cases (97%). The third experiment considered the alignment of image pairs with the same staining (H&E) coming from a stack of 4 sections. The success rate for alignment dropped from 93.8% in adjacent sections to 22% for sections furthest away. The proposed method is both reliable and fast and therefore well suited

Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes

Directory of Open Access Journals (Sweden)

Hoggard N

2012-05-01

Full Text Available Nigel Hoggard1, Abdelali Agouni2, Nimesh Mody2, Mirela Delibegovic21Rowett Institute of Nutrition and Health, 2Integrative Physiology, University of Aberdeen, Aberdeen, UKBackground: Retinol-binding protein 4 (RBP4 is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B expression levels as well as other genes involved in the endoplasmic reticulum (ER stress response are increased in adipose tissue of obese, high-fat-diet-fed mice. In this study we investigated if serum and/or adipose tissue RBP4 protein levels and expression levels of PTP1B and other ER stress-response genes are altered in obese and obese/diabetic men resident in northeast Scotland.Methods: We studied three groups of male volunteers: (1 normal/overweight (body mass index [BMI] < 30, (2 obese (BMI > 30, and (3 obese/diabetic (BMI > 30 controlling their diabetes either by diet or the antidiabetic drug metformin. We analyzed their serum and adipose tissue RBP4 protein levels as well as adipose tissue mRNA expression of PTP1B, binding immunoglobulin protein (BIP, activated transcription factor 4 (ATF4, and glucose-regulated protein 94 (GRP94 alongside other markers of adiposity (percentage body fat, leptin, cholesterol, triglycerides and insulin resistance (oral glucose tolerance tests, insulin, homeostatic model assessment–insulin resistance, C-reactive protein, and adiponectin.Results: We found that obese Scottish subjects had significantly higher serum RBP4 protein levels in comparison to the normal/overweight subjects (P < 0.01. Serum RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (P < 0.05. Adipose tissue RBP4 protein levels were comparable between all three groups of subjects as were serum and adipose transthyretin levels. Adipose tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (P < 0.05; however diet and/or metformin

Integrating Research on Thyroid Cancer after Chernobyl — the Chernobyl Tissue Bank

Science.gov (United States)

Thomas, G.A.; Bethel, J.A.; Galpine, A.; Krznaric, M.; Unger, K.

2011-01-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer after Chernobyl, the Chernobyl Tissue Bank was established. The project is supported by the governments of Ukraine and Russia, and financially supported (in total around US$3million) by the European Commission, the National Cancer Institute of the USA and the Sasakawa Memorial Health Foundation of Japan. The project began collecting a variety of biological samples from patients on 1 October 1988, and has supplied material to 21 research projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue Bank has facilitated cooperation between these research projects and the combination of clinical and research data provides a paradigm for cancer research in the molecular biological age. PMID:21345659

Monitoring soft tissue coagulation by optical spectroscopy

Science.gov (United States)

Lihachev, A.; Lihacova, I.; Heinrichs, H.; Spigulis, J.; Trebst, T.; Wehner, M.

2017-12-01

Laser tissue welding (LTW) or laser tissue soldering (LTS) is investigated since many years for treatment of incisions, wound closure and anastomosis of vessels [1, 2]. Depending on the process, a certain temperature in the range between 65 °C to 85 °C must be reached and held for a few seconds. Care has to be taken not to overheat the tissue, otherwise necrosis or tissue carbonization may occur and will impair wound healing. Usually the temperature is monitored during the process to control the laser power [3]. This requires either bulky equipment or expensive and fragile infrared fibers to feed the temperature signal to an infrared detector. Alternatively, changes in tissue morphology can be directly observed by analysis of spectral reflectance. We investigate spectral changes in the range between 400 nm to 900 nm wavelength. Characteristic spectral changes occur when the temperature of tissue samples increase above 70 °C which is a typical setpoint value for temperature control of coagulation. We conclude that simple spectroscopy in the visible range can provide valuable information during LTS and LTW and probably replace the delicate measurement of temperature. A major advantage is that optical measurements can be performed using standard optical fibers and can be easily integrated into a surgical tool.

Tissue-specific functional networks for prioritizing phenotype and disease genes.

Directory of Open Access Journals (Sweden)

Yuanfang Guan

Full Text Available Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

Biobanking of Fresh-Frozen Cancer Tissue: RNA Is Stable Independent of Tissue Type with Less Than 1 Hour of Cold Ischemia.

Science.gov (United States)

Song, Sang Yong; Jun, Jonghyun; Park, Miyeon; Park, Seo Kyu; Choi, Wonju; Park, Kyunghee; Jang, Kee-Taek; Lee, Myoyong

2018-02-01

The effects of preanalytical variables in tissue processing and storage periods on RNA quality of tissues have been well documented in each type of cancer. However, few studies have been performed on a comparative assessment of the impacts across different cancer tissues, even though it is well known that RNase activity is highly variable in various tissue types and RNase-rich tissues have been found to yield low-quality RNA. We investigated the impacts of cold ischemia times and long-term storage on RNA integrity in various types of cancer tissue, which had been fresh-frozen and collected at the Samsung Medical Center Biobank. RNA quality was also evaluated with regard to histopathological variables. We analyzed RNA integrity number (RIN) data, which had been obtained from our quality control (QC) processes over the last 7 years. Approximately 2% of samples were randomly selected and processed to measure RIN quarterly and after 6 years of storage for QC purposes. Fresh-frozen tumor tissues yielded high-quality RNA regardless of tumor type and histopathological features. Up to 1-hour cold ischemia times and up to 6-year storage times did not adversely influence RNA integrity. Only 3 samples showed RIN of <7 out of a total of 396 analyzed tumor tissues. Tissue quality was not adversely affected by long-term storage or limited variations of cold ischemia times. The low-quality samples could be correlated with the structural composition or intratumoral heterogeneity of tissues. The strict application of standardized protocols for tissue collection is the key for high-quality biobanking.

Mechanically robust cryogels with injectability and bioprinting supportability for adipose tissue engineering.

Science.gov (United States)

Qi, Dianjun; Wu, Shaohua; Kuss, Mitchell A; Shi, Wen; Chung, Soonkyu; Deegan, Paul T; Kamenskiy, Alexey; He, Yini; Duan, Bin

2018-05-26

Bioengineered adipose tissues have gained increased interest as a promising alternative to autologous tissue flaps and synthetic adipose fillers for soft tissue augmentation and defect reconstruction in clinic. Although many scaffolding materials and biofabrication methods have been investigated for adipose tissue engineering in the last decades, there are still challenges to recapitulate the appropriate adipose tissue microenvironment, maintain volume stability, and induce vascularization to achieve long-term function and integration. In the present research, we fabricated cryogels consisting of methacrylated gelatin, methacrylated hyaluronic acid, and 4arm poly(ethylene glycol) acrylate (PEG-4A) by using cryopolymerization. The cryogels were repeatedly injectable and stretchable, and the addition of PEG-4A improved the robustness and mechanical properties. The cryogels supported human adipose progenitor cell (HWA) and adipose derived mesenchymal stromal cell adhesion, proliferation, and adipogenic differentiation and maturation, regardless of the addition of PEG-4A. The HWA laden cryogels facilitated the co-culture of human umbilical vein endothelial cells (HUVEC) and capillary-like network formation, which in return also promoted adipogenesis. We further combined cryogels with 3D bioprinting to generate handleable adipose constructs with clinically relevant size. 3D bioprinting enabled the deposition of multiple bioinks onto the cryogels. The bioprinted flap-like constructs had an integrated structure without delamination and supported vascularization. Adipose tissue engineering is promising for reconstruction of soft tissue defects, and also challenging for restoring and maintaining soft tissue volume and shape, and achieving vascularization and integration. In this study, we fabricated cryogels with mechanical robustness, injectability, and stretchability by using cryopolymerization. The cryogels promoted cell adhesion, proliferation, and adipogenic

Method for increasing nuclear magnetic resonance signals in living biological tissue

International Nuclear Information System (INIS)

Krongrad, A.

1995-01-01

A method of enhancing a magnetic resonance comprising the steps of administering a quantity of a selected magnetic isotope to a living biological tissue at a concentration greater than the naturally occurring concentration of such isotope and detecting magnetic resonance signal from the administered magnetic isotope in the living biological tissue. (author)

Comprehensive comparison of large-scale tissue expression datasets

DEFF Research Database (Denmark)

Santos Delgado, Alberto; Tsafou, Kalliopi; Stolte, Christian

2015-01-01

a comprehensive evaluation of tissue expression data from a variety of experimental techniques and show that these agree surprisingly well with each other and with results from literature curation and text mining. We further found that most datasets support the assumed but not demonstrated distinction between......For tissues to carry out their functions, they rely on the right proteins to be present. Several high-throughput technologies have been used to map out which proteins are expressed in which tissues; however, the data have not previously been systematically compared and integrated. We present......://tissues.jensenlab.org), which makes all the scored and integrated data available through a single user-friendly web interface....

[Connective tissue and inflammation].

Science.gov (United States)

Jakab, Lajos

2014-03-23

The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

Science.gov (United States)

Kim, Myunghoo; Kim, Chang H

2016-10-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats.

Directory of Open Access Journals (Sweden)

Mônica G Corrêa

Full Text Available This study investigated some immunological features by experimental periodontitis (EP and rheumatoid arthritis (RA disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund's adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF and anti-citrullinated protein antibody (ACCPA were measured before the induction of EP (T1 and at 28 days after (T2 by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases.

Framework methodology for increased energy efficiency and renewable feedstock integration in industrial clusters

International Nuclear Information System (INIS)

Hackl, Roman; Harvey, Simon

2013-01-01

Highlights: • Framework methodology for energy efficiency of process plants and total sites. • Identification of suitable biorefinery based on host site future energy systems. • Case study results show large energy savings of site wide heat integration. • Case study on refrigeration systems: 15% shaft work savings potential. • Case study on biorefinery integration: utility savings potential of up to 37%. - Abstract: Energy intensive industries, such as the bulk chemical industry, are facing major challenges and adopting strategies to face these challenges. This paper investigates options for clusters of chemical process plants to decrease their energy and emission footprints. There is a wide range of technologies and process integration opportunities available for achieving these objectives, including (i) decreasing fossil fuel and electricity demand by increasing heat integration within individual processes and across the total cluster site; (ii) replacing fossil feedstocks with renewables and biorefinery integration with the existing cluster; (iii) increasing external utilization of excess process heat wherever possible. This paper presents an overview of the use of process integration methods for development of chemical clusters. Process simulation, pinch analysis, Total Site Analysis (TSA) and exergy concepts are combined in a holistic approach to identify opportunities to improve energy efficiency and integrate renewable feedstocks within such clusters. The methodology is illustrated by application to a chemical cluster in Stenungsund on the West Coast of Sweden consisting of five different companies operating six process plants. The paper emphasizes and quantifies the gains that can be made by adopting a total site approach for targeting energy efficiency measures within the cluster and when investigating integration opportunities for advanced biorefinery concepts compared to restricting the analysis to the individual constituent plants. The

US of tissue banking and transplantation in North America

International Nuclear Information System (INIS)

Strong, M.; Moogk, M.

1999-01-01

Tissue banking in North America began as surgical bone banking in individual hospitals and progressed to recovery of cadaveric tissues, initially by the United States Navy Tissue Bank and more recently to regional tissue banks throughout North America. The American Association of Tissue Banks was established in 1976 to develop standards for tissue banking and the eventual inspection and accreditation of tissue banks. The gathering of statistics of tissue banking practices was first undertaken in 1992, from accredited tissue banks. The most recent statistics were compiled in 1997 and will be reported at this conference.There are currently 63 accredited tissue banks in North America, 60 in the United States and three in Canada. Overall, tissue donation has increased by 48% during this 5 year reporting time. During the same period, the number of living surgical bone donors has decreased from nearly 3,000 to less than 500. This impact is largely due to the new regulations that have been implemented by the Food and Drug Administration (FDA). There were over 340,000 bone grafts distributed in 1996, an increase of 20% over 1992, 33% were not sterilized, 21% were sterilized using irradiation, and 45% were demineralized. Only 1% were processed using ethylene oxide as a sterilant, a decrease from 15% in 1992. The primary mode of preservation and storage is freeze-drying with 90% of the tissues falling into this category and the rest being frozen. The second largest number of grafts distributed were skin grafts. Total tissue grafts distributed including cornea was 445,417. In January 1998, the FDA Final Rule regarding regulation of tissue banking became effective. The elements of that Final Rule and new tissue banking rules the FDA has proposed will be discussed along with regulations recently published by the Health and Human Services Department relative to organ and tissue donor referrals. Tissue Banking in North America continues to evolve and has become more and more

Tissue-electronics interfaces: from implantable devices to engineered tissues

Science.gov (United States)

Feiner, Ron; Dvir, Tal

2018-01-01

Biomedical electronic devices are interfaced with the human body to extract precise medical data and to interfere with tissue function by providing electrical stimuli. In this Review, we outline physiologically and pathologically relevant tissue properties and processes that are important for designing implantable electronic devices. We summarize design principles for flexible and stretchable electronics that adapt to the mechanics of soft tissues, such as those including conducting polymers, liquid metal alloys, metallic buckling and meandering architectures. We further discuss technologies for inserting devices into the body in a minimally invasive manner and for eliminating them without further intervention. Finally, we introduce the concept of integrating electronic devices with biomaterials and cells, and we envision how such technologies may lead to the development of bionic organs for regenerative medicine.

The Chernobyl Tissue Bank: integrating research on radiation-induced thyroid cancer.

Science.gov (United States)

Thomas, G A

2012-03-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. Cancer is a complicated disease and it is unclear whether the mechanism by which radiation gives rise to cancer differs from that involved in the generation of cancers of the same type by other environmental stimuli. The Chernobyl Tissue Bank was established in response to the scientific interest in studying the molecular biology of thyroid cancer after Chernobyl to address this question. The project is supported by the governments of Ukraine and Russia, and financially supported (in total around US$3 million) by the European Commission, the National Cancer Institute of the USA and the Sasakawa Memorial Health Foundation of Japan. The project began collecting a variety of biological samples from patients on 1 October 1988, and has supplied material to 23 research projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue Bank has facilitated co-operation between these research projects and the combination of clinical and research data provides a paradigm for cancer research in the molecular biological age.

The Chernobyl Tissue Bank: integrating research on radiation-induced thyroid cancer

International Nuclear Information System (INIS)

Thomas, G A

2012-01-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. Cancer is a complicated disease and it is unclear whether the mechanism by which radiation gives rise to cancer differs from that involved in the generation of cancers of the same type by other environmental stimuli. The Chernobyl Tissue Bank was established in response to the scientific interest in studying the molecular biology of thyroid cancer after Chernobyl to address this question. The project is supported by the governments of Ukraine and Russia, and financially supported (in total around US$3 million) by the European Commission, the National Cancer Institute of the USA and the Sasakawa Memorial Health Foundation of Japan. The project began collecting a variety of biological samples from patients on 1 October 1988, and has supplied material to 23 research projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue Bank has facilitated co-operation between these research projects and the combination of clinical and research data provides a paradigm for cancer research in the molecular biological age. (note)

Increase in tumor control and normal tissue complication probabilities in advanced head-and-neck cancer for dose-escalated intensity-modulated photon and proton therapy

Directory of Open Access Journals (Sweden)

Annika eJakobi

2015-11-01

Full Text Available Introduction:Presently used radio-chemotherapy regimens result in moderate local control rates for patients with advanced head and neck squamous cell carcinoma (HNSCC. Dose escalation (DE may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT or proton therapy (IMPT.Materials and Methods:For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 Gy and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP and normal tissue complication probabilities (NTCP.Results:An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences < 2% in all models, except for the risk of aspiration, which increased on average by 8% and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. Conclusions:Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose response description, e.g., ulcers.

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

Science.gov (United States)

Babur, Betul Kul; Kabiri, Mahboubeh; Klein, Travis Jacob; Lott, William B; Doran, Michael Robert

2015-01-01

We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

3D bioprinting and nanotechnology in tissue engineering and regenerative medicine

CERN Document Server

Zhang, Lijie Grace; Leong, Kam

2015-01-01

3D Bioprinting and Nanotechnology in Tissue Engineering provides an in depth introduction to these two technologies and their industrial applications. Stem cells in tissue regeneration are covered, along with nanobiomaterials. Commercialization, legal and regulatory considerations are also discussed in order to help you translate nanotechnology and 3D printing-based products to the marketplace and the clinic. Dr. Zhang's and Dr. Fishers' team of expert contributors have pooled their expertise in order to provide a summary of the suitability, sustainability and limitations of each technique for each specific application. The increasing availability and decreasing costs of nanotechnologies and 3D printing technologies are driving their use to meet medical needs, and this book provides an overview of these technologies and their integration. It shows how nanotechnology can increase the clinical efficiency of prosthesis or artificial tissues made by bioprinting or biofabrication. Students and professionals will r...

The materials used in bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Tereshchenko, V. P., E-mail: tervp@ngs.ru; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M. [Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk (Russian Federation)

2015-11-17

Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

Bone Tissue Collagen Maturity and Mineral Content Increase With Sustained Hyperglycemia in the KK-Ay Murine Model of Type 2 Diabetes.

Science.gov (United States)

Hunt, Heather B; Pearl, Jared C; Diaz, David R; King, Karen B; Donnelly, Eve

2018-05-01

Type 2 diabetes mellitus (T2DM) increases fracture risk for a given bone mineral density (BMD), which suggests that T2DM changes bone tissue properties independently of bone mass. In this study, we assessed the effects of hyperglycemia on bone tissue compositional properties, enzymatic collagen crosslinks, and advanced glycation end-products (AGEs) in the KK-Ay murine model of T2DM using Fourier transform infrared (FTIR) imaging and high-performance liquid chromatography (HPLC). Compared to KK-aa littermate controls (n = 8), proximal femoral bone tissue of KK-Ay mice (n = 14) exhibited increased collagen maturity, increased mineral content, and less heterogeneous mineral properties. AGE accumulation assessed by the concentration of pentosidine, as well as the concentrations of the nonenzymatic crosslinks hydroxylysylpyridinoline (HP) and lysyl pyridinoline (LP), did not differ in the proximal femurs of KK-Ay mice compared to controls. The observed differences in tissue-level compositional properties in the KK-Ay mice are consistent with bone that is older and echo observations of reduced remodeling in T2DM. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Fundamentals of bladder tissue engineering | Mahfouz | African ...

African Journals Online (AJOL)

Fundamentals of bladder tissue engineering. ... could affect the bladder and lead to eventual loss of its integrity, with the need for replacement or repair. ... Tissue engineering relies upon three essential pillars; the scaffold, the cells seeded on ...

FINANCIAL-ECONOMIC INTEGRATION AS A TOOL FOR INCREASE OF INVESTMENT SUPPORT OF AGRO-INDUSTRIAL PRODUCTION

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E. R. Zakirova

2017-01-01

Full Text Available The article reveals the essence and systematizes the advantages of financial and economic integration. In the agro-industrial complex, this kind of integration contributes to attracting investments and reducing risks for investors, increasing the competitiveness and economic growth of the region. The relevance of the study is due to insufficiently researched remains many aspects of the functioning of integrated business systems in relation to individual industries, in particular, to agroindustrial production. The aim of the article is to study theoretical approaches to the essence of financial and economic integration in agro-industrial production and analyze the mechanism of investment support for the Russian agrarian sector, taking into account financial and economic integration. In preparing the article, general scientific methods of research were used: analysis and synthesis, generalization, comparison, classification. Results. The interpretation of financial and economic integration in Russian and foreign scientific publications is generalized. Distinctions of financial and economic integration are distinguished from other economic processes. The advantages of financial and economic integration for the economy and business entities are systematized. The importance of integrating industries and business entities in the agro-industrial complex, which is of strategic importance for ensuring Russia's food security, was noted. The branch structure of the agro-industrial complex is analyzed. The scheme of the integrated financial and economic mechanism in the agroindustrial complex is described. The importance of an optimal balance between cooperation and integration was underscored. The insufficiency of the methodological level of studies of agro-industrial integration is grounded. The components of the effect of financial and economic integration are considered. Positive effects of integration processes in the agroindustrial complex are

iTRAQ-Based Proteomics Analysis and Network Integration for Kernel Tissue Development in Maize

Science.gov (United States)

Dong, Yongbin; Wang, Qilei; Du, Chunguang; Xiong, Wenwei; Li, Xinyu; Zhu, Sailan; Li, Yuling

2017-01-01

Grain weight is one of the most important yield components and a developmentally complex structure comprised of two major compartments (endosperm and pericarp) in maize (Zea mays L.), however, very little is known concerning the coordinated accumulation of the numerous proteins involved. Herein, we used isobaric tags for relative and absolute quantitation (iTRAQ)-based comparative proteomic method to analyze the characteristics of dynamic proteomics for endosperm and pericarp during grain development. Totally, 9539 proteins were identified for both components at four development stages, among which 1401 proteins were non-redundant, 232 proteins were specific in pericarp and 153 proteins were specific in endosperm. A functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the tissue development. Three and 76 proteins involved in 49 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were integrated for the specific endosperm and pericarp proteins, respectively, reflecting their complex metabolic interactions. In addition, four proteins with important functions and different expression levels were chosen for gene cloning and expression analysis. Different concordance between mRNA level and the protein abundance was observed across different proteins, stages, and tissues as in previous research. These results could provide useful message for understanding the developmental mechanisms in grain development in maize. PMID:28837076

Increased of the capacity integral bridge with reinforced concrete beams for single span

Science.gov (United States)

Setiati, N. Retno

2017-11-01

Sinapeul Bridge that was built in 2012 in Sumedang is a bridge type using a full integral system. The prototype of integral bridge with reinforced concrete girder and single span 20 meters until this year had decreased capacity. The bridge was conducted monitoring of strain that occurs in the abutment in 2014. Monitoring results show that based on the data recorded, the maximum strain occurs at the abutment on the location of the integration of the girder of 10.59 x 10-6 tensile stress of 0.25 MPa (smaller than 150 x 10-6) with 3 MPa tensile stress as limit the occurrence of cracks in concrete. Sinapeul bridge abutment with integral system is still in the intact condition. Deflection of the bridge at the time of load test is 1.31 mm. But this time the bridge has decreased exceeded permission deflection (deflection occurred by 40 mm). Besides that, the slab also suffered destruction. One cause of the destruction of the bridge slab is the load factor. It is necessary for required effort to increase the capacity of the integral bridge with retrofitting. Retrofitting method also aims to restore the capacity of the bridge structure due to deterioration. Retrofitting can be done by shortening of the span or using Fibre Reinforced Polymer (FRC). Based on the results obtained by analysis of that method of retrofitting with Fibre Reinforced Polymer (FRC) is more simple and effective. Retrofitting with FRP can increase the capacity of the shear and bending moment becomes 41% of the existing bridge. Retrofitting with FRP method does not change the integral system on the bridge Sinapeul become conventional bridges.

Novel scalable silicone elastomer and poly(2-hydroxyethyl methacrylate) (PHEMA) composite materials for tissue engineering and drug delivery applications

DEFF Research Database (Denmark)

Mohanty, Soumyaranjan; Hemmingsen, Mette; Wojcik, Magdalena

2013-01-01

material with increased hydrophilicity in regard to virgin silicone elastomer, making it suitable as a scaffold for tissue engineering and with the concomitant possibility for delivering drug from the scaffold to the tissue. Interpenetrating polymer networks (IPNs) of silicone elastomer and PHEMA......In recent years hydrogels have received increasing attention as potential materials for applications in regenerative medicine. They can be used for scaffold materials providing structural integrity to tissue constructs, for controlled delivery of drugs and proteins to cell and tissues......, and for support materials in tissue growth. However, the real challenge is to obtain sufficiently good mechanical properties of the hydrogel. The present study shows the combination of two normally non-compatible materials, silicone elastomer and poly(2-hydroxyethyl methacrylate) (PHEMA), into a novel composite...

Vertical integration increases opportunities for patient flow.

Science.gov (United States)

Radoccia, R A; Benvenuto, J A; Blancett, L

1991-08-01

New sources of patients will become more and more important in the next decade as hospitals continue to feel the squeeze of a competitive marketplace. Vertical integration, a distribution tool used in other industries, will be a significant tool for health care administrators. In the following article, the authors explain the vertical integration model that shows promise for other institutions.

Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs

International Nuclear Information System (INIS)

Horton, J.W.

1987-01-01

An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h or hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace [ 14 C]inulin, values (ml H 2 O/g dry wt) for control nonshocked myocardial slices were 4.03 /plus minus/ 0.11 (SE) for total water, 2.16 /plus minus/ 0.07 for inulin impermeable space, and 1.76 /plus minus/ 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation. After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo

Tissue Equivalents Based on Cell-Seeded Biodegradable Microfluidic Constructs

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Sarah L. Tao

2010-03-01

Full Text Available One of the principal challenges in the field of tissue engineering and regenerative medicine is the formation of functional microvascular networks capable of sustaining tissue constructs. Complex tissues and vital organs require a means to support oxygen and nutrient transport during the development of constructs both prior to and after host integration, and current approaches have not demonstrated robust solutions to this challenge. Here, we present a technology platform encompassing the design, construction, cell seeding and functional evaluation of tissue equivalents for wound healing and other clinical applications. These tissue equivalents are comprised of biodegradable microfluidic scaffolds lined with microvascular cells and designed to replicate microenvironmental cues necessary to generate and sustain cell populations to replace dermal and/or epidermal tissues lost due to trauma or disease. Initial results demonstrate that these biodegradable microfluidic devices promote cell adherence and support basic cell functions. These systems represent a promising pathway towards highly integrated three-dimensional engineered tissue constructs for a wide range of clinical applications.

Development of multilayer constructs for tissue engineering

NARCIS (Netherlands)

Bettahalli, N. M. S.; Groen, N.; Steg, H.; Unadkat, H.; de Boer, J.; van Blitterswijk, C. A.; Wessling, M.; Stamatialis, D.

The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

Development of multilayer constructs for tissue engineering

NARCIS (Netherlands)

Bettahalli Narasimha, M.S.; Groen, N.; Steg, H.; Unadkat, H.V.; de Boer, Jan; van Blitterswijk, Clemens; Wessling, Matthias; Stamatialis, Dimitrios

2014-01-01

The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

Science.gov (United States)

Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

2010-08-24

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

Endothelial dysfunction in high fructose containing diet fed rats: Increased nitric oxide and decreased endothelin-1 levels in liver tissue

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Zeki Arı

2010-09-01

Full Text Available Objectives: Dietary high fructose consumption which is closely associated with endothelial dysfunction via insulin re-sistance has recently increased in developed countries. Insulin resistance has a promoter effect on many metabolic disorders such as syndrome X, polycystic ovary syndrome, Type 2 diabetes mellitus etc. Our aim in this study is to understand the impact of increased fructose intake on metabolisms of glucose, insulin and endothelial dysfunction by measuring nitric oxide (NO and endothelin-1 (ET-1 levels in hepatic tissue which is crucial in fructose metabolism.Materials and Methods: We designed an animal study to understand increased fructose intake on hepatic endothe-lium. Twenty adult male albino rats were divided into two groups; the study group (group 1, n=10 received isocaloric fructose enriched diet (fructose-fed rats, containing 18.3% protein, 60.3% fructose and 5.2% fat while the control group received purified regular chow (group 2, n=10 for 2 weeks. After feeding period, blood and hepatic tissue samples were collected and glucose, insulin, NO and ET-1 levels were analysed.Results: We found increased fasting glucose and insulin levels and impaired glucose tolerance in fructose fed rats. Higher NO and lower ET–1 levels were also detected in hepatic tissue samples of the group 1.Conclusion: Increased fructose consumption has deleterious effects on glucose tolerance, insulin resistance and may cause to endothelial dysfunction.

Increasing quality and managing complexity in neuroinformatics software development with continuous integration

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Yury V. Zaytsev

2013-01-01

Full Text Available High quality neuroscience research requires accurate, reliable and well maintained neuroinformatics applications. As software projects become larger, offering more functionality and developing a denser web of interdependence between their component parts, we need more sophisticated methods to manage their complexity. If complexity is allowed to get out of hand, either the quality of the software or the speed of development suffer, and in many cases both. To address this issue, here we develop a scalable, low-cost and open source solution for continuous integration (CI, a technique which ensures the quality of changes to the code base during the development procedure, rather than relying on a pre-release integration phase. We demonstrate that a CI based workflow, due to rapid feedback about code integration problems and tracking of code health measures, enabled substantial increases in productivity for a major neuroinformatics project and additional benefits for three further projects. Beyond the scope of the current study, we identify multiple areas in which CI can be employed to further increase the quality of neuroinformatics projects by improving development practices and incorporating appropriate development tools. Finally, we discuss what measures can be taken to lower the barrier for developers of neuroinformatics applications to adopt this useful technique.

Increasing quality and managing complexity in neuroinformatics software development with continuous integration.

Science.gov (United States)

Zaytsev, Yury V; Morrison, Abigail

2012-01-01

High quality neuroscience research requires accurate, reliable and well maintained neuroinformatics applications. As software projects become larger, offering more functionality and developing a denser web of interdependence between their component parts, we need more sophisticated methods to manage their complexity. If complexity is allowed to get out of hand, either the quality of the software or the speed of development suffer, and in many cases both. To address this issue, here we develop a scalable, low-cost and open source solution for continuous integration (CI), a technique which ensures the quality of changes to the code base during the development procedure, rather than relying on a pre-release integration phase. We demonstrate that a CI-based workflow, due to rapid feedback about code integration problems and tracking of code health measures, enabled substantial increases in productivity for a major neuroinformatics project and additional benefits for three further projects. Beyond the scope of the current study, we identify multiple areas in which CI can be employed to further increase the quality of neuroinformatics projects by improving development practices and incorporating appropriate development tools. Finally, we discuss what measures can be taken to lower the barrier for developers of neuroinformatics applications to adopt this useful technique.

Increase of Efficiency of Enterprise Financial Control through Application of the Integration Process

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Hulay Ivanna O.

2014-02-01

Full Text Available The article analyses the modern state of an enterprise as of a socio-economic system, which consists of interconnected elements. The article states that each of these elements could be an individual structural subdivision of an enterprise. Establishment and maintenance of close links between the elements ensures increase of controllability of an enterprise and, at the same time, increase of economic indicators of enterprise activity. The article justifies urgency of integration, which should be realised not only at the level of an enterprise, but also at the level of each structural subdivision. It specifies selection of methods and approaches to the process of integration and shows that it is different for each enterprise and depends on goals and tasks, which have to be achieved in the result of realisation of each individual project. The article offers to use the process of integration at an enterprise, the goal of which is achievement of the system effect through unification of financial, material, information and human capital of an enterprise.

Integral dose conservation in radiotherapy

International Nuclear Information System (INIS)

Reese, Adam S.; Das, Shiva K.; Curle, Charles; Marks, Lawrence B.

2009-01-01

Treatment planners frequently modify beam arrangements and use IMRT to improve target dose coverage while satisfying dose constraints on normal tissues. The authors herein analyze the limitations of these strategies and quantitatively assess the extent to which dose can be redistributed within the patient volume. Specifically, the authors hypothesize that (1) the normalized integral dose is constant across concentric shells of normal tissue surrounding the target (normalized to the average integral shell dose), (2) the normalized integral shell dose is constant across plans with different numbers and orientations of beams, and (3) the normalized integral shell dose is constant across plans when reducing the dose to a critical structure. Using the images of seven patients previously irradiated for cancer of brain or prostate cancer and one idealized scenario, competing three-dimensional conformal and IMRT plans were generated using different beam configurations. Within a given plan and for competing plans with a constant mean target dose, the normalized integral doses within concentric ''shells'' of surrounding normal tissue were quantitatively compared. Within each patient, the normalized integral dose to shells of normal tissue surrounding the target was relatively constant (1). Similarly, for each clinical scenario, the normalized integral dose for a given shell was also relatively constant regardless of the number and orientation of beams (2) or degree of sparing of a critical structure (3). 3D and IMRT planning tools can redistribute, rather than eliminate dose to the surrounding normal tissues (intuitively known by planners). More specifically, dose cannot be moved between shells surrounding the target but only within a shell. This implies that there are limitations in the extent to which a critical structure can be spared based on the location and geometry of the critical structure relative to the target.

Effects of storage temperature on the quantity and integrity of genomic DNA extracted from mice tissues: A comparison of recovery methods

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Huda H. Al-Griw

2017-08-01

Full Text Available Efficient extraction of genomic DNA (gDNA from biological materials found in harsh environments is the first step for successful forensic DNA profiling. This study aimed to evaluate two methods for DNA recovery from animal tissues (livers, muscles, focusing on the best storage temperature for DNA yield in term of quality, quantity, and integrity for use in several downstream molecular techniques. Six male Swiss albino mice were sacrificed, liver and muscle tissues (n=32 were then harvested and stored for one week in different temperatures, -20C, 4C, 25C and 40C. The conditioned animal tissues were used for DNA extraction by Chelex-100 method or NucleoSpin Blood and Tissue kit. The extracted gDNA was visualized on 1.5% agarose gel electrophoresis to determine the quality of gDNA and analysed spectrophotometrically to determine the DNA concentration and the purity. Both methods, Chelex-100 and NucleoSpin Blood and Tissue kit found to be appropriate for yielding high quantity of gDNA, with the Chelex100 method yielding a greater quantity (P < 0.045 than the kit. At -20C, 4C, and 25C temperatures, the concentration of DNA yield was numerically lower than at 40C. The NucleoSpin Blood and Tissue kit produced a higher (P=0.031 purity product than the Chelex-100 method, particularly for muscle tissues. The Chelex-100 method is cheap, fast, effective, and is a crucial tool for yielding DNA from animal tissues (livers, muscles exposed to harsh environment with little limitations.

INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE

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Sedat IŞIKAY

2015-12-01

Full Text Available Background - Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. Objective - In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. Methods - A total of 175 children with the diagnosis of celiac disease (study group and 99 age- and sex-matched healthy children as controls (control group were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. Results - Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3% of newly diagnosed and in 2 (1.5% of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0% of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively. Conclusion - We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients

Integrating viscoelastic mass spring dampers into position-based dynamics to simulate soft tissue deformation in real time.

Science.gov (United States)

Xu, Lang; Lu, Yuhua; Liu, Qian

2018-02-01

We propose a novel method to simulate soft tissue deformation for virtual surgery applications. The method considers the mechanical properties of soft tissue, such as its viscoelasticity, nonlinearity and incompressibility; its speed, stability and accuracy also meet the requirements for a surgery simulator. Modifying the traditional equation for mass spring dampers (MSD) introduces nonlinearity and viscoelasticity into the calculation of elastic force. Then, the elastic force is used in the constraint projection step for naturally reducing constraint potential. The node position is enforced by the combined spring force and constraint conservative force through Newton's second law. We conduct a comparison study of conventional MSD and position-based dynamics for our new integrating method. Our approach enables stable, fast and large step simulation by freely controlling visual effects based on nonlinearity, viscoelasticity and incompressibility. We implement a laparoscopic cholecystectomy simulator to demonstrate the practicality of our method, in which liver and gallbladder deformation can be simulated in real time. Our method is an appropriate choice for the development of real-time virtual surgery applications.

In vivo outcomes of tissue-engineered osteochondral grafts.

Science.gov (United States)

Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

2010-04-01

Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum.

Science.gov (United States)

Gorgels, Theo G M F; Waarsing, Jan H; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J; Bergen, Arthur A B

2011-11-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6 (-/-) mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6 (-/-) and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6 ( -/- ) mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6 (-/-) mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K.

Historical nitrogen content of bryophyte tissue as an indicator of increased nitrogen deposition in the Cape Metropolitan Area, South Africa

International Nuclear Information System (INIS)

Wilson, D.; Stock, W.D.; Hedderson, T.

2009-01-01

Information on changes in precipitation chemistry in the rapidly expanding Cape Metropolitan Area (CMA) of South Africa is scarce. To obtain a long-term record of N deposition we investigated changes in moss foliar N, C:N ratios and nitrogen isotope values that might reflect precipitation chemistry. Tissue from 9 species was obtained from herbarium specimens collected between 1875 and 2000 while field samples were collected in 2001/2002. There is a strong trend of increasing foliar N content in all mosses collected over the past century (1.32-1.69 %N). Differences exist between ectohydric mosses which have higher foliar N than the mixohydric group. C:N ratios declined while foliar δ 15 N values showed no distinct pattern. From relationships between moss tissue N and N deposition rates we estimated an increase of 6-13 kg N ha -1 a -1 since 1950. Enhanced N deposition rates of this magnitude could lead to biodiversity losses in native ecosystems. - This study of bryophyte tissue nutrient contents shows a historical increase in N deposition rates to the low nutrient adapted plant biodiversity hotspot in the Western Cape, South Africa

Historical nitrogen content of bryophyte tissue as an indicator of increased nitrogen deposition in the Cape Metropolitan Area, South Africa

Energy Technology Data Exchange (ETDEWEB)

Wilson, D. [Botany Department, University of Cape Town, Rondebosch 7701 (South Africa); Stock, W.D. [Botany Department, University of Cape Town, Rondebosch 7701 (South Africa); Centre for Ecosystem Management, School of Natural Sciences, Edith Cowan University, 100 Joondalup Drive, Joondalup, Perth, WA 6027 (Australia)], E-mail: w.stock@ecu.edu.au; Hedderson, T. [Botany Department, University of Cape Town, Rondebosch 7701 (South Africa)

2009-03-15

Information on changes in precipitation chemistry in the rapidly expanding Cape Metropolitan Area (CMA) of South Africa is scarce. To obtain a long-term record of N deposition we investigated changes in moss foliar N, C:N ratios and nitrogen isotope values that might reflect precipitation chemistry. Tissue from 9 species was obtained from herbarium specimens collected between 1875 and 2000 while field samples were collected in 2001/2002. There is a strong trend of increasing foliar N content in all mosses collected over the past century (1.32-1.69 %N). Differences exist between ectohydric mosses which have higher foliar N than the mixohydric group. C:N ratios declined while foliar {delta}{sup 15}N values showed no distinct pattern. From relationships between moss tissue N and N deposition rates we estimated an increase of 6-13 kg N ha{sup -1} a{sup -1} since 1950. Enhanced N deposition rates of this magnitude could lead to biodiversity losses in native ecosystems. - This study of bryophyte tissue nutrient contents shows a historical increase in N deposition rates to the low nutrient adapted plant biodiversity hotspot in the Western Cape, South Africa.

Tissue irradiator

International Nuclear Information System (INIS)

Hungate, F.P.; Riemath, W.F.; Bunnell, L.R.

1975-01-01

A tissue irradiator is provided for the in-vivo irradiation of body tissue. The irradiator comprises a radiation source material contained and completely encapsulated within vitreous carbon. An embodiment for use as an in-vivo blood irradiator comprises a cylindrical body having an axial bore therethrough. A radioisotope is contained within a first portion of vitreous carbon cylindrically surrounding the axial bore, and a containment portion of vitreous carbon surrounds the radioisotope containing portion, the two portions of vitreous carbon being integrally formed as a single unit. Connecting means are provided at each end of the cylindrical body to permit connections to blood-carrying vessels and to provide for passage of blood through the bore. In a preferred embodiment, the radioisotope is thulium-170 which is present in the irradiator in the form of thulium oxide. A method of producing the preferred blood irradiator is also provided, whereby nonradioactive thulium-169 is dispersed within a polyfurfuryl alcohol resin which is carbonized and fired to form the integral vitreous carbon body and the device is activated by neutron bombardment of the thulium-169 to produce the beta-emitting thulium-170

Increased adsorption of histidine-tagged proteins onto tissue culture polystyrene.

Science.gov (United States)

Holmberg, Maria; Hansen, Thomas Steen; Lind, Johan Ulrik; Hjortø, Gertrud Malene

2012-04-01

In this study we compare histidine-tagged and native proteins with regards to adsorption properties. We observe significantly increased adsorption of proteins with an incorporated polyhistidine amino acid motif (HIS-tag) onto tissue culture polystyrene (TCPS) compared to similar proteins without a HIS-tag. The effect is not observed on polystyrene (PS). Adsorption experiments have been performed at physiological pH (7.4) and the effect was only observed for the investigated proteins that have pI values below or around 7.4. Competitive adsorption experiments with imidazole and ethylenediaminetetraacetic acid (EDTA), as well as adsorption performed at different pH and ionic strength indicates that the high adsorption is caused by electrostatic interaction between negatively charged carboxylate groups on the TCPS surface and positively charged histidine residues in the proteins. Pre-adsorption of bovine serum albumin (BSA) does not decrease the adsorption of HIS-tagged proteins onto TCPS. Our findings identify a potential problem in using HIS-tagged signalling molecule in assays with cells cultured on TCPS, since the concentration of the molecule in solution might be affected and this could critically influence the assay outcome. Copyright © 2011 Elsevier B.V. All rights reserved.

Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity.

Science.gov (United States)

Groselj, Blaz; Ruan, Jia-Ling; Scott, Helen; Gorrill, Jessica; Nicholson, Judith; Kelly, Jacqueline; Anbalagan, Selvakumar; Thompson, James; Stratford, Michael R L; Jevons, Sarah J; Hammond, Ester M; Scudamore, Cheryl L; Kerr, Martin; Kiltie, Anne E

2018-02-01

As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitizing agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity severity in intestine and bladder in vivo , using novel radiotherapy techniques on a small animal radiation research platform (SARRP). The effects of panobinostat on in vivo tumor growth delay were evaluated using subcutaneous xenografts in athymic nude mice. Panobinostat concentration levels in xenografts, plasma, and normal tissues were measured in CD1-nude mice. CD1-nude mice were treated with drug/irradiation combinations to assess acute normal tissue effects in small intestine using the intestinal crypt assay, and later effects in small and large intestine at 11 weeks by stool assessment and at 12 weeks by histologic examination. In vitro effects of panobinostat were assessed by qPCR and of panobinostat, TMP195, and mocetinostat by clonogenic assay, and Western blot analysis. Panobinostat resulted in growth delay in RT112 bladder cancer xenografts but did not significantly increase acute (3.75 days) or 12 weeks' normal tissue radiation toxicity. Radiosensitization by panobinostat was effective in hypoxic bladder cancer cells and associated with class I HDAC inhibition, and protein downregulation of HDAC2 and MRE11. Pan-HDAC inhibition is a promising strategy for radiosensitization, but more selective agents may be more useful radiosensitizers clinically, resulting in fewer systemic side effects. Mol Cancer Ther; 17(2); 381-92. ©2017 AACR See all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology." ©2017 American Association for Cancer Research.

Cartilage Integration: Evaluation of the reasons for failure of integration during cartilage repair. A review

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IM Khan

2008-09-01

Full Text Available Articular cartilage is a challenging tissue to reconstruct or replace principally because of its avascular nature; large chondral lesions in the tissue do not spontaneously heal. Where lesions do penetrate the bony subchondral plate, formation of hematomas and the migration of mesenchymal stem cells provide an inferior and transient fibrocartilagenous replacement for hyaline cartilage. To circumvent the poor intrinsic reparative response of articular cartilage several surgical techniques based on tissue transplantation have emerged. One characteristic shared by intrinsic reparative processes and the new surgical therapies is an apparent lack of lateral integration of repair or graft tissue with the host cartilage that can lead to poor prognosis. Many factors have been cited as impeding cartilage:cartilage integration including; chondrocyte cell death, chondrocyte dedifferentiation, the nature of the collagenous and proteoglycan networks that constitute the extracellular matrix, the type of biomaterial scaffold employed in repair and the origin of the cells used to repopulate the defect or lesion. This review addresses the principal intrinsic and extrinsic factors that impede integration and describe how manipulation of these factors using a host of strategies can positively influence cartilage integration.

Meditation is associated with increased brain network integration.

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van Lutterveld, Remko; van Dellen, Edwin; Pal, Prasanta; Yang, Hua; Stam, Cornelis Jan; Brewer, Judson

2017-09-01

This study aims to identify novel quantitative EEG measures associated with mindfulness meditation. As there is some evidence that meditation is associated with higher integration of brain networks, we focused on EEG measures of network integration. Sixteen novice meditators and sixteen experienced meditators participated in the study. Novice meditators performed a basic meditation practice that supported effortless awareness, which is an important quality of experience related to mindfulness practices, while their EEG was recorded. Experienced meditators performed a self-selected meditation practice that supported effortless awareness. Network integration was analyzed with maximum betweenness centrality and leaf fraction (which both correlate positively with network integration) as well as with diameter and average eccentricity (which both correlate negatively with network integration), based on a phase-lag index (PLI) and minimum spanning tree (MST) approach. Differences between groups were assessed using repeated-measures ANOVA for the theta (4-8 Hz), alpha (8-13 Hz) and lower beta (13-20 Hz) frequency bands. Maximum betweenness centrality was significantly higher in experienced meditators than in novices (P = 0.012) in the alpha band. In the same frequency band, leaf fraction showed a trend toward being significantly higher in experienced meditators than in novices (P = 0.056), while diameter and average eccentricity were significantly lower in experienced meditators than in novices (P = 0.016 and P = 0.028 respectively). No significant differences between groups were observed for the theta and beta frequency bands. These results show that alpha band functional network topology is better integrated in experienced meditators than in novice meditators during meditation. This novel finding provides the rationale to investigate the temporal relation between measures of functional connectivity network integration and meditation quality, for example using

Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in patients with occlusive carotid artery disease: increased oxygen transport to hypoperfused brain

DEFF Research Database (Denmark)

Ashkanian, Mahmoud; Gjedde, Albert; Mouridsen, Kim

2009-01-01

to inhaled oxygen (the mixture known as carbogen). In the present study, we measured CBF by positron emission tomography (PET) during inhalation of test gases (O(2), carbogen, and atmospheric air) in healthy volunteers (n = 10) and in patients with occlusive carotid artery disease (n = 6). Statistical...... and Sa(O2) are readily obtained with carbogen, while oxygen increases only Sa(O2). Thus, carbogen improves oxygen transport to brain tissue more efficiently than oxygen alone. Further studies with more subjects are, however, needed to investigate the applicability of carbogen for long-term inhalation...

Does Integration Help Adapt to Climate Change? Case of Increased US Corn Yield Volatility

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Verma, M.; Diffenbaugh, N. S.; Hertel, T. W.

2012-12-01

In absence of of new crop varieties or significant shifts in the geography of corn production, US national corn yields variation could double by the year 2040 as a result of climate change and without adaptation this could lead the variability in US corn prices to quadruple (Diffenbaugh et al. 2012). In addition to climate induced price changes, analysis of recent commodity price spikes suggests that interventionist trade policies are partly to blame. Assuming we cannot much influence the future climate outcome, what policies can we undertake to adapt better? Can we use markets to blunt this edge? Diffenbaugh et al. find that sale of corn- ethanol for use in liquid fuel, when governed by quotas such as US Renewable Fuel Standard (RFS), could make US corn prices even more variable; in contrast the same food-fuel market link (we refer to it as intersectoral link) may well dampen price volatility when the sale of corn to ethanol industry is driven by higher future oil prices. The latter however comes at the cost of exposing corn prices to the greater volatility in oil markets. Similarly intervention in corn trade can make US corn prices less or more volatile by distorting international corn price transmission. A negative US corn yield shock shows that domestic corn supply falls and domestic prices to go up irrespective of whether or not markets are integrated. How much the prices go up depends on how much demand adjusts to accommodate the supply shock. Based on the forgoing analysis, one should expect that demand would adjust more readily when markets are integrated and therefore reduce the resulting price fluctuation. Simulation results confirm this response of corn markets. In terms of relative comparisons however a policy driven intersectoral integration is least effective and prices rise much more. Similarly, a positive world oil price shock makes the US oil imports expensive and with oil being used to produce gasoline blends, it increases the price of gasoline

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

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Betul Kul Babur

Full Text Available We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage

Iodine application increased ascorbic acid content and modified the vascular tissue in opuntia ficus-indica

International Nuclear Information System (INIS)

Osuna, H.T.G.; Morales, R.; Rubio, E.M.; Mendoza, A.B.; Ruvalcaba, R.M

2014-01-01

The objective of this study was to discern the effect of applying both iodide and iodate to Opuntia ficus indica irrigation. The effect of iodate (KIO/sub 3/, 10-4 M) and iodide (KI, 10-4 M) on plant growth, yield and morphology was studied. Experiments were carried in three samples under tunnel conditions. In the last sampling, iodine species (KIO/sub 3/, KI) caused a negative effect in biomass. The amount of ascorbic acid, however, was increased over 51% in both iodine treatments. Phosphorus (0.26%), iron (50 ppm), and magnesium (1402 ppm) increases were also observed with iodate treatment in the first sampling, and increases in potassium (46.8 ppm) were apparent in the second. Iodide treatment increased the amounts of copper (1.02 ppm) and manganese (32.80 ppm) in the first sampling. Iodate treatment modified the number of xylem vessels and increased both the mucilage area and amount of druses. In general this study shows that iodate increases the amount of ascorbic acid and the morphology of the vascular tissue. (author)

Study of temperature increase and optic depth penetration in photo irradiated human tissues

International Nuclear Information System (INIS)

Stolik, Suren; Delgado, Jose A.; Perez, Arllene M.; Anasagasti, Lorenzo

2009-01-01

Optical radiation is widely applied in the treatment and diagnosis of different pathologies. If the power density of the incident light is sufficiently high to induce a significant temperature rise in the irradiated tissue, then it is also needed the knowledge of the thermal properties of the tissue for a complete understanding of the therapeutic effects. The thermal penetration depth of several human tissues has been measured applying the diffusion approximation of the radiative transfer equation for the distribution of optical radiation. The method, the experimental setup and the results are presented and discussed. (Author)

Integrating three-dimensional printing and nanotechnology for musculoskeletal regeneration

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Nowicki, Margaret; Castro, Nathan J.; Rao, Raj; Plesniak, Michael; Zhang, Lijie Grace

2017-09-01

The field of tissue engineering is advancing steadily, partly due to advancements in rapid prototyping technology. Even with increasing focus, successful complex tissue regeneration of vascularized bone, cartilage and the osteochondral interface remains largely illusive. This review examines current three-dimensional printing techniques and their application towards bone, cartilage and osteochondral regeneration. The importance of, and benefit to, nanomaterial integration is also highlighted with recent published examples. Early-stage successes and challenges of recent studies are discussed, with an outlook to future research in the related areas.

Acción fisiopatológica integrada de las hormonas sobre el tejido óseo: Physiopathological integrated action of hormones on the bone tissue

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Julio César Sánchez Cruz

2006-08-01

Full Text Available La estatura definitiva que puede lograr un individuo, así como la adecuada salud e integración de su tejido óseo, dependen en gran medida de su constante interacción con las hormonas, desde la etapa embrionaria hasta los últimos momentos de la vida. Teniendo en cuenta que en los libros de texto la relación entre las hormonas con el hueso solo se describe de forma separada y sin integralidad entre lo fisiológico y lo patológico, se realiza una amplia revisión bibliográfica mediante la unificación de criterios y puntos de vista de diferentes autores, con el objetivo de lograr una comprensión más exacta de las funciones que realizan las hormonas sobre el tejido óseo y tener una visión más integral y razonada de la etiopatogenia de afecciones tales como la osteoporosis, las bajas y altas tallas (de causa endocrina y la craneosinostosis, entre otras. Se obtuvo como resultado un documento que explica, de forma más amena e integral, las acciones fisiopatológicas de las hormonas sobre el tejido óseo de un organismo vivo.The definitive height an individual can reach, as well as the adequate health and integration of his bone tissue depends in a great extent on his constant interaction with hormones from the embrionary stage to the last moments of his life. Taking into consideration that the relation between the hormones and the bone is only described in the textbooks in a separate way and with no integrality between the physiological and the pathological aspect, a wide bibliographic review is made by unifying criteria and points of view of different authors aimed at attaining a more accurate understanding of the functions of the hormones on the bone tissue, and at having a more comprehensive and reasoned vision of the etiopathogenesis of affections such as osteoporosis, short and tall stature (of endocrine cause and craniosinostosis, among others. As a result, it was obtained a document that explained in a clearer and more integral way

Effect of multiple cycles of freeze-thawing on the RNA quality of lung cancer tissues.

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Yu, Keke; Xing, Jie; Zhang, Jie; Zhao, Ruiying; Zhang, Ye; Zhao, Lanxiang

2017-09-01

RNA degradation is a major problem in tissue banking. We explored the effect of thawing flash-frozen biospecimens on the quality and integrity of RNA for genetic testing as well as for other cancer research studies. The histological quality of the frozen tumor sections was evaluated by using hematoxylin and eosin staining. RNA extraction from 60 lung cancer tissue samples subjected to various freeze/thaw cycles was performed using the RNeasy Plus isolation kit. RNA integrity was assessed by using an Agilent bioanalyzer to obtain RNA integrity numbers (RIN). Furthermore, RNA from different groups was used for fluorescence Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) fusion gene mutation to verify whether it can be used for research or clinical testing. Highly variable RIN values were observed among the samples, which showed no correlation with the number of freeze/thaw cycles conducted. However, after 3 freeze/thaw cycles (each thaw event lasted for 10 min), an increasing number of changes in peak intensity in RINs were observed. After 5 freeze/thaw cycles, RNA integrity decreased to approximately 35%. After 3 freeze/thaw cycles, the RNA could still be used for RT-PCR analysis of EML4-ALK fusion gene mutations; whereas those subjected to 5 freeze/thaw cycles could not. Limited (cycles did not adversely affect the quality of RNA extracted from tumor tissues and subsequent RT-PCR analysis. Our data could be utilized in the establishment of a standardized procedure for tissue biospecimen collection and storage.

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise.

Science.gov (United States)

Abu-Farha, Mohamed; Cherian, Preethi; Al-Khairi, Irina; Madhu, Dhanya; Tiss, Ali; Warsam, Samia; Alhubail, Asma; Sriraman, Devarajan; Al-Refaei, Faisal; Abubaker, Jehad

2017-01-01

ANGPTL7 is a member of the Angiopoietin-like (ANGPTL) protein family that is composed of eight proteins (1-8). Increasing evidence is associating ANGPTL proteins to obesity and insulin resistance. The biological role of ANGPTL7 is yet to be understood except for a recently proposed role in the pathophysiology of glaucoma. This study was designed to shed light on the function of ANGPTL7 in obesity and its modulation by physical exercise as well as its potential association with lipid profile. A total of 144 subjects were enrolled in this study and finished three months of physical exercise. The participants were classified based on their BMI, 82 subjects were non-obese and 62 obese. ANGPTL7 levels in plasma and adipose tissue were measured by ELISA, RT-PCR and immunohistochemistry. In this study, we showed that ANGPTL7 level was increased in the plasma of obese subjects (1249.05± 130.39 pg/mL) as compared to non-obese (930.34 ± 87.27 pg/mL) (p-Value = 0.032). ANGPTL7 Gene and protein expression levels in adipose tissue also showed over two fold increase. Physical exercise reduced circulating level of ANGPTL7 in the obese subjects to 740.98± 127.18 pg/mL, (p-Value = 0.007). ANGPTL7 expression in adipose tissue was also reduced after exercise. Finally, ANGPTL7 circulating level showed significant association with TG level in the obese subjects (R2 = 0.183, p-Value = 0.03). In conclusion, our data shows for the first time that obesity increases the level of ANGPTL7 in both plasma and adipose tissue. Increased expression of ANGPTL7 might play a minor role in the regulation of TG level in obese subjects either directly or through interaction with other ANGPTL protein members. Physical exercise reduced the level of ANGPTL7 highlighting the potential for targeting this protein as a therapeutic target for regulating dyslipidemia.

Effects of surface hydrophilicity and microtopography on early stages of soft and hard tissue integration at non-submerged titanium implants: an immunohistochemical study in dogs.

Science.gov (United States)

Schwarz, Frank; Ferrari, Daniel; Herten, Monika; Mihatovic, Ilja; Wieland, Marco; Sager, Martin; Becker, Jürgen

2007-11-01

The aim of the present study was to investigate the effects of surface hydrophilicity and microtopography on soft and hard tissue integration at non-submerged titanium implants. Implantation of conventional sand-blasted large grit and acid-etched (SLA) and chemically modified SLA (modSLA) titanium implants with differently structured transmucosal surfaces (SLA implants: machined [M-SLA] or SLA [SLA-SLA]; modSLA implants: mod acid-etched [modA] [modA-modSLA] or modSLA [modSLA-modSLA]) was performed bilaterally in the upper and lower jaws of 15 beagle dogs. The animals were sacrificed after 1, 4, 7, 14, or 28 days. Tissue reactions were assessed histomorphometrically and immunohistochemically using monoclonal antibodies to transglutaminase II (angiogenesis) and osteocalcin. Although the junctional epithelium commonly was separated from M-SLA and SLA-SLA implants by a gap, the epithelial cells appeared to be in close contact with modA-modSLA surfaces after 14 days of healing. Moreover, modA-modSLA and modSLA-modSLA groups showed a well-vascularized subepithelial connective tissue exhibiting collagen fibers that started to extend and attach partially perpendicular to the implant surface. The highest and statistically significant mean bone-to-implant contact areas were observed in the modA-modSLA and modSLA-modSLA groups at days 7, 14, and 28. Within the limits of this study, it may be concluded that soft and hard tissue integration was influenced mainly by surface hydrophilicity rather than by microtopography.

Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

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Lu, Helen H.; Thomopoulos, Stavros

2014-01-01

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

Science.gov (United States)

Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

2012-01-01

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response.

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Martha Lappas

Full Text Available Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3 plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM. Thus, the aims of this study were (i to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.

Controlled destruction and temperature distributions in biological tissues subjected to monoactive electrocoagulation.

Science.gov (United States)

Erez, A; Shitzer, A

1980-02-01

An analysis of the temperature fields developed in a biological tissue undergoing a monoactive electrical coagulating process is presented, including thermal recovery following prolonged heating. The analysis is performed for the passage of alternating current and assumes a homogeneous and isotropic tissue model which is uniformly perfused by blood at arterial temperature. Solution for the one-dimensional spherical geometry is obtained by a Laplace transform and numerical integrations. Results obtained indicate the major role which blood perfusion plays in determining the effects of the coagulating process; tissue temperatures and depth of destruction are drastically reduced as blood perfusion increases. Metabolic heat generation rate is found to have negligible effects on tissue temperatures whereas electrode thermal inertia affects temperature levels appreciably. However, electrodes employed in practice would have a low thermal inertia which might be regarded as zero for all practical purposes. It is also found that the depth of tissue destruction is almost directly proportional to the electrical power and duration of application. To avoid excessively high temperatures and charring, it would be advantageous to reduce power and increase the time of application. Results of this study should be regarded as a first approximation to the rather complex phenomena associated with electrocoagulation. They may, nevertheless, serve as preliminary guidelines to practicing surgeons applying this technique.

Vascular Tissue Engineering: Effects of Integrating Collagen into a PCL Based Nanofiber Material

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Ulf Bertram

2017-01-01

Full Text Available The engineering of vascular grafts is a growing field in regenerative medicine. Although numerous attempts have been made, the current vascular grafts made of polyurethane (PU, Dacron®, or Teflon® still display unsatisfying results. Electrospinning of biopolymers and native proteins has been in the focus of research to imitate the extracellular matrix (ECM of vessels to produce a small caliber, off-the-shelf tissue engineered vascular graft (TEVG as a substitute for poorly performing PU, Dacron, or Teflon prostheses. Blended poly-ε-caprolactone (PCL/collagen grafts have shown promising results regarding biomechanical and cell supporting features. In order to find a suitable PCL/collagen blend, we fabricated plane electrospun PCL scaffolds using various collagen type I concentrations ranging from 5% to 75%. We analyzed biocompatibility and morphological aspects in vitro. Our results show beneficial features of collagen I integration regarding cell viability and functionality, but also adverse effects like the loss of a confluent monolayer at high concentrations of collagen. Furthermore, electrospun PCL scaffolds containing 25% collagen I seem to be ideal for engineering vascular grafts.

Tissue engineering

CERN Document Server

Fisher, John P; Bronzino, Joseph D

2007-01-01

Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice.

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Danny Gauvreau

Full Text Available BACKGROUND: Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP, and C5a, involved in innate immunity. AIM: We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl and C5L2 knock-out (C5L2(-/- mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO conditions. RESULTS: In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold both over time and with DIO. By contrast, in C5L2(-/-, there was no change in C5aR in WAT. C5L2(-/- mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro- vs M2 (anti-inflammatory macrophage proportion was unchanged but C5L2(-/- adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2(-/- mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2(-/- mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance. CONCLUSION: Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities.

Intra-population variability of ocean acidification impacts on the physiology of Baltic blue mussels (Mytilus edulis): integrating tissue and organism response.

Science.gov (United States)

Stapp, L S; Thomsen, J; Schade, H; Bock, C; Melzner, F; Pörtner, H O; Lannig, G

2017-05-01

Increased maintenance costs at cellular, and consequently organism level, are thought to be involved in shaping the sensitivity of marine calcifiers to ocean acidification (OA). Yet, knowledge of the capacity of marine calcifiers to undergo metabolic adaptation is sparse. In Kiel Fjord, blue mussels thrive despite periodically high seawater PCO 2 , making this population interesting for studying metabolic adaptation under OA. Consequently, we conducted a multi-generation experiment and compared physiological responses of F1 mussels from 'tolerant' and 'sensitive' families exposed to OA for 1 year. Family classifications were based on larval survival; tolerant families settled at all PCO 2 levels (700, 1120, 2400 µatm) while sensitive families did not settle at the highest PCO 2 (≥99.8% mortality). We found similar filtration rates between family types at the control and intermediate PCO 2 level. However, at 2400 µatm, filtration and metabolic scope of gill tissue decreased in tolerant families, indicating functional limitations at the tissue level. Routine metabolic rates (RMR) and summed tissue respiration (gill and outer mantle tissue) of tolerant families were increased at intermediate PCO 2 , indicating elevated cellular homeostatic costs in various tissues. By contrast, OA did not affect tissue and routine metabolism of sensitive families. However, tolerant mussels were characterised by lower RMR at control PCO 2 than sensitive families, which had variable RMR. This might provide the energetic scope to cover increased energetic demands under OA, highlighting the importance of analysing intra-population variability. The mechanisms shaping such difference in RMR and scope, and thus species' adaptation potential, remain to be identified.

The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

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Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

1985-01-01

The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

The use of microtechnology and nanotechnology in fabricating vascularized tissues.

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Obregón, Raquel; Ramón-Azcón, Javier; Ahadian, Samad; Shiku, Hitoshi; Bae, Hojae; Ramalingam, Murugan; Matsue, Tomokazu

2014-01-01

Tissue engineering (TE) is a multidisciplinary research area that combines medicine, biology, and material science. In recent decades, microtechnology and nanotechnology have also been gradually integrated into this field and have become essential components of TE research. Tissues and complex organs in the body depend on a branched blood vessel system. One of the main objectives for TE researchers is to replicate this vessel system and obtain functional vascularized structures within engineered tissues or organs. With the help of new nanotechnology and microtechnology, significant progress has been made. Achievements include the design of nanoscale-level scaffolds with new functionalities, development of integrated and rapid nanotechnology methods for biofabrication of vascular tissues, discovery of new composite materials to direct differentiation of stem and inducible pluripotent stem cells into the vascular phenotype. Although numerous challenges to replicating vascularized tissue for clinical uses remain, the combination of these new advances has yielded new tools for producing functional vascular tissues in the near future.

Integrated CLOS and PN Guidance for Increased Effectiveness of Surface to Air Missiles

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Binte Fatima Tuz ZAHRA

2017-06-01

Full Text Available In this paper, a novel approach has been presented to integrate command to line-of-sight (CLOS guidance and proportional navigation (PN guidance in order to reduce miss distance and to increase the effectiveness of surface to air missiles. Initially a comparison of command to line-of-sight guidance and proportional navigation has been presented. Miss distance, variation of angle-of-attack, normal and lateral accelerations and error of missile flight path from direct line-of-sight have been used as noteworthy criteria for comparison of the two guidance laws. Following this comparison a new approach has been proposed for determining the most suitable guidance gains in order to minimize miss distance and improve accuracy of the missile in delivering the warhead, while using CLOS guidance. This proposed technique is based on constrained nonlinear minimization to optimize the guidance gains. CLOS guidance has a further limitation of significant increase in normal and lateral acceleration demands during the terminal phase of missile flight. Furthermore, at large elevation angles, the required angle-of-attack during the terminal phase increases beyond design specifications. Subsequently, a missile with optical sensors only and following just the CLOS guidance has less likelihood to hit high speed targets beyond 45º in elevation plane. A novel approach has thus been proposed to overcome such limitations of CLOS-only guidance for surface to air missiles. In this approach, an integrated guidance algorithm has been proposed whereby the initial guidance law during rocket motor burnout phase remains CLOS, whereas immediately after this phase, the guidance law is automatically switched to PN guidance. This integrated approach has not only resulted in slight increase in range of the missile but also has significantly improved its likelihood to hit targets beyond 30 degrees in elevation plane, thus successfully overcoming various limitations of CLOS

Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs.

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Colosi, Cristina; Costantini, Marco; Barbetta, Andrea; Dentini, Mariella

2017-01-01

3D bioprinting is an emerging field that can be described as a robotic additive biofabrication technology that has the potential to build tissues or organs. In general, bioprinting uses a computer-controlled printing device to accurately deposit cells and biomaterials into precise architectures with the goal of creating on demand organized multicellular tissue structures and eventually intra-organ vascular networks. The latter, in turn, will promote the host integration of the engineered tissue/organ in situ once implanted. Existing biofabrication techniques still lay behind this goal. Here, we describe a novel microfluidic printing head-integrated within a custom 3D bioprinter-that allows for the deposition of multimaterial and/or multicellular within a single scaffold by extruding simultaneously different bioinks or by rapidly switching between one bioink and another. The designed bioprinting method effectively moves toward the direction of creating viable tissues and organs for implantation in clinic and research in lab environments.

Increased adipose tissue lipolysis after a 2-week high-fat diet in sedentary overweight/obese men.

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Howe, Harold R; Heidal, Kimberly; Choi, Myung Dong; Kraus, Ray M; Boyle, Kristen; Hickner, Robert C

2011-07-01

The purpose of this study was to determine if a high-fat diet would result in a higher lipolytic rate in subcutaneous adipose tissue than a lower-fat diet in sedentary nonlean men. Six participants (healthy males; 18-40 years old; body mass index, 25-37 kg/m(2)) underwent 2 weeks on a high-fat or well-balanced diet of similar energy content (approximately 6695 kJ) in randomized order with a 10-day washout period between diets. Subcutaneous abdominal adipose tissue lipolysis was determined over the course of a day using microdialysis after both 2-week diet sessions. Average interstitial glycerol concentrations (index of lipolysis) as determined using microdialysis were higher after the high-fat diet (210.8 ± 27.9 μmol/L) than after a well-balanced diet (175.6 ± 23.3 μmol/L; P = .026). There was no difference in adipose tissue microvascular blood flow as determined using the microdialysis ethanol technique. These results demonstrate that healthy nonlean men who diet on the high-fat plan have a higher lipolytic rate in subcutaneous abdominal adipose tissue than when they diet on a well-balanced diet plan. This higher rate of lipolysis may result in a higher rate of fat mass loss on the high-fat diet; however, it remains to be determined if this higher lipolytic rate in men on the high-fat diet results in a more rapid net loss of triglyceride from the abdominal adipose depots, or if the higher lipolytic rate is counteracted by an increased rate of lipid storage. Copyright © 2011 Elsevier Inc. All rights reserved.

Studying cytokinesis in Drosophila epithelial tissues.

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Pinheiro, D; Bellaïche, Y

2017-01-01

Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased expression of Interleukin-13 and connective tissue growth factor, and their potential roles during foreign body encapsulation of subcutaneous implants.

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Ward, W Kenneth; Li, Allen G; Siddiqui, Yasmin; Federiuk, Isaac F; Wang, Xiao-Jing

2008-01-01

The purpose of this study was to better understand whether interleukin-13 (IL-13) and connective tissue growth factor (CTGF) are highly expressed during foreign body encapsulation of subcutaneous devices. Mock biosensors were implanted into rats for three lengths of time (7-, 21- and 48-55 days) to address different stages of the foreign body response. Using quantitative real-time PCR and immunofluorescence, the expression of IL13, CTGF, collagen 1, decorin and fibronectin were measured in this tissue. IL-13, a product of Th2 cells, was highly expressed at all time points, with greatest expression at day 21. The IL-13 expression was paralleled by increased presence of T-cells at all time points. CTGF was also found to be more highly expressed in foreign body tissue than in controls. Collagen and decorin were highly expressed at the middle and later stages. Given the increased expression of IL-13 and CTGF in foreign body tissue, and their roles in other fibrotic disorders, these cytokines may well contribute to the formation of the foreign body capsule. Since the peak gene expression of IL-13 occurred later than the previously-reported TGFbeta expression peak, IL-13 is probably not the major stimulus to TGFbeta expression during foreign body encapsulation and may contribute to fibrosis independently.

Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

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Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

2012-12-01

Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

The tissue microarray OWL schema: An open-source tool for sharing tissue microarray data

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Hyunseok P Kang

2010-01-01

Full Text Available Background: Tissue microarrays (TMAs are enormously useful tools for translational research, but incompatibilities in database systems between various researchers and institutions prevent the efficient sharing of data that could help realize their full potential. Resource Description Framework (RDF provides a flexible method to represent knowledge in triples, which take the form Subject- Predicate-Object. All data resources are described using Uniform Resource Identifiers (URIs, which are global in scope. We present an OWL (Web Ontology Language schema that expands upon the TMA data exchange specification to address this issue and assist in data sharing and integration. Methods: A minimal OWL schema was designed containing only concepts specific to TMA experiments. More general data elements were incorporated from predefined ontologies such as the NCI thesaurus. URIs were assigned using the Linked Data format. Results: We present examples of files utilizing the schema and conversion of XML data (similar to the TMA DES to OWL. Conclusion: By utilizing predefined ontologies and global unique identifiers, this OWL schema provides a solution to the limitations of XML, which represents concepts defined in a localized setting. This will help increase the utilization of tissue resources, facilitating collaborative translational research efforts.

Dopaminergic Immunofluorescence Studies in Kidney Tissue.

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Gildea, J J; Van Sciver, R E; McGrath, H E; Kemp, B A; Jose, P A; Carey, R M; Felder, R A

2017-01-01

The kidney is a highly integrated system of specialized differentiated cells that are responsible for fluid and electrolyte balance in the body. While much of today's research focuses on isolated nephron segments or cells from nephron segments grown in tissue culture, an often overlooked technique that can provide a unique view of many cell types in the kidney is slice culture. Here, we describe techniques that use freshly excised kidney tissue from rats to perform a variety of experiments shortly after isolating the tissue. By slicing the rat kidney in a "bread loaf" format, multiple studies can be performed on slices from the same tissue in parallel. Cryosectioning and staining of the tissue allow for the evaluation of physiological or biochemical responses in a wide variety of specific nephron segments. The procedures described within this chapter can also be extended to human or mouse kidney tissue.

Stress-sensitive tissue regeneration in viscoelastic biomaterials subjected to modulated tensile strain.

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Belfiore, Laurence A; Floren, Michael L; Paulino, Alexandre T; Belfiore, Carol J

2011-09-01

This research contribution addresses the mechanochemistry of intra-tissue mass transfer for nutrients, oxygen, growth factors, and other essential ingredients that anchorage-dependent cells require for successful proliferation on biocompatible surfaces. The unsteady state reaction-diffusion equation (i.e., modified diffusion equation) is solved according to the von Kármán-Pohlhausen integral method of boundary layer analysis when nutrient consumption and tissue regeneration are stimulated by harmonically imposed stress. The mass balance with diffusion and stress-sensitive kinetics represents a rare example where the Damköhler and Deborah numbers appear together in an effort to simulate the development of mass transfer boundary layers in porous viscoelastic biomaterials. The Boltzmann superposition integral is employed to calculate time-dependent strain in terms of the real and imaginary components of dynamic compliance for viscoelastic solids that transmit harmonic excitation to anchorage-dependent cells. Rates of nutrient consumption under stress-free conditions are described by third-order kinetics which include local mass densities of nutrients, oxygen, and attached cells that maintain dynamic equilibrium with active protein sites in the porous matrix. Thinner nutrient mass transfer boundary layers are stabilized at shorter dimensionless diffusion times when the stress-free intra-tissue Damköhler number increases above its initial-condition-sensitive critical value. The critical stress-sensitive intra-tissue Damköhler number, above which it is necessary to consider the effect of harmonic strain on nutrient consumption and tissue regeneration, is proportional to the Deborah number and corresponds to a larger fraction of the stress-free intra-tissue Damköhler number in rigid biomaterials. Copyright © 2011 Elsevier B.V. All rights reserved.

Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

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Griko, Y. V.; Yan, Xiaoli

2016-01-01

Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing

Principles, Techniques, and Applications of Tissue Microfluidics

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Wade, Lawrence A.; Kartalov, Emil P.; Shibata, Darryl; Taylor, Clive

2011-01-01

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called "tissue microfluidics" because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets.

Embroidered polymer-collagen hybrid scaffold variants for ligament tissue engineering.

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Hoyer, M; Drechsel, N; Meyer, M; Meier, C; Hinüber, C; Breier, A; Hahner, J; Heinrich, G; Rentsch, C; Garbe, L-A; Ertel, W; Schulze-Tanzil, G; Lohan, A

2014-10-01

Embroidery techniques and patterns used for scaffold production allow the adaption of biomechanical scaffold properties. The integration of collagen into embroidered polylactide-co-caprolactone [P(LA-CL)] and polydioxanone (PDS) scaffolds could stimulate neo-tissue formation by anterior cruciate ligament (ACL) cells. Therefore, the aim of this study was to test embroidered P(LA-CL) and PDS scaffolds as hybrid scaffolds in combination with collagen hydrogel, sponge or foam for ligament tissue engineering. ACL cells were cultured on embroidered P(LA-CL) and PDS scaffolds without or with collagen supplementation. Cell adherence, vitality, morphology and ECM synthesis were analyzed. Irrespective of thread size, ACL cells seeded on P(LA-CL) scaffolds without collagen adhered and spread over the threads, whereas the cells formed clusters on PDS and larger areas remained cell-free. Using the collagen hydrogel, the scaffold colonization was limited by the gel instability. The collagen sponge layers integrated into the scaffolds were hardly penetrated by the cells. Collagen foams increased scaffold colonization in P(LA-CL) but did not facilitate direct cell-thread contacts in the PDS scaffolds. The results suggest embroidered P(LA-CL) scaffolds as a more promising basis for tissue engineering an ACL substitute than PDS due to superior cell attachment. Supplementation with a collagen foam presents a promising functionalization strategy. Copyright © 2014 Elsevier B.V. All rights reserved.

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

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Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Neves, Maria José; Botion, Leida Maria; Chaves, Valéria Ernestânia

2018-06-01

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets. Copyright © 2018. Published by Elsevier Inc.

Soft tissue deformation using a Hierarchical Finite Element Model.

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Faraci, Alessandro; Bello, Fernando; Darzi, Ara

2004-01-01

Simulating soft tissue deformation in real-time has become increasingly important in order to provide a realistic virtual environment for training surgical skills. Several methods have been proposed with the aim of rendering in real-time the mechanical and physiological behaviour of human organs, one of the most popular being Finite Element Method (FEM). In this paper we present a new approach to the solution of the FEM problem introducing the concept of parent and child mesh within the development of a hierarchical FEM. The online selection of the child mesh is presented with the purpose to adapt the mesh hierarchy in real-time. This permits further refinement of the child mesh increasing the detail of the deformation without slowing down the simulation and giving the possibility of integrating force feedback. The results presented demonstrate the application of our proposed framework using a desktop virtual reality (VR) system that incorporates stereo vision with integrated haptics co-location via a desktop Phantom force feedback device.

An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia

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El-Dahdah, Hamid; Wang, Bei; He, Guanglong; Xu, Ronald X.

2015-01-01

We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multi-modal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics. PMID:20082532

Bone integration capability of nanopolymorphic crystalline hydroxyapatite coated on titanium implants

Directory of Open Access Journals (Sweden)

Suzuki T

2012-02-01

Full Text Available Masahiro Yamada*, Takeshi Ueno*, Naoki Tsukimura, Takayuki Ikeda, Kaori Nakagawa, Norio Hori, Takeo Suzuki, Takahiro OgawaLaboratory of Bone and Implant Sciences, The Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA *These authors contributed equally to this workAbstract: The mechanism by which hydroxyapatite (HA-coated titanium promotes bone–implant integration is largely unknown. Furthermore, refining the fabrication of nanostructured HA to the level applicable to the mass production process for titanium implants is challenging. This study reports successful creation of nanopolymorphic crystalline HA on microroughened titanium surfaces using a combination of flame spray and low-temperature calcination and tests its biological capability to enhance bone–implant integration. Sandblasted microroughened titanium implants and sandblasted + HA-coated titanium implants were subjected to biomechanical and histomorphometric analyses in a rat model. The HA was 55% crystallized and consisted of nanoscale needle-like architectures developed in various diameters, lengths, and orientations, which resulted in a 70% increase in surface area compared to noncoated microroughened surfaces. The HA was free from impurity contaminants, with a calcium/phosphorus ratio of 1.66 being equivalent to that of stoichiometric HA. As compared to microroughened implants, HA-coated implants increased the strength of bone–implant integration consistently at both early and late stages of healing. HA-coated implants showed an increased percentage of bone–implant contact and bone volume within 50 µm proximity of the implant surface, as well as a remarkably reduced percentage of soft tissue intervention between bone and the implant surface. In contrast, bone volume outside the 50 µm border was lower around HA-coated implants. Thus, this study

Fish collagen/alginate/chitooligosaccharides integrated scaffold for skin tissue regeneration application.

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Chandika, Pathum; Ko, Seok-Chun; Oh, Gun-Woo; Heo, Seong-Yeong; Nguyen, Van-Tinh; Jeon, You-Jin; Lee, Bonggi; Jang, Chul Ho; Kim, GeunHyung; Park, Won Sun; Chang, Wonseok; Choi, Il-Whan; Jung, Won-Kyo

2015-11-01

An emerging paradigm in wound healing techniques is that a tissue-engineered skin substitute offers an alternative approach to create functional skin tissue. Here we developed a fish collagen/alginate (FCA) sponge scaffold that was functionalized by different molecular weights of chitooligosaccharides (COSs) with the use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as a cross-linking agent. The effects of cross-linking were analyzed by Fourier transform infrared spectroscopy. The results indicate that the homogeneous materials blending and cross-linking intensity were dependent on the molecular weights of COSs. The highly interconnected porous architecture with 160-260μm pore size and over 90% porosity and COS's MW driven swelling and retention capacity, tensile property and in vitro biodegradation behavior guaranteed the FCA/COS scaffolds for skin tissue engineering application. Further improvement of these properties enhanced the cytocompatibility of all the scaffolds, especially the scaffolds containing COSs with MW in the range of 1-3kDa (FCA/COS1) showed the best cytocompatibility. These physicochemical, mechanical, and biological properties suggest that the FCA/COS1 scaffold is a superior candidate that can be used for skin tissue regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

A Tissue Retrieval and Postharvest Processing Regimen for Rodent Reproductive Tissues Compatible with Long-Term Storage on the International Space Station and Postflight Biospecimen Sharing Program

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Vijayalaxmi Gupta

2015-01-01

Full Text Available Collection and processing of tissues to preserve space flight effects from animals after return to Earth is challenging. Specimens must be harvested with minimal time after landing to minimize postflight readaptation alterations in protein expression/translation, posttranslational modifications, and expression, as well as changes in gene expression and tissue histological degradation after euthanasia. We report the development of a widely applicable strategy for determining the window of optimal species-specific and tissue-specific posteuthanasia harvest that can be utilized to integrate into multi-investigator Biospecimen Sharing Programs. We also determined methods for ISS-compatible long-term tissue storage (10 months at −80°C that yield recovery of high quality mRNA and protein for western analysis after sample return. Our focus was reproductive tissues. The time following euthanasia where tissues could be collected and histological integrity was maintained varied with tissue and species ranging between 1 and 3 hours. RNA quality was preserved in key reproductive tissues fixed in RNAlater up to 40 min after euthanasia. Postfixation processing was also standardized for safe shipment back to our laboratory. Our strategy can be adapted for other tissues under NASA’s Biospecimen Sharing Program or similar multi-investigator tissue sharing opportunities.

White adipose tissue: Getting nervous

NARCIS (Netherlands)

Fliers, E.; Kreier, F.; Voshol, P. J.; Havekes, L. M.; Sauerwein, H. P.; Kalsbeek, A.; Buijs, R. M.; Romijn, J. A.

2003-01-01

Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative

Expression and activity levels of chymase in mast cells of burn wound tissues increase during the healing process in a hamster model.

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Dong, Xianglin; Xu, Tao; Ma, Shaolin; Wen, Hao

2015-06-01

The present study aimed to investigate the changes in the expression levels and activity of mast cell chymase in the process of burn wound healing in a hamster model of deep second-degree burn. The hamster model was established by exposing a ~3 cm diameter area of bare skin to hot water (75°C) for 0, 6, 8, 10 or 12 sec. Tissue specimens were collected 24 h after burning and histological analysis revealed that hot water contact for 12 sec was required to produce a deep second-degree burn. Quantitative polymerase chain reaction and a radioimmunoassay were used to the determine changes in chymase mRNA expression levels and activity. The mRNA expression levels and activity of chymase were increased in the burn wound tissues when compared with the normal skin. However, no statistically significant differences were observed in mast cell chymase activity amongst the various post-burn stages. Chymase mRNA expression levels peaked at day 1 post-burn, subsequently decreasing at days 3 and 7 post-burn and finally increasing again at day 14 post-burn. In summary, a hamster model of deep second-degree burn can be created by bringing the skin into contact with water at 75°C for 12 sec. Furthermore, the mRNA expression levels and activity of chymase in the burn wound tissues increased when compared with those in normal skin tissues.

3D bioprinting for vascularized tissue fabrication

Science.gov (United States)

Richards, Dylan; Jia, Jia; Yost, Michael; Markwald, Roger; Mei, Ying

2016-01-01

3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineering constructs. Given its scalability, reproducibility, and precise multi-dimensional control that traditional fabrication methods do not provide, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. Moderate success of current tissue engineering strategies have been attributed to the current inability to fabricate thick tissue engineering constructs that contain endogenous, engineered vasculature or nutrient channels that can integrate with the host tissue. Successful fabrication of a vascularized tissue construct requires synergy between high throughput, high-resolution bioprinting of larger perfusable channels and instructive bioink that promotes angiogenic sprouting and neovascularization. This review aims to cover the recent progress in the field of 3D bioprinting of vascularized tissues. It will cover the methods of bioprinting vascularized constructs, bioink for vascularization, and perspectives on recent innovations in 3D printing and biomaterials for the next generation of 3D bioprinting for vascularized tissue fabrication. PMID:27230253

How the integration of traditional birth attendants with formal health systems can increase skilled birth attendance.

Science.gov (United States)

Byrne, Abbey; Morgan, Alison

2011-11-01

Forty years of safe motherhood programming has demonstrated that isolated interventions will not reduce maternal mortality sufficiently to achieve MDG 5. Although skilled birth attendants (SBAs) can intervene to save lives, traditional birth attendants (TBAs) are often preferred by communities. Considering the value of both TBAs and SBAs, it is important to review strategies for maximizing their respective strengths. To describe mechanisms to integrate TBAs with the health system to increase skilled birth attendance and examine the components of successful integration. A systematic review of interventions linking TBAs and formal health workers, measuring outcomes of skilled birth attendance, referrals, and facility deliveries. Thirty-three articles met the selection criteria. Mechanisms used for integration included training and supervision of TBAs, collaboration skills for health workers, inclusion of TBAs at health facilities, communication systems, and clear definition of roles. Impact on skilled birth attendance depended on selection of TBAs, community participation, and addressing barriers to access. Successful approaches were context-specific. The integration of TBAs with formal health systems increases skilled birth attendance. The greatest impact is seen when TBA integration is combined with complementary actions to overcome context-specific barriers to contact among SBAs, TBAs, and women. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

[Application of silk-based tissue engineering scaffold for tendon / ligament regeneration].

Science.gov (United States)

Hu, Yejun; Le, Huihui; Jin, Zhangchu; Chen, Xiao; Yin, Zi; Shen, Weiliang; Ouyang, Hongwei

2016-03-01

Tendon/ligament injury is one of the most common impairments in sports medicine. The traditional treatments of damaged tissue repair are unsatisfactory, especially for athletes, due to lack of donor and immune rejection. The strategy of tissue engineering may break through these limitations, and bring new hopes to tendon/ligament repair, even regeneration. Silk is a kind of natural biomaterials, which has good biocompatibility, wide range of mechanical properties and tunable physical structures; so it could be applied as tendon/ligament tissue engineering scaffolds. The silk-based scaffold has robust mechanical properties; combined with other biological ingredients, it could increase the surface area, promote more cell adhesion and improve the biocompatibility. The potential clinical application of silk-based scaffold has been confirmed by in vivo studies on tendon/ligament repairing, such as anterior cruciate ligament, medial collateral ligament, achilles tendon and rotator cuff. To develop novel biomechanically stable and host integrated tissue engineered tendon/ligament needs more further micro and macro studies, combined with product development and clinical application, which will give new hope to patients with tendon/ligament injury.

Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

DEFF Research Database (Denmark)

Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

2011-01-01

Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

Science.gov (United States)

Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

2015-08-01

Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

How to store plant tissues in the absence of liquid nitrogen? Ethanol preserves the RNA integrity of Cannabis sativa stem tissues

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Lauralie Mangeot-Peter

2016-09-01

Full Text Available The preservation of intact RNA is a limiting step when gene expression profiling is performed using field-collected plant material. The use of liquid nitrogen ensures the optimal preservation of RNA, however it is not always practical, especially if the plant material has to be sampled in remote locations. Ethanol is known to preserve DNA in plant tissues even after a long storage period and here its suitability to preserve the RNA of textile hemp cortical tissues was tested. Hemp (Cannabis sativa L. is an economically important fibre crop because it supplies cellulosic bast fibres used in different industrial sectors. In this study we demonstrate the suitability of ethanol for RNA preservation by analyzing tissues stored at 4 °C for 1, 2, 4 and 8 days. We show that in all the cases the extracted RNA is intact. We finally analyze hemp stem tissues stored in ethanol for 1 month and demonstrate the preservation of the tissue structure, particularly of bast fibres.

Pulsed-wave tissue Doppler and color tissue Doppler echocardiography: calibration with M-mode, agreement, and reproducibility in a clinical setting

DEFF Research Database (Denmark)

Olsen, Niels Thue; Jons, Christian; Fritz-Hansen, Thomas

2009-01-01

BACKGROUND: Myocardial velocities can be measured with both pulsed-wave tissue Doppler (PWTD) and color tissue Doppler (CTD) echocardiography. We aimed to (A) to explore which of the two methods better approximates true tissue motion and (B) to examine the agreement and the reproducibility...... of the two methods in a routine clinical setting. METHODS: For Study A, the displacements of 63 basal myocardial segments from 13 patients were examined with M-mode and compared with the velocity-time integral of PWTD and CTD velocities. For Study B, the basal lateral segments from 58 patients were examined...... with PWTD and CTD, and the peak myocardial velocities during systole (Sm), early diastole (Em), and late diastole (Am) were measured. RESULTS: Study A: CTD-based measurements of displacement were 12% lower than M-mode measurements (95% CI: -18%; -6%). PWTD velocity-time integrals measured at the outer edge...

Tissue protein metabolism in parasitized animals

International Nuclear Information System (INIS)

Symons, L.E.A.; Steel, J.W.; Jones, W.O.

1981-01-01

The effects of gastrointestinal nematode infection of mammals, particularly of the small intestine of the sheep, on protein metabolism of skeletal muscle, liver, the gastrointestinal tract and wool are described. These changes have been integrated to explain poor growth and production in the sheep heavily infected with Trichostrongylus colubriformis. The rates of both synthesis and catabolism of muscle protein are depressed, but nitrogen is lost from this tissue because the depression of synthesis exceeds that of catabolism. Anorexia is the major cause of these changes. Although the effect on liver protein synthesis is unclear, it is probable that the leakage of plasma proteins into the gastrointestinal tract stimulates an early increase in the rate of synthesis of these proteins, but this eventually declines and is insufficient to correct developing hypoalbuminaemia. Changes in the intestinal tract are complex. Exogenous nitrogen is reduced by anorexia, but the flow of nitrogen through the tract from abomasum to faeces is above normal because of the increase of endogenous protein from leakage of plasma protein and, presumably, from exfoliated epithelial cells. There is evidence that protein metabolism of intestinal tissue, particularly in the uninfected distal two-thirds, is increased. Synthesis of wool protein is decreased. As the result of anorexia, intestinal loss of endogenous protein and an increased rate of intestinal protein metabolism there is a net movement of amino nitrogen from muscle, liver and possibly skin to the intestine of the heavily infected sheep. Thus, the availability of amino nitrogen for growth and wool production is reduced. (author)

Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

Directory of Open Access Journals (Sweden)

Karine M Yamashita

2014-05-01

Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

A dynamic, mechanistic model of metabolism in adipose tissue of lactating dairy cattle.

Science.gov (United States)

McNamara, J P; Huber, K; Kenéz, A

2016-07-01

Research in dairy cattle biology has resulted in a large body of knowledge on nutrition and metabolism in support of milk production and efficiency. This quantitative knowledge has been compiled in several model systems to balance and evaluate rations and predict requirements. There are also systems models for metabolism and reproduction in the cow that can be used to support research programs. Adipose tissue plays a significant role in the success and efficiency of lactation, and recent research has resulted in several data sets on genomic differences and changes in gene transcription of adipose tissue in dairy cattle. To fully use this knowledge, we need to build and expand mechanistic, dynamic models that integrate control of metabolism and production. Therefore, we constructed a second-generation dynamic, mechanistic model of adipose tissue metabolism of dairy cattle. The model describes the biochemical interconversions of glucose, acetate, β-hydroxybutyrate (BHB), glycerol, C16 fatty acids, and triacylglycerols. Data gathered from our own research and published references were used to set equation forms and parameter values. Acetate, glucose, BHB, and fatty acids are taken up from blood. The fatty acids are activated to the acyl coenzyme A moieties. Enzymatically catalyzed reactions are explicitly described with parameters including maximal velocity and substrate sensitivity. The control of enzyme activity is partially carried out by insulin and norepinephrine, portraying control in the cow. Model behavior was adequate, with sensitive responses to changing substrates and hormones. Increased nutrient uptake and increased insulin stimulate triacylglycerol synthesis, whereas a reduction in nutrient availability or increase in norepinephrine increases triacylglycerol hydrolysis and free fatty acid release to blood. This model can form a basis for more sophisticated integration of existing knowledge and future studies on metabolic efficiency of dairy cattle

Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate

NARCIS (Netherlands)

Mizutani, Makoto; Ito, Yasuhiko; Mizuno, Masashi; Nishimura, Hayato; Suzuki, Yasuhiro; Hattori, Ryohei; Matsukawa, Yoshihisa; Imai, Masaki; Oliver, Noelynn; Goldschmeding, Roel; Aten, Jan; Krediet, Raymond T.; Yuzawa, Yukio; Matsuo, Seiichi

2010-01-01

Mizutani M, Ito Y, Mizuno M, Nishimura H, Suzuki Y, Hattori R, Matsukawa Y, Imai M, Oliver N, Goldschmeding R, Aten J, Krediet RT, Yuzawa Y, Matsuo S. Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate. Am J Physiol

Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

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Seok Joong Yun

2016-06-01

Full Text Available Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs in the urine of prostate cancer (CaP patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH, 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001. Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9. Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.

Dynamic impact indentation of hydrated biological tissues and tissue surrogate gels

Science.gov (United States)

Ilke Kalcioglu, Z.; Qu, Meng; Strawhecker, Kenneth E.; Shazly, Tarek; Edelman, Elazer; VanLandingham, Mark R.; Smith, James F.; Van Vliet, Krystyn J.

2011-03-01

For both materials engineering research and applied biomedicine, a growing need exists to quantify mechanical behaviour of tissues under defined hydration and loading conditions. In particular, characterisation under dynamic contact-loading conditions can enable quantitative predictions of deformation due to high rate 'impact' events typical of industrial accidents and ballistic insults. The impact indentation responses were examined of both hydrated tissues and candidate tissue surrogate materials. The goals of this work were to determine the mechanical response of fully hydrated soft tissues under defined dynamic loading conditions, and to identify design principles by which synthetic, air-stable polymers could mimic those responses. Soft tissues from two organs (liver and heart), a commercially available tissue surrogate gel (Perma-Gel™) and three styrenic block copolymer gels were investigated. Impact indentation enabled quantification of resistance to penetration and energy dissipative constants under the rates and energy densities of interest for tissue surrogate applications. These analyses indicated that the energy dissipation capacity under dynamic impact increased with increasing diblock concentration in the styrenic gels. Under the impact rates employed (2 mm/s to 20 mm/s, corresponding to approximate strain energy densities from 0.4 kJ/m3 to 20 kJ/m3), the energy dissipation capacities of fully hydrated soft tissues were ultimately well matched by a 50/50 triblock/diblock composition that is stable in ambient environments. More generally, the methodologies detailed here facilitate further optimisation of impact energy dissipation capacity of polymer-based tissue surrogate materials, either in air or in fluids.

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

Science.gov (United States)

Mählmann, K; Hamza, E; Marti, E; Dolf, G; Klukowska, J; Gerber, V; Koch, C

2014-12-01

Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intra-operative tissue oxygen tension is increased by local insufflation of humidified-warm CO2 during open abdominal surgery in a rat model.

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Jean K Marshall

Full Text Available Maintenance of high tissue oxygenation (PtO2 is recommended during surgery because PtO2 is highly predictive of surgical site infection and colonic anastomotic leakage. However, surgical site perfusion is often sub-optimal, creating an obstructive hurdle for traditional, systemically applied therapies to maintain or increase surgical site PtO2. This research tested the hypothesis that insufflation of humidified-warm CO2 into the abdominal cavity would increase sub-peritoneal PtO2 during open abdominal surgery.15 Wistar rats underwent laparotomy under general anesthesia. Three sets of randomized cross-over experiments were conducted in which the abdominal cavity was subjected to alternating exposure to 1 humidified-warm CO2 & ambient air; 2 humidified-warm CO2 & dry-cold CO2; and 3 dry-cold CO2 & ambient air. Sub-peritoneal PtO2 and tissue temperature were measured with a polarographic oxygen probe.Upon insufflation of humidified-warm CO2, PtO2 increased by 29.8 mmHg (SD 13.3; p<0.001, or 96.6% (SD 51.9, and tissue temperature by 3.0°C (SD 1.7 p<0.001, in comparison with exposure to ambient air. Smaller, but significant, increases in PtO2 were seen in experiments 2 and 3. Tissue temperature decreased upon exposure to dry-cold CO2 compared with ambient air (-1.4°C, SD 0.5, p = 0.001.In a rat model, insufflation of humidified-warm CO2 into the abdominal cavity during open abdominal surgery causes an immediate and potentially clinically significant increase in PtO2. The effect is an additive result of the delivery of CO2 and avoidance of evaporative cooling via the delivery of the CO2 gas humidified at body temperature.

Integral dose investigation of non-coplanar treatment beam geometries in radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Dan; Dong, Peng; Ruan, Dan; Low, Daniel A.; Sheng, Ke, E-mail: ksheng@mednet.ucla.edu [Department of Radiation Oncology, University of California, Los Angeles, California 90095 (United States); Long, Troy; Romeijn, Edwin [Department of Industrial and Operations, University of Michigan, Ann Arbor, Michigan 48109 (United States)

2014-01-15

Purpose: Automated planning and delivery of non-coplanar plans such as 4π radiotherapy involving a large number of fields have been developed to take advantage of the newly available automated couch and gantry on C-arm gantry linacs. However, there is an increasing concern regarding the potential changes in the integral dose that needs to be investigated. Methods: A digital torso phantom and 22 lung and liver stereotactic body radiation therapy (SBRT) patients were included in the study. The digital phantom was constructed as a water equivalent elliptical cylinder with a major axis length of 35.4 cm and minor axis of 23.6 cm. A 4.5 cm diameter target was positioned at varying depths along the major axis. Integral doses from intensity modulated, non-coplanar beams forming a conical pattern were compared against the equally spaced coplanar beam plans. Integral dose dependence on the phantom geometry and the beam number was also quantified. For the patient plans, the non-coplanar and coplanar beams and fluences were optimized using a column generation and pricing approach and compared against clinical VMAT plans using two full (lung) or partial coplanar arcs (liver) entering at the side proximal to the tumor. Both the average dose to the normal tissue volume and the total volumes receiving greater than 2 Gy (V2) and 5 Gy (V5) were evaluated and compared. Results: The ratio of integral dose from the non-coplanar and coplanar plans depended on the tumor depth for the phantom; for tumors shallower than 10 cm, the non-coplanar integral doses were lower than coplanar integral doses for non-coplanar angles less than 60°. Similar patterns were observed in the patient plans. The smallest non-coplanar integral doses were observed for tumor 6–8 cm deep. For the phantom, the integral dose was independent of the number of beams, consistent with the liver SBRT patients but the lung SBRT patients showed slight increase in the integral dose when more beams were used. Larger

[Effects of prebiotics and probiotics on gastrointestinal tract lymphoid tissue in hiv infected patients].

Science.gov (United States)

Feria, Manuel G; Taborda, Natalia A; Hernandez, Juan C; Rugeles, María T

2017-02-01

HIV infection induces alterations in almost all immune cell populations, mainly in CD4+ T cells, leading to the development of opportunistic infections. The gut-associated lymphoid tissue (GALT) constitutes the most important site for viral replication, because the main target cells, memory T-cells, reside in this tissue. It is currently known that alterations in GALT are critical during the course of the infection, as HIV-1 induces loss of tissue integrity and promotes translocation of microbial products from the intestinal lumen to the systemic circulation, leading to a persistent immune activation state and immune exhaustion. Although antiretroviral treatment decreases viral load and substantially improves the prognosis of the infection, the alterations in GALT remains, having a great impact on the ability to establish effective immune responses. This emphasizes the importance of developing new therapeutic alternatives that may promote structural and functional integrity of this tissue. In this regard, therapy with probiotics/prebiotics has beneficial effects in GALT, mainly in syndromes characterized by intestinal dysbiosis, including the HIV-1 infection. In these patients, the consumption of probiotics/prebiotics decreased microbial products in plasma and CD4+ T cell activation, increased CD4+ T cell frequency, in particular Th17, and improved the intestinal flora. In this review, the most important findings on the potential impact of the probiotics/prebiotics therapy are discussed.

Applications of condensed matter understanding to medical tissues and disease progression: Elemental analysis and structural integrity of tissue scaffolds

Energy Technology Data Exchange (ETDEWEB)

Bradley, D.A., E-mail: d.a.bradley@surrey.ac.u [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Farquharson, M.J. [Department of Radiography, School of Community and Health Sciences, City University, London (United Kingdom); Gundogdu, O. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Al-Ebraheem, Alia [Department of Radiography, School of Community and Health Sciences, City University, London (United Kingdom); Che Ismail, Elna [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Kaabar, W., E-mail: w.kaabar@surrey.ac.u [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom); Bunk, O. [Paul Scherrer Institute, CH-5232 Villigen (Switzerland); Pfeiffer, F. [Paul Scherrer Institute, CH-5232 Villigen (Switzerland); Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne (Switzerland); Falkenberg, G. [Hamburger Synchrotronstrahlungslabor HASYLAB at Deutsches Elektronensynchrotron DESY, Notkestr. 85, D-22603 Hamburg (Germany); Bailey, M. [Surrey Ion Beam Centre, Advanced Technology Institute, University of Surrey, Guildford GU2 7XH (United Kingdom)

2010-02-15

The investigations reported herein link tissue structure and elemental presence with issues of environmental health and disease, exemplified by uptake and storage of potentially toxic elements in the body, the osteoarthritic condition and malignancy in the breast and other soft tissues. Focus is placed on application of state-of-the-art ionizing radiation techniques, including, micro-synchrotron X-ray fluorescence (mu-SXRF) and particle-induced X-ray emission/Rutherford backscattering mapping (mu-PIXE/RBS), coherent small-angle X-ray scattering (cSAXS) and X-ray phase-contrast imaging, providing information on elemental make-up, the large-scale organisation of collagen and anatomical features of moderate and low atomic number media. For the particular situations under investigation, use of such facilities is allowing information to be obtained at an unprecedented level of detail, yielding new understanding of the affected tissues and the progression of disease.

Applications of condensed matter understanding to medical tissues and disease progression: Elemental analysis and structural integrity of tissue scaffolds

International Nuclear Information System (INIS)

Bradley, D.A.; Farquharson, M.J.; Gundogdu, O.; Al-Ebraheem, Alia; Che Ismail, Elna; Kaabar, W.; Bunk, O.; Pfeiffer, F.; Falkenberg, G.; Bailey, M.

2010-01-01

The investigations reported herein link tissue structure and elemental presence with issues of environmental health and disease, exemplified by uptake and storage of potentially toxic elements in the body, the osteoarthritic condition and malignancy in the breast and other soft tissues. Focus is placed on application of state-of-the-art ionizing radiation techniques, including, micro-synchrotron X-ray fluorescence (μ-SXRF) and particle-induced X-ray emission/Rutherford backscattering mapping (μ-PIXE/RBS), coherent small-angle X-ray scattering (cSAXS) and X-ray phase-contrast imaging, providing information on elemental make-up, the large-scale organisation of collagen and anatomical features of moderate and low atomic number media. For the particular situations under investigation, use of such facilities is allowing information to be obtained at an unprecedented level of detail, yielding new understanding of the affected tissues and the progression of disease.

Increasing competitiveness with intercompany integration of logistics and marketing functions

Directory of Open Access Journals (Sweden)

Darja Topolšek

2016-03-01

Full Text Available Researchers of different scientific disciplines, such as management strategies, organizational theories and marketing, have in the past explored relations of mutual influences and the importance of cooperation between different functions in a company. The increased focus on the logistics function has potential to increase competitiveness. This is especially true for globally aimed production companies. In any company, logistics functions cooperate with various related functions such as production, marketing, procurement, engineering or developing new products as well as with financial functions. Each of the aforementioned connections or cooperation among logistics and its complementary functions can have a decisive effect on the company's competitiveness. Using a survey, we determined which activities in the surveyed companies are performed by the logistical function together with the marketing function and which activities they suggest should be performed together but are currently not, meaning they are co-dependent. Since interfunctional integration between logistics and marketing increases the success of a company, we also examined the connection between the current joint performance of activities and the suggested joint performance of activities among the before mentioned sectors, connected to the effectiveness of the company. To examine the mentioned connections among the logistical and marketing functions, Explanatory Factor Analysis (EFA, Confirmatory Factor Analysis (CFA and Structural Equation Modelling (SEM were performed.

Green Tea Increases the Concentration of Total Mercury in the Blood of Rats following an Oral Fish Tissue Bolus

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Elsa M. Janle

2015-01-01

Full Text Available Fish has many health benefits but is also the most common source of methylmercury. The bioavailability of methylmercury in fish may be affected by other meal components. In this study, the effect of green tea on the bioavailability of methylmercury from an oral bolus of fish muscle tissue was studied in rats and compared to a water treated control group and a group treated with meso-2,3-dimercaptosuccinic acid (DMSA, a compound used medically to chelate mercury. Rats were given a single oral dose of fish tissue via gavage and one of the treatments. Rats were given access to food for 3 h at 12 h intervals. They were dosed with each of the treatments with each meal. Blood samples were collected for 95 hours. Green tea significantly increased the concentration of total mercury in blood relative to the control, whereas DMSA significantly decreased it. In addition, feeding caused a slight increase in blood mercury for several meals following the initial dose.

Increased technetium-99 m hydroxy diphosphonate soft tissue uptake on bone scintigraphy in chronic kidney disease patients with secondary hyperparathyroidism

DEFF Research Database (Denmark)

Enevoldsen, Lotte Hahn; Heaf, James Goya; Højgaard, Liselotte

2017-01-01

In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and/or hyperphosphata......In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and...... patients diagnosed with secondary hyperparathyroidism admitted for Tc-99 m-HDP bone scan. Baseline characteristics and mean concentrations of biochemical markers (including P-calcium and P-phosphate) taken 0-3 months prior to the bone scans were collected. Soft tissue uptake was detected on bone scans....../or hyperphosphataemia. As human vascular smooth muscle cells produce hydroxyapatite during cell culture with increased phosphate levels and as Tc-99 m-HDP/MDP primarily binds to hydroxyapatite, we hypothesized that soft tissue accumulation would be found in patients with hyperphosphataemia. We identified 63 CKD...

Bayesian models and meta analysis for multiple tissue gene expression data following corticosteroid administration

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Kelemen Arpad

2008-08-01

Full Text Available Abstract Background This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug. Results and conclusion Bayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential/non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle.

A multicellular view of cytokinesis in epithelial tissue.

Science.gov (United States)

Herszterg, Sophie; Pinheiro, Diana; Bellaïche, Yohanns

2014-05-01

The study of cytokinesis in single-cell systems provided a wealth of knowledge on the molecular and biophysical mechanisms controlling daughter cell separation. In this review, we outline recent advances in the understanding of cytokinesis in epithelial tissues. These findings provide evidence for how the cytokinetic machinery adapts to a multicellular context and how the cytokinetic machinery is itself exploited by the tissue for the preservation of tissue function and architecture during proliferation. We propose that cytokinesis in epithelia should be viewed as a multicellular process, whereby the biochemical and mechanical interactions between the dividing cell and its neighbors are essential for successful daughter cell separation while defining epithelial tissue organization and preserving tissue integrity. Copyright © 2013 Elsevier Ltd. All rights reserved.

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

Science.gov (United States)

Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

Tissue Engineering Applications of Three-Dimensional Bioprinting.

Science.gov (United States)

Zhang, Xiaoying; Zhang, Yangde

2015-07-01

Recent advances in tissue engineering have adapted the additive manufacturing technology, also known as three-dimensional printing, which is used in several industrial applications, for the fabrication of bioscaffolds and viable tissue and/or organs to overcome the limitations of other in vitro conventional methods. 3D bioprinting technology has gained enormous attention as it enabled 3D printing of a multitude of biocompatible materials, different types of cells and other supporting growth factors into complex functional living tissues in a 3D format. A major advantage of this technology is its ability for simultaneously 3D printing various cell types in defined spatial locations, which makes this technology applicable to regenerative medicine to meet the need for suitable for transplantation suitable organs and tissues. 3D bioprinting is yet to successfully overcome the many challenges related to building 3D structures that closely resemble native organs and tissues, which are complex structures with defined microarchitecture and a variety of cell types in a confined area. An integrated approach with a combination of technologies from the fields of engineering, biomaterials science, cell biology, physics, and medicine is required to address these complexities. Meeting this challenge is being made possible by directing the 3D bioprinting to manufacture biomimetic-shaped 3D structures, using organ/tissue images, obtained from magnetic resonance imaging and computerized tomography, and employing computer-aided design and manufacturing technologies. Applications of 3D bioprinting include the generation of multilayered skin, bone, vascular grafts, heart valves, etc. The current 3D bioprinting technologies need to be improved with respect to the mechanical strength and integrity in the manufactured constructs as the presently used biomaterials are not of optimal viscosity. A better understanding of the tissue/organ microenvironment, which consists of multiple types of

Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

Science.gov (United States)

Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

2016-12-01

Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

Science.gov (United States)

Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

2015-07-01

Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

The comparison of thermal tissue injuries caused by ultrasonic scalpel and electrocautery use in rabbit tongue tissue

Science.gov (United States)

Beriat, Guclu Kaan; Akmansu, Sefik Halit; Ezerarslan, Hande; Dogan, Cem; Han, Unsal; Saglam, Mehmet; Senel, Oytun Okan; Kocaturk, Sinan

2012-01-01

The aim of this study compares to the increase in tissue temperature and the thermal histological effects of ultrasonic scalpel, bipolar and unipolar electrosurgery incisions in the tongue tissue of rabbits. This study evaluates the histopathological changes related to thermal change and the maximum temperature values in the peripheral tissue brought about by the incisions carried out by the three methods in a comparative way. To assess thermal tissue damage induced by the three instruments, maximum tissue temperatures were measured during the surgical procedure and tongue tissue samples were examined histopathologically following the surgery. The mean maximum temperature values of the groups were 93.93±2.76 C° for the unipolar electrocautery group, whereas 85.07±5.95 C° for the bipolar electrocautery group, and 108.23±7.64 C° for the ultrasonic scalpel group. There was a statistically significant relationship between the increase in maximum temperature values and the separation among tissue layers, edema, congestion, necrosis, hemorrhage, destruction in blood vessel walls and fibrin accumulation, and between the existence of fibrin thrombus and tissue damage depth (pelectrocautery use gives way to less temperature increase in the tissues and less thermal tissue damage in comparison to the other methods. PMID:22938541

Biocompatibility of hydrogel-based scaffolds for tissue engineering applications.

Science.gov (United States)

Naahidi, Sheva; Jafari, Mousa; Logan, Megan; Wang, Yujie; Yuan, Yongfang; Bae, Hojae; Dixon, Brian; Chen, P

2017-09-01

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds. Copyright © 2017 Elsevier Inc. All rights reserved.

Three-dimensional bioprinting of thick vascularized tissues

Science.gov (United States)

Kolesky, David B.; Homan, Kimberly A.; Skylar-Scott, Mark A.; Lewis, Jennifer A.

2016-03-01

The advancement of tissue and, ultimately, organ engineering requires the ability to pattern human tissues composed of cells, extracellular matrix, and vasculature with controlled microenvironments that can be sustained over prolonged time periods. To date, bioprinting methods have yielded thin tissues that only survive for short durations. To improve their physiological relevance, we report a method for bioprinting 3D cell-laden, vascularized tissues that exceed 1 cm in thickness and can be perfused on chip for long time periods (>6 wk). Specifically, we integrate parenchyma, stroma, and endothelium into a single thick tissue by coprinting multiple inks composed of human mesenchymal stem cells (hMSCs) and human neonatal dermal fibroblasts (hNDFs) within a customized extracellular matrix alongside embedded vasculature, which is subsequently lined with human umbilical vein endothelial cells (HUVECs). These thick vascularized tissues are actively perfused with growth factors to differentiate hMSCs toward an osteogenic lineage in situ. This longitudinal study of emergent biological phenomena in complex microenvironments represents a foundational step in human tissue generation.

An Overview of Recent Patents on Musculoskeletal Interface Tissue Engineering

Science.gov (United States)

Rao, Rohit T.; Browe, Daniel P.; Lowe, Christopher J.; Freeman, Joseph W.

2018-01-01

Interface tissue engineering involves the development of engineered grafts that promote integration between multiple tissue types. Musculoskeletal tissue interfaces are critical to the safe and efficient transmission of mechanical forces between multiple musculoskeletal tissues e.g. between ligament and bone tissue. However, these interfaces often do not physiologically regenerate upon injury, resulting in impaired tissue function. Therefore, interface tissue engineering approaches are considered to be particularly relevant for the structural restoration of musculoskeletal tissues interfaces. In this article we provide an overview of the various strategies used for engineering musculoskeletal tissue interfaces with a specific focus on the recent important patents that have been issued for inventions that were specifically designed for engineering musculoskeletal interfaces as well as those that show promise to be adapted for this purpose. PMID:26577344

Classification of breast tissue using a laboratory system for small-angle x-ray scattering (SAXS)

International Nuclear Information System (INIS)

Sidhu, S; Siu, K K W; Falzon, G; Hart, S A; Fox, J G; Lewis, R A

2011-01-01

Structural changes in breast tissue at the nanometre scale have been shown to differentiate between tissue types using synchrotron SAXS techniques. Classification of breast tissues using information acquired from a laboratory SAXS camera source could possibly provide a means of adopting SAXS as a viable diagnostic procedure. Tissue samples were obtained from surgical waste from 66 patients and structural components of the tissues were examined between q = 0.25 and 2.3 nm -1 . Principal component analysis showed that the amplitude of the fifth-order axial Bragg peak, the magnitude of the integrated intensity and the full-width at half-maximum of the fat peak were significantly different between tissue types. A discriminant analysis showed that excellent classification can be achieved; however, only 30% of the tissue samples provided the 16 variables required for classification. This suggests that the presence of disease is represented by a combination of factors, rather than one specific trait. A closer examination of the amorphous scattering intensity showed not only a trend of increased scattering intensity with disease severity, but also a corresponding decrease in the size of the scatterers contributing to this intensity.

Real-time haptic cutting of high-resolution soft tissues.

Science.gov (United States)

Wu, Jun; Westermann, Rüdiger; Dick, Christian

2014-01-01

We present our systematic efforts in advancing the computational performance of physically accurate soft tissue cutting simulation, which is at the core of surgery simulators in general. We demonstrate a real-time performance of 15 simulation frames per second for haptic soft tissue cutting of a deformable body at an effective resolution of 170,000 finite elements. This is achieved by the following innovative components: (1) a linked octree discretization of the deformable body, which allows for fast and robust topological modifications of the simulation domain, (2) a composite finite element formulation, which thoroughly reduces the number of simulation degrees of freedom and thus enables to carefully balance simulation performance and accuracy, (3) a highly efficient geometric multigrid solver for solving the linear systems of equations arising from implicit time integration, (4) an efficient collision detection algorithm that effectively exploits the composition structure, and (5) a stable haptic rendering algorithm for computing the feedback forces. Considering that our method increases the finite element resolution for physically accurate real-time soft tissue cutting simulation by an order of magnitude, our technique has a high potential to significantly advance the realism of surgery simulators.

Photothermal effects of laser tissue soldering

International Nuclear Information System (INIS)

McNally, K.M.; Sorg, B.S.; Welch, A.J.; Dawes, J.M.; Owen, E.R.

1999-01-01

Low-strength anastomoses and thermal damage of tissue are major concerns in laser tissue welding techniques where laser energy is used to induce thermal changes in the molecular structure of the tissues being joined, hence allowing them to bond together. Laser tissue soldering, on the other hand, is a bonding technique in which a protein solder is applied to the tissue surfaces to be joined, and laser energy is used to bond the solder to the tissue surfaces. The addition of protein solders to augment tissue repair procedures significantly reduces the problems of low strength and thermal damage associated with laser tissue welding techniques. Investigations were conducted to determine optimal solder and laser parameters for tissue repair in terms of tensile strength, temperature rise and damage and the microscopic nature of the bonds formed. An in vitro study was performed using an 808 nm diode laser in conjunction with indocyanine green (ICG)-doped albumin protein solders to repair bovine aorta specimens. Liquid and solid protein solders prepared from 25% and 60% bovine serum albumin (BSA), respectively, were compared. The efficacy of temperature feedback control in enhancing the soldering process was also investigated. Increasing the BSA concentration from 25% to 60% greatly increased the tensile strength of the repairs. A reduction in dye concentration from 2.5mgml -1 to 0.25mgml -1 was also found to result in an increase in tensile strength. Increasing the laser irradiance and thus surface temperature resulted in an increased severity of histological injury. Thermal denaturation of tissue collagen and necrosis of the intimal layer smooth muscle cells increased laterally and in depth with higher temperatures. The strongest repairs were produced with an irradiance of 6.4Wcm -2 using a solid protein solder composed of 60% BSA and 0.25mgml -1 ICG. Using this combination of laser and solder parameters, surface temperatures were observed to reach 85±5 deg. C with a

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss.

Science.gov (United States)

Schmitz, J; Evers, N; Awazawa, M; Nicholls, H T; Brönneke, H S; Dietrich, A; Mauer, J; Blüher, M; Brüning, J C

2016-05-01

Obesity represents a major risk factor for the development of type 2 diabetes mellitus, atherosclerosis and certain cancer entities. Treatment of obesity is hindered by the long-term maintenance of initially reduced body weight, and it remains unclear whether all pathologies associated with obesity are fully reversible even upon successfully maintained weight loss. We compared high fat diet-fed, weight reduced and lean mice in terms of body weight development, adipose tissue and liver insulin sensitivity as well as inflammatory gene expression. Moreover, we assessed similar parameters in a human cohort before and after bariatric surgery. Compared to lean animals, mice that demonstrated successful weight reduction showed increased weight gain following exposure to ad libitum control diet. However, pair-feeding weight-reduced mice with lean controls efficiently stabilized body weight, indicating that hyperphagia was the predominant cause for the observed weight regain. Additionally, whereas glucose tolerance improved rapidly after weight loss, systemic insulin resistance was retained and ameliorated only upon prolonged pair-feeding. Weight loss enhanced insulin action and resolved pro-inflammatory gene expression exclusively in the liver, whereas visceral adipose tissue displayed no significant improvement of metabolic and inflammatory parameters compared to obese mice. Similarly, bariatric surgery in humans (n = 55) resulted in massive weight reduction, improved hepatic inflammation and systemic glucose homeostasis, while adipose tissue inflammation remained unaffected and adipocyte-autonomous insulin action only exhibit minor improvements in a subgroup of patients (42%). These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals

Directory of Open Access Journals (Sweden)

Coker Robert H

2012-12-01

Full Text Available Abstract Background Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. Methods In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR. We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day: 1 EAAMR or a 2 competitive meal replacement (CMR in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. Results By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. Conclusion The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

Directory of Open Access Journals (Sweden)

J. Schmitz

2016-05-01

Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels.

Science.gov (United States)

Cuchiara, Michael P; Gould, Daniel J; McHale, Melissa K; Dickinson, Mary E; West, Jennifer L

2012-11-07

Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled micro-vascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo.

Developing 3D microstructures for tissue engineering

DEFF Research Database (Denmark)

Mohanty, Soumyaranjan

casting process to generate various large scale tissue engineering constructs with single pore geometry with the desired mechanical stiffness and porosity. In addition, a new technique was developed to fa bricate dual-pore scaffolds for various tissue-engineering applications where 3D printing...... materials have been developed and tested for enhancing the differentiation of hiPSC-derived hepatocytes and fabricating biodegradable scaffolds for in-vivo tissue engineering applications. Along with various scaffolds fabrication methods we finally presented an optimized study of hepatic differentiation...... of hiPSC-derived DE cells cultured for 25 days in a 3D perfusion bioreactor system with an array of 16 small-scale tissue-bioreactors with integrated dual-pore pore scaffolds and flow rates. Hepatic differentiation and functionality of hiPSC-derived hepatocytes were successfully assessed and compared...

Brain–gut–adipose-tissue communication pathways at a glance

Directory of Open Access Journals (Sweden)

Chun-Xia Yi

2012-09-01

Full Text Available One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

NARCIS (Netherlands)

A. Grefhorst (Aldo); J.C. van den Beukel (Anneke); A.F. van Houten (A.); J. Steenbergen (Jacobie); J.A. Visser (Jenny); A.P.N. Themmen (Axel)

2015-01-01

textabstractBackground: In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed

A portrait of tissue phosphoprotein stability in the clinical tissue procurement process.

Science.gov (United States)

Espina, Virginia; Edmiston, Kirsten H; Heiby, Michael; Pierobon, Mariaelena; Sciro, Manuela; Merritt, Barbara; Banks, Stacey; Deng, Jianghong; VanMeter, Amy J; Geho, David H; Pastore, Lucia; Sennesh, Joel; Petricoin, Emanuel F; Liotta, Lance A

2008-10-01

Little is known about the preanalytical fluctuations of phosphoproteins during tissue procurement for molecular profiling. This information is crucial to establish guidelines for the reliable measurement of these analytes. To develop phosphoprotein profiles of tissue subjected to the trauma of excision, we measured the fidelity of 53 signal pathway phosphoproteins over time in tissue specimens procured in a community clinical practice. This information provides strategies for potential surrogate markers of stability and the design of phosphoprotein preservative/fixation solutions. Eleven different specimen collection time course experiments revealed augmentation (+/-20% from the time 0 sample) of signal pathway phosphoprotein levels as well as decreases over time independent of tissue type, post-translational modification, and protein subcellular location (tissues included breast, colon, lung, ovary, and uterus (endometrium/myometrium) and metastatic melanoma). Comparison across tissue specimens showed an >20% decrease of protein kinase B (AKT) Ser-473 (p 20% increases within 90-min postprocurement. Endothelial nitric-oxide synthase Ser-1177 did not change over the time period evaluated with breast or leiomyoma tissue. Treatment with phosphatase or kinase inhibitors alone revealed that tissue kinase pathways are active ex vivo. Combinations of kinase and phosphatase inhibitors appeared to stabilize proteins that exhibited increases in the presence of phosphatase inhibitors alone (ATF-2 Thr-71, SAPK/JNK Thr-183/Tyr-185, STAT1 Tyr-701, JAK1 Tyr-1022/1023, and PAK1/PAK2 Ser-199/204/192/197). This time course study 1) establishes the dynamic nature of specific phosphoproteins in excised tissue, 2) demonstrates augmented phosphorylation in the presence of phosphatase inhibitors, 3) shows that kinase inhibitors block the upsurge in phosphorylation of phosphoproteins, 4) provides a rational strategy for room temperature preservation of proteins, and 5) constitutes a

Increased abundance of ADAM9 transcripts in the blood is associated with tissue damage [version 2; referees: 2 approved, 1 approved with reservations

Directory of Open Access Journals (Sweden)

Darawan Rinchai

2016-10-01

Full Text Available Background: Members of the ADAM (a disintegrin and metalloprotease domain family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1 The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2 changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs. 3 Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes.

Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance

Directory of Open Access Journals (Sweden)

Nathan L. Price

2018-02-01

Full Text Available While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects of long-term anti-miR-33 therapies and predisposition of miR-33−/− mice to obesity and metabolic dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work provides an in-depth characterization of miR-33−/− mice and explores the mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic tissues. Contrary to previous reports, our data do not support a direct role for SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in adipose tissue of miR-33−/− mice, we observe increased pre-adipocyte proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we demonstrate that the driving force behind these abnormalities is increased food intake, which can be prevented by pair feeding with wild-type animals.

Growth hormone receptor antagonist (GHA) transgenic mice have increased subcutaneous adipose tissue mass, altered glucose homeostasis, and no change in white adipose tissue cellular senescence

Science.gov (United States)

Comisford, Ross; Lubbers, Ellen R.; Householder, Lara; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L.; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

2015-01-01

Background Growth hormone (GH) resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests long-lived GH resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. OBJECTIVE The objective of this study was to examine white adipose tissue (WAT) senescence, WAT distribution, and glucose homeostasis in dwarf growth hormone receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. METHODS 18mo old female GHA mice and wild type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose, and glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase (SA-β-gal) staining to quantify the senescent cell burden and real time qPCR to quantify gene expression of senescence markers p16 and IL-6. RESULTS GHA mice had a 22% reduction in total body weight, 33% reduction in lean mass, and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p<.05) and a 1.7 fold increase in extra-/intraperitoneal WAT ratio compared to controls (p<.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. CONCLUSIONS Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin

Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity.

Science.gov (United States)

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Salvador, Javier; Frühbeck, Gema

2012-10-01

Obesity is associated with an altered inflammatory and extracellular matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with proinflammatory effects. We aimed to explore the expression levels of TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular fraction cells (SVFC) as well as its impact on inflammation and ECM regulation. We also analyzed the effect of the stimulation with TNF-α and lipopolysaccharide (LPS) on both SVFC and adipocytes. Samples obtained from 75 subjects were used in the study. Expression levels of TNC, TLR4, MMP2, and MMP9 were analyzed in visceral adipose tissue (VAT) as well as in both adipocytes and SVFC. In addition, Tnc expression was measured in two mice models of obesity. We show, for the first time, that VAT expression levels of TNC are increased in normoglycemic and type 2 diabetic obese patients (Pobese patients with nonalcoholic steatohepatitis (Pobesity were significantly increased (Pexogenous TNC induced (Pobesity via visceral adipose tissue inflammation representing a link with ECM remodeling.

Increased cytotoxicity and streptolysin O activity in group G streptococcal strains causing invasive tissue infections

DEFF Research Database (Denmark)

Siemens, Nikolai; Kittang, Bård R; Chakrakodi, Bhavya

2015-01-01

Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 6...

Vitamin D3 increases in abdominal subcutaneous fat tissue after supplementation with vitamin D3

DEFF Research Database (Denmark)

Didriksen, Allan; Burild, Anders; Jakobsen, Jette

2015-01-01

stored in all adipose tissue in the body, the median body store was 6.6 mg vitamin D-3 and 0.12 mg 25(OH)D-3 in those given vitamin D-3. Conclusions: Subcutaneous adipose tissue may store large amounts of vitamin D-3. The clinical importance of this storage needs to be determined.......Objective: The objective was to assess the amount of vitamin D-3 stored in adipose tissue after long-term supplementation with high dose vitamin D-3. Design: A cross-sectional study on 29 subjects with impaired glucose tolerance who had participated in a randomized controlled trial with vitamin D-3...... 20 000 IU (500 mu g) per week vs placebo for 3-5 years. Methods: Abdominal subcutaneous fat tissue was obtained by needle biopsy for the measurements of vitamin D-3 and 25-hydroxyvitamin D-3 (25(OH)D-3). Body fat was measured with dual-energy X-ray absorptiometry, and serum 25(OH)D-3 level...

Lymphatic Filariasis Increases Tissue Compressibility and Extracellular Fluid in Lower Limbs of Asymptomatic Young People in Central Myanmar

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Janet Douglass

2017-09-01

Full Text Available When normal lymphatic function is hampered, imperceptible subcutaneous edema can develop and progress to overt lymphedema. Low-cost reliable devices for objective assessment of lymphedema are well accepted in clinical practice and research on breast-cancer related lymphedema but are untested in populations with lymphatic filariasis (LF. This is a cross-sectional analysis of baseline data in a longitudinal study on asymptomatic, LF antigen-positive and -negative young people in Myanmar. Rapid field screening was used to identify antigen-positive cases and a group of antigen-negative controls of similar age and gender were invited to continue in the study. Tissue compressibility was assessed with three tissue tonometers, and free fluids were assessed using bio-impedance spectroscopy (BIS. Infection status was confirmed by Og4C3 antigen assay. At baseline (n = 98, antigen-positive cases had clinically relevant increases in tissue compressibility at the calf using a digital Indurometer (11.1%, p = 0.021, and in whole-leg free fluid using BIS (9.2%, p = 0.053. Regression analysis for moderating factors (age, gender, hydration reinforced the between-infection group differences. Results demonstrate that sub-clinical changes associated with infection can be detected in asymptomatic cases. Further exploration of these low-cost devices in clinical and research settings on filariasis-related lymphedema are warranted.

Increased p50/p50 NF-κB Activation in Human Papillomavirus Type 6- or Type 11-Induced Laryngeal Papilloma Tissue

Science.gov (United States)

Vancurova, Ivana; Wu, Rong; Miskolci, Veronika; Sun, Shishinn

2002-01-01

We have observed elevated NF-κB DNA-binding activity in nuclear extracts from human papillomavirus type 6- and 11-infected laryngeal papilloma tissues. The predominant DNA-binding species is the p50/p50 homodimer. The elevated NF-κB activity could be correlated with a reduced level of cytoplasmic IκBβ and could be associated with the overexpression of p21CIP1/WAF1 in papilloma cells. Increased NF-κB activity and cytoplasmic accumulation of p21CIP1/WAF1 might counteract death-promoting effects elicited by overexpressed PTEN and reduced activation of Akt and STAT3 previously noted in these tissues. PMID:11773428

Histomorphology of the Olfactory Mucosa and Spinal Tissue Sparing Following Transplantation in the Partial Spinal Cord Injury in Rats

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H Delaviz

2011-01-01

Full Text Available Introduction & Objective: Nowadays, cellular and tissues transplant has become the focus of attention for spinal cord injury. It has been shown olfactory nerve cells or olfactory mucosa whi have more efficient on nervous tissue repair and they have been more studied in experimental study. Furthermore, they were used in a few clinical centers for spinal defect. But mucosa tissue and spinal tissue have different structure and there is doubt about the integration of mucosa tissue in nervous tissue. Thus, in this research the morphology and the effect of the fetal olfactory mucosa (FOM on spinal tissue sparing were studied after transplanted into the spinal cord hemisection in rats. Materials & Methods: This experimental study was conducted at Iran University of Medical Sciences in 2008. Of thirty eight female Sprague-Dawley (200-250g rats twenty- eight were spinally hemisected at the L1 spinal level and were randomized into two groups of 14 animals. Treatment group received FOM graft and the control group received fetal respiratory mucosa graft (FRM. The other animals received surgical procedure without spinal cord injury as a sham group. The morphology of the transplant region and spinal tissue sparing was examined histological eight weeks after transplantation. The collected data was analyzed by the SPSS software using ANOVA and the morphology of the transplant region were studied by light microscope. Results: Histological study showed that the both mucosa tissues could not integrate with the parenchyma of the spinal tissue. Although the FOM were fused more than the FRM with the host tissue but clear boundary was seen at the graft–host interface. The mean spinal tissue sparing of the treatment group increased a little compare to the control but a significant difference was not apparent whereas, the spinal tissue sparing in treatment and control groups compare to the sham group decreased significantly (P < 0.05. Conclusion: Transplantation of

Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs.

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Navaei, Ali; Saini, Harpinder; Christenson, Wayne; Sullivan, Ryan Tanner; Ros, Robert; Nikkhah, Mehdi

2016-09-01

The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly

Soft tissue expansion before vertical ridge augmentation: Inflatable silicone balloons or self-filling osmotic tissue expanders?

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Prasad Vijayrao Dhadse

2014-01-01

Full Text Available Recent advances in periodontal plastic surgical procedures allow the clinician to reconstruct deficient alveolar ridges in more predictable ways than previously possible. Placement of implant/s in resorbed ridges poses numerous challenges to the clinician for successful esthetic and functional rehabilitation. The reconstruction frequently utilizes one or combination of periodontal plastic surgical procedures in conjunction with autogenous bone grafting, allogenic bone block grafting, ridge split techniques, distraction osteogenesis, or guided bone regeneration (GBR for most predictable outcomes. Current surgical modalities used in reconstruction of alveolar ridge (horizontal and/or vertical component often involve the need of flap transfer. Moreover, there is compromise in tissue integrity and color match owing to different surgical site and the tissue utilized is insufficient in quantity leading to post surgical graft exposition and/or loss of grafted bone. Soft tissue expansion (STE by implantation of inflatable silicone balloon or self filling osmotic tissue expanders before reconstructive surgery can overcome these disadvantages and certainly holds a promise for effective method for generation of soft tissue thereby achieving predictable augmentation of deficient alveolar ridges for the implant success. This article focuses and compares these distinct tissue expanders for their clinical efficacy of achieving excess tissue that predominantly seems to be prerequisite for ridge augmentation which can be reasonably followed by successful placement of endosseous fixtures.

Near-infrared spectral tomography integrated with digital breast tomosynthesis: Effects of tissue scattering on optical data acquisition design

Energy Technology Data Exchange (ETDEWEB)

Michaelsen, Kelly; Krishnaswamy, Venkat; Pogue, Brian W.; Poplack, Steven P.; Paulsen, Keith D. [Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755 (United States); Department of Diagnostic Radiology, Dartmouth Medical School, Lebanon, New Hampshire 03756 (United States); Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755 and Department of Diagnostic Radiology, Dartmouth Medical School, Lebanon, New Hampshire 03756 (United States)

2012-07-15

Purpose: Design optimization and phantom validation of an integrated digital breast tomosynthesis (DBT) and near-infrared spectral tomography (NIRST) system targeting improvement in sensitivity and specificity of breast cancer detection is presented. Factors affecting instrumentation design include minimization of cost, complexity, and examination time while maintaining high fidelity NIRST measurements with sufficient information to recover accurate optical property maps. Methods: Reconstructed DBT slices from eight patients with abnormal mammograms provided anatomical information for the NIRST simulations. A limited frequency domain (FD) and extensive continuous wave (CW) NIRST system was modeled. The FD components provided tissue scattering estimations used in the reconstruction of the CW data. Scattering estimates were perturbed to study the effects on hemoglobin recovery. Breast mimicking agar phantoms with inclusions were imaged using the combined DBT/NIRST system for comparison with simulation results. Results: Patient simulations derived from DBT images show successful reconstruction of both normal and malignant lesions in the breast. They also demonstrate the importance of accurately quantifying tissue scattering. Specifically, 20% errors in optical scattering resulted in 22.6% or 35.1% error in quantification of total hemoglobin concentrations, depending on whether scattering was over- or underestimated, respectively. Limited frequency-domain optical signal sampling provided two regions scattering estimates (for fat and fibroglandular tissues) that led to hemoglobin concentrations that reduced the error in the tumor region by 31% relative to when a single estimate of optical scattering was used throughout the breast volume of interest. Acquiring frequency-domain data with six wavelengths instead of three did not significantly improve the hemoglobin concentration estimates. Simulation results were confirmed through experiments in two-region breast mimicking

Near-infrared spectral tomography integrated with digital breast tomosynthesis: Effects of tissue scattering on optical data acquisition design

International Nuclear Information System (INIS)

Michaelsen, Kelly; Krishnaswamy, Venkat; Pogue, Brian W.; Poplack, Steven P.; Paulsen, Keith D.

2012-01-01

Purpose: Design optimization and phantom validation of an integrated digital breast tomosynthesis (DBT) and near-infrared spectral tomography (NIRST) system targeting improvement in sensitivity and specificity of breast cancer detection is presented. Factors affecting instrumentation design include minimization of cost, complexity, and examination time while maintaining high fidelity NIRST measurements with sufficient information to recover accurate optical property maps. Methods: Reconstructed DBT slices from eight patients with abnormal mammograms provided anatomical information for the NIRST simulations. A limited frequency domain (FD) and extensive continuous wave (CW) NIRST system was modeled. The FD components provided tissue scattering estimations used in the reconstruction of the CW data. Scattering estimates were perturbed to study the effects on hemoglobin recovery. Breast mimicking agar phantoms with inclusions were imaged using the combined DBT/NIRST system for comparison with simulation results. Results: Patient simulations derived from DBT images show successful reconstruction of both normal and malignant lesions in the breast. They also demonstrate the importance of accurately quantifying tissue scattering. Specifically, 20% errors in optical scattering resulted in 22.6% or 35.1% error in quantification of total hemoglobin concentrations, depending on whether scattering was over- or underestimated, respectively. Limited frequency-domain optical signal sampling provided two regions scattering estimates (for fat and fibroglandular tissues) that led to hemoglobin concentrations that reduced the error in the tumor region by 31% relative to when a single estimate of optical scattering was used throughout the breast volume of interest. Acquiring frequency-domain data with six wavelengths instead of three did not significantly improve the hemoglobin concentration estimates. Simulation results were confirmed through experiments in two-region breast mimicking

3D bioprinting of tissues and organs.

Science.gov (United States)

Murphy, Sean V; Atala, Anthony

2014-08-01

Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

Science.gov (United States)

Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

2016-05-17

Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

Disturbance of the gut-associated lymphoid tissue is associated with disease progression in chronic HIV infection.

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Hofer, Ursula; Speck, Roberto F

2009-07-01

Why and how HIV makes people sick is highly debated. Recent evidence implicates heightened immune activation due to breakdown of the gastrointestinal barrier as a determining factor of lentiviral pathogenesis. HIV-mediated loss of Th17 cells from the gut-associated lymphoid tissue (GALT) impairs mucosal integrity and innate defense mechanisms against gut microbes. Translocation of microbial products from the gut, in turn, correlates with increased immune activation in chronic HIV infection and may further damage the immune system by increasing viral and activation-induced T cell death, by reducing T cell reconstitution due to tissue scarring, and by impairing the function of other cell types, such as gammadelta T cells and epithelial cells. Maintaining a healthy GALT may be the key to reducing the pathogenic potential of HIV.

Effect of experimentally increased protein supply to postpartum dairy cows on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis.

Science.gov (United States)

Larsen, M; Røntved, C M; Theil, P K; Khatun, M; Lauridsen, C; Kristensen, N B

2017-05-01

The effect of experimentally increasing the postpartum protein supply on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis was studied using 8 periparturient Holstein cows in a complete randomized design. At calving, cows were assigned to abomasal infusion of water (CTRL) or casein (CAS) in addition to a lactation diet. Casein infusion was gradually decreased from 696 ± 1 g/d at +2 d relative to calving (DRTC) to 212 ± 10 g/d at +29 DRTC to avoid excessive supply. Synthesis rate of plasma proteins was measured at -14, +4, +15, and +29 DRTC by measuring [C]Phe isotopic enrichment in arterial plasma free Phe, total plasma proteins, and albumin after 3, 5, and 7 h of jugular ring[C]Phe infusion. Plasma volume was determined at +4 and +29 DRTC by dilution of a [I]BSA dose. Synthesis rate of tissue protein in biopsied rumen papillae was determined by measuring [C]Phe isotopic enrichment, and mRNA expression of selected genes was measured by real-time qPCR. Total and differential leukocyte counts were performed and immune responsiveness of monocytes was evaluated by tumor necrosis factor ɑ (TNFɑ) concentration on ex vivo whole blood stimulation with Escherichia coli lipopolysaccharide (LPS) and responsiveness of T-lymphocytes by interferon γ (IFNγ) concentration on stimulation with Staphylococcus aureus enterotoxin β (SEB). Further, ELISA plasma concentrations of IgM, IgA, and IgG were determined. The DRTC affected the majority of investigated parameters as expected. The CAS treatment increased milk protein yield (P = 0.04), and tended to lower TNFɑ (P = 0.06), and lowered IFNγ (P = 0.03) responsiveness per monocyte and lymphocyte, respectively, compared with CTRL. Further, fractional synthesis rate of albumin was greater at +4 DRTC for CAS compared with CTRL but did not differ by +29 DRTC (interaction: P = 0.01). In rumen papillae, synthesis rate of tissue protein was greater for CAS compared with CTRL (P protein supply seem to

Fructose increases corticosterone production in association with NADPH metabolism alterations in rat epididymal white adipose tissue.

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Prince, Paula D; Santander, Yanina A; Gerez, Estefania M; Höcht, Christian; Polizio, Ariel H; Mayer, Marcos A; Taira, Carlos A; Fraga, Cesar G; Galleano, Monica; Carranza, Andrea

2017-08-01

Metabolic syndrome is an array of closely metabolic disorders that includes glucose intolerance/insulin resistance, central obesity, dyslipidemia, and hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects in adipose tissue, and has been associated with the etiopathology of many components of the metabolic syndrome. In adipocytes, the enzyme 11 β-HSD1 amplifies local glucocorticoid production, being a key player in the pathogenesis of central obesity and metabolic syndrome. 11 β-HSD1 reductase activity is dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic reticulum. Our focus was to explore the effect of fructose overload on epididymal white adipose tissue (EWAT) machinery involved in glucocorticoid production and NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose solution (10% (w/v) in tap water) during 9 weeks developed some characteristic features of metabolic syndrome, such as hypertriglyceridemia, and hypertension. In addition, high levels of plasma and EWAT corticosterone were detected. Activities and expressions of H6PD and 11 β-HSD1, NAPDH content, superoxide anion production, expression of NADPH oxidase 2 subunits, and indicators of oxidative metabolism were measured. Fructose overloaded rats showed an increased potential in oxidant production respect to control rats. In parallel, in EWAT from fructose overloaded rats we found higher expression/activity of H6PD and 11 β-HSD1, and NADPH/NADP + ratio. Our in vivo results support that fructose overload installs in EWAT conditions favoring glucocorticoid production through higher H6PD expression/activity supplying NADPH for enhanced 11 β-HSD1 expression/activity, becoming this tissue a potential extra-adrenal source of corticosterone under these experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

Science.gov (United States)

Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

2016-03-21

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

Directory of Open Access Journals (Sweden)

Tegan L Cheng

2015-10-01

Full Text Available Sucrose acetate isobutyrate (SAIB is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2 and found synergy when co-delivering zoledronic acid (ZA and hydroxyapatite (HA nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP nor Bioglass (BG 45S5 had a significant effect on bone volume (BV alone or in combination with the ZA. 14C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%, and BV was further increased with ZA–adsorbed micro-HA and nano-HA (+530% and +889%. These data support the use of ZA–adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering.

Endurance training blocks uncoupling protein 1 up-regulation in brown adipose tissue while increasing uncoupling protein 3 in the muscle tissue of rats fed with a high-sugar diet.

Science.gov (United States)

de Queiroz, Karina Barbosa; Rodovalho, Gisele Vieira; Guimarães, Juliana Bohnen; de Lima, Daniel Carvalho; Coimbra, Cândido Celso; Evangelista, Elísio Alberto; Guerra-Sá, Renata

2012-09-01

The mitochondrial uncoupling proteins (UCPs) of interscapular brown adipose tissue (iBAT) and of muscles play important roles in energy balance. For instance, the expression of UCP1 and UCP3 are modulated by free fatty acid gradients induced by high-sugar diets and acute exercise that is dependent on sympathetic stimulation. However, the effects of endurance training in animals fed with high-sugar diets are unknown. This study aims to evaluate the long-term effects of diet and exercise on UCP1 and UCP3 levels and energy balance efficiency. Rats fed with standard or high-sugar (HSD) diets were simultaneously subjected to running training over an 8-week period. After the training period, the rats were decapitated, and the iBAT and gastrocnemius muscle tissues were removed for evaluation of the β₃-receptor, Ucp1, and Ucp3 mRNA and protein expression, which were analyzed by quantitative reverse transcriptase polymerase chain reaction and Western blot, respectively. Groups fed with an HSD displayed a higher adiposity index and iBAT weight (P < .05), whereas exhibited an up-regulation of Ucp1 mRNA and protein levels (P < .05). Training increased β₃-receptor mRNA in iBAT and reduced the Ucp3 mRNA in muscle tissues. In association with an HSD, training restored the increasing β₃-receptor mRNA and greatly up-regulated the levels of Ucp3 mRNA. Therefore, training blocked the HSD-induced up-regulation of UCP1 expression in iBAT, whereas it up-regulated the expression of Ucp3 mRNA in muscle. These results suggest that training enhances the relationship between Ucp1/Ucp3 mRNA levels, which could result in higher energy efficiency, but not when HSD-induced elevated sympathetic activity is maintained. Copyright © 2012. Published by Elsevier Inc.

Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference

International Nuclear Information System (INIS)

Wan Hong; South, Andrew P.; Hart, Ian R.

2007-01-01

The intercellular adhesive junction desmosomes are essential for the maintenance of tissue structure and integrity in skin. Desmoplakin (Dp) is a major obligate plaque protein which plays a fundamental role in anchoring intermediate filaments to desmosomal cadherins. Evidence from hereditary human disease caused by mutations in the gene encoding Dp, e.g. Dp haploinsufficiency, suggests that alterations in Dp expression result not only in the disruption of tissue structure and integrity but also could evoke changes in keratinocyte proliferation. We have used transient RNA interference (RNAi) to downregulate Dp specifically in HaCaT keratinocytes. We showed that this Dp downregulation also caused reduced expression of several other desmosomal proteins. Increased cell proliferation and enhanced G 1 -to-S-phase entry in the cell cycle, as monitored by colonial cellular density and BrdU incorporation, were seen in Dp RNAi-treated cells. These proliferative changes were associated with elevated phospho-ERK1/2 and phospho-Akt levels. Furthermore, this increase in phospho-ERK/1/2 and phospho-Akt levels was sustained in Dp RNAi-treated cells at confluence whereas in control cells there was a significant reduction in phosphorylation of ERK1/2. This study indicates that Dp may participate in the regulation of keratinocyte cell proliferation by, in part at least, regulating cell cycle progression

Association between increased epicardial adipose tissue volume and coronary plaque composition

OpenAIRE

Yamashita, Kennosuke; Yamamoto, Myong Hwa; Ebara, Seitarou; Okabe, Toshitaka; Saito, Shigeo; Hoshimoto, Koichi; Yakushiji, Tadayuki; Isomura, Naoei; Araki, Hiroshi; Obara, Chiaki; Ochiai, Masahiko

2013-01-01

To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or ...

The complementarity of the technical tools of tissue engineering and the concepts of artificial organs for the design of functional bioartificial tissues.

Science.gov (United States)

Lenas, Petros; Moreno, Angel; Ikonomou, Laertis; Mayer, Joerg; Honda, Hiroyuki; Novellino, Antonio; Pizarro, Camilo; Nicodemou-Lena, Eleni; Rodergas, Silvia; Pintor, Jesus

2008-09-01

Although tissue engineering uses powerful biological tools, it still has a weak conceptual foundation, which is restricted at the cell level. The design criteria at the cell level are not directly related with the tissue functions, and consequently, such functions cannot be implemented in bioartificial tissues with the currently used methods. On the contrary, the field of artificial organs focuses on the function of the artificial organs that are treated in the design as integral entities, instead of the optimization of the artificial organ components. The field of artificial organs has already developed and tested methodologies that are based on system concepts and mathematical-computational methods that connect the component properties with the desired global organ function. Such methodologies are needed in tissue engineering for the design of bioartificial tissues with tissue functions. Under the framework of biomedical engineering, artificial organs and tissue engineering do not present competitive approaches, but are rather complementary and should therefore design a common future for the benefit of patients.

Tissue Engineering: Toward a New Era of Medicine.

Science.gov (United States)

Shafiee, Ashkan; Atala, Anthony

2017-01-14

The goal of tissue engineering is to mitigate the critical shortage of donor organs via in vitro fabrication of functional biological structures. Tissue engineering is one of the most prominent examples of interdisciplinary fields, where scientists with different backgrounds work together to boost the quality of life by addressing critical health issues. Many different fields, such as developmental and molecular biology, as well as technologies, such as micro- and nanotechnologies and additive manufacturing, have been integral for advancing the field of tissue engineering. Over the past 20 years, spectacular advancements have been achieved to harness nature's ability to cure diseased tissues and organs. Patients have received laboratory-grown tissues and organs made out of their own cells, thus eliminating the risk of rejection. However, challenges remain when addressing more complex solid organs such as the heart, liver, and kidney. Herein, we review recent accomplishments as well as challenges that must be addressed in the field of tissue engineering and provide a perspective regarding strategies in further development.

Differentiated embryonic chondrocytes 1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis.

Science.gov (United States)

Hu, Shenlin; Shang, Wei; Yue, Haitao; Chen, Ruini; Dong, Zheng; Hu, Jinhua; Mao, Zhao; Yang, Jian

2015-04-01

To evaluate the DEC1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis. 20 non-smoking patients with chronic periodontitis and 20 healthy individuals were enrolled. Periodontal ligament tissue and gingival tissue samples from healthy subjects were collected during teeth extraction for orthodontic reason or the third molar extraction. The parallel samples from patients with chronic periodontitis were obtained during periodontal flap operations or teeth extraction as part of periodontal treatment. The DEC1 expression and the alkaline phosphatase (ALP) activity of both the periodontal ligament tissue and gingival tissue were determined by Western blot, Immunohistochemistry and ALP Detection Kit. The DEC1 expression of periodontal ligament tissue in the patients with chronic periodontitis decreased significantly along with the decreased ALP activity. On the contrary, the DEC1 expression of gingival tissue in the patients with chronic periodontitis increased significantly. Further study found that the DEC1 expression of gingival tissue increased mainly in the suprabasal layer of gingival epithelial cells but decreased in the gingival connective tissue of the patients with chronic periodontitis. The DEC1 expression decreases in the periodontal ligament tissue which is related to the osteogenic capacity, whereas the DEC1 expression increases in the suprabasal layer of gingival epithelial cells which are involved in immune inflammatory response in the patients with chronic periodontitis. The findings provide a new target to explore the pathology and the therapy of periodontitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synovial tissue research

DEFF Research Database (Denmark)

Orr, Carl; Sousa, Elsa; Boyle, David L

2017-01-01

The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable...... easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly...... diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis...

Application of Hanging Drop Technique for Kidney Tissue Culture.

Science.gov (United States)

Wang, Shaohui; Wang, Ximing; Boone, Jasmine; Wie, Jin; Yip, Kay-Pong; Zhang, Jie; Wang, Lei; Liu, Ruisheng

2017-01-01

The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli. © 2017 The Author(s). Published by S. Karger AG, Basel.

Application of Hanging Drop Technique for Kidney Tissue Culture

Directory of Open Access Journals (Sweden)

Shaohui Wang

2017-05-01

Full Text Available Background/Aims: The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. Methods: In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. Results: The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. Conclusions: We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli.

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.

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Gregory N Ruegsegger

Full Text Available In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA. IPA was chosen to assist in the understanding of complex 'omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10-11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05 between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

Comparison Between Several Integrase-defective Lentiviral Vectors Reveals Increased Integration of an HIV Vector Bearing a D167H Mutant

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Muhammad Qamar Saeed

2014-01-01

Full Text Available HIV-1 derived vectors are among the most efficient for gene transduction in mammalian tissues. As the parent virus, they carry out vector genome insertion into the host cell chromatin. Consequently, their preferential integration in transcribed genes raises several conceptual and safety issues. To address part of these questions, HIV-derived vectors have been engineered to be nonintegrating. This was mainly achieved by mutating HIV-1 integrase at functional hotspots of the enzyme enabling the development of streamlined nuclear DNA circles functional for transgene expression. Few integrase mutant vectors have been successfully tested so far for gene transfer. They are cleared with time in mitotic cells, but stable within nondividing retina cells or neurons. Here, we compared six HIV vectors carrying different integrases, either wild type or with different mutations (D64V, D167H, Q168A, K186Q+Q214L+Q216L, and RRK262-264AAH shown to modify integrase enzymatic activity, oligomerization, or interaction with key cellular cofactor of HIV DNA integration as LEDGF/p75 or TNPO3. We show that these mutations differently affect the transduction efficiency as well as rates and patterns of integration of HIV-derived vectors suggesting their different processing in the nucleus. Surprisingly and most interestingly, we report that an integrase carrying the D167H substitution improves vector transduction efficiency and integration in both HEK-293T and primary CD34+ cells.

The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears.

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Rothrauff, Benjamin B; Pauyo, Thierry; Debski, Richard E; Rodosky, Mark W; Tuan, Rocky S; Musahl, Volker

2017-08-01

The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.

Silk: a potential medium for tissue engineering.

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Sobajo, Cassandra; Behzad, Farhad; Yuan, Xue-Feng; Bayat, Ardeshir

2008-01-01

Human skin is a complex bilayered organ that serves as a protective barrier against the environment. The loss of integrity of skin by traumatic experiences such as burns and ulcers may result in considerable disability or ultimately death. Therefore, in skin injuries, adequate dermal substitutes are among primary care targets, aimed at replacing the structural and functional properties of native skin. To date, there are very few single application tissue-engineered dermal constructs fulfilling this criterion. Silk produced by the domestic silkworm, Bombyx mori, has a long history of use in medicine. It has recently been increasingly investigated as a promising biomaterial for dermal constructs. Silk contains 2 fibrous proteins, sericin and fibroin. Each one exhibits unique mechanical and biological properties. Comprehensive review of randomized-controlled trials investigating current dermal constructs and the structures and properties of silk-based constructs on wound healing. This review revealed that silk-fibroin is regarded as the most promising biomaterial, providing options for the construction of tissue-engineered skin. The research available indicates that silk fibroin is a suitable biomaterial scaffold for the provision of adequate dermal constructs.

Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

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BA Walter

2016-07-01

Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

Suramin Inhibits Osteoarthritic Cartilage Degradation by Increasing Extracellular Levels of Chondroprotective Tissue Inhibitor of Metalloproteinases 3.

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Chanalaris, Anastasios; Doherty, Christine; Marsden, Brian D; Bambridge, Gabriel; Wren, Stephen P; Nagase, Hideaki; Troeberg, Linda

2017-10-01

Osteoarthritis is a common degenerative joint disease for which no disease-modifying drugs are currently available. Attempts to treat the disease with small molecule inhibitors of the metalloproteinases that degrade the cartilage matrix have been hampered by a lack of specificity. We aimed to inhibit cartilage degradation by augmenting levels of the endogenous metalloproteinase inhibitor, tissue inhibitor of metalloproteinases (TIMP)-3, through blocking its interaction with the endocytic scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1). We discovered that suramin (C 51 H 40 N 6 O 23 S 6 ) bound to TIMP-3 with a K D value of 1.9 ± 0.2 nM and inhibited its endocytosis via LRP1, thus increasing extracellular levels of TIMP-3 and inhibiting cartilage degradation by the TIMP-3 target enzyme, adamalysin-like metalloproteinase with thrombospondin motifs 5. NF279 (8,8'-[carbonyl bis (imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)] bis -1,3,5-naphthalenetrisulfonic acid hexasodium salt), a structural analog of suramin, has an increased affinity for TIMP-3 and increased ability to inhibit TIMP-3 endocytosis and protect cartilage. Suramin is thus a promising scaffold for the development of novel therapeutics to increase TIMP-3 levels and inhibit cartilage degradation in osteoarthritis. Copyright © 2017 by The Author(s).

Practical experience in post-mortem tissue donation in consideration of the European tissue law.

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Karbe, Thomas; Braun, Christian; Wulff, Birgit; Schröder, Ann Sophie; Püschel, Klaus; Bratzke, Hansjürgen; Parzeller, Markus

2010-03-01

In consequence of the European guidelines of safety and quality standards for the donation, retrieval, storing and distribution of human tissues and cells the purpose of tissue transplantation was implemented into German legislation in May 2007. The law came into effect on August 1st 2007 considering of the European rules. The Institutes for Legal Medicine of the University of Frankfurt/Main and the University Medical Center Hamburg-Eppendorf developed a model for tissue retrieval. The Institute of Legal Medicine (I.f.R.) at the University Medical Center Hamburg cooperates with the German Institute of Cell and Tissue Replacement (Deutsches Institut für Zell--und Gewebeersatz DIZG). Potential post-mortem tissue donors (PMTD) among the deceased are selected by standardized sets of defined criteria. The procedure is guided by the intended exclusion criteria of the tissue regulation draft (German Transplant Law TPG GewV) in accordance with the European Guideline (2006/17/EC). Following the identification of the donor and subsequent removal of tissue, the retrieved samples were sent to the DIZG, a non-profit tissue bank according to the tissue regulation. Here the final processing into transplantable tissue grafts takes place, which then results in the allocation of tissue to hospitals in Germany and other European countries. The Center of Legal Medicine at the Johann Wolfgang Goethe-University Medical Center Frankfurt/Main cooperates since 2000 with Tutogen, a pharmaceutical company. Harvesting of musculoskeletal tissues follows corresponding regulations. To verify the outcome of PMTD at the I.f.R. Hamburg, two-statistic analysis over 12 and 4 months have been implemented. Our results have shown an increasing number of potential appropriate PMTD within the second inquiry interval but a relatively small and unvaryingly rate of successful post-mortem tissue retrievals similar to the first examination period. Thus, the aim of the model developed by the I.f.R. is to

Functionally enhanced brown adipose tissue in Ames dwarf mice.

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Darcy, Justin; Bartke, Andrzej

2017-01-02

Reduced insulin-like growth factor 1/insulin signaling (IIS) has been linked to extended longevity in species ranging from yeast to mammals. In mammals, this is exemplified in Ames dwarf (Prop1 df/df ) mice, which have a 40%-60% increase in longevity (males and females, respectively) due to their recessive Prop1 loss-of-function mutation that results in lack of growth hormone (GH), thyroid-stimulating hormone and prolactin. Our laboratory has previously shown that Ames dwarf mice have functionally unique white adipose tissue (WAT) that improves, rather than impairs, insulin sensitivity. Because GH and thyroid hormone are integral to adipose tissue development and function, we hypothesized that brown adipose tissue (BAT) in Ames dwarf mice may also be functionally unique and/or enhanced. Here, we elaborate on our recent findings, which demonstrate that BAT is functionally enhanced in Ames dwarf mice, and suggest that BAT removal in these mice results in utilization of WAT depots as an energy source. We also discuss how our findings compare to those in other long-lived dwarf mice with altered IIS, which unlike Ames dwarf mice, are essentially euthyroid. Lastly, we provide some insights into the implications of these findings and discuss some of the necessary future work in this area.

Fabrication of scaffolds in tissue engineering: A review

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Zhao, Peng; Gu, Haibing; Mi, Haoyang; Rao, Chengchen; Fu, Jianzhong; Turng, Lih-sheng

2018-03-01

Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

Brown adipose tissue (BAT specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation

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Juliane Weiner

2017-06-01

Full Text Available Objective: Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT biology. Methods: We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT and plasma levels. Vaspin expression was analyzed in isolated white and brown adipocytes during adipogenesis and in response to adrenergic stimuli. DNA-methylation within the vaspin promoter was analyzed to investigate acute epigenetic changes after cold-exposure in BAT. Results: Our results demonstrate a strong induction of vaspin mRNA and protein expression specifically in BAT of both cold-exposed and high-fat (HF or high-sugar (HS fed mice. While obesogenic diets also upregulated hepatic vaspin mRNA levels, cold exposure tended to increase vaspin gene expression of inguinal white adipose tissue (iWAT depots. Concomitantly, vaspin plasma levels were decreased upon obesogenic or thermogenic triggers. Vaspin expression was increased during adipogenesis but unaffected by sympathetic activation in brown adipocytes. Analysis of vaspin promoter methylation in AT revealed lowest methylation levels in BAT, which were acutely reduced after cold exposure. Conclusions: Our data demonstrate a novel BAT-specific regulation of vaspin gene expression upon physiological stimuli in vivo with acute epigenetic changes that may contribute to cold-induced expression in BAT. We conclude that these findings indicate functional relevance and potentially beneficial effects of vaspin in BAT function. Keywords: Brown adipose tissue, Browning, Cold exposure, DNA methylation, High-fat diet, High-sucrose diet, SerpinA12, Thermogenesis

Potential application of Chinese traditional medicine (CTM) as enhancer for tissue optical clearing

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Chen, Wei; Jiang, Jingying; Wang, Ruikang K.; Xu, Kexin

2009-02-01

Many biocompatible hyperosmotic agents such as dimethyl sulfoxide(DMSO) have been used as enhancers for tissue optical clearing technique. However, previous investigations showed that DMSO can induce bradycardia, respiratory problems, and alterations in blood pressure. Also, DMSO could potentially alter the chemical structure, and hence the functional properties, of cell membranes. In this talk, Borneol among natural and nontoxic CTMs was introduced as new enhancer for optical clearing of porcine skin tissue since it has been widely used as new penetration promoter in the field of trandermial drug delivery system(TDDS) and been proved to be effective. In the first, the spectral characteristics of borneol was obtained and analyzed by Fourier Transformation Infrared (FTIR) spectrophotometer. And further experimental studies were performed to probe if borneol is capable of optical clearing of porcine skin tissue in vitro with near infrared spectroscopy, double integrating-spheres system and Inverse Adding-Doubling(IAD) algorithm. Spectral results show that light penetration depth into skin tissue got the increase. Meanwhile, absorption coefficient and scattering coefficient of porcine skin treated by borneol got the decrease during the permeation of Borneol. Therefore, Borneol could be potentially used as enhancer for tissue optical clearing to improve non-invasive light-based diagnostic and imaging techniques while practically optical application and clinical safety are under consideration.

Indirect Low-Intensity Ultrasonic Stimulation for Tissue Engineering

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Hyoungshin Park

2010-01-01

Full Text Available Low-intensity ultrasound (LIUS treatment has been shown to increase mass transport, which could benefit tissue grafts during the immediate postimplant period, when blood supply to the implanted tissue is suboptimal. In this in vitro study, we investigated effects of LIUS stimulation on dye diffusion, proliferation, metabolism, and tropomyosin expression of muscle cells (C2C12 and on tissue viability and gene expression of human adipose tissue organoids. We found that LIUS increased dye diffusion within adjacent tissue culture wells and caused anisotropic diffusion patterns. This effect was confirmed by a hydrophone measurement resulting in acoustic pressure 150–341 Pa in wells. Cellular studies showed that LIUS significantly increased proliferation, metabolic activity, and expression of tropomyosin. Adipose tissue treated with LIUS showed significantly increased metabolic activity and the cells had similar morphology to normal unilocular adipocytes. Gene analysis showed that tumor necrosis factor-alpha expression (a marker for tissue damage was significantly lower for stimulated organoids than for control groups. Our data suggests that LIUS could be a useful modality for improving graft survival in vivo.

Soft Tissue Tumor Immunohistochemistry Update: Illustrative Examples of Diagnostic Pearls to Avoid Pitfalls.

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Wei, Shi; Henderson-Jackson, Evita; Qian, Xiaohua; Bui, Marilyn M

2017-08-01

- Current 2013 World Health Organization classification of tumors of soft tissue arranges these tumors into 12 groups according to their histogenesis. Tumor behavior is classified as benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant. In our practice, a general approach to reaching a definitive diagnosis of soft tissue tumors is to first evaluate clinicoradiologic, histomorphologic, and cytomorphologic features of the tumor to generate some pertinent differential diagnoses. These include the potential line of histogenesis and whether the tumor is benign or malignant, and low or high grade. Although molecular/genetic testing is increasingly finding its applications in characterizing soft tissue tumors, currently immunohistochemistry still not only plays an indispensable role in defining tumor histogenesis, but also serves as a surrogate for underlining molecular/genetic alterations. Objective- To provide an overview focusing on the current concepts in the classification and diagnosis of soft tissue tumors, incorporating immunohistochemistry. This article uses examples to discuss how to use the traditional and new immunohistochemical markers for the diagnosis of soft tissue tumors. Practical diagnostic pearls, summary tables, and figures are used to show how to avoid diagnostic pitfalls. - Data were obtained from pertinent peer-reviewed English-language literature and the authors' first-hand experience as bone and soft tissue pathologists. - -The ultimate goal for a pathologist is to render a specific diagnosis that provides diagnostic, prognostic, and therapeutic information to guide patient care. Immunohistochemistry is integral to the diagnosis and management of soft tissue tumors.

Hybrid piezoresistive-optical tactile sensor for simultaneous measurement of tissue stiffness and detection of tissue discontinuity in robot-assisted minimally invasive surgery

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Bandari, Naghmeh M.; Ahmadi, Roozbeh; Hooshiar, Amir; Dargahi, Javad; Packirisamy, Muthukumaran

2017-07-01

To compensate for the lack of touch during minimally invasive and robotic surgeries, tactile sensors are integrated with surgical instruments. Surgical tools with tactile sensors have been used mainly for distinguishing among different tissues and detecting malignant tissues or tumors. Studies have revealed that malignant tissue is most likely stiffer than normal. This would lead to the formation of a sharp discontinuity in tissue mechanical properties. A hybrid piezoresistive-optical-fiber sensor is proposed. This sensor is investigated for its capabilities in tissue distinction and detection of a sharp discontinuity. The dynamic interaction of the sensor and tissue is studied using finite element method. The tissue is modeled as a two-term Mooney-Rivlin hyperelastic material. For experimental verification, the sensor was microfabricated and tested under the same conditions as of the simulations. The simulation and experimental results are in a fair agreement. The sensor exhibits an acceptable linearity, repeatability, and sensitivity in characterizing the stiffness of different tissue phantoms. Also, it is capable of locating the position of a sharp discontinuity in the tissue. Due to the simplicity of its sensing principle, the proposed hybrid sensor could also be used for industrial applications.

Harmonic motion imaging for focused ultrasound (HMIFU): a fully integrated technique for sonication and monitoring of thermal ablation in tissues

International Nuclear Information System (INIS)

Maleke, C; Konofagou, E E

2008-01-01

FUS (focused ultrasound), or HIFU (high-intensity-focused ultrasound) therapy, a minimally or non-invasive procedure that uses ultrasound to generate thermal necrosis, has been proven successful in several clinical applications. This paper discusses a method for monitoring thermal treatment at different sonication durations (10 s, 20 s and 30 s) using the amplitude-modulated (AM) harmonic motion imaging for focused ultrasound (HMIFU) technique in bovine liver samples in vitro. The feasibility of HMI for characterizing mechanical tissue properties has previously been demonstrated. Here, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) transducer, was used. The therapy transducer was driven by a low-frequency AM continuous signal at 25 Hz, producing a stable harmonic radiation force oscillating at the modulation frequency. A pulser/receiver was used to drive the pulse-echo transducer at a pulse repetition frequency (PRF) of 5.4 kHz. Radio-frequency (RF) signals were acquired using a standard pulse-echo technique. The temperature near the ablation region was simultaneously monitored. Both RF signals and temperature measurements were obtained before, during and after sonication. The resulting axial tissue displacement was estimated using one-dimensional cross correlation. When temperature at the focal zone was above 48 deg. C during heating, the coagulation necrosis occurred and tissue damage was irreversible. The HMI displacement profiles in relation to the temperature and sonication durations were analyzed. At the beginning of heating, the temperature at the focus increased sharply, while the tissue stiffness decreased resulting in higher HMI displacements. This was confirmed by an increase of 0.8 μm deg. C -1 (r = 0.93, p -1 , r = -0.92, p -1 , prior to and after lesion formation in seven bovine liver samples, respectively. This technique was thus capable of following the protein-denatured lesion formation based on the

Tissue Multiplatform-Based Metabolomics/Metabonomics for Enhanced Metabolome Coverage.

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Vorkas, Panagiotis A; Abellona U, M R; Li, Jia V

2018-01-01

The use of tissue as a matrix to elucidate disease pathology or explore intervention comes with several advantages. It allows investigation of the target alteration directly at the focal location and facilitates the detection of molecules that could become elusive after secretion into biofluids. However, tissue metabolomics/metabonomics comes with challenges not encountered in biofluid analyses. Furthermore, tissue heterogeneity does not allow for tissue aliquoting. Here we describe a multiplatform, multi-method workflow which enables metabolic profiling analysis of tissue samples, while it can deliver enhanced metabolome coverage. After applying a dual consecutive extraction (organic followed by aqueous), tissue extracts are analyzed by reversed-phase (RP-) and hydrophilic interaction liquid chromatography (HILIC-) ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) and nuclear magnetic resonance (NMR) spectroscopy. This pipeline incorporates the required quality control features, enhances versatility, allows provisional aliquoting of tissue extracts for future guided analyses, expands the range of metabolites robustly detected, and supports data integration. It has been successfully employed for the analysis of a wide range of tissue types.

Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

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Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

Dihydrotestosterone induces pro-angiogenic factors and assists homing of MSC into the cardiac tissue.

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Popa, Mirel-Adrian; Mihai, Maria-Cristina; Constantin, Alina; Şuică, Viorel; Ţucureanu, Cătălin; Costache, Raluca; Antohe, Felicia; Dubey, Raghvendra K; Simionescu, Maya

2018-01-01

The use of mesenchymal stem cells (MSC) as a therapeutic tool in cardiovascular diseases is promising. Since androgens exert some beneficial actions on the cardiovascular system, we tested our hypothesis that this hormone could promote MSC-mediated repair processes, also. Cultured MSCs isolated from Wharton's jelly were exposed to 30 nM dihydrotestosterone (DHT) for 1 or 4 days and the effects of the hormone on their growth/migration/adhesion and the underlying mechanisms were assessed. Results were obtained by real-time cell impedance measurements, and DNA quantification showed that DHT increased MSC proliferation by ~30%. As determined by xCELLigence system, DHT augmented (~2 folds) the migration of MSC toward cardiac tissue slices (at 12 h), and this effect was blocked by flutamide, an androgen receptor (AR) antagonist. Exposure of cells to DHT, upregulated the gene and protein expression of AR , EMMPRIN and MMP-9 and downregulated the expression of MMP-2 DHT significantly induced the release of nitric oxide by MSC (≥2-fold) and flutamide blocked this effect. When MSCs were co-cultured with cardiac slices, immunohistochemical analysis and qRT-PCR showed that the integration of DHT-stimulated MSC was significantly higher than that of in controls. In conclusion, our findings provide the first evidence that DHT promotes MSC growth, migration and integration into the cardiac slices. The modulating effects of DHT were associated with upregulation of ARs and of key molecules known to promote tissue remodeling and angiogenesis. Our findings suggest that priming of MSC with DHT may potentially increase their capability to regenerate cardiac tissue; in vivo studies are needed to confirm our in vitro findings. © 2018 Society for Endocrinology.

Fluoxetine induces lean phenotype in rat by increasing the brown/white adipose tissue ratio and UCP1 expression.

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da Silva, A I; Braz, G R F; Pedroza, A A; Nascimento, L; Freitas, C M; Ferreira, D J S; Manhães de Castro, R; Lagranha, C J

2015-08-01

The serotonergic system plays a crucial role in the energy balance regulation. Energy balance is mediated by food intake and caloric expenditure. Thus, the present study investigated the mechanisms that might be associated with fluoxetine treatment-induced weight reduction. Wistar male rat pups received daily injections with subcutaneous fluoxetine (Fx-group) or vehicle solution (Ct-group) from day 1 until 21 days of age. Several analyses were conducted to verify the involvement of mitochondria in weight reduction. We found that body weight in the Fx-group was lower compared to control. In association to lower fat mass in the Fx-group (25%). Neither neonatal caloric intake nor food intake reveals significant differences. Evaluating caloric expenditure (locomotor activity and temperature after stimulus), we did not observe differences in locomotor activity. However, we observed that the Fx group had a higher capacity to maintain body temperature in a cold environment compared with the Ct-group. Since brown adipose tissue-(BAT) is specialized for heat production and the rate of heat production is related to mitochondrial function, we found that Fx-treatment increases respiration by 36%, although after addition of GDP respiration returned to Ct-levels. Examining ROS production we observe that Fx-group produced less ROS than control group. Evaluating uncoupling protein (UCP) expression we found that Fx-treatment increases the expression by 23%. Taken together, our results suggest that modulation of serotonin system results in positive modulation of UCP and mitochondrial bioenergetics in brown fat tissue.

From cells to tissue: A continuum model of epithelial mechanics

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Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

2017-08-01

A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

Can Integration of Agriculture With International Trade Increase ...

African Journals Online (AJOL)

Human activity is greatly constituted by transactions and exchange that can impoverish primary producers while unfairly making others rich in an inequitable manner. Integration of agriculture into international trade is always thought and assumed to bring greater income benefit to farmers, but is this really the case, ...

Increasing Secondary Teachers' Capacity to Integrate the Arts

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Richard, Byron; Treichel, Christa J.

2013-01-01

Examples from a team of collaborating secondary teachers--one visual arts teacher and one science teacher--highlight key aspects of this professional development project in arts integration. The article traces a regional network designed to build teacher capacity with implications for the design, effectiveness, and sustainability of professional…

Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

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Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

2016-10-01

In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modification of PLGA Nanofibrous Mats by Electron Beam Irradiation for Soft Tissue Regeneration

Directory of Open Access Journals (Sweden)

Jae Baek Lee

2015-01-01

Full Text Available Biodegradable poly(lactide-co-glycolide (PLGA has found widespread use in modern medical practice. However, the degradation rate of PLGA should be adjusted for specific biomedical applications such as tissue engineering, drug delivery, and surgical implantation. This study focused on the effect of electron beam radiation on nanofibrous PLGA mats in terms of physical properties and degradation behavior with cell proliferation. PLGA nanofiber mats were prepared by electrospinning, and electron beam was irradiated at doses of 50, 100, 150, 200, 250, and 300 kGy. PLGA mats showed dimensional integrity after electron beam irradiation without change of fiber diameter. The degradation behavior of a control PLGA nanofiber (0 kGy and electron beam-irradiated PLGA nanofibers was analyzed by measuring the molecular weight, weight loss, change of chemical structure, and fibrous morphology. The molecular weight of the PLGA nanofibers decreased with increasing electron beam radiation dose. The mechanical properties of the PLGA nanofibrous mats were decreased with increasing electron beam irradiation dose. Cell proliferation behavior on all electron beam irradiated PLGA mats was similar to the control PLGA mats. Electron beam irradiation of PLGA nanofibrous mats is a potentially useful approach for modulating the biodegradation rate of tissue-specific nonwoven nanofibrous scaffolds, specifically for soft tissue engineering applications.

Ultrasound Imaging Techniques for Spatiotemporal Characterization of Composition, Microstructure, and Mechanical Properties in Tissue Engineering.

Science.gov (United States)

Deng, Cheri X; Hong, Xiaowei; Stegemann, Jan P

2016-08-01

Ultrasound techniques are increasingly being used to quantitatively characterize both native and engineered tissues. This review provides an overview and selected examples of the main techniques used in these applications. Grayscale imaging has been used to characterize extracellular matrix deposition, and quantitative ultrasound imaging based on the integrated backscatter coefficient has been applied to estimating cell concentrations and matrix morphology in tissue engineering. Spectral analysis has been employed to characterize the concentration and spatial distribution of mineral particles in a construct, as well as to monitor mineral deposition by cells over time. Ultrasound techniques have also been used to measure the mechanical properties of native and engineered tissues. Conventional ultrasound elasticity imaging and acoustic radiation force imaging have been applied to detect regions of altered stiffness within tissues. Sonorheometry and monitoring of steady-state excitation and recovery have been used to characterize viscoelastic properties of tissue using a single transducer to both deform and image the sample. Dual-mode ultrasound elastography uses separate ultrasound transducers to produce a more potent deformation force to microscale characterization of viscoelasticity of hydrogel constructs. These ultrasound-based techniques have high potential to impact the field of tissue engineering as they are further developed and their range of applications expands.

Microgravity Stress: Bone and Connective Tissue.

Science.gov (United States)

Bloomfield, Susan A; Martinez, Daniel A; Boudreaux, Ramon D; Mantri, Anita V

2016-03-15

The major alterations in bone and the dense connective tissues in humans and animals exposed to microgravity illustrate the dependency of these tissues' function on normal gravitational loading. Whether these alterations depend solely on the reduced mechanical loading of zero g or are compounded by fluid shifts, altered tissue blood flow, radiation exposure, and altered nutritional status is not yet well defined. Changes in the dense connective tissues and intervertebral disks are generally smaller in magnitude but occur more rapidly than those in mineralized bone with transitions to 0 g and during recovery once back to the loading provided by 1 g conditions. However, joint injuries are projected to occur much more often than the more catastrophic bone fracture during exploration class missions, so protecting the integrity of both tissues is important. This review focuses on the research performed over the last 20 years in humans and animals exposed to actual spaceflight, as well as on knowledge gained from pertinent ground-based models such as bed rest in humans and hindlimb unloading in rodents. Significant progress has been made in our understanding of the mechanisms for alterations in bone and connective tissues with exposure to microgravity, but intriguing questions remain to be solved, particularly with reference to biomedical risks associated with prolonged exploration missions. Copyright © 2016 John Wiley & Sons, Inc.

Increased tissue factor, MMP-8, and D-dimer expression in diabetic patients with unstable advanced carotid atherosclerosis

Directory of Open Access Journals (Sweden)

Jerzy Krupinski

2007-09-01

Full Text Available Jerzy Krupinski1,2, Marta M Turu1,2, M Angels Font1, Nesser Ahmed3, Matthew Sullivan3, Ana Luque1,2, Francisco Rubio1, Lina Badimon2, Mark Slevin31Department of Neurology, Stroke Unit, University Hospital of Bellvitge (HUB, Fundacio IDIBELL, Barcelona, Spain; 2Cardiovascular Research Centre, IIBB/CSIC-HSCSP-UAB, Barcelona, Spain; 3School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, United KingdomAbstract: Advanced atherogenesis is characterized by the presence of markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and by clinical conditions associated with defective coagulation. Diabetes may be associated with enhanced lesion instability and atherosclerotic plaque rupture. Plaques obtained from 206 patients undergoing carotid endarterectomy were divided into diabetic (type 2 and nondiabetic and analyzed by Western blotting and immunohistochemistry to detect tissue factor (TF, metalloproteinases (MMP-2, -8, -9, and fibrin/fibrinogen related antigens, and in situ zymography to detect MMP activity. Plasma samples were quantified for TF procoagulant activity, C-reactive protein, fibrinogen and D-dimer. Diabetic and symptomatic patients with hypoechogenic plaques had increased plasma TF activity and D-dimer, compared with those with hyperechogenic plaques (p = 0.03, p = 0.007, respectively. Diabetic, symptomatic patients had higher plasma D-dimer levels than asymptomatic patients (p = 0.03. There was a significant correlation between intramural TF levels and D-dimer in diabetic patients with symptomatic disease (p = 0.001, r2 = 0.4. In diabetic patients, plasma fibrinogen levels were higher in patients with hypoechogenic plaques (p = 0.007. Diabetic patients with ulcerated plaques had higher plasma D-dimer and MMP-8 levels than those with fibrous plaques (p = 0.02, p = 0.01, respectively. This data suggests that currently available circulating markers may be clinically useful to select

Translational Research in Pediatrics IV: Solid Tissue Collection and Processing.

Science.gov (United States)

Gillio-Meina, Carolina; Zielke, H Ronald; Fraser, Douglas D

2016-01-01

Solid tissues are critical for child-health research. Specimens are commonly obtained at the time of biopsy/surgery or postmortem. Research tissues can also be obtained at the time of organ retrieval for donation or from tissue that would otherwise have been discarded. Navigating the ethics of solid tissue collection from children is challenging, and optimal handling practices are imperative to maximize tissue quality. Fresh biopsy/surgical specimens can be affected by a variety of factors, including age, gender, BMI, relative humidity, freeze/thaw steps, and tissue fixation solutions. Postmortem tissues are also vulnerable to agonal factors, body storage temperature, and postmortem intervals. Nonoptimal tissue handling practices result in nucleotide degradation, decreased protein stability, artificial posttranslational protein modifications, and altered lipid concentrations. Tissue pH and tryptophan levels are 2 methods to judge the quality of solid tissue collected for research purposes; however, the RNA integrity number, together with analyses of housekeeping genes, is the new standard. A comprehensive clinical data set accompanying all tissue samples is imperative. In this review, we examined: the ethical standards relating to solid tissue procurement from children; potential sources of solid tissues; optimal practices for solid tissue processing, handling, and storage; and reliable markers of solid tissue quality. Copyright © 2016 by the American Academy of Pediatrics.

Soft tissue grafting to improve implant esthetics

Directory of Open Access Journals (Sweden)

Moawia M Kassab

2010-09-01

Full Text Available Moawia M KassabDivision of Periodontics, Marquette University, School of Dentistry, Milwaukee, WI, USAAbstract: Dental implants are becoming the treatment of choice to replace missing teeth, especially if the adjacent teeth are free of restorations. When minimal bone width is present, implant placement becomes a challenge and often resulting in recession and dehiscence around the implant that leads to subsequent gingival recession. To correct such defect, the author turned to soft tissue autografting and allografting to correct a buccal dehiscence around tooth #24 after a malpositioned implant placed by a different surgeon. A 25-year-old woman presented with the chief complaint of gingival recession and exposure of implant threads around tooth #24. The patient received three soft tissue grafting procedures to augment the gingival tissue. The first surgery included a connective tissue graft to increase the width of the keratinized gingival tissue. The second surgery included the use of autografting (connective tissue graft to coronally position the soft tissue and achieve implant coverage. The third and final surgery included the use of allografting material Alloderm to increase and mask the implant from showing through the gingiva. Healing period was uneventful for the patient. After three surgical procedures, it appears that soft tissue grafting has increased the width and height of the gingiva surrounding the implant. The accomplished thickness of gingival tissue appeared to mask the showing of implant threads through the gingival tissue and allowed for achieving the desired esthetic that the patient desired. The aim of the study is to present a clinical case with soft tissue grafting procedures.Keywords: case report, connective tissue, dental implants, allograft, coronally positioned flap

Addressing the instability of DNA nanostructures in tissue culture.

Science.gov (United States)

Hahn, Jaeseung; Wickham, Shelley F J; Shih, William M; Perrault, Steven D

2014-09-23

DNA nanotechnology is an advanced technique that could contribute diagnostic, therapeutic, and biomedical research devices to nanomedicine. Although such devices are often developed and demonstrated using in vitro tissue culture models, these conditions may not be compatible with DNA nanostructure integrity and function. The purpose of this study was to characterize the sensitivity of 3D DNA nanostructures produced via the origami method to the in vitro tissue culture environment and identify solutions to prevent loss of nanostructure integrity. We examined whether the physiological cation concentrations of cell culture medium and the nucleases present in fetal bovine serum (FBS) used as a medium supplement result in denaturation and digestion, respectively. DNA nanostructure denaturation due to cation depletion was design- and time-dependent, with one of four tested designs remaining intact after 24 h at 37 °C. Adjustment of medium by addition of MgSO4 prevented denaturation. Digestion of nanostructures by FBS nucleases in Mg(2+)-adjusted medium did not appear design-dependent and became significant within 24 h and when medium was supplemented with greater than 5% FBS. We estimated that medium supplemented with 10% FBS contains greater than 256 U/L equivalent of DNase I activity in digestion of DNA nanostructures. Heat inactivation at 75 °C and inclusion of actin protein in medium inactivated and inhibited nuclease activity, respectively. We examined the impact of medium adjustments on cell growth, viability, and phenotype. Adjustment of Mg(2+) to 6 mM did not appear to have a detrimental impact on cells. Heat inactivation was found to be incompatible with in vitro tissue culture, whereas inclusion of actin had no observable effect on growth and viability. In two in vitro assays, immune cell activation and nanoparticle endocytosis, we show that using conditions compatible with cell phenotype and nanostructure integrity is critical for obtaining reliable

The Influence of Tissue Procurement Procedures on RNA Integrity, Gene Expression, and Morphology in Porcine and Human Liver Tissue

Czech Academy of Sciences Publication Activity Database

Kap, M.; Sieuwerts, A.M.; Kubista, Mikael; Oomen, M.; Arshad, S.; Riegman, P.

2015-01-01

Roč. 13, č. 3 (2015), s. 200-206 ISSN 1947-5535 Institutional support: RVO:86652036 Keywords : WARM ISCHEMIA * SPECIMENS * FROZEN TISSUE * PURPOSE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.804, year: 2015

Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Qiongshi Lu

2017-07-01

Full Text Available Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD. Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

Science.gov (United States)

Lu, Qiongshi; Powles, Ryan L; Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

2017-07-01

Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

Analysis of Electronic Densities and Integrated Doses in Multiform Glioblastomas Stereotactic Radiotherapy

International Nuclear Information System (INIS)

Baron-Aznar, C.; Moreno-Jimenez, S.; Celis, M. A.; Ballesteros-Zebadua, P.; Larraga-Gutierrez, J. M.

2008-01-01

Integrated dose is the total energy delivered in a radiotherapy target. This physical parameter could be a predictor for complications such as brain edema and radionecrosis after stereotactic radiotherapy treatments for brain tumors. Integrated Dose depends on the tissue density and volume. Using CT patients images from the National Institute of Neurology and Neurosurgery and BrainScan(c) software, this work presents the mean density of 21 multiform glioblastomas, comparative results for normal tissue and estimated integrated dose for each case. The relationship between integrated dose and the probability of complications is discussed

Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis.

Science.gov (United States)

Martínez-Zamora, M A; Mattioli, L; Parera, J; Abad, E; Coloma, J L; van Babel, B; Galceran, M T; Balasch, J; Carmona, F

2015-05-01

Are the levels of biologically active and the most toxic dioxin-like substances in adipose tissue of patients with deep infiltrating endometriosis (DIE) higher than in a control group without endometriosis? DIE patients have higher levels of dioxins and polychlorinated biphenyls (PCBs) in adipose tissue compared with controls without endometriosis. Some studies have investigated the levels of dioxin-like substances, in serum samples, in patients with endometriosis, with inconsistent results. Case-control study including two groups of patients. The study group (DIE group) consisted of 30 patients undergoing laparoscopic surgery because of DIE. In all patients, an extensive preoperative work-up was performed including clinical exploration, magnetic resonance imaging (MRI) and transvaginal sonography. All patients with DIE underwent a confirmatory histological study for DIE after surgery. The non-endometriosis control group (control group), included the next consecutive patient undergoing laparoscopic surgery in our center due to adnexal benign gynecological disease (ovarian or tubal procedures other than endometriosis) after each DIE patient, and who did not present any type of endometriosis. During the surgical procedure 1-2 g of adipose tissue from the omentum were obtained. Dioxin-like substances were analyzed in adipose tissue in DIE patients and controls without endometriosis. The total toxic equivalence and concentrations of both dioxins and PCBs were significantly higher in patients with DIE in comparison with the control group (P dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin [2,3,7,8-TCDD] and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]) (P dioxins and PCBs widely vary in different countries. Furthermore, the strict eligibility criteria used may preclude generalization of the results to other populations and the surgery-based sampling frame may induce a selection bias. Finally, adipose tissue was obtained only from the omentum, and not from other

Sources and fate of antimicrobials in integrated fish-pig and non-integrated tilapia farms.

Science.gov (United States)

Li, Kang; Liu, Liping; Zhan, Jia; Scippo, Marie-Louise; Hvidtfeldt, Kristian; Liu, Yuan; Dalsgaard, Anders

2017-10-01

Antimicrobial contamination in aquaculture products constitutes a food safety hazard, but little is known about the introduction and accumulation of antimicrobials in integrated fish-pig aquaculture. This study, conducted in 2013, aimed to determine the residues of 11 types of antimicrobials by UPLC-MS/MS analysis in fish feed (n=37), pig feed (n=9), pig manure (n=9), pond sediment (n=20), fish skin (n=20) and muscle tissue (n=20) sampled from integrated tilapia-pig farms, non-integrated tilapia farms and fish feed supply shops. There was a higher occurrence of antimicrobial residues in fish skin from both integrated and non-integrated farms, and in pig manure. Enrofloxacin (3.9-129.3μg/kg) and sulfadiazine (0.7-7.8μg/kg) were commonly detected in fish skin and muscle, pig manure and pond sediment from integrated farms, with different types of antimicrobials found in pig manure and tilapia samples. In non-integrated farms, sulfadiazine (2.5-89.9μg/kg) was the predominant antimicrobial detected in fish skin and muscle, fish feed and pond sediment. In general, antimicrobials seemed not to be commonly transmitted from pig to fish in tilapia-pig integrated farms, and fish feed, pig feed and pond sediment did not seem as important sources of the antimicrobials found in fish from both systems. The frequent findings of antimicrobial residues in fish skin compared with fish muscle was probably due to different pharmacokinetics in different tissue types, which have practical food safety implications since antimicrobial residues monitoring is usually performed analyzing mixed skin and fish muscle samples. Copyright © 2017 Elsevier B.V. All rights reserved.

In Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration.

Science.gov (United States)

Geng, Hua; Bu, Heng-Fu; Liu, Fangyi; Wu, Longtao; Pfeifer, Karl; Chou, Pauline M; Wang, Xiao; Sun, Jiaren; Lu, Lu; Pandey, Ashutosh; Bartolomei, Marisa S; De Plaen, Isabelle G; Wang, Peng; Yu, Jindan; Qian, Jiaming; Tan, Xiao-Di

2018-04-03

Inflammation affects regeneration of the intestinal epithelia; long non-coding RNAs (lncRNAs) regulate cell functions, such as proliferation, differentiation, and migration. We investigated the mechanisms by which the lncRNA H19, imprinted maternally expressed transcript (H19) regulates regeneration of intestinal epithelium using cell cultures and mouse models of inflammation. We performed RNA-sequencing transcriptome analyses of intestinal tissues from mice with lipopolysaccharide (LPS)-induced sepsis to identify lncRNAs associated with inflammation; findings were confirmed by quantitative real-time polymerase chain reaction and in situ hybridization analyses of intestinal tissues from mice with sepsis or dextran sulfate sodium (DSS)-induced mucosal wound healing and patients with ulcerative colitis compared to healthy individuals (controls). We screened cytokines for their ability to induce expression of H19 in HT-29 cells and intestinal epithelial cells (IECs), and confirmed findings in crypt epithelial organoids derived from mouse small intestine. IECs were incubated with different signal transduction inhibitors and effects on H19 lncRNA levels were measured. We assessed intestinal epithelial proliferation or regeneration in H19 ΔEx1/+ mice given LPS or DSS vs wild-type littermates (control mice). H19 was overexpressed in IECs using lentiviral vectors and cell proliferation was measured. We performed RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays to study functions of H19 in IECs. In RNA-sequencing transcriptome analysis of lncRNA expression in intestinal tissues from mice, we found levels of H19 only changed significantly with LPS exposure. Levels of H19 lncRNA increased in intestinal tissues of patients with ulcerative colitis, mice with LPS-induced sepsis, or mice with DSS-induced colitis, compared with controls. Increased H19 lncRNA localized to epithelial cells in the intestine, regardless of Lgr5 messenger RNA

Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging

DEFF Research Database (Denmark)

Reichkendler, M. H.; Auerbach, P.; Rosenkilde, M.

2013-01-01

abdominal SAT compared with CON but not in either intra- or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose...

Integrative Radiation Biology

Energy Technology Data Exchange (ETDEWEB)

Barcellos-Hoff, Mary Helen [New York University School of Medicine, NY (United States)

2015-02-27

We plan to study tissue-level mechanisms important to human breast radiation carcinogenesis. We propose that the cell biology of irradiated tissues reveals a coordinated multicellular damage response program in which individual cell contributions are primarily directed towards suppression of carcinogenesis and reestablishment of homeostasis. We identified transforming growth factor β1 (TGFβ) as a pivotal signal. Notably, we have discovered that TGFβ suppresses genomic instability by controlling the intrinsic DNA damage response and centrosome integrity. However, TGFβ also mediates disruption of microenvironment interactions, which drive epithelial to mesenchymal transition in irradiated human mammary epithelial cells. This apparent paradox of positive and negative controls by TGFβ is the topic of the present proposal. First, we postulate that these phenotypes manifest differentially following fractionated or chronic exposures; second, that the interactions of multiple cell types in tissues modify the responses evident in this single cell type culture models. The goals are to: 1) study the effect of low dose rate and fractionated radiation exposure in combination with TGFβ on the irradiated phenotype and genomic instability of non-malignant human epithelial cells; and 2) determine whether stromal-epithelial interactions suppress the irradiated phenotype in cell culture and the humanized mammary mouse model. These data will be used to 3) develop a systems biology model that integrates radiation effects across multiple levels of tissue organization and time. Modeling multicellular radiation responses coordinated via extracellular signaling could have a significant impact on the extrapolation of human health risks from high dose to low dose/rate radiation exposure.

Disinfection of human musculoskeletal allografts in tissue banking: a systematic review.

Science.gov (United States)

Mohr, J; Germain, M; Winters, M; Fraser, S; Duong, A; Garibaldi, A; Simunovic, N; Alsop, D; Dao, D; Bessemer, R; Ayeni, O R

2016-12-01

Musculoskeletal allografts are typically disinfected using antibiotics, irradiation or chemical methods but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of microorganism kill; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. A systematic review of three databases found 68 laboratory and clinical studies that analyzed the microbial bioburden or contamination rates of musculoskeletal allografts. The use of peracetic acid-ethanol or ionizing radiation was found to be most effective for disinfection of tissues. The use of irradiation is the most frequently published method for the terminal sterilization of musculoskeletal allografts; it is widely used and its efficacy is well documented in the literature. However, effective disinfection results were still observed using the BioCleanse™ Tissue Sterilization process, pulsatile lavage with antibiotics, ethylene oxide, and chlorhexidine. The variety of effective methods to reduce contamination rate or bioburden, in conjunction with limited high quality evidence provides little support for the recommendation of a single bioburden reduction method.

The integrative epigenomic-transcriptomic landscape of ER positive breast cancer.

Science.gov (United States)

Gao, Yang; Jones, Allison; Fasching, Peter A; Ruebner, Matthias; Beckmann, Matthias W; Widschwendter, Martin; Teschendorff, Andrew E

2015-01-01

While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events. Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample. Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is

Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen.

Science.gov (United States)

Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin

2013-02-01

Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca(2+) waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O(2) tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca(2+) activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.

Teripang Pasir Meningkatkan Kandungan Antioksidan Superoksida Dismutase pada Pankreas Tikus Diabetes (SEA CUCUMBER INCREASED ANTIOXIDANT SUPEROXIDE DISMUTASE IN THE PANCREATIC TISSUE OF DIABETIC RATS

Directory of Open Access Journals (Sweden)

Tutik Wresdiyati

2015-05-01

Full Text Available High level of blood glucose is an indicator for diabetes mellitus (DM condition. The condition iscaused by low level of insulin secretion or impairement of insulin receptor. The number of DM patientincreases every year. The World Health Organization reported that the number of DM patient in Indonesiawas the 4th highest in the world, after following China, India, and the United States of America, respectively.This study was conducted to analyze the effect of sea cucumber (Holothuria scabra J on the profile ofantioxidant copper, zinc-superoxide dismutase (Cu, Zn-SOD in the pancreatic tissues of diabetic rats. Atotal of 25 male white rats (Sprague Dawley were used in this study. They were divided into five groups;(1 negative control (KN, (2 positive control, diabetic rats (KP, (3 diabetic rats treated with hydrolyzatedprotein of sea cucumber (HDL, (4 diabetic rats treated with concentrated protein of sea cucumber (KST,and (5 diabetic rats treated with isolated protein of sea cucumber (ISL, respectively. Diabetic conditionwas obtained by alloxan injection 110 mg/kg bw. The treatments were done for 28 days. At the end oftreatment period, the rats were sacrificed and pancreatic tissues were collected and fixed in Bouin solution and then processed to paraffin embedding standard method. The tissues were then stained withimmunohistochemical staining techniques using monoclonal antibody of Cu, Zn-SOD. The results showedthat treatment of HDL, KST, and ISL of sea cucumber (Holothuria scabra J increased the content ofantioxidant Cu, Zn-SOD either in Langerhans islets and acinar cells of pancreatic tissues-diabetic rats.The HDL of sea cucumber treatment gave the best effect in increasing the antioxidant content of Cu, Zn-SOD in pancreatic tissue of diabetic rats.

Lack of retinoic acid leads to increased langerin-expressing dendritic cells in gut-associated lymphoid tissues.

Science.gov (United States)

Chang, Sun-Young; Cha, Hye-Ran; Chang, Jae-Hoon; Ko, Hyun-Jeong; Yang, Hyungjun; Malissen, Bernard; Iwata, Makoto; Kweon, Mi-Na

2010-04-01

Retinoic acid (RA) is a crucial factor for maintaining homeostasis in the gut, including lymphocyte homing, immunoglobulin (Ig) A production, and T regulatory cells (Treg) and T helper cell 17 (T(H)17) generation. Until now, most attention has focused on the function of dendritic cells (DCs) to initiate adaptive immunity including T and B lymphocytes through RA. To investigate the effects of RA on DCs of gut-associated lymphoid tissue (GALT), we analyzed the phenotype and function of DC subsets from GALT of vitamin A-deficient (VAD) mice. VAD mice were prepared by feeding them a VAD diet over 12 weeks from gestational days 10-14. Here, we report that tremendous increase of langerin(+) DCs occurred in the mesenteric lymph nodes (MLNs) and gut lamina propria of VAD mice dependent on CCR7 signaling. Langerin(+) DCs have phenotypes more similar to those of bone marrow-derived dermal langerin(+) DCs than epidermal Langerhans cells. Moreover, RA receptor antagonists enhance the differentiation of langerin(+) DCs from mouse and human precursors of bone marrow and peripheral blood. Langerin(+) DCs were highly differentiated but less inflammatory than langerin(-) DCs of MLNs of VAD mice. Moreover, tolerance to orally delivered antigen was completely abrogated by depletion of langerin(+) DCs in the VAD mice. These results suggest that generation of langerin(+) DCs in the GALT is tightly regulated by RA and that the microenvironment of tissues determines the phenotype of DCs. 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Computational Modeling for Enhancing Soft Tissue Image Guided Surgery: An Application in Neurosurgery.

Science.gov (United States)

Miga, Michael I

2016-01-01

With the recent advances in computing, the opportunities to translate computational models to more integrated roles in patient treatment are expanding at an exciting rate. One area of considerable development has been directed towards correcting soft tissue deformation within image guided neurosurgery applications. This review captures the efforts that have been undertaken towards enhancing neuronavigation by the integration of soft tissue biomechanical models, imaging and sensing technologies, and algorithmic developments. In addition, the review speaks to the evolving role of modeling frameworks within surgery and concludes with some future directions beyond neurosurgical applications.

Soil Hydrological Attributes of an Integrated Crop-Livestock Agroecosystem: Increased Adaptation through Resistance to Soil Change

International Nuclear Information System (INIS)

Liebig, M.A; Tanaka, D.L; Kronberg, S.L; Karn, J.F; Scholljegerdes, E.J

2011-01-01

Integrated crop-livestock systems have been purported to have significant agronomic and environmental benefits compared to specialized, single-enterprise production systems. However, concerns exist regarding the effect of livestock in integrated systems to cause soil compaction, thereby decreasing infiltration of water into soil. Such concerns are compounded by projections of more frequent high-intensity rainfall events from anticipated climate change, which would act to increase surface runoff and soil erosion. A study was conducted to evaluate the effects of residue management, frequency of hoof traffic, season, and production system (e.g., integrated annual cropping versus perennial grass) on infiltration rates from 2001 through 2008 in central North Dakota, USA. Imposed treatments had no effect on infiltration rate at three, six, and nine years after study establishment, implying that agricultural producers should not be concerned with inhibited infiltration in integrated annual cropping systems, where winter grazing is used. The use of no-till management, coupled with annual freeze/thaw and wet/dry cycles, likely conferred an inherent resistance to change in near-surface soil properties affecting soil hydrological attributes. Accordingly, caution should be exercised in applying these results to other regions or management systems.

Radiotherapy in patients with connective tissue diseases.

Science.gov (United States)

Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

2016-03-01

The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The behaviours of nurses that increase student accountability for learning in clinical practice: An integrative review.

Science.gov (United States)

Perry, Christina; Henderson, Amanda; Grealish, Laurie

2018-06-01

To identify nurses' behaviours that promote student accountability for learning in clinical practice. Health care services are experiencing significant strain in meeting clinical education requirements of increasing numbers of nursing students enrolled in undergraduate nursing programs. Internationally, the transition to university based education for nurses has seen the emergence of issues for busy clinicians trying to manage increasing workloads with responsibility for student learning. An understanding of what types of supervisor behaviours promote student accountability for learning, may support clinicians to more effectively manage their dual roles of clinical care and student support. An integrative approach was adopted for this review. A search of the Cumulative Index of Nursing and Allied Health Literature, Pubmed, Scopus and Embase was undertaken, limited to articles published between 2000 and March 2017. Whittemore and Knafls' (2005) framework for conducting integrative reviews was used to ensure a methodological and rigorous approach. Nine studies were considered. Behaviours emerged in relation to four themes including: belongingness associated with a genuine partnership; empowerment and increasing student self-efficacy; trust linked to increasing and staged independence; and balancing clinical and educational requirements. Behaviours of nurses significantly influence students' accountability for learning and accordingly, their ability to be adequately prepared for professional nursing practice. Understanding behaviours that impact on students' approach to clinical placement can guide nurses in their approach to facilitating student learning, in particular, behaviours that increase student responsibility and independence over the continuum of clinical education. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nanoparticles for bone tissue engineering.

Science.gov (United States)

Vieira, Sílvia; Vial, Stephanie; Reis, Rui L; Oliveira, J Miguel

2017-05-01

Tissue engineering (TE) envisions the creation of functional substitutes for damaged tissues through integrated solutions, where medical, biological, and engineering principles are combined. Bone regeneration is one of the areas in which designing a model that mimics all tissue properties is still a challenge. The hierarchical structure and high vascularization of bone hampers a TE approach, especially in large bone defects. Nanotechnology can open up a new era for TE, allowing the creation of nanostructures that are comparable in size to those appearing in natural bone. Therefore, nanoengineered systems are now able to more closely mimic the structures observed in naturally occurring systems, and it is also possible to combine several approaches - such as drug delivery and cell labeling - within a single system. This review aims to cover the most recent developments on the use of different nanoparticles for bone TE, with emphasis on their application for scaffolds improvement; drug and gene delivery carriers, and labeling techniques. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:590-611, 2017. © 2017 American Institute of Chemical Engineers.

Brown adipose tissue (BAT) specific vaspin expression is increased after obesogenic diets and cold exposure and linked to acute changes in DNA-methylation.

Science.gov (United States)

Weiner, Juliane; Rohde, Kerstin; Krause, Kerstin; Zieger, Konstanze; Klöting, Nora; Kralisch, Susan; Kovacs, Peter; Stumvoll, Michael; Blüher, Matthias; Böttcher, Yvonne; Heiker, John T

2017-06-01

Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology. We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels. Vaspin expression was analyzed in isolated white and brown adipocytes during adipogenesis and in response to adrenergic stimuli. DNA-methylation within the vaspin promoter was analyzed to investigate acute epigenetic changes after cold-exposure in BAT. Our results demonstrate a strong induction of vaspin mRNA and protein expression specifically in BAT of both cold-exposed and high-fat (HF) or high-sugar (HS) fed mice. While obesogenic diets also upregulated hepatic vaspin mRNA levels, cold exposure tended to increase vaspin gene expression of inguinal white adipose tissue (iWAT) depots. Concomitantly, vaspin plasma levels were decreased upon obesogenic or thermogenic triggers. Vaspin expression was increased during adipogenesis but unaffected by sympathetic activation in brown adipocytes. Analysis of vaspin promoter methylation in AT revealed lowest methylation levels in BAT, which were acutely reduced after cold exposure. Our data demonstrate a novel BAT-specific regulation of vaspin gene expression upon physiological stimuli in vivo with acute epigenetic changes that may contribute to cold-induced expression in BAT. We conclude that these findings indicate functional relevance and potentially beneficial effects of vaspin in BAT function.

Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

Science.gov (United States)

Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

2015-09-01

Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

Increased variability of bone tissue mineral density resulting from estrogen deficiency influences creep behavior in a rat vertebral body.

Science.gov (United States)

Kim, Do-Gyoon; Navalgund, Anand R; Tee, Boon Ching; Noble, Garrett J; Hart, Richard T; Lee, Hye Ri

2012-11-01

Progressive vertebral deformation increases the fracture risk of a vertebral body in the postmenopausal patient. Many studies have observed that bone can demonstrate creep behavior, defined as continued time-dependent deformation even when mechanical loading is held constant. Creep is a characteristic of viscoelastic behavior, which is common in biological materials. We hypothesized that estrogen deficiency-dependent alteration of the mineral distribution of bone at the tissue level could influence the progressive postmenopausal vertebral deformity that is observed as the creep response at the organ level. The objective of this study was thus to examine whether the creep behavior of vertebral bone is changed by estrogen deficiency, and to determine which bone property parameters are responsible for the creep response of vertebral bone at physiological loading levels using an ovariectomized (OVX) rat model. Correlations of creep parameters with bone mineral density (BMD), tissue mineral density (TMD) and architectural parameters of both OVX and sham surgery vertebral bone were tested. As the vertebral creep was not fully recovered during the post-creep unloading period, there was substantial residual displacement for both the sham and OVX groups. A strong positive correlation between loading creep and residual displacement was found (r=0.868, pcreep behavior of the OVX group (pcreep caused progressive, permanent reduction in vertebral height for both the sham and OVX groups. In addition, estrogen deficiency-induced active bone remodeling increased variability of trabecular TMD in the OVX group. Taken together, these results suggest that increased variability of trabecular TMD resulting from high bone turnover influences creep behavior of the OVX vertebrae. Copyright © 2012 Elsevier Inc. All rights reserved.

Inhibition of Intracellular Triglyceride Lipolysis Suppresses Cold-Induced Brown Adipose Tissue Metabolism and Increases Shivering in Humans.

Science.gov (United States)

Blondin, Denis P; Frisch, Frédérique; Phoenix, Serge; Guérin, Brigitte; Turcotte, Éric E; Haman, François; Richard, Denis; Carpentier, André C

2017-02-07

Indirect evidence from human studies suggests that brown adipose tissue (BAT) thermogenesis is fueled predominantly by fatty acids hydrolyzed from intracellular triglycerides (TGs). However, no direct experimental evidence to support this assumption currently exists in humans. The aim of this study was to determine the role of intracellular TG in BAT thermogenesis, in cold-exposed men. Using positron emission tomography with 11 C-acetate and 18 F-fluorodeoxyglucose, we showed that oral nicotinic acid (NiAc) administration, an inhibitor of intracellular TG lipolysis, suppressed the cold-induced increase in BAT oxidative metabolism and glucose uptake, despite no difference in BAT blood flow. There was a commensurate increase in shivering intensity and shift toward a greater reliance on glycolytic muscle fibers without modifying total heat production. Together, these findings show that intracellular TG lipolysis is critical for BAT thermogenesis and provides experimental evidence for a reciprocal role of BAT thermogenesis and shivering in cold-induced thermogenesis in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic

Energy Technology Data Exchange (ETDEWEB)

Ghanaati, Shahram; Barbeck, Mike; Kirkpatrick, C James [REPAIR-Lab, Institute of Pathology, Johannes Gutenberg University, Mainz (Germany); Schlee, Markus [Bayreuther Strasse 39, D-91301, Forchheim (Germany); Webber, Matthew J [Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208 (United States); Willershausen, Ines [Institute for Dental Material Sciences and Technology, University Medical Center of the Johannes Gutenberg University, Mainz (Germany); Balic, Ela; Goerlach, Christoph [Geistlich Pharma AG, Wolhusen (Switzerland); Stupp, Samuel I [Department of Materials Science and Engineering, Chemistry, and Medicine, Northwestern University, Evanston, IL 60208 (United States); Sader, Robert A, E-mail: ghanaati@uni-mainz.de [Clinic for Maxillofacial and Plastic Surgery, Johann Wolfgang Goethe University, Frankfurt Am Main (Germany)

2011-02-15

This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body response, did not include the presence of multinucleated giant cells, lymphocytes, or granulation tissue. In the context of translation, we show preliminary results from the clinical use of this biomaterial applied to soft tissue regeneration in the treatment of gingival tissue recession and exposed roots of human teeth. Such a condition would greatly benefit from guided tissue regeneration strategies. Our findings demonstrate that this material successfully promoted the ingrowth of gingival tissue and reversed gingival tissue recession. Of particular importance is the fact that the histological evidence from these human studies corroborates our findings in the murine model, with the barrier layer preventing unspecific tissue ingrowth, as the scaffold becomes infiltrated by mesenchymal cells from adjacent tissue into the porous layer. Also in the clinical situation no multinucleated giant cells, no granulation tissue and no evidence of a marked inflammatory response were observed. In conclusion, this bilayered matrix elicits a favorable tissue reaction, demonstrates potential as a barrier for preferential tissue ingrowth, and achieves a desirable therapeutic result when applied in humans for soft tissue regeneration.

Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic

International Nuclear Information System (INIS)

Ghanaati, Shahram; Barbeck, Mike; Kirkpatrick, C James; Schlee, Markus; Webber, Matthew J; Willershausen, Ines; Balic, Ela; Goerlach, Christoph; Stupp, Samuel I; Sader, Robert A

2011-01-01

This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body response, did not include the presence of multinucleated giant cells, lymphocytes, or granulation tissue. In the context of translation, we show preliminary results from the clinical use of this biomaterial applied to soft tissue regeneration in the treatment of gingival tissue recession and exposed roots of human teeth. Such a condition would greatly benefit from guided tissue regeneration strategies. Our findings demonstrate that this material successfully promoted the ingrowth of gingival tissue and reversed gingival tissue recession. Of particular importance is the fact that the histological evidence from these human studies corroborates our findings in the murine model, with the barrier layer preventing unspecific tissue ingrowth, as the scaffold becomes infiltrated by mesenchymal cells from adjacent tissue into the porous layer. Also in the clinical situation no multinucleated giant cells, no granulation tissue and no evidence of a marked inflammatory response were observed. In conclusion, this bilayered matrix elicits a favorable tissue reaction, demonstrates potential as a barrier for preferential tissue ingrowth, and achieves a desirable therapeutic result when applied in humans for soft tissue regeneration.

Connective tissue injury in calf muscle tears and return to play: MRI correlation.

Science.gov (United States)

Prakash, Ashutosh; Entwisle, Tom; Schneider, Michal; Brukner, Peter; Connell, David

2017-10-26

The aim of our study was to assess a group of patients with calf muscle tears and evaluate the integrity of the connective tissue boundaries and interfaces. Further, we propose a novel MRI grading system based on integrity of the connective tissue and assess any correlation between the grading score and time to return to play. We have also reviewed the anatomy of the calf muscles. We retrospectively evaluated 100 consecutive patients with clinical suspicion and MRI confirmation of calf muscle injury. We evaluated each calf muscle tear with MRI for the particular muscle injured, location of injury within the muscle and integrity of the connective tissue structure at the interface. The muscle tears were graded 0-3 depending on the degree of muscle and connective tissue injury. The time to return to play for each patient and each injury was found from the injury records and respective sports doctors. In 100 patients, 114 injuries were detected. Connective tissue involvement was observed in 63 out of 100 patients and failure (grade 3 injury) in 18. Mean time to return to play with grade 0 injuries was 8 days, grade 1 tears was 17 days, grade 2 tears was 25 days and grade 3 tears was 48 days (pmuscle tears. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Integrative exercise and lifestyle intervention increases leisure-time activity in breast cancer patients

DEFF Research Database (Denmark)

Casla, Soraya; Hojman, Pernille; Cubedo, Ricardo

2014-01-01

BACKGROUND: Physical activity has been demonstrated to increase survival in breast cancer patients, but few breast cancer patients meet the general recommendations for physical activity. The aim of this pilot study was to investigate if a supervised integrated counseling and group-based exercise...... program could increase leisure-time activity in women with breast cancer. METHODS: This pilot project, designed as a single-arm study with pre-post testing, consisted of 24 classes of combined aerobic and strength exercise training as well as classes on dietary and health behavior. A total of 48 women...... with breast cancer who were undergoing or had recently completed anticancer treatment completed the study. Leisure-time physical activity, grip strength, functional capacity, quality of life (QoL), and depression were assessed at baseline, after intervention, and at the 12-week follow-up after intervention...

Herbivory mitigation through increased water-use efficiency in a leaf-mining moth-apple tree relationship.

Science.gov (United States)

Pincebourde, Sylvain; Frak, Ela; Sinoquet, Hervé; Regnard, Jean Luc; Casas, Jérôme

2006-12-01

Herbivory alters plant gas exchange but the effects depend on the type of leaf damage. In contrast to ectophagous insects, leaf miners, by living inside the leaf tissues, do not affect the integrity of the leaf surface. Thus, the effect of leaf miners on CO2 uptake and water-use efficiency by leaves remains unclear. We explored the impacts of the leaf-mining moth Phyllonorycter blancardella (Lepidoptera: Gracillariidae) on light responses of the apple leaf gas exchanges to determine the balance between the negative effects of reduced photosynthesis and potential positive impacts of increased water-use efficiency (WUE). Gas exchange in intact and mined leaf tissues was measured using an infrared gas analyser. The maximal assimilation rate was slightly reduced but the light response of net photosynthesis was not affected in mined leaf tissues. The transpiration rate was far more affected than the assimilation rate in the mine integument as a result of stomatal closure from moderate to high irradiance level. The WUE was about 200% higher in the mined leaf tissues than in intact leaf portions. Our results illustrate a novel mechanism by which plants might minimize losses from herbivore attacks; via trade-offs between the negative impacts on photosynthesis and the positive effects of increased WUE.

The effect of hypoxia on thermosensitive poly(N-vinylcaprolactam) hydrogels with tunable mechanical integrity for cartilage tissue engineering.

Science.gov (United States)

Lynch, Brandon; Crawford, Kristopher; Baruti, Omari; Abdulahad, Asem; Webster, Martial; Puetzer, Jennifer; Ryu, Chang; Bonassar, Lawrence J; Mendenhall, Juana

2017-10-01

Cartilage repair presents a daunting challenge in tissue engineering applications due to the low oxygen conditions (hypoxia) affiliated in diseased states. Hence, the use of biomaterial scaffolds with unique variability is imperative to treat diseased or damaged cartilage. Thermosensitive hydrogels show promise as injectable materials that can be used as tissue scaffolds for cartilage tissue regeneration. However, uses in clinical applications are limited to due mechanical stability and therapeutic efficacy to treat diseased tissue. In this study, several composite hydrogels containing poly(N-vinylcaprolactam) (PVCL) and methacrylated hyaluronic acid (meHA) were prepared using free radical polymerization to produce PVCL-graft-HA (PVCL-g-HA) and characterized using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and scanning electron microscopy. Lower critical solution temperatures and gelation temperatures were confirmed in the range of 33-34°C and 41-45°C, respectively. Using dynamic sheer rheology, the temperature dependence of elastic (G') and viscous (G″) modulus between 25°C and 45°C, revealed that PVCL-g-HA hydrogels at 5% (w/v) concentration exhibited the moduli of 7 Pa (G') to 4 Pa (G″). After 10 days at 1% oxygen, collagen production on PVCL-g-HA hydrogels was 153 ± 25 μg/mg (20%) and 106 ± 18 μg/mg showing a 10-fold increase compared to meHA controls. These studies show promise in PVCL-g-HA hydrogels for the treatment of diseased or damaged articular cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1863-1873, 2017. © 2016 Wiley Periodicals, Inc.

Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease

Science.gov (United States)

Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K.; Zhao, Hongyu

2017-01-01

Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer’s disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson’s disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline. PMID:28742084

γδ T cells in homeostasis and host defence of epithelial barrier tissues

DEFF Research Database (Denmark)

Nielsen, Morten M.; Witherden, Deborah A.; Havran, Wendy L.

2017-01-01

Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue...... homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body — namely, the epidermis and the intestine — and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity...

Integrating desalination to reservoir operation to increase redundancy for more secure water supply

Science.gov (United States)

Bhushan, Rashi; Ng, Tze Ling

2016-08-01

We investigate the potential of integrating desalination to existing reservoir systems to mitigate supply uncertainty. Desalinated seawater and wastewater are relatively reliable but expensive. Water from natural resources like reservoirs is generally cheaper but climate sensitive. We propose combining the operation of a reservoir and seawater and wastewater desalination plants for an overall system that is less vulnerable to scarcity and uncertainty, while constraining total cost. The joint system is modeled as a multiobjective optimization problem with the double objectives of minimizing risk and vulnerability, subject to a minimum limit on resilience. The joint model is applied to two cases, one based on the climate and demands of a location in India and the other of a location in California. The results for the Indian case indicate that it is possible for the joint system to reduce risk and vulnerability to zero given a budget increase of 20-120% under current climate conditions and 30-150% under projected future conditions. For the Californian case, this would require budget increases of 20-80% and 30-140% under current and future conditions, respectively. Further, our analysis shows a two-way interaction between the reservoir and desalination plants where the optimal operation of the former is just as much affected by the latter as the latter by the former. This highlights the importance of an integrated management approach. This study contributes to a greater quantitative understanding of desalination as a redundancy measure for adapting water supply infrastructures for a future of greater scarcity and uncertainty.

An electromechanical based deformable model for soft tissue simulation.

Science.gov (United States)

Zhong, Yongmin; Shirinzadeh, Bijan; Smith, Julian; Gu, Chengfan

2009-11-01

Soft tissue deformation is of great importance to surgery simulation. Although a significant amount of research efforts have been dedicated to simulating the behaviours of soft tissues, modelling of soft tissue deformation is still a challenging problem. This paper presents a new deformable model for simulation of soft tissue deformation from the electromechanical viewpoint of soft tissues. Soft tissue deformation is formulated as a reaction-diffusion process coupled with a mechanical load. The mechanical load applied to a soft tissue to cause a deformation is incorporated into the reaction-diffusion system, and consequently distributed among mass points of the soft tissue. Reaction-diffusion of mechanical load and non-rigid mechanics of motion are combined to govern the simulation dynamics of soft tissue deformation. An improved reaction-diffusion model is developed to describe the distribution of the mechanical load in soft tissues. A three-layer artificial cellular neural network is constructed to solve the reaction-diffusion model for real-time simulation of soft tissue deformation. A gradient based method is established to derive internal forces from the distribution of the mechanical load. Integration with a haptic device has also been achieved to simulate soft tissue deformation with haptic feedback. The proposed methodology does not only predict the typical behaviours of living tissues, but it also accepts both local and large-range deformations. It also accommodates isotropic, anisotropic and inhomogeneous deformations by simple modification of diffusion coefficients.

A family of hyperelastic models for human brain tissue

Science.gov (United States)

Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

2017-09-01

Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

From stem to roots: Tissue engineering in endodontics

Science.gov (United States)

Kala, M.; Banthia, Priyank; Banthia, Ruchi

2012-01-01

The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics is an exciting new concept that seeks to apply the advances in tissue engineering to the regeneration of the pulp-dentin complex. The basic logic behind this approach is that patient-specific tissue-derived cell populations can be used to functionally replace integral tooth tissues. The development of such ‘test tube teeth’ requires precise regulation of the regenerative events in order to achieve proper tooth size and shape, as well as the development of new technologies to facilitate these processes. This article provides an extensive review of literature on the concept of tissue engineering and its application in endodontics, providing an insight into the new developmental approaches on the horizon. Key words:Regenerative, tissue engineering, stem cells, scaffold. PMID:24558528

Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends.

Science.gov (United States)

Oliveira, Sara M; Reis, Rui L; Mano, João F

2015-11-01

The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation are achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemical control than top-down strategies, and are the main focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell–scaffold interaction within engineered tissue

Energy Technology Data Exchange (ETDEWEB)

Chen, Haiping; Liu, Yuanyuan, E-mail: Yuanyuan_liu@shu.edu.cn; Jiang, Zhenglong; Chen, Weihua; Yu, Yongzhe; Hu, Qingxi

2014-05-01

The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.

Cell-based and biomaterial approaches to connective tissue repair

Science.gov (United States)

Stalling, Simone Suzette

Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in

Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release

Directory of Open Access Journals (Sweden)

Marco Goeijenbier

2015-03-01

Full Text Available Puumala virus (PUUV infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVECs and subsequently specifically to PUUV virus particles. Infection of HUVECs with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1 compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased tissue factor expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.

Tissue Engineering Using Transfected Growth-Factor Genes

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Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

2005-01-01

A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

Thermal and molecular investigation of laser tissue welding

Energy Technology Data Exchange (ETDEWEB)

Small, W., IV

1998-06-01

Despite the growing number of successful animal and human trials, the exact mechanisms of laser tissue welding remain unknown. Furthermore, the effects of laser heating on tissue on the molecular scale are not fully understood. To address these issues, a multi-front attack oil both extrinsic (solder/patch mediated) and intrinsic (laser only) tissue welding was launched using two-color infrared thermometry, computer modeling, weld strength assessment, biochemical assays, and vibrational spectroscopy. The coupling of experimentally measured surface temperatures with the predictive numerical simulations provided insight into the sub-surface dynamics of the laser tissue welding process. Quantification of the acute strength of the welds following the welding procedure enabled comparison among trials during an experiment, with previous experiments, and with other studies in the literature. The acute weld integrity also provided an indication of tile probability of long-term success. Molecular effects induced In the tissue by laser irradiation were investigated by measuring tile concentrations of specific collagen covalent crosslinks and characterizing the Fourier-Transform infrared (FTIR) spectra before and after the laser exposure.

Rap1 integrates tissue polarity, lumen formation, and tumorigenicpotential in human breast epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Itoh, Masahiko; Nelson, Celeste M.; Myers, Connie A.; Bissell,Mina J.

2006-09-29

Maintenance of apico-basal polarity in normal breast epithelial acini requires a balance between cell proliferation, cell death, and proper cell-cell and cell-extracellular matrix signaling. Aberrations in any of these processes can disrupt tissue architecture and initiate tumor formation. Here we show that the small GTPase Rap1 is a crucial element in organizing acinar structure and inducing lumen formation. Rap1 activity in malignant HMT-3522 T4-2 cells is appreciably higher than in S1 cells, their non-malignant counterparts. Expression of dominant-negative Rap1 resulted in phenotypic reversion of T4-2 cells, led to formation of acinar structures with correct apico-basal polarity, and dramatically reduced tumor incidence despite the persistence of genomic abnormalities. The resulting acini contained prominent central lumina not observed when other reverting agents were used. Conversely, expression of dominant-active Rap1 in T4-2 cells inhibited phenotypic reversion and led to increased invasiveness and tumorigenicity. Thus, Rap1 acts as a central regulator of breast architecture, with normal levels of activation instructing apical polarity during acinar morphogenesis, and increased activation inducing tumor formation and progression to malignancy.

Effects of experimentally increased protein supply to postpartum dairy cows on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis

DEFF Research Database (Denmark)

Larsen, Mogens; Røntved, Christine Maria; Theil, Peter Kappel

2017-01-01

The effect of experimentally increasing the postpartum protein supply on plasma protein synthesis, rumen tissue proliferation, and immune homeostasis was studied using 8 periparturient Holstein cows in a complete randomized design. At calving, cows were assigned to abomasal infusion of water (CTRL......) or casein (CAS) in addition to a lactation diet. Casein infusion was gradually decreased from 696 ± 1 g/d at +2 d relative to calving (DRTC) to 212 ± 10 g/d at +29 DRTC to avoid excessive supply. Synthesis rate of plasma proteins was measured at –14, +4, +15, and +29 DRTC by measuring [13C]Phe isotopic...... enrichment in arterial plasma free Phe, total plasma proteins, and albumin after 3, 5, and 7 h of jugular ring[13C]Phe infusion. Plasma volume was determined at +4 and +29 DRTC by dilution of a [125I]BSA dose. Synthesis rate of tissue protein in biopsied rumen papillae was determined by measuring [13C...

Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

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Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

2011-08-01

Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Thermal-mechanical deformation modelling of soft tissues for thermal ablation.

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Li, Xin; Zhong, Yongmin; Jazar, Reza; Subic, Aleksandar

2014-01-01

Modeling of thermal-induced mechanical behaviors of soft tissues is of great importance for thermal ablation. This paper presents a method by integrating the heating process with thermal-induced mechanical deformations of soft tissues for simulation and analysis of the thermal ablation process. This method combines bio-heat transfer theories, constitutive elastic material law under thermal loads as well as non-rigid motion dynamics to predict and analyze thermal-mechanical deformations of soft tissues. The 3D governing equations of thermal-mechanical soft tissue deformation are discretized by using the finite difference scheme and are subsequently solved by numerical algorithms. Experimental results show that the proposed method can effectively predict the thermal-induced mechanical behaviors of soft tissues, and can be used for the thermal ablation therapy to effectively control the delivered heat energy for cancer treatment.

Nondestructive evaluation of a new hydrolytically degradable and photo-clickable PEG hydrogel for cartilage tissue engineering.

Science.gov (United States)

Neumann, Alexander J; Quinn, Timothy; Bryant, Stephanie J

2016-07-15

Photopolymerizable and hydrolytically labile poly(ethylene glycol) (PEG) hydrogels formed from photo-clickable reactions were investigated as cell delivery platforms for cartilage tissue engineering (TE). PEG hydrogels were formed from thiol-norbornene PEG macromers whereby the crosslinks contained caprolactone segments with hydrolytically labile ester linkages. Juvenile bovine chondrocytes encapsulated in the hydrogels were cultured for up to four weeks and assessed biochemically and histologically, using standard destructive assays, and for mechanical and ultrasound properties, as nondestructive assays. Bulk degradation of acellular hydrogels was confirmed by a decrease in compressive modulus and an increase in mass swelling ratio over time. Chondrocytes deposited increasing amounts of sulfated glycosaminoglycans and collagens in the hydrogels with time. Spatially, collagen type II and aggrecan were present in the neotissue with formation of a territorial matrix beginning at day 21. Nondestructive measurements revealed an 8-fold increase in compressive modulus from days 7 to 28, which correlated with total collagen content. Ultrasound measurements revealed changes in the constructs over time, which differed from the mechanical properties, and appeared to correlate with ECM structure and organization shown by immunohistochemical analysis. Overall, non-destructive and destructive measurements show that this new hydrolytically degradable PEG hydrogel is promising for cartilage TE. Designing synthetic hydrogels whose degradation matches tissue growth is critical to maintaining mechanical integrity as the hydrogel degrades and new tissue forms, but is challenging due to the nature of the hydrogel crosslinks that inhibit diffusion of tissue matrix molecules. This study details a promising, new, photo-clickable and synthetic hydrogel whose degradation supports cartilaginous tissue matrix growth leading to the formation of a territorial matrix, concomitant with an

Generalized connective tissue disease in Crtap-/- mouse.

Directory of Open Access Journals (Sweden)

Dustin Baldridge

2010-05-01

Full Text Available Mutations in CRTAP (coding for cartilage-associated protein, LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1] or PPIB (coding for Cyclophilin B [CYPB] cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in alpha1(I and alpha1(II chains, there was also loss of 3Hyp at proline 986 in alpha2(V chains. In contrast, at two of the known 3Hyp sites in alpha1(IV chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin.

Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration

DEFF Research Database (Denmark)

Ohki, Makiko; Ohki, Yuichi; Ishihara, Makoto

2010-01-01

tissue regeneration is not well understood. Bone marrow (BM)-derived myeloid cells facilitate angiogenesis during tissue regeneration. Here, we report that a serpin-resistant form of tPA by activating the extracellular proteases matrix metalloproteinase-9 and plasmin expands the myeloid cell pool......-A. Remarkably, transplantation of BM-derived tPA-mobilized CD11b(+) cells and VEGFR-1(+) cells, but not carrier-mobilized cells or CD11b(-) cells, accelerates neovascularization and ischemic tissue regeneration. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb...... and mobilizes CD45(+)CD11b(+) proangiogenic, myeloid cells, a process dependent on vascular endothelial growth factor-A (VEGF-A) and Kit ligand signaling. tPA improves the incorporation of CD11b(+) cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF...

Lasers in Esthetic Dentistry: Soft Tissue Photobiomodulation, Hard Tissue Decontamination, and Ceramics Conditioning

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Karen Müller Ramalho

2014-01-01

Full Text Available The increasing concern and the search for conservative dental treatments have resulted in the development of several new technologies. Low and high power lasers can be cited as one of these new technologies. Low power lasers act at cellular level leading to pain reduction, modulation of inflammation, and improvement of tissue healing. High power lasers act by increasing temperature and have the potential to promote microbial reduction and ablation of hard and soft tissues. The clinical application of both low and high power lasers requires specific knowledge concerning laser interaction with biological tissues, so that the correct irradiation protocol can be established. The present case report describes the clinical steps of two metal-ceramic crowns development in a 60-year-old patient. Three different laser wavelengths were applied throughout the treatment with different purposes: Nd:YAG laser (1,064 nm for dentin decontamination, diode (660 nm for soft tissue biomodulation, and Er:YAG laser (2,940 nm for inner ceramic surface conditioning. Lasers were successfully applied in the present case report as coadjutant in the treatment. This coadjutant technology can be a potential tool to assist treatment to reach the final success.

Bioprinting of Micro-Organ Tissue Analog for Drug Metabolism Study

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Sun, Wei

An evolving application of tissue engineering is to develop in vitro 3D cell/tissue models for drug screening and pharmacological study. In order to test in space, these in vitro models are mostly manufactured through micro-fabrication techniques and incorporate living cells with MEMS or microfluidic devices. These cell-integrated microfluidic devices, or referred as microorgans, are effective in furnishing reliable and inexpensive drug metabolism and toxicity studies [1-3]. This paper will present an on-going research collaborated between Drexel University and NASA JSC Radiation Physics Laboratory for applying a direct cell printing technique to freeform fabrication of 3D liver tissue analog in drug metabolism study. The paper will discuss modeling, design, and solid freeform fabrication of micro-fluidic flow patterns and bioprinting of 3D micro-liver chamber that biomimics liver physiological microenvironment for enhanced drug metabolization. Technical details to address bioprinting of 3D liver tissue analog, integration with a microfluidic device, and basic drug metabolism study for NASA's interests will presented. 1. Holtorf H. Leslie J. Chang R, Nam J, Culbertson C, Sun W, Gonda S, "Development of a Three-Dimensional Tissue-on-a-Chip Micro-Organ Device for Pharmacokinetic Analysis", the 47th Annual Meeting of the American Society for Cell Biology, Washington, DC, December 1-5, 2007. 2. Chang, R., Nam, J., Culbertson C., Holtorf, H., Jeevarajan, A., Gonda, S. and Sun, W., "Bio-printing and Modeling of Flow Patterns for Cell Encapsulated 3D Liver Chambers For Pharmacokinetic Study", TERMIS North America 2007 Conference and Exposition, Westin Harbour Castle, Toronto, Canada, June 13-16, 2007. 3.Starly, B., Chang, R., Sun, W., Culbertson, C., Holtorf, H. and Gonda, S., "Bioprinted Tissue-on-chip Application for Pharmacokinetic Studies", Proceedings of World Congress on Tissue Engineering and Regenerative Medicine, Pittsburgh, PA, USA, April 24-27, 2006.

The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

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Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

2014-09-01

Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

Increasing Employability by Implementing a Work-Integrated Learning Partnership Model in South Africa--A Student Perspective

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Taylor, Susanne; Govender, Cookie M.

2017-01-01

In South Africa, 70 per cent of the population is under 35 years old. South Africa has a vision to increase youth employment by focusing on education, training and skills development that will promote employment opportunities. A work-integrated learning (WIL) partnership model was developed to provide students with work experience and to increase…

Application of Texture Analysis to Study Small Vessel Disease and Blood–Brain Barrier Integrity

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Maria del C. Valdés Hernández

2017-07-01

Full Text Available ObjectivesWe evaluate the alternative use of texture analysis for evaluating the role of blood–brain barrier (BBB in small vessel disease (SVD.MethodsWe used brain magnetic resonance imaging from 204 stroke patients, acquired before and 20 min after intravenous gadolinium administration. We segmented tissues, white matter hyperintensities (WMH and applied validated visual scores. We measured textural features in all tissues pre- and post-contrast and used ANCOVA to evaluate the effect of SVD indicators on the pre-/post-contrast change, Kruskal–Wallis for significance between patient groups and linear mixed models for pre-/post-contrast variations in cerebrospinal fluid (CSF with Fazekas scores.ResultsTextural “homogeneity” increase in normal tissues with higher presence of SVD indicators was consistently more overt than in abnormal tissues. Textural “homogeneity” increased with age, basal ganglia perivascular spaces scores (p < 0.01 and SVD scores (p < 0.05 and was significantly higher in hypertensive patients (p < 0.002 and lacunar stroke (p = 0.04. Hypertension (74% patients, WMH load (median = 1.5 ± 1.6% of intracranial volume, and age (mean = 65.6 years, SD = 11.3 predicted the pre/post-contrast change in normal white matter, WMH, and index stroke lesion. CSF signal increased with increasing SVD post-contrast.ConclusionA consistent general pattern of increasing textural “homogeneity” with increasing SVD and post-contrast change in CSF with increasing WMH suggest that texture analysis may be useful for the study of BBB integrity.

Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine

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Gnanalingham, MG; Mostyn, A; Forhead, AJ; Fowden, AL; Symonds, ME; Stephenson, T

2005-01-01

The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2) in fetal adipose tissue in the sheep during late gestation. Perirenal–abdominal adipose tissue was sampled from ovine fetuses to which either cortisol (2–3 mg kg−1 day−1) or saline was infused for 5 days up to 127–130 days gestation, or near term fetuses (i.e. 142–145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age-matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11βHSD1 mRNA and decrease in 11βHSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11βHSD2 mRNA abundance, but negatively correlated with 11βHSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation. PMID:15961419

Integrated Giant Magnetoresistance Technology for Approachable Weak Biomagnetic Signal Detections.

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Shen, Hui-Min; Hu, Liang; Fu, Xin

2018-01-07

With the extensive applications of biomagnetic signals derived from active biological tissue in both clinical diagnoses and human-computer-interaction, there is an increasing need for approachable weak biomagnetic sensing technology. The inherent merits of giant magnetoresistance (GMR) and its high integration with multiple technologies makes it possible to detect weak biomagnetic signals with micron-sized, non-cooled and low-cost sensors, considering that the magnetic field intensity attenuates rapidly with distance. This paper focuses on the state-of-art in integrated GMR technology for approachable biomagnetic sensing from the perspective of discipline fusion between them. The progress in integrated GMR to overcome the challenges in weak biomagnetic signal detection towards high resolution portable applications is addressed. The various strategies for 1/ f noise reduction and sensitivity enhancement in integrated GMR technology for sub-pT biomagnetic signal recording are discussed. In this paper, we review the developments of integrated GMR technology for in vivo/vitro biomagnetic source imaging and demonstrate how integrated GMR can be utilized for biomagnetic field detection. Since the field sensitivity of integrated GMR technology is being pushed to fT/Hz 0.5 with the focused efforts, it is believed that the potential of integrated GMR technology will make it preferred choice in weak biomagnetic signal detection in the future.

An Integrated Intervention for Increasing Clinical Nurses’ Knowledge of HIV/AIDS-Related Occupational Safety

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Liping He

2016-11-01

Full Text Available Background: Approximately 35 new HIV (Human Immunodeficiency Virus, HIV cases and at least 1000 serious infections are transmitted annually to health care workers. In China, HIV prevalence is increasing and nursing personnel are encountering these individuals more than in the past. Contaminated needle-stick injuries represent a significant occupational burden for nurses. Evidence suggests that nurses in China may not fully understand HIV/AIDS (Acquired immunodeficiency syndrome, AIDS and HIV-related occupational safety. At this time, universal protection precautions are not strictly implemented in Chinese hospitals. Lack of training may place nurses at risk for occupational exposure to blood-borne pathogens. Objectives: To assess the effectiveness of integrated interventions on nurses’ knowledge improvement about reducing the risk of occupationally acquired HIV infection. Methods: We audited integrated interventions using 300 questionnaires collected from nurses at the Affiliated Hospital of Xiangnan University, a public polyclinic in Hunan Province. The intervention studied was multifaceted and included appropriate and targeted training content for hospital, department and individual levels. After three months of occupational safety integrated interventions, 234 participants who completed the program were assessed. Results: Of the subjects studied, 94.3% (283/300 were injured one or more times by medical sharp instruments or splashed by body fluids in the last year and 95.3% considered their risk of occupational exposure high or very high. After the intervention, awareness of HIV/AIDS-related knowledge improved significantly (χ2 = 86.34, p = 0.00, and correct answers increased from 67.9% to 82.34%. Correct answers regarding risk perception were significantly different between pre-test (54.4% and post-test (66.6% (χ2 = 73.2, p = 0.00. When coming into contact with patient body fluids and blood only 24.0% of subjects used gloves regularly

HMP-1/α-catenin promotes junctional mechanical integrity during morphogenesis.

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Thanh Thi Kim Vuong-Brender

Full Text Available Adherens junctions (AJs are key structures regulating tissue integrity and maintaining adhesion between cells. During morphogenesis, junctional proteins cooperate closely with the actomyosin network to drive cell movement and shape changes. How the junctions integrate the mechanical forces in space and in time during an in vivo morphogenetic event is still largely unknown, due to a lack of quantitative data. To address this issue, we inserted a functional Fluorescence Resonance Energy Transfer (FRET-based force biosensor within HMP-1/α-catenin of Caenorhabditis elegans. We find that the tension exerted on HMP-1 has a cell-specific distribution, is actomyosin-dependent, but is regulated differently from the tension on the actin cortex during embryonic elongation. By using time-lapse analysis of mutants and tissue-specific rescue experiments, we confirm the role of VAB-9/Claudin as an actin bundle anchor. Nevertheless, the tension exerted on HMP-1 did not increase in the absence of VAB-9/Claudin, suggesting that HMP-1 activity is not upregulated to compensate for loss of VAB-9. Our data indicate that HMP-1 does not modulate HMR-1/E-cadherin turnover, is required to recruit junctional actin but not stress fiber-like actin bundles. Altogether, our data suggest that HMP-1/α-catenin acts to promote the mechanical integrity of adherens junctions.

Information and Announcements Refresher Course in Animal Tissue ...

Indian Academy of Sciences (India)

Srimath

2009-03-23

Mar 23, 2009 ... Animal tissue culture is an integral and important part of Biotechnology teaching from the point of view of improved medical care in terms of improved diagnostics, vaccines; production of biomolecules of importance; testing efficacy of drugs; possibilities in regenerative medicine etc. This course proposes to ...

In vitro evaluation of tissue adhesives composed of hydrophobically modified gelatins and disuccinimidyl tartrate

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Miyuki Matsuda

2012-01-01

Full Text Available The effect of the hydrophobic group content in gelatin on the bonding strength of novel tissue–penetrating tissue adhesives was evaluated. The hydrophobic groups introduced into gelatin were the saturated hexanoyl, palmitoyl, and stearoyl groups, and the unsaturated oleoyl group. A collagen casing was employed as an adherend to model soft tissue for the in vitro determination of bonding strength of tissue adhesives composed of various hydrophobically modified gelatins and disuccinimidyl tartrate. The adhesive composed of stearoyl-modified gelatin (7.4% stearoyl; 10Ste and disuccinimidyl tartrate showed the highest bonding strength. The bonding strength of the adhesives decreased as the degree of substitution of the hydrophobic groups increased. Cell culture experiments demonstrated that fluorescein isothiocyanate-labeled 10Ste was integrated onto the surface of smooth muscle cells and showed no cytotoxicity. These results suggest that 10Ste interacted with the hydrophobic domains of collagen casings, such as hydrophobic amino acid residues and cell membranes. Therefore, 10Ste–disuccinimidyl tartrate is a promising adhesive for use in aortic dissection.

Multimodal nonlinear microscopy: A powerful label-free method for supporting standard diagnostics on biological tissues

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Riccardo Cicchi

2014-09-01

Full Text Available The large use of nonlinear laser scanning microscopy in the past decade paved the way for potential clinical application of this imaging technique. Modern nonlinear microscopy techniques offer promising label-free solutions to improve diagnostic performances on tissues. In particular, the combination of multiple nonlinear imaging techniques in the same microscope allows integrating morphological with functional information in a morpho-functional scheme. Such approach provides a high-resolution label-free alternative to both histological and immunohistochemical examination of tissues and is becoming increasingly popular among the clinical community. Nevertheless, several technical improvements, including automatic scanning and image analysis, are required before the technique represents a standard diagnostic method. In this review paper, we highlight the capabilities of multimodal nonlinear microscopy for tissue imaging, by providing various examples on colon, arterial and skin tissues. The comparison between images acquired using multimodal nonlinear microscopy and histology shows a good agreement between the two methods. The results demonstrate that multimodal nonlinear microscopy is a powerful label-free alternative to standard histopathological methods and has the potential to find a stable place in the clinical setting in the near future.

Adipose tissue as an endocrine organ.

Science.gov (United States)

McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

2014-02-01

Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

Transforming growth factor-β (TGF-β) expression is increased in the subsynovial connective tissues of patients with idiopathic carpal tunnel syndrome.

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Chikenji, Takako; Gingery, Anne; Zhao, Chunfeng; Passe, Sandra M; Ozasa, Yasuhiro; Larson, Dirk; An, Kai-Nan; Amadio, Peter C

2014-01-01

Non-inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its relationship to the development of CTS remain poorly understood. Recent studies have found that transforming growth factor-β (TGF-β) plays a central role in fibrosis. The purpose of this study was to investigate the expression of TGF-β and connective tissue growth factor (CTGF), a downstream mediator of TGF-β, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic CTS patients with specimens from 10 human cadaver controls with no previous diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF-β1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF-β1 (p tissue. In addition, a strong positive correlation was found between TGF-β1 and CTGF, (R(2) = 0.80, p < 0.01) and a moderate positive correlation between Col3 and TGF-β1 (R(2) = 0.49, p < 0.01). These finding suggest that there is an increased expression of TGF-β and CTGF, a TGF-β regulated protein, and that this TGF-β activation may be responsible for SSCT fibrosis in CTS patients. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Formation of proteoglycan and collagen-rich scaffold-free stiff cartilaginous tissue using two-step culture methods with combinations of growth factors.

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Miyazaki, Tatsuya; Miyauchi, Satoshi; Matsuzaka, Satoshi; Yamagishi, Chie; Kobayashi, Kohei

2010-05-01

Tissue-engineered cartilage may be expected to serve as an alternative to autologous chondrocyte transplantation treatment. Several methods for producing cartilaginous tissue have been reported. In this study, we describe the production of scaffold-free stiff cartilaginous tissue of pig and human, using allogeneic serum and growth factors. The tissue was formed in a mold using chondrocytes recovered from alginate bead culture and maintained in a medium with transforming growth factor-beta and several other additives. In the case of porcine tissue, the tear strength of the tissue and the contents of proteoglycan (PG) and collagen per unit of DNA increased dose-dependently with transforming growth factor-beta. The length of culture was significantly and positively correlated with thickness, tear strength, and PG and collagen contents. Tear strength showed positive high correlations with both PG and collagen contents. A positive correlation was also seen between PG content and collagen content. Similar results were obtained with human cartilaginous tissue formed from chondrocytes expanded in monolayer culture. Further, an in vivo pilot study using pig articular cartilage defect model demonstrated that the cartilaginous tissue was well integrated with surrounding tissue at 13 weeks after the implantation. In conclusion, we successfully produced implantable scaffold-free stiff cartilaginous tissue, which characterized high PG and collagen contents.

Three-dimensional bioprinting in tissue engineering and regenerative medicine.

Science.gov (United States)

Gao, Guifang; Cui, Xiaofeng

2016-02-01

With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

Effect of lunar materials on plant tissue culture.

Science.gov (United States)

Walkinshaw, C. H.; Venketeswaran, S.; Baur, P. S.; Croley, T. E.; Scholes, V. E.; Weete, J. D.; Halliwell, R. S.; Hall, R. H.

1973-01-01

Lunar material collected during the Apollo 11, 12, 14, and 15 missions has been used to treat 12 species of higher plant tissue cultures. Biochemical and morphological studies have been conducted on several of these species. Tobacco tissue cultures treated with 0.22 g of lunar material exhibited increased greening more complex chloroplasts, less cytoplasmic vacuolation and greater vesiculation. Pine tissue cultures reacted to treatment by an increased deposition of tannin-like materials. The percentage of dry weight and soluble protein was increased in cultures treated with either lunar or terrestrial rock materials.

Effect of whole-body gamma radiation on tissue sulfhydryl contents in experimental rats

International Nuclear Information System (INIS)

Sarkar, S.R.; Singh, L.R.; Uniyal, B.P.

1985-01-01

It has been postulated that vital constituents of cell membranes concerned with the maintenance of cellular integrity are affected by ionizing radiation. Sulfhydryl contents, which form an integral component of cell membranes play vital roles in maintaining cellular integrity. The purpose was to evaluate non-protein and protein sulfhydryl contents in tissues of irradiated rats. Adult male Sprague Dawley rats were exposed to whole-body gamma irradiation of 4 Gy and 10 Gy and non-protein and protein sulfhydryl contents of blood, heart and spleen were studied on postirradiation day 1, 3 and 6. Both groups of experimental rats exhibited unchanged blood non-protein sulfhydryl contents on first day after irradiation with significant diminution subsequently. In contrast, blood protein sulfhydryl groups of both groups of rats were increased on first day post exposure, which became normal on sixth day. Myocardial non-protein and protein sulfhydryl contents of both groups of rats remained unchanged in the initial stage of radiation exposure indicating radioresistance nature of rat heart. Both groups of rats demonstrated biphasic nature of non-protein sulfhydryl contents in spleen, asrevealed by initial increase with subsequent decrease. Protein sulfhydryl contents of rats of 4 Gy group showed significant diminution post exposure throughout, while the same of 10 Gy behaved in opposite way. (author)

The influence of freezing and tissue porosity on the material properties of vegetable tissues

International Nuclear Information System (INIS)

Ralfs, Julie D.

2002-01-01

Tissue porosity and fluid flow have been shown to be important parameters affecting the mechanical and sensorial behaviour of edible plant tissues. The quantity of fluid and the manner with which it was released on compression of the plant tissue were also important regarding the sensory perception and a good indication of any structural damage resulting from freezing, for example. Potato, carrot and Chinese water chestnut were used to study the effects freezing has on model plant tissues. Mechanical and structural measurements of the plant tissue were correlated with sensory analysis. Conventional freezing was shown to cause severe structural damage predominantly in the form of cavities between or through cells, resulting in decreases in mechanical strength and stiffness, and samples that were perceived in the mouth as 'soft' and 'wet'. The location and size of the cavities formed from ice crystals, depended on the particular plant tissue being frozen, the processing it was subjected to prior to freezing, the size of the sample and the cooling regime employed to freeze the tissue. Cavitation in the tissue resulted in an increase in tissue porosity, which enabled fluid to flow more easily from the tissue on compression, thus affecting the mechanical properties and sensory perception. Freezing damage to plant tissues was shown to be reduced, and sometimes prevented, when active antifreeze proteins (AFPs) were introduced into the tissues by vacuum infiltration or transformation and the tissue was frozen at a suitable cooling rate. Theoretical modelling was applied to the fluid flow and porosity data to test the validity of the models and to subsequently predict the mechanical behaviour of potato from the structural properties of the tissue. (author)

Integrative analysis of copy number and gene expression in breast cancer using formalin-fixed paraffin-embedded core biopsy tissue: a feasibility study.

Science.gov (United States)

Iddawela, Mahesh; Rueda, Oscar; Eremin, Jenny; Eremin, Oleg; Cowley, Jed; Earl, Helena M; Caldas, Carlos

2017-07-11

An absence of reliable molecular markers has hampered individualised breast cancer treatments, and a major limitation for translational research is the lack of fresh tissue. There are, however, abundant banks of formalin-fixed paraffin-embedded (FFPE) tissue. This study evaluated two platforms available for the analysis of DNA copy number and gene expression using FFPE samples. The cDNA-mediated annealing, selection, extension, and ligation assay (DASL™) has been developed for gene expression analysis and the Molecular Inversion Probes assay (Oncoscan™), were used for copy number analysis using FFPE tissues. Gene expression and copy number were evaluated in core-biopsy samples from patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Forty-three core-biopsies were evaluated and characteristic copy number changes in breast cancers, gains in 1q, 8q, 11q, 17q and 20q and losses in 6q, 8p, 13q and 16q, were confirmed. Regions that frequently exhibited gains in tumours showing a pathological complete response (pCR) to NAC were 1q (55%), 8q (40%) and 17q (40%), whereas 11q11 (37%) gain was the most frequent change in non-pCR tumours. Gains associated with poor survival were 11q13 (62%), 8q24 (54%) and 20q (47%). Gene expression assessed by DASL correlated with immunohistochemistry (IHC) analysis for oestrogen receptor (ER) [area under the curve (AUC) = 0.95], progesterone receptor (PR)(AUC = 0.90) and human epidermal growth factor type-2 receptor (HER-2) (AUC = 0.96). Differential expression analysis between ER+ and ER- cancers identified over-expression of TTF1, LAF-4 and C-MYB (p ≤ 0.05), and between pCR vs non-pCRs, over-expression of CXCL9, AREG, B-MYB and under-expression of ABCG2. This study was an integrative analysis of copy number and gene expression using FFPE core biopsies and showed that molecular marker data from FFPE tissues were consistent with those in previous studies using fresh-frozen samples. FFPE tissue can provide