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Sample records for healthy tissue tolerance

  1. Dose effect comparisons between HFR and BMRR irradiated dogs with respect to healthy tissue tolerance

    International Nuclear Information System (INIS)

    Huiskamp, R.; Philipp, K.H.I.; Gavin, P.R.; Wheeler, F.J.; Siefert, A.

    1993-01-01

    Epithermal neutron beams are being developed for the application of boron neutron capture therapy (BNCT) of deep seated tumors, like glioblastoma and astrocytomas, through the intact skin. Epithermal neutrons will be moderated by the tissue mass between skin and tumour to produce the thermal neutrons necessary for the 10 B(n,α) 7 Li reaction in the target tissue. Although the neutron capture cross-sections of elements in normal tissue are several orders of magnitude lower that for boron, the high abundance of hydrogen and nitrogen will cause a significant contribution to the total absorbed radiation dose through the 1 H(n,γ) 2 H and the 14 N(n,p) 14 C reaction, respectively. Due to inevitable incomplete filtration, an epithermal beam will also contain a fast neutron component, i.e. neutrons with energies ≥ 10 keV, and a γ-photon component originating from the reactor and produced in structural and filter materials. Therefore, the resultant radiation consists of a complex of low and high LET radiation of which the constitutents vary rapidly with depth in tissue. Based on the ongoing canine healthy tissue tolerance study at the Brookhaven Medical Research Reactor (BMRR) using the epithermal beam without BSH, the relative biological effectiveness (RBE) of the fast neutron beam component has been determined for skin reactions. In addition, a open-quotes compound factorclose quotes, i.e geometry x RBE, for the 10 B(n,α) 7 Li reaction was derived for dogs irradiated at the BMRR with the epithermal beam and BSH (Gavin et al.). Currently, a healthy tissue tolerance study with BSH is being carried out at the HB11 epithermal beam of the High Flux Reactor at Petten. The present paper describes preliminary dose effect comparisons between High Flux Reactor (HFR) and BMRR irradiated dogs with respect to healthy tissue tolerance in order to refine the BSH compound factors and the fast neutron RBE for skin and brain

  2. Evaluation of dose components for healthy tissue tolerance studies on dogs at the HFR Petten

    International Nuclear Information System (INIS)

    Watkins, P.; Moss, R.L.; Siefert, A.; Huiskamp, R.; Gavin, P.; Konijnenberg, M.

    1993-01-01

    Before the start of clinical trails of BNCT on glioma patients at the Petten reactor, certain preconditions must be determined. In particular the tolerance of healthy brain tissue exposed to the epithermal neutron beam requires investigation. In these studies, beagle dogs have been subjected to different levels of irradiation and 10 B, the latter in the form of BSH. To support this work a treatment planning tool is being developed to predict the various dose components within the treatment volume. A Monte Carlo code, MCNP, has been used to simulate the particle transport and to predict the different dose rate distributions. The doses rates generated by MCNP are manipulated with a processing code, TREAT, to give irradiation times, peak dose positions and to display the required data in a graphical format. This paper explains the basic methodology used in the system and a practical case is presented for one of the healthy tissue tolerance dogs. Doses, both physical and RBE weighted, have been produced for pre-treatment planning studies

  3. In situ FTIR assessment of desiccation-tolerant tissues

    NARCIS (Netherlands)

    Wolkers, W.F.; Hoekstra, F.A.

    2003-01-01

    This essay shows how Fourier transform infrared (FTIR) microspectroscopy can be applied to study thermodynamic parameters and conformation of endogenous biomolecules in desiccation-tolerant biological tissues. Desiccation tolerance is the remarkable ability of some organisms to survive complete

  4. Impaired glucose tolerance in healthy men with low body weight

    Directory of Open Access Journals (Sweden)

    Schmoller André

    2011-02-01

    Full Text Available Abstract Background Impaired glucose tolerance (IGT and high body mass index (BMI are recognized risk factors for type 2 diabetes mellitus (T2DM. However, data suggest that also underweight predisposes people to develop T2DM. Here, we experimentally tested if already moderate underweight is associated with impaired glucose tolerance as compared to normal weight controls. Obese subjects were included as additional reference group. Method We included three groups of low weight, normal weight, and obese subjects comprising 15 healthy male participants each. All participants underwent a standardized hyperinsulinemic-euglycemic glucose clamp intervention to determine glucose tolerance. In addition, insulin sensitivity index (ISI was calculated by established equation. Results ISI values were higher in low and normal weight than in obese subjects (P P = 0.303. Comparable to obese participants (P = 0.178, glucose tolerance was found decreased in low weight as compared with normal weight subjects (P = 0.007. Pearson's correlation analysis revealed a positive relationship between glucose tolerance and BMI in low (P = 0.043 and normal weight subjects (P = 0.021, an effect that was found inverse in obese participants (P = 0.028. Conclusion Our study demonstrates that not only obese but also healthy people with moderate underweight display glucose intolerance. It is therefore suggested that all deviations from normal BMI may be accompanied by an increased risk of developing T2DM in later life indicating that the maintenance of body weight within the normal range has first priority in the prevention of this disease.

  5. Catalase activity in healthy and inflamed pulp tissues of permanent ...

    African Journals Online (AJOL)

    2015-11-02

    Nov 2, 2015 ... pulps, which is due to pulpitis in comparison to healthy dental pulp. Key words: .... human dental pulp cells by Porphyromonas endodontalis lipopolysaccharide. J Endod ... Biology of disease: Free radicals and tissue injury.

  6. Impaired Glucose Tolerance in Healthy Men Treated with St. John's Wort

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard

    2016-01-01

    The purpose of this study was to examine if the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions; A: Baseline, B: After 21 days...

  7. St. John's wort impairs glucose tolerance by reducing insulin response in healthy men

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard

    2015-01-01

    The purpose of this study was to examine if the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions; A: Baseline, B: After 21 days...

  8. Tissue tolerance under the combination treatment of maxillary cancer

    International Nuclear Information System (INIS)

    Egawa, Jun; Ono, Isamu; Suzuki, Kunio; Takeda, Chisato; Ebihara, Satoshi.

    1977-01-01

    The tissue tolerance doses of the maxillary sinus structures were estimated when they were subjected to treatment for maxillary cancer by the usual combination of surgery, radiotherapy and regional arterial infusion of 5-fluorouracil. Equivalent single dose calculation was applied with irreversible tissue damage as an indicator. The retardation of epithelialization of the maxillary sinus operated upon appeared to be correlated with the dose delivered. The study indicated that 2,200 rad expressed by equivalent single dose is a safe dose level for sufficient epithelialization. The safety dose level for the bony structure, exposed by surgery, seemed to be at 1,800 rad. (auth.)

  9. Tissue tolerance under the combination treatment of maxillary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Egawa, J [Teikyo Univ., Tokyo (Japan). Faculty of Medicine; Ono, I; Suzuki, K; Takeda, C; Ebihara, S

    1977-06-01

    The tissue tolerance doses of the maxillary sinus structures were estimated when they were subjected to treatment for maxillary cancer by the usual combination of surgery, radiotherapy, and regional arterial infusion of 5-fluorouracil. Equivalent single dose calculation was applied with irreversible tissue damage as an indicator. The retardation of epithelialization of the maxillary sinus operated upon appeared to be correlated with the dose delivered. The study indicated that 2,200 rad expressed by equivalent single dose is a safe dose level for sufficient epithelialization. The safety dose level for the bony structure, exposed by surgery, seemed to be at 1,800 rad.

  10. Efficacy of Tissue Tolerable Plasma (TTP against Ixodes ricinus

    Directory of Open Access Journals (Sweden)

    Bender, Claudia

    2014-03-01

    Full Text Available [english] The efficacy of Tissue Tolerable Plasma (TTP against ticks was tested, as data from the literature has demonstrated its efficacy against other acari.The study was carried out by using the KINPen09 (Argon as carrier gas on (n=24. Treatment times of 1 and 3 minutes led to a reversible inactivation of the ticks. After 5 min of treatment, they died.Thanks to the acaricidal effect of TPP, a new treatment strategy using the KINPen09 for tick-infested pets is now available.

  11. Extracellular matrix fragmentation in young, healthy cartilaginous tissues.

    Science.gov (United States)

    Craddock, R J; Hodson, N W; Ozols, M; Shearer, T; Hoyland, J A; Sherratt, M J

    2018-02-09

    Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC) and the nucleus pulposus (NP) of the intervertebral disc (IVD). Whilst structural heterogeneity of intact aggrecan ( containing three globular domains) is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months), bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 %) were fragmented (lacking one or more globular domains). Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa) comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis). As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2) as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2), it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally) and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

  12. Extracellular matrix fragmentation in young, healthy cartilaginous tissues

    Directory of Open Access Journals (Sweden)

    RJ Craddock

    2018-02-01

    Full Text Available Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC and the nucleus pulposus (NP of the intervertebral disc (IVD. Whilst structural heterogeneity of intact aggrecan ( containing three globular domains is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months, bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 % were fragmented (lacking one or more globular domains. Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p < 0.0001. In contrast, fibrillar collagen appeared structurally intact and tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis. As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2 as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2, it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

  13. Normal tissue tolerance to external beam radiation therapy: Adult bone

    International Nuclear Information System (INIS)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G.; Huchet, A.; Italiano, A.

    2010-01-01

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  14. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

    International Nuclear Information System (INIS)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

    2010-01-01

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  15. Feast and famine: Adipose tissue adaptations for healthy aging.

    Science.gov (United States)

    Lettieri Barbato, Daniele; Aquilano, Katia

    2016-07-01

    Proper adipose tissue function controls energy balance with favourable effects on metabolic health and longevity. The molecular and metabolic asset of adipose tissue quickly and dynamically readapts in response to nutrient fluctuations. Once delivered into cells, nutrients are managed by mitochondria that represent a key bioenergetics node. A persistent nutrient overload generates mitochondrial exhaustion and uncontrolled reactive oxygen species ((mt)ROS) production. In adipocytes, metabolic/molecular reorganization is triggered culminating in the acquirement of a hypertrophic and hypersecretory phenotype that accelerates aging. Conversely, dietary regimens such as caloric restriction or time-controlled fasting endorse mitochondrial functionality and (mt)ROS-mediated signalling, thus promoting geroprotection. In this perspective view, we argued some important molecular and metabolic aspects related to adipocyte response to nutrient stress. Finally we delineated hypothetical routes by which molecularly and metabolically readapted adipose tissue promotes healthy aging. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Newly Identified Wild Rice Accessions Conferring High Salt Tolerance Might Use a Tissue Tolerance Mechanism in Leaf

    Science.gov (United States)

    Prusty, Manas R.; Kim, Sung-Ryul; Vinarao, Ricky; Entila, Frederickson; Egdane, James; Diaz, Maria G. Q.; Jena, Kshirod K.

    2018-01-01

    Cultivated rice (Oryza sativa L.) is very sensitive to salt stress. So far a few rice landraces have been identified as a source of salt tolerance and utilized in rice improvement. These tolerant lines primarily use Na+ exclusion mechanism in root which removes Na+ from the xylem stream by membrane Na+ and K+ transporters, and resulted in low Na+ accumulation in shoot. Identification of a new donor source conferring high salt tolerance is imperative. Wild relatives of rice having wide genetic diversity are regarded as a potential source for crop improvement. However, they have been less exploited against salt stress. Here, we simultaneously evaluated all 22 wild Oryza species along with the cultivated tolerant lines including Pokkali, Nona Bokra, and FL478, and sensitive check varieties under high salinity (240 mM NaCl). Based on the visual salt injury score, three species (O. alta, O. latifolia, and O. coarctata) and four species (O. rhizomatis, O. eichingeri, O. minuta, and O. grandiglumis) showed higher and similar level of tolerance compared to the tolerant checks, respectively. All three CCDD genome species exhibited salt tolerance, suggesting that the CCDD genome might possess the common genetic factors for salt tolerance. Physiological and biochemical experiments were conducted using the newly isolated tolerant species together with checks under 180 mM NaCl. Interestingly, all wild species showed high Na+ concentration in shoot and low concentration in root unlike the tolerant checks. In addition, the wild-tolerant accessions showed a tendency of a high tissue tolerance in leaf, low malondialdehyde level in shoot, and high retention of chlorophyll in the young leaves. These results suggest that the wild species employ tissue tolerance mechanism to manage salt stress. Gene expression analyses of the key salt tolerance-related genes suggested that high Na+ in leaf of wild species might be affected by OsHKT1;4-mediated Na+ exclusion in leaf and the following Na

  17. Large animal normal tissue tolerance with boron neutron capture.

    Science.gov (United States)

    Gavin, P R; Kraft, S L; DeHaan, C E; Swartz, C D; Griebenow, M L

    1994-03-30

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

  18. Large animal normal tissue tolerance with boron neutron capture

    International Nuclear Information System (INIS)

    Gavin, P.R.; Swartz, C.D.; Kraft, S.L.; Briebenow, M.L.; DeHaan, C.E.

    1994-01-01

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA 2 B 12 H 11 SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs

  19. The interbranchial lymphoid tissue likely contributes to immune tolerance and defense in the gills of Atlantic salmon.

    Science.gov (United States)

    Aas, Ida Bergva; Austbø, Lars; Falk, Knut; Hordvik, Ivar; Koppang, Erling Olaf

    2017-11-01

    Central and peripheral immune tolerance is together with defense mechanisms a hallmark of all lymphoid tissues. In fish, such tolerance is especially important in the gills, where the intimate contact between gill tissue and the aqueous environment would otherwise lead to continual immune stimulation by innocuous antigens. In this paper, we focus on the expression of genes associated with immune regulation by the interbranchial lymphoid tissue (ILT) in an attempt to understand its role in maintaining immune homeostasis. Both healthy and virus-challenged fish were investigated, and transcript levels were examined from laser-dissected ILT, gills, head kidney and intestine. Lack of Aire expression in the ILT excluded its involvement in central tolerance and any possibility of its being an analogue to the thymus. On the other hand, the ILT appears to participate in peripheral immune tolerance due to its relatively high expression of forkhead box protein 3 (Foxp3) and other genes associated with regulatory T cells (Tregs) and immune suppression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Evaluating relative contribution of osmotolerance and tissue tolerance mechanisms toward salinity stress tolerance in three Brassica species.

    Science.gov (United States)

    Chakraborty, Koushik; Bose, Jayakumar; Shabala, Lana; Eyles, Alieta; Shabala, Sergey

    2016-10-01

    Three different species of Brassica, with differential salt sensitivity were used to understand physiological mechanisms of salt tolerance operating in these species and to evaluate the relative contribution of different strategies to cope with salt load. Brassica napus was the most tolerant species in terms of the overall performance, with Brassica juncea and Brassica oleracea being much more sensitive to salt stress with no obvious difference between them. While prominent reduction in net CO2 assimilation was observed in both sensitive species, physiological mechanisms beyond this reduction differed strongly. Brassica juncea plants possessed high osmotolerance and were able to maintain high transpiration rate but showed a significant reduction in leaf chlorophyll content and efficiency of leaf photochemistry. On the contrary, B. oleracea plants possessed the highest (among the three species) tissue tolerance but showed a very significant stomatal limitation of photosynthesis. Electrophysiological experiments revealed that the high tissue tolerance in B. oleracea was related to the ability of leaf mesophyll cells to maintain highly negative membrane potential in the presence of high apoplastic Na(+) . In addition to high osmotolerance, the most tolerant B. napus showed also lesser accumulation of toxic Na(+) and Cl(-) in the leaf, possessed moderate tissue tolerance and had a superior K(+) retention ability. Taken together, the results from this study indicate that the three Brassica species employ very different mechanisms to cope with salinity and, despite its overall sensitivity to salinity, B. oleracea could be recommended as a valuable 'donor' of tissue tolerance genes to confer this trait for marker-assisted breeding programs. © 2016 Scandinavian Plant Physiology Society.

  1. Tolerance of natural baby skin-care products on healthy, full-term infants and toddlers

    OpenAIRE

    Coret, Catherine D; Suero, Michael B; Tierney, Neena K

    2014-01-01

    Catherine D Coret, Michael B Suero, Neena K Tierney Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, USA Purpose: To evaluate the tolerance of baby skin-care products with at least 95% naturally derived ingredients on infants and toddlers. Materials and methods: Healthy, full-term infants and toddlers aged 1–36 months were enrolled. In study 1, a lightly fragranced natural baby hair and body wash (n=30), a lightly fragranced natural baby shampoo (n=30), or a lightly...

  2. Normal tissue tolerance to external beam radiation therapy: The stomach

    International Nuclear Information System (INIS)

    Oberdiac, P.; Mineur, L.

    2010-01-01

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  3. Validity and interobserver agreement of lower extremity local tissue water measurements in healthy women using tissue dielectric constant

    DEFF Research Database (Denmark)

    Jensen, Mads R; Birkballe, Susanne; Nørregaard, Susan

    2012-01-01

    Tissue dielectric constant (TDC) measurement may become an important tool in the clinical evaluation of chronic lower extremity swelling in women; however, several factors are known to influence TDC measurements, and comparative data on healthy lower extremities are few.......Tissue dielectric constant (TDC) measurement may become an important tool in the clinical evaluation of chronic lower extremity swelling in women; however, several factors are known to influence TDC measurements, and comparative data on healthy lower extremities are few....

  4. Improvement of potato tolerance to salinity using tissue culture techniques and irradiation with in vitro selection

    International Nuclear Information System (INIS)

    Al-Safadi, B.; Arabi, M. I. E.

    2006-01-01

    A mutation breeding program was conducted to improve potato (Solanum tuberosum) tolerance to salinity. In vitro cultured explants from potato cvs. Draga, Diamant, Spunta were irradiated with gamma doses 25, 30, and 35 Gy. Mutants were isolated to get rid of chimeral tissues and subsequently propagated for in vitro and pot selection pressure. Cultivar Sponta produced the highest number of tolerant plants (4) and only one plant was obtained from Diamant. (authors)

  5. Linking salinity stress tolerance with tissue-specific Na+ sequestration in wheat roots

    Directory of Open Access Journals (Sweden)

    Honghong eWu

    2015-02-01

    Full Text Available Salinity stress tolerance is a physiologically complex trait that is conferred by the large array of interacting mechanisms. Among these, vacuolar Na+ sequestration has always been considered as one of the key components differentiating between sensitive and tolerant species and genotypes. However, vacuolar Na+ sequestration has been rarely considered in the context of the tissue-specific expression and regulation of appropriate transporters contributing to Na+ removal from the cytosol. In this work, six bread wheat varieties contrasting in their salinity tolerance (three tolerant and three sensitive were used to understand the essentiality of vacuolar Na+ sequestration between functionally different root tissues, and link it with the overall salinity stress tolerance in this species. Roots of 4-d old wheat seedlings were treated with 100 mM NaCl for 3 days, and then Na+ distribution between cytosol and vacuole was quantified by CoroNa Green fluorescent dye imaging. Our major observations were as follows: 1 salinity stress tolerance correlated positively with vacuolar Na+ sequestration ability in the mature root zone but not in the root apex; 2 Contrary to expectations, cytosolic Na+ levels in root meristem were significantly higher in salt tolerant than sensitive group, while vacuolar Na+ levels showed an opposite trend. These results are interpreted as meristem cells playing a role of the salt sensor; 3 No significant difference in the vacuolar Na+ sequestration ability was found between sensitive and tolerant group in either transition or elongation zones; 4 The overall Na+ accumulation was highest in the elongation zone, suggesting its role in osmotic adjustment and turgor maintenance required to drive root expansion growth. Overall, the reported results suggest high tissue-specificity of Na+ uptake, signalling, and sequestration in wheat root. The implications of these findings for plant breeding for salinity stress tolerance are discussed.

  6. Exercise increases pressure pain tolerance but not pressure and heat pain thresholds in healthy young men.

    Science.gov (United States)

    Vaegter, H B; Hoeger Bement, M; Madsen, A B; Fridriksson, J; Dasa, M; Graven-Nielsen, T

    2017-01-01

    Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. On three different days, 20 healthy young men performed two submaximal isometric knee extensions (30% maximal voluntary contraction in 3 min) and a control condition (quiet rest). Before and immediately after exercise and rest, the sensitivity to heat pain and pressure pain was assessed in randomized and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. Cuff pressure pain tolerance was significantly increased after exercise compared with baseline and rest (p  0.77) compared with HPT (intraclass correlation = 0.54). The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. The effect of isometric exercise on pain tolerance may be relevant for patients in chronic musculoskeletal pain as a pain-coping strategy. WHAT DOES THIS STUDY ADD?: The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the heat and pressure pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. © 2016 European Pain Federation - EFIC®.

  7. Normal tissue tolerance to external beam radiation therapy: Esophagus

    International Nuclear Information System (INIS)

    Bera, G.; Pointreau, Y.; Denis, F.; Dupuis, O.; Orain, I.; Crehange, G.

    2010-01-01

    The esophagus is a musculo-membranous tube through which food passes from the pharynx to the stomach. Due to its anatomical location, it can be exposed to ionizing radiation in many external radiotherapy indications. Radiation-induced esophageal mucositis is clinically revealed by dysphagia and odynophagia, and usually begins 3 to 4 weeks after the start of radiation treatment. With the rise of multimodality treatments (e.g., concurrent chemoradiotherapy, dose escalation and accelerated fractionation schemes), esophageal toxicity has become a significant dose-limiting issue. Understanding the predictive factors of esophageal injury may improve the optimal delivery of treatment plans. It may help to minimize the risks, hence increasing the therapeutic ratio. Based on a large literature review, our study describes both early and late radiation-induced esophageal injuries and highlights some of the predictive factors for cervical and thoracic esophagus toxicity. These clinical and dosimetric parameters are numerous but none is consensual. The large number of dosimetric parameters strengthens the need of an overall analysis of the dose/volume histograms. The data provided is insufficient to recommend their routine use to prevent radiation-induced esophagitis. Defining guidelines for the tolerance of the esophagus to ionizing radiation remains essential for a safe and efficient treatment. (authors)

  8. The ability of natural tolerance to be applied to allogeneic tissue: determinants and limits

    Directory of Open Access Journals (Sweden)

    Razavy Haide

    2007-04-01

    Full Text Available Abstract Background Transplant rejection has been considered to occur primarily because donor antigens are not present during the development of the recipient's immune system to induce tolerance. Thus, transplantation prior to recipient immune system development (pre-immunocompetence transplants should induce natural tolerance to the donor. Surprisingly, tolerance was often not the outcome in such 'natural tolerance models'. We explored the ability of natural tolerance to prevent immune responses to alloantigens, and the reasons for the disparate outcomes of pre-immunocompetence transplants. Results We found that internal transplants mismatched for a single minor-H antigen and 'healed-in' before immune system development were not ignored but instead induced natural tolerance. In contrast, multiple minor-H or MHC mismatched transplants did not consistently induce natural tolerance unless they carried chimerism generating passenger lymphocytes. To determine whether the systemic nature of passenger lymphocytes was required for their tolerizing capacity, we generated a model of localized vs. systemic donor lymphocytes. We identified the peritoneal cavity as a site that protects allogeneic lymphocytes from killing by NK cells, and found that systemic chimerism, but not chimerism restricted to the peritoneum, was capable of generating natural tolerance. Conclusion These data provide an explanation for the variable results with pre-immunocompetence transplants and suggest that natural tolerance to transplants is governed by the systemic vs. localized nature of donor antigen, the site of transplantation, and the antigenic disparity. Furthermore, in the absence of systemic lymphocyte chimerism the capacity to establish natural tolerance to allogeneic tissue appears strikingly limited. Reviewers This article was reviewed by Matthias von Herrath, Irun Cohen, and Wei-Ping Min (nominated by David Scott.

  9. Mechanistic Insight into Salt Tolerance of Acacia auriculiformis: The Importance of Ion Selectivity, Osmoprotection, Tissue Tolerance, and Na+ Exclusion

    Science.gov (United States)

    Rahman, Md. M.; Rahman, Md. A.; Miah, Md. G.; Saha, Satya R.; Karim, M. A.; Mostofa, Mohammad G.

    2017-01-01

    Salinity, one of the major environmental constraints, threatens soil health and consequently agricultural productivity worldwide. Acacia auriculiformis, being a halophyte, offers diverse benefits against soil salinity; however, the defense mechanisms underlying salt-tolerant capacity in A. auriculiformis are still elusive. In this study, we aimed to elucidate mechanisms regulating the adaptability of the multi-purpose perennial species A. auriculiformis to salt stress. The growth, ion homeostasis, osmoprotection, tissue tolerance and Na+ exclusion, and anatomical adjustments of A. auriculiformis grown in varied doses of seawater for 90 and 150 days were assessed. Results showed that diluted seawater caused notable reductions in the level of growth-related parameters, relative water content, stomatal conductance, photosynthetic pigments, proteins, and carbohydrates in dose- and time-dependent manners. However, the percent reduction of these parameters did not exceed 50% of those of control plants. Na+ contents in phyllodes and roots increased with increasing levels of salinity, whereas K+ contents and K+/Na+ ratio decreased significantly in comparison with control plants. A. auriculiformis retained more Na+ in the roots and maintained higher levels of K+, Ca2+ and Mg2+, and K+/Na+ ratio in phyllodes than roots through ion selective capacity. The contents of proline, total free amino acids, total sugars and reducing sugars significantly accumulated together with the levels of malondialdehyde and electrolyte leakage in the phyllodes, particularly at day 150th of salt treatment. Anatomical investigations revealed various anatomical changes in the tissues of phyllodes, stems and roots by salt stress, such as increase in the size of spongy parenchyma of phyllodes, endodermal thickness of stems and roots, and the diameter of root vascular bundle, relative to control counterparts. Furthermore, the estimated values for Na+ exclusion and tissue tolerance index suggested that

  10. Foxp3 Expression is Required for the Induction of Therapeutic Tissue Tolerance1

    Science.gov (United States)

    Regateiro, Frederico S.; Chen, Ye; Kendal, Adrian R.; Hilbrands, Robert; Adams, Elizabeth; Cobbold, Stephen P.; Ma, Jianbo; Andersen, Kristian G.; Betz, Alexander G.; Zhang, Mindy; Madhiwalla, Shruti; Roberts, Bruce; Waldmann, Herman; Nolan, Kathleen F.; Howie, Duncan

    2012-01-01

    CD4+Foxp3+ Treg are essential for immune homeostasis and maintenance of self-tolerance. They are produced in the thymus and also generated de novo in the periphery in a TGFβ dependent manner. Foxp3+ Treg are also required to achieve tolerance to transplanted tissues when induced by co receptor or co stimulation blockade. Using TCR transgenic mice to avoid issues of autoimmune pathology, we show that Foxp3 expression is both necessary and sufficient for tissue tolerance by coreceptor blockade. Moreover, the known need in tolerance induction for TGFβ signalling to T cells can wholly be explained by its role in induction of Foxp3, as such signalling proved dispensable for the suppressive process. We analysed the relative contribution of TGFβ and Foxp3 to the transcriptome of TGFβ-induced Treg and showed that TGFβ elicited a large set of down-regulated signature genes. The number of genes uniquely modulated due to the influence of Foxp3 alone was surprisingly limited. Thus, despite the large genetic influence of TGFβ exposure on iTreg, the crucial Foxp3-influenced signature independent of TGFβ is small. Retroviral mediated conditional nuclear expression of Foxp3 proved sufficient to confer transplant-suppressive potency on CD4+ T cells, and was lost once nuclear Foxp3 expression was extinguished. These data support a dual role for TGFβ and Foxp3 in induced tolerance, where TGFβ stimulates Foxp3 expression, whose sustained expression is then associated with acquisition of tolerance. PMID:22988034

  11. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Ashwinikumar A Raut

    2012-01-01

    Full Text Available Ashwagandha (Withania somnifera (WS, a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30 were enrolled. After baseline investigations, they received WS capsules (Rx (aqueous extract, 8:1 daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day x10 days, 1 000 mg/day x 10 days, 1 250 mg/day x 10 days. Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar′s test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  12. Catalase activity in healthy and inflamed pulp tissues of permanent ...

    African Journals Online (AJOL)

    Aim: To evaluate catalase (CAT, EC 1.11.1.6) activity in healthy and inflamed dental pulp of young patient's teeth and to investigate if an active defense system oxidizing agents is present as a response to bacterial invasion. Materials and Methods: Twenty young patients between 15 and 25 ages, who were diagnosed to be ...

  13. Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants

    Directory of Open Access Journals (Sweden)

    Marunycz John D

    2009-06-01

    Full Text Available Abstract Background Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional. Up to one-half of formula-fed infants experience a formula change during the first six months of life. Methods The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy, term infants. Infants (335 were randomized to receive either a standard intact cow milk protein formula (INTACT or a partially hydrolyzed cow milk protein formula (PH in a 60 day non-inferiority trial. Discontinuance due to study physician-assessed formula intolerance was the primary outcome. Secondary outcomes included number of infants who discontinued for any reason, including parent-assessed. Results Formula intolerance between groups (INTACT, 12.3% vs. PH, 13.7% was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance. Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants (14.4 vs.11.1% was significantly different (P = 0.001. Conclusion This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy, term infants over a 60-day feeding trial, suggesting nonstandard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants. Parents frequently perceived infant behavior as formula intolerance, paralleling previous reports of unnecessary formula changes. Trial Registration clinicaltrials.gov: NCT00666120

  14. Identification of novel adipokines in the joint. Differential expression in healthy and osteoarthritis tissues.

    Directory of Open Access Journals (Sweden)

    Javier Conde

    Full Text Available Emerging data suggest that several metabolic factors, released mainly by white adipose tissue (WAT and joint tissues, and collectively named adipokines, might have a role in the pathophysiology of OA. Recently, novel adipokines such as SERPINE2, WISP2, GPNMB and ITIH5 have been identified in WAT. The main goal of this study was to analyse the expression of these novel adipokines in synovium, infrapatellar fat pad and chondrocytes and to compare the expression of these molecules in healthy and OA tissues.Synovial tissues, infrapatellar fat pad and chondrocytes were obtained from 36 OA patients (age 52-85; mean BMI 28.9 who underwent total knee replacement surgery. Healthy synovial tissues and infrapatellar fat pad were obtained from 15 traumatic knee patients (age 23-53; mean BMI 23.5. mRNA and protein expression were determined by qRT-PCR and western blot analysis respectively.All the novel adipokines, matter of our study, are expressed in OA synovium, infrapatellar fat pad and chondrocytes. Moreover, we detected a differential expression of SERPINE2 and ITIH5 in OA synovial tissues as compared to healthy samples. Finally, we also observed an increased expression of WISP2 in OA infrapatellar fat pad in comparison to healthy controls.In this study we demonstrated for the first time the expression of four novel adipokines in different joint tissues and how these molecules are differentially expressed in healthy and OA joint tissues.

  15. Side effects of ionizing radiation on healthy tissues and organs at risk

    International Nuclear Information System (INIS)

    Cosset, J.M.

    2010-01-01

    Ionizing radiations induce cell death, causing deterministic or stochastic side-effects. This paper briefly summarizes the biological mechanisms of early and late side-effects of ionizing radiations on healthy tissue. (author)

  16. Improvement of potato tolerance to salinity using tissue culture techniques and irradiation with in vitro selection

    International Nuclear Information System (INIS)

    Al-Safadi, B.; Arabi, M. I. E.

    2005-06-01

    A mutation breeding program was conducted to improve potato (Solanum tuberosum) tolerance to salinity. In vitro cultured explants from potato cvs. Draga, Diamant, Spunta were irradiated with gamma doses 25, 30, and 35 Gy.Growing shoots were cut and re-cultured every 2 weeks until the 4th generation (MV 4 ) to make sure no chimeral tissues still existed in the mutant material. Plantlets were subsequently propagated to obtain enough explants for in vitro selection pressure. Around 3000 plantlets from the three cultivars were subjected to selection pressure. MV 4 explants were cultured on MS medium supplemented with the NaCl in varying concentrations ranging between 50 to 200 mM. Surviving plantlets were propagated and re-cultured on a similar medium to insure their tolerance to salinity. Tolerant plantlets were acclimatized and transferred to pots and grown under glasshouse conditions. Plants were later subjected to another selection pressure, by irrigating them using water containing NaCl in concentrations ranging between 50-250 mM in addition to controls irrigated with normal water. Cultivar Spunta produced the highest number of tolerant plants. Four plants of Spunta appeared to be tolerant to salinity whereas only one plant from Diamant and was tolerant and no plants from cultivar Draga were tolerant. Mutant plants varied in number of produced minitubers from 8 - 14. Also, weight of these minitubers varied from less than 1 to 31 grams. (author)

  17. Histochemical characterization of human osteochondral tissue: comparison between healthy cartilage, arthrotic tissues, and cartilage defect treated with MACI technique

    Directory of Open Access Journals (Sweden)

    F. Tessarolo

    2011-01-01

    Full Text Available Matrix-induced sutologous chondrocytes implantation (MACI is a promising technique for the treatment of articular cartilage lesions, but long time outcome have to be established. We developed and optimized specific techniques of histochemical staining to characterize healthy and pathologic osteochondral tissue. Seven different staining protocols were applied to assess tissue architecture, cells morphology, proteoglycan content, and collagen fibers distribution. Potentialities of histochemical staining and histomorphology of biopsies from second look arthroscopy will be presented.

  18. Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

    Science.gov (United States)

    Abma, E; Peremans, K; De Vos, F; Bosmans, T; Kitshoff, A M; Daminet, S; Ni, Y; Dockx, R; de Rooster, H

    2018-01-04

    Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 μSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients. © 2018 John Wiley & Sons Ltd.

  19. Ultrasonic wave transmission through healthy and diseased tissues

    International Nuclear Information System (INIS)

    Edee, M.K.A.

    1985-12-01

    We calculated the distribution of the spectral density of the ultrasonic energy transmitted by the reference specimen which was water. Let σsub(i0) 2 be this parameter for the frequency fsub(i). In the same manner, we evaluated σsub(i) 2 for the ultrasonic energy transmitted by the biological tissue. We superposed on the curve Log σsub(i0) 2 =F(fsub(i)), each of the curves Log σsub(i) 2 =F(fsub(i)), corresponding to the different kinds of tissues studied. By doing so, we brought into light a ''zone'' between those curves. The judicious exploitation of that ''zone'' by calculating the spectral density coefficients β, made it possible to differentiate one tissue from another. We compared the results so obtained using a probe vibrating at 1.5 MHz with those we obtained by another probe and another method. Both sets of results are in agreement within an approximation of 10%. (author)

  20. Tolerance of natural baby skin-care products on healthy, full-term infants and toddlers.

    Science.gov (United States)

    Coret, Catherine D; Suero, Michael B; Tierney, Neena K

    2014-01-01

    To evaluate the tolerance of baby skin-care products with at least 95% naturally derived ingredients on infants and toddlers. Healthy, full-term infants and toddlers aged 1-36 months were enrolled. In study 1, a lightly fragranced natural baby hair and body wash (n=30), a lightly fragranced natural baby shampoo (n=30), or a lightly fragranced natural baby lotion (n=32) were assessed over 2 weeks. In study 2, a lightly fragranced natural baby hair and body wash and a lightly fragranced natural baby lotion (n=33) were assessed as a regimen over 4 weeks. The wash and shampoo were used three or more times per week, but not more than once daily. Lotions were applied in the morning or after a bath. Clinicians assessed the arms, legs, torso, or scalp for erythema, dryness, peeling/flakiness (study 1 only), tactile roughness, edema (study 1 only), rash/irritation (study 2 only), and overall skin condition (study 2 only) at baseline, week 1, and weeks 2 or 4. Parents completed skin assessment questionnaires. In study 2, stratum corneum hydration was measured. Subjects were monitored for adverse events. No significant changes in clinical grading scores were observed, indicating that all products were well tolerated. By the end of each study, >90% of parents/caregivers believed each product was mild and gentle. In study 2, improvement in stratum corneum hydration was observed (+37% at week 1 and +48% at week 4, Pproduct-related adverse events. The natural baby skin-care products were well tolerated by infants and toddlers when used alone or as part of a skin-care regimen.

  1. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    Science.gov (United States)

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Catalase activity in healthy and inflamed pulp tissues of permanent teeth in young people.

    Science.gov (United States)

    Topcu, Kmc; Kırıcı, D Ö; Evcil, M S

    2016-01-01

    To evaluate catalase (CAT, EC 1.11.1.6) activity in healthy and inflamed dental pulp of young patient's teeth and to investigate if an active defense system oxidizing agents is present as a response to bacterial invasion. Twenty young patients between 15 and 25 ages, who were diagnosed to be healthy, were the source of the pulp tissue. The situation of the dental pulps was evaluated using clinical and radiographic assessments. The patients were divided two groups from healthy, and inflamed pulp tissues were obtained; each participant provided one pulp tissue specimens. The specimens were collected during endodontic treatment or by longitudinally grooving and splitting the teeth (if extracted). Catalase activity was determined through spectrophotometric methods and an independent sample t-test assessed the significance of differences between the groups. There was statistically a difference between healthy pulp tissue and inflamed pulp tissue (P catalase activity of healthy group was significantly lower than inflamed pulp groups. The present study has shown that a significant increase in catalase activity is determined in inflamed dental pulps, which is due to pulpitis in comparison to healthy dental pulp.

  3. Alternative Promoter Usage in Healthy and Inflamed Tissue

    DEFF Research Database (Denmark)

    Lilje, Berit

    and cell-lines covering the entire human body. This provides a unique dataset to study gene expression, with promoter level precision. Here we use this large collection of data to study alternative transcription start site usage throughout the human body. We find that many alternative transcription start...... with tumour necrosis factor alpha, and on tissue from mice subjected to carbon nanotubes. Both systems show a strong response, with especially alternative transcription start sites being differentially regulated. Taken together this shows that alternative transcription start sites add an important layer...

  4. Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite Allograft Transplantation

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-2-0042 TITLE: Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite...2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Adult Tissue-Derived Stem Cells and Tolerance Induction...Distribution Unlimited 13. SUPPLEMENTARY NOTES The utilization of adult derived adipose stem cells administration in composite tissue transplantation

  5. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    is linked to a different set of circumstances than the ones suggested by existing models in contemporary democratic theory. Reorienting the discussion of tolerance, the book raises the question of how to disclose new possibilities within our given context of affect and perception. Once we move away from......Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated...... by the desire to experiment and to become otherwise. The objective is to discuss what gets lost, conceptually as well as politically, when we neglect the subsistence of active tolerance within other practices of tolerance, and to develop a theory of active tolerance in which tolerance's mobilizing character...

  6. Liver Transplantation in the Mouse: Insights Into Liver Immunobiology, Tissue Injury and Allograft Tolerance

    Science.gov (United States)

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.

    2016-01-01

    The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949

  7. Tolerability, pharmacokinetics and pharmacodynamics of TA-8995, a selective cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects

    NARCIS (Netherlands)

    Ford, John; Lawson, Matt; Fowler, David; Maruyama, Nobuko; Mito, Seiji; Tomiyasu, Koichi; Kinoshita, Shuji; Suzuki, Chisa; Kawaguchi, Atsuhiro; Round, Patrick; Boyce, Malcolm; Warrington, Steve; Weber, Werner; van Deventer, Sander; Kastelein, John J. P.

    2014-01-01

    Two double-blind, randomized studies were conducted to assess the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995, a new cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Study 1: Subjects received single doses of TA-8995 or placebo (fasted). Doses were 5,

  8. GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

    Science.gov (United States)

    Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

    2014-12-15

    GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

  9. Tolerance of natural baby skin-care products on healthy, full-term infants and toddlers

    Directory of Open Access Journals (Sweden)

    Coret CD

    2014-02-01

    Full Text Available Catherine D Coret, Michael B Suero, Neena K Tierney Johnson & Johnson Consumer Companies, Inc, Skillman, NJ, USA Purpose: To evaluate the tolerance of baby skin-care products with at least 95% naturally derived ingredients on infants and toddlers. Materials and methods: Healthy, full-term infants and toddlers aged 1–36 months were enrolled. In study 1, a lightly fragranced natural baby hair and body wash (n=30, a lightly fragranced natural baby shampoo (n=30, or a lightly fragranced natural baby lotion (n=32 were assessed over 2 weeks. In study 2, a lightly fragranced natural baby hair and body wash and a lightly fragranced natural baby lotion (n=33 were assessed as a regimen over 4 weeks. The wash and shampoo were used three or more times per week, but not more than once daily. Lotions were applied in the morning or after a bath. Clinicians assessed the arms, legs, torso, or scalp for erythema, dryness, peeling/flakiness (study 1 only, tactile roughness, edema (study 1 only, rash/irritation (study 2 only, and overall skin condition (study 2 only at baseline, week 1, and weeks 2 or 4. Parents completed skin assessment questionnaires. In study 2, stratum corneum hydration was measured. Subjects were monitored for adverse events. Results: No significant changes in clinical grading scores were observed, indicating that all products were well tolerated. By the end of each study, >90% of parents/caregivers believed each product was mild and gentle. In study 2, improvement in stratum corneum hydration was observed (+37% at week 1 and +48% at week 4, P<0.05 for both. In study 1, one baby experienced mild erythema on the neck and scalp after using the shampoo (possibly related to treatment. In study 2, there were no product-related adverse events. Conclusion: The natural baby skin-care products were well tolerated by infants and toddlers when used alone or as part of a skin-care regimen. Keywords: bath, cleanser, natural, infant, lotion, shampoo

  10. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  11. Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

    Science.gov (United States)

    Nel, Annalene M; Coplan, Paul; van de Wijgert, Janneke H; Kapiga, Saidi H; von Mollendorf, Claire; Geubbels, Eveline; Vyankandondera, Joseph; Rees, Helen V; Masenga, Gileard; Kiwelu, Ireen; Moyes, Jocelyn; Smythe, Shanique C

    2009-07-31

    To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine. Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less. Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.

  12. Comparison of tissue damage caused by various laser systems with tissue tolerable plasma by light and laser scan microscopy

    International Nuclear Information System (INIS)

    Vandersee, Staffan; Lademann, Jürgen; Richter, Heike; Patzelt, Alexa; Lange-Asschenfeldt, Bernhard

    2013-01-01

    Tissue tolerable plasma (TTP) represents a novel therapeutic method with promising capabilities in the field of dermatological interventions, in particular disinfection but also wound antisepsis and regeneration. The energy transfer by plasma into living tissue is not easily educible, as a variety of features such as the medium’s actual molecule-stream, the ions, electrons and free radicals involved, as well as the emission of ultraviolet, visible and infrared light contribute to its increasingly well characterized effects. Thus, relating possible adversary effects, especially of prolonged exposure to a single component of the plasma’s mode of action, is difficult. Until now, severe adverse events connected to plasma exposure have not been reported when conducted according to existing therapeutic protocols. In this study, we have compared the tissue damage-potential of CO 2 and dye lasers with TTP in a porcine model. After exposure of pig ear skin to the three treatment modalities, all specimens were examined histologically and by means of laser scan microscopy (LSM). Light microscopical tissue damage could only be shown in the case of the CO 2 laser, whereas dye laser and plasma treatment resulted in no detectable impairment of the specimens. In the case of TTP, LSM examination revealed only an impairment of the uppermost corneal layers of the skin, thus stressing its safety when used in vivo. (letter)

  13. Inflammation reduces physiological tissue tolerance in the development of work-related musculoskeletal disorders.

    Science.gov (United States)

    Barr, Ann E; Barbe, Mary F

    2004-02-01

    Work-related musculoskeletal disorders (MSDs) cause substantial worker discomfort, disability and loss of productivity. Due to the difficulty in analyzing the tissues of patients in the early stages of work-related MSD, there is controversy concerning the pathomechanisms of the development of these disorders. The pathophysiology of work-related MSD can be studied more easily in animal models. The purpose of this review is to relate theories of the development of tissue injury due to repeated motion to findings of recent investigations in animals that address the role of the inflammatory response in propagating tissue injury and contributing to chronic or recurring tissue injury. These tissue effects are related to behavioral indicators of discomfort and movement dysfunction with the aim of clarifying key time points for specific intervention approaches. The results from animal models of MSD are discussed in the light of findings in patients, whose tissues are examined at a much later phase of MSD development. Finally, a conceptual model of the potentially negative impact of inflammation on tissue tolerance is proposed along with suggestions for future research directions.

  14. Iso-effect tables for tolerance of irradiated normal human tissues

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on a radiation injury to human tissues (lung, brain, kidney and intestine) was surveyed. A parameter search program (RAD3) was used to derive best-fitting cell kinetic parameters, on the assumption that radiation injury arises from depletion of parenchymal cells in the irradiated organs. From these parameters iso-effect tables were constructed for a wide range of treatment schedules, including daily treatment as well as fractionation at longer intervals, for each tissue. The tables provide a set of limiting doses, above which the risk of radiation injury becomes substantial. Tolerance limits and dose-time-factors were substantially different in the four tissues. It is concluded that computed iso-effect tables provide a more reliable guide to treatment than conventional time-dose equations

  15. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men

    DEFF Research Database (Denmark)

    Asmar, Ali; Asmar, Meena; Simonsen, Lene

    2017-01-01

    In healthy subjects, we recently demonstrated that during acute administration of GLP-1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP-1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and....../or splanchnic tissues. Nine healthy men were examined twice in random order during a 2-hour infusion of either GLP-1 (1.5 pmol kg(-1) min(-1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra-arterial blood pressure. Subcutaneous, abdominal adipose...... and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP-1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP-1 increases cardiac...

  16. Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

    Science.gov (United States)

    Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

    2016-02-01

    Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

  17. A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

    Science.gov (United States)

    Sood, Sanjana; Gallagher, Iain J; Lunnon, Katie; Rullman, Eric; Keohane, Aoife; Crossland, Hannah; Phillips, Bethan E; Cederholm, Tommy; Jensen, Thomas; van Loon, Luc J C; Lannfelt, Lars; Kraus, William E; Atherton, Philip J; Howard, Robert; Gustafsson, Thomas; Hodges, Angela; Timmons, James A

    2015-09-07

    Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

  18. The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers.

    Science.gov (United States)

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Gertsik, Lev; Dutta, Sandeep

    2014-06-01

    ABT-288 is a potent and selective H3 receptor antagonist with procognitive effects in several preclinical models. In previous studies, 3 mg once daily was the maximal tolerated dose in healthy volunteers. This study characterized the safety, tolerability and pharmacokinetics of ABT-288 in stable subjects with schizophrenia. This was a randomized, double-blind, placebo-controlled, dose-escalating study of ABT-288 (10 dose levels, from 1 to 60 mg once daily for 14 days) in stable subjects with schizophrenia treated with an atypical antipsychotic. In each dose group, five to seven and two to three participants were assigned to ABT-288 and placebo, respectively. Of the 67 participants enrolled, nine participants (on ABT-288) were prematurely discontinued, in seven of these due to adverse events. ABT-288 was generally safe and tolerated at doses up to 45 mg once daily. The most common adverse events, in decreasing frequency (from 31 to 5%), were abnormal dreams, headache, insomnia, dizziness, somnolence, dysgeusia, dry mouth, psychotic disorder, parosmia and tachycardia. Adverse events causing early termination were psychotic events (four) and increased creatine phosphokinase, pyrexia and insomnia (one each). The half-life of ABT-288 ranged from 28 to 51 h, and steady state was achieved by day 12 of dosing. At comparable multiple doses, ABT-288 exposure in subjects with schizophrenia was 45% lower than that previously observed in healthy subjects. At trough, ABT-288 cerebrospinal fluid concentrations were 40% of the total plasma concentrations. ABT-288 was tolerated at a 15-fold higher dose and 12-fold higher exposures in subjects with schizophrenia than previously observed in healthy volunteers. The greater ABT-288 tolerability was not due to limited brain uptake. © 2013 The British Pharmacological Society.

  19. DNA methylation age is elevated in breast tissue of healthy women.

    Science.gov (United States)

    Sehl, Mary E; Henry, Jill E; Storniolo, Anna Maria; Ganz, Patricia A; Horvath, Steve

    2017-07-01

    Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10 -11 ). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = -0.53, p = 4.4 × 10 -4 ). Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.

  20. Quantitative tissue parameters of Achilles tendon and plantar fascia in healthy subjects using a handheld myotonometer.

    Science.gov (United States)

    Orner, Sarah; Kratzer, Wolfgang; Schmidberger, Julian; Grüner, Beate

    2018-01-01

    The aim of the study was to examine the quantitative tissue properties of the Achilles tendon and plantar fascia using a handheld, non-invasive MyotonPRO device, in order to generate normal values and examine the biomechanical relationship of both structures. Prospective study of a large, healthy sample population. The study sample included 207 healthy subjects (87 males and 120 females) for the Achilles tendon and 176 healthy subjects (73 males and 103 females) for the plantar fascia. For the correlations of the tissue parameters of the Achilles tendon and plantar fascia an intersection of both groups was formed which included 150 healthy subjects (65 males and 85 females). All participants were measured in a prone position. Consecutive measurements of the Achilles tendon and plantar fascia were performed by MyotonPRO device at defined sites. For the left and right Achilles tendons and plantar fasciae all five MyotonPRO parameters (Frequency [Hz], Decrement, Stiffness [N/m], Creep and Relaxation Time [ms]) were calculated of healthy males and females. The correlation of the tissue parameters of the Achilles tendon and plantar fascia showed a significant positive correlation of all parameters on the left as well as on the right side. The MyotonPRO is a feasible device for easy measurement of passive tissue properties of the Achilles tendon and plantar fascia in a clinical setting. The generated normal values of the Achilles tendon and plantar fascia are important for detecting abnormalities in patients with Achilles tendinopathy or plantar fasciitis in the future. Biomechanically, both structures are positively correlated. This may provide new aspects in the diagnostics and therapy of plantar fasciitis and Achilles tendinopathy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Moeko Noguchi-Shinohara

    Full Text Available The aim of this study was to evaluate the safety, tolerability and pharmacokinetics of single dose of Melissa officinalis extract which contained rosmarinic acid, including food-effects in healthy individuals. A total of eleven healthy individuals were randomly assigned to treatment arms in the two studies [Study 1 (fasted state and Study 2 (fed state]. Rosmarinic acid in serum was measured by a coulometric detection method using High-Performance Liquid Chromatography electrochemical detector. The serum concentration of total rosmarinic acid peaked at 1 hour after administration of Melissa officinalis extract containing 500mg rosmarinic acid in fasted state, with a maximum serum concentration 162.20 nmol/ L. The area under the curve for intact rosmarinic acid was calculated from the serum concentration-time profile to be 832.13 nmol • hour/ L. Food intake increases area under the curve and delayed time at which the maximum serum concentration. Rosmarinic acid supplementation did not affect liver, kidney, or blood cell function parameters. No adverse event was reported by any of the participants due to the study treatment. Single dose of Melissa officinalis extract containing 500 mg rosmarinic acid appears to be safe and tolerable in healthy individuals. Food intake increased the exposure of rosmarinic acid and delayed absorption of rosmarinic acid in healthy individuals.

  2. Polarimetry based partial least square classification of ex vivo healthy and basal cell carcinoma human skin tissues.

    Science.gov (United States)

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ikram, Masroor

    2016-06-01

    Optical polarimetry was employed for assessment of ex vivo healthy and basal cell carcinoma (BCC) tissue samples from human skin. Polarimetric analyses revealed that depolarization and retardance for healthy tissue group were significantly higher (ppolarimetry together with PLS statistics hold promise for automated pathology classification. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Diurnal variation of connective tissue metabolites in early and long-standing rheumatoid arthritis and in healthy individuals

    DEFF Research Database (Denmark)

    Lottenburger, T; Junker, P; Hørslev-Petersen, K

    2011-01-01

    To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals.......To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals....

  4. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    Directory of Open Access Journals (Sweden)

    Aimee L. Dordevic

    2015-07-01

    Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

  5. Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals.

    Science.gov (United States)

    Machado, Christiano Bittencourt; Pereira, Wagner Coelho de Albuquerque; Meziri, Mahmoud; Laugier, Pascal

    2006-05-01

    This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.

  6. Effect of cold compress application on tissue temperature in healthy dogs.

    Science.gov (United States)

    Millard, Ralph P; Towle-Millard, Heather A; Rankin, David C; Roush, James K

    2013-03-01

    To measure the effect of cold compress application on tissue temperature in healthy dogs. 10 healthy mixed-breed dogs. Dogs were sedated with hydromorphone (0.1 mg/kg, IV) and diazepam (0.25 mg/kg, IV). Three 24-gauge thermocouple needles were inserted to a depth of 0.5 (superficial), 1.0 (middle), and 1.5 (deep) cm into a shaved, lumbar, epaxial region to measure tissue temperature. Cold (-16.8°C) compresses were applied with gravity dependence for periods of 5, 10, and 20 minutes. Tissue temperature was recorded before compress application and at intervals for up to 80 minutes after application. Control data were collected while dogs received identical sedation but with no cold compress. Mean temperature associated with 5 minutes of application at the superficial depth was significantly decreased, compared with control temperatures. Application for 10 and 20 minutes significantly reduced the temperature at all depths, compared with controls and 5 minutes of application. Twenty minutes of application significantly decreased temperature at only the middle depth, compared with 10 minutes of application. With this method of cold treatment, increasing application time from 10 to 20 minutes caused a further significant temperature change at only the middle tissue depth; however, for maximal cooling, the minimum time of application should be 20 minutes. Possible changes in tissue temperature and adverse effects of application > 20 minutes require further evaluation.

  7. Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

    Science.gov (United States)

    Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

    2014-04-01

    Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

  8. Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls.

    Science.gov (United States)

    Kabasakal, Y; Elvins, D M; Ring, E F; McHugh, N J

    1996-01-01

    OBJECTIVE: To describe and quantify the morphological characteristics of nailfold capillaries that distinguish different forms of connective tissue disease from healthy controls. METHODS: A CCD video microscope with fibreoptic illumination and PC based image processing was used to visualise nailfold capillaries and to quantify findings in 23 patients with systemic sclerosis (SSc), 22 patients with systemic lupus erythematosus (SLE), 21 patients with undifferentiated connective tissue disease (UCTD), and 38 healthy controls. RESULTS: Capillary density was reduced in SSc (5.2 (SD 1.3) capillaries/mm) compared with other patient groups and controls. The average number of enlarged capillaries/finger was high in all disease groups (5.5-6.6) compared with controls (2). However, giant capillaries were most frequent in SSc (43%) and were not present in controls. Mild and moderate avascular areas were present in all groups (35%-68%), but severe avascularity was most frequent in SSc (44%) compared with other patients (18%-19%) and controls (0%). The greatest frequency of extensive haemorrhage was in SSc (35%). CONCLUSIONS: There is a range of abnormal capillary findings in patients with connective tissue disease and healthy controls. However, certain abnormalities such as a reduced number of capillaries, severe avascularity, giant capillaries, and haemorrhage are most commonly associated with SSc. Videomicroscopy with image processing offers many technical advantages that can be exploited in further studies of nailfold capillaries. Images PMID:8774177

  9. Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

    Science.gov (United States)

    Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

    2015-05-01

    The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. Copyright

  10. Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations

    DEFF Research Database (Denmark)

    Wiuff, C.; Lykkesfeldt, J.; Aarestrup, Frank Møller

    2002-01-01

    The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum...... administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5-day dosing regimen with i.m. and p.o. administration were....... On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route....

  11. Exercise increases pressure pain tolerance but not pressure and heat pain thresholds in healthy young men

    DEFF Research Database (Denmark)

    Vaegter, H. B.; Bement, M. Hoeger; Madsen, A. B.

    2017-01-01

    BACKGROUND: Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. METHODS...... and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. RESULTS: Cuff pressure pain tolerance...... to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. SIGNIFICANCE: The effect of isometric exercise on pain tolerance may be relevant for patients in chronic musculoskeletal pain as a pain...

  12. Studies on salt and drought tolerance of lavender using tissue culture and gamma rays

    International Nuclear Information System (INIS)

    Essam, K.E.; El-Sharnoby, M.E.

    2005-01-01

    The present study was carried out to investigate the propagation and chemical composition of Lavandula spica using different cytokinins (BA, Ki and 2ip) on MS medium,, besides medium strength. Also, GA3 concentrations, auxin types, gamma irradiation (0, 2, 4, 6 and 8 Krad), different concentrations of mannitol (10, 20, 40, 80 and 100 mg/l) as well as different salinity concentrations of CaCl 2 or NaCl or both at levels 250, 500, 750 and 1000 ppm were used in the study. Maximum proliferation parameter was produced on MS medium supplemented with 1 mg/l BA than other cytokinin types. Growing the explant of Lavandula. spica on MS medium, containing 3 mg/l BA, gave the highest proliferation, growth and greening parameters. However, using MS medium at half strength supplemented with 3 mg/l BA resulted in significant increase in both shoot elongation and greening parameters as compared with the other medium strengths, while 4 mg/l GA induced the best shoot elongation. Adding 1 mg/l IBA enhanced rooting and also the obtained results showed that increasing gamma irradiation decreased growth and proliferation parameters. Moreover, increasing drought stress induced an adverse effect on tissue culture parameter while some chemical analysis parameters were increased to maximum degree of their tolerance to drought stress. Also, using different salinity treatment by NaCl, CaCl 2 and their combinations showed adverse effects on tissue culture parameters chemical composition

  13. Long-term gastrointestinal tolerance of NUTRIOSE®FB in healthy men

    NARCIS (Netherlands)

    Pasman, W.; Wils, D.; Saniez, M.H.; Kardinaal, A.

    2006-01-01

    Objective: To determine the gastrointestinal (GI) tolerance of NUTRIOSE®FB in men. Design: A randomized, placebo-contro lled, parallel, double-blind study. Setting: The metabolic ward of TNO Quality of Life. Subjects: Forty-eight subjects started the study: 16 men participated in one of the three

  14. Efficacy of hidden markov model over support vector machine on multiclass classification of healthy and cancerous cervical tissues

    Science.gov (United States)

    Mukhopadhyay, Sabyasachi; Kurmi, Indrajit; Pratiher, Sawon; Mukherjee, Sukanya; Barman, Ritwik; Ghosh, Nirmalya; Panigrahi, Prasanta K.

    2018-02-01

    In this paper, a comparative study between SVM and HMM has been carried out for multiclass classification of cervical healthy and cancerous tissues. In our study, the HMM methodology is more promising to produce higher accuracy in classification.

  15. Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer

    International Nuclear Information System (INIS)

    Khlifi, Rim; Olmedo, Pablo; Gil, Fernando; Hammami, Bouthaina; Chakroun, Amine; Rebai, Ahmed; Hamza-Chaffai, Amel

    2013-01-01

    Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p 60 years) in both never-smokers and ever-smokers (< 20 and ≥ 20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population. - Highlights: ► Heavy metal levels in tumor tissues were higher than those in healthy tissues. ► Tumor tissue Cd levels were positively associated with age in smokers. ► Tumor tissue metal levels were higher in men than in women. ► The highest Cd and Cr concentrations among workers were observed in tumor tissues. ► Heavy metal exposure via occupational exposures may increase the risk of HNC

  16. Long-term gastrointestinal tolerance of NUTRIOSE FB in healthy men.

    Science.gov (United States)

    Pasman, W; Wils, D; Saniez, M-H; Kardinaal, A

    2006-08-01

    To determine the gastrointestinal (GI) tolerance of NUTRIOSE FB in men. A randomized, placebo-controlled, parallel, double-blind study. The metabolic ward of TNO Quality of Life. Forty-eight subjects started the study: 16 men participated in one of the three treatments. SUBJECTS consumed either 22.5 g of pure maltodextrin (Glucidex 6), or 30 or 45 g of the dextrin NUTRIOSE FB daily for 4-5 weeks. Forty-three subjects completed the study (age: 34.7 +/- 8.2 years; BMI 24.9 +/- 3.3 kg m2). Tolerance of NUTRIOSE FB was examined with a GI complaints questionnaire; effectiveness on colonic flora was examined by faecal analysis; fermentation by breath hydrogen excretion measurement. Furthermore, the effect on body weight (BW), energy intake and blood parameters were examined in the study. Both doses of NUTRIOSE FB were very well tolerated and GI complaints hardly differed from the placebo treatment. No diarrhoea was reported due to NUTRIOSE FB supplementation. In the course of the study, some habituation and adaptation of GI symptoms were found. Fermentation and faecal characteristics (pH and enzyme activity) were significantly positively affected with NUTRIOSE FB treatment. Body weight in both NUTRIOSE FB groups remained stable over time, although the placebo-treated group showed a small increase in BW (Deltaday35-1 0.8 +/- 1.0 kg) (P = 0.07). However, total food intake and macronutrient composition of the diet remained the same throughout the study. No significant differences were found between the three treatment groups in hunger and satiety scores and food preferences. Long-term supplementation of 30 or 45 g of the dextrin NUTRIOSE FB per day was well tolerated, and may act as a pre-biotic supplement. TNO Quality of Life was assigned by Roquette Frères to perform the study.

  17. Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies.

    Directory of Open Access Journals (Sweden)

    Claus Lindner

    Full Text Available The in vivo optical and hemodynamic properties of the healthy (n = 22 and pathological (n = 2 human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS and diffuse correlation spectroscopy (DCS system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs' at three wavelengths (690, 785 and 830 nm to derive total hemoglobin concentration (THC and oxygen saturation (StO2. DCS measured the microvascular blood flow index (BFI. Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s, while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%, yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

  18. Effect of warm compress application on tissue temperature in healthy dogs.

    Science.gov (United States)

    Millard, Ralph P; Towle-Millard, Heather A; Rankin, David C; Roush, James K

    2013-03-01

    To measure the effect of warm compress application on tissue temperature in healthy dogs. 10 healthy mixed-breed dogs. Dogs were sedated with hydromorphone (0.1 mg/kg, IV) and diazepam (0.25 mg/kg, IV). Three 24-gauge thermocouple needles were inserted to a depth of 0.5 cm (superficial), 1.0 cm (middle), and 1.5 cm (deep) into a shaved, lumbar, epaxial region to measure tissue temperature. Warm (47°C) compresses were applied with gravity dependence for periods of 5, 10, and 20 minutes. Tissue temperature was recorded before compress application and at intervals for up to 80 minutes after application. Control data were collected while dogs received identical sedation but with no warm compress. Mean temperature associated with 5 minutes of heat application at the superficial, middle, and deep depths was significantly increased, compared with the control temperature. Application for 10 minutes significantly increased the temperature at all depths, compared with 5 minutes of application. Mean temperature associated with 20 minutes of application was not different at the superficial or middle depths, compared with 10 minutes of application. Temperature at the deep depth associated with 10 minutes of application was significantly higher, compared with 20 minutes of application, but all temperature increases at this depth were minimal. Results suggested that application of a warm compress should be performed for 10 minutes. Changes in temperature at a tissue depth of 1.5 cm were minimal or not detected. The optimal compress temperature to achieve therapeutic benefits was not determined.

  19. Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women

    NARCIS (Netherlands)

    Nel, Annalene M.; Coplan, Paul; van de Wijgert, Janneke H.; Kapiga, Saidi H.; von Mollendorf, Claire; Geubbels, Eveline; Vyankandondera, Joseph; Rees, Helen V.; Masenga, Gileard; Kiwelu, Ireen; Moyes, Jocelyn; Smythe, Shanique C.

    2009-01-01

    To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa

  20. Chemical And Physiological Studies On Drought Stress Tolerance Of Irradiated Communis Pear Using Tissue Culture

    International Nuclear Information System (INIS)

    Zaied, N.S.; Ragab, E.A.

    2007-01-01

    The rooted in vitro irradiated pear rootstocks (Pyrus communis) were subjected to drought stress by using different concentrations of mannitol (20, 40, 60, 80 and 100 gm/l), polyethylene glycol (PEG) at concentrations 2, 4, 6, 8 and 10 % to culture medium and also agar at concentrations 6, 8, 10, 12 and 14 gm/l to study their effects on tissue culture and chemical analysis and their tolerance to drought stress. The obtained results showed that the number of shoots, shoot length and number of leaves were higher at 20 and 40 gm/l mannitol. Increasing mannitol concentration enhanced the increase of chlorophyll b, reducing sugars, total indoles and total phenols up to the highest level at 100 gm/l. Adding PEG at concentration 2% to the culture medium encouraged significant increases in the number of shoots and number of leaves and increase chlorophyll a, and non-reducing sugars as well as significant decrease in number of shoots, shoots length, number of leaves, root length and number of roots with increasing agar concentrations to the culture medium. However, decreasing agar concentration in the culture medium induced increase in chlorophyll A and non-reducing sugar

  1. Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs: a blind, randomized, placebo-controlled study.

    Science.gov (United States)

    Maina, E; Pelst, M; Hesta, M; Cox, E

    2017-01-18

    Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 μg of peanut extract daily for 7 to 14 days. All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions

  2. Action of nitric oxide on healthy and inflamed human dental pulp tissue.

    Science.gov (United States)

    da Silva, Leopoldo Penteado Nucci; Issa, João Paulo Mardegan; Del Bel, Elaine Aparecida

    2008-10-01

    Irreversible pulpitis has been associated with pain and an increase in the number of pulp inflammatory cells. Based on the action of nitric oxide (NO) elsewhere, NO may possibly participate in the sensory and autonomic innervation of the dental pulp, and may influence local inflammatory responses. The purpose of this study was to analyze normal and inflamed human dental pulp for the presence of NADPH-diaphorase (NADPH-d), as an index of NO system activity. Six non-carious second premolar pulp tissue samples were obtained from young patients who required extractions for orthodontic reasons and six inflamed samples were obtained from symptomatic carious second premolars clinically diagnosed with irreversible pulpitis. Pulp tissue was carefully removed, fixed by immersion in a cold 4% PFA buffered solution for 120 min, rinsed in cold phosphate buffer, and quickly-frozen for cryostat sectioning. Pulp tissue was sectioned perpendicularly to the vertical axis of the tooth at 20 microm and processed for histochemistry. Sections of each specimen were stained with hematoxylin-eosin and other sections were subjected to histochemical NADPH-d detection. Results indicated the presence of NADPH reactivity within the pulps of both normal and carious teeth. In the normal teeth NADPH-d activity was detected in a small number of vascular endothelial cells and fibroblasts. The inflammatory response of the pulp from carious premolars was detected in connective tissue by the presence of an increased number of fibroblasts, angioblasts and collagen fibers. It was possible to determine the extent of odontoblast reactivity since the odontoblast layer was usually absent in these split-peel preparations. There were no obvious signs of stained pulpal nerve fibers. Overall NADPH-d staining was significantly more intense within inflamed pulp tissues compared to normal healthy samples (Mann-Whitney test, pfunctions of NO in human dental pulp in pathophysiological situations.

  3. Arsenic, cadmium, chromium and nickel in cancerous and healthy tissues from patients with head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khlifi, Rim, E-mail: rimkhlifi@yahoo.fr [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia); Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Olmedo, Pablo; Gil, Fernando [Department of Legal Medicine and Toxicology, University of Granada (Spain); Hammami, Bouthaina; Chakroun, Amine [Department of Otorhinolaryngology, HUC Habib Borguiba Hospital, Sfax (Tunisia); Rebai, Ahmed [Bioinformatics Unit, Centre of Biotechnology of Sfax, BP 1177, 3018 Sfax (Tunisia); Hamza-Chaffai, Amel [Marine Ecotoxicology, UR 09-03, Sfax University, IPEIS, BP 805, 3018 Sfax (Tunisia)

    2013-05-01

    Chronic exposure to heavy metals has long been recognized as being capable to increase head and neck cancer incidence among exposed human populations. Head and neck cancer is a significant public health issue in Tunisia. The aim of the present study was to evaluate the concentrations of As, Cd, Cr and Ni in healthy and tumor tissues of head and neck cancer patients. Metal concentrations were determined in tumor and healthy tissues of 101 head and neck cancer patients, using Atomic Absorption Spectrometry. The As, Cd, Cr, and Ni levels in tumor tissues were 3.4, 2.5, 1.3 and 1.5 times higher than those of healthy tissues (p < 0.05), respectively. Tumor tissue metal levels were higher in men than in women. As and Cd levels in tumor and healthy tissue samples of patients smokers are significantly higher than those of non-smokers (p < 0.05). A strong effect of cumulative smoking as expressed in the number of pack per year, and tumor tissue Cd levels were positively associated with three groups of age (< 40, 51–60 and > 60 years) in both never-smokers and ever-smokers (< 20 and ≥ 20 pack per year). Healthy tissue Cd levels were negatively associated with age in those three groups of smokers. The highest Cd and Cr concentrations among both workers and non-workers were observed in tumor tissues. The Cd and Cr in tissues of farmers, bricklayers and painters were all significantly higher among the workers as compared with the non-workers group. Tissue metal levels have increased due to smoking and occupational exposure. Heavy metal exposure via tobacco smoking and occupational exposures may increase the risk of head and neck in the Tunisian population. - Highlights: ► Heavy metal levels in tumor tissues were higher than those in healthy tissues. ► Tumor tissue Cd levels were positively associated with age in smokers. ► Tumor tissue metal levels were higher in men than in women. ► The highest Cd and Cr concentrations among workers were observed in tumor tissues

  4. Pharmacokinetics and tolerability of the new second-generation nonnucleoside reverse- transcriptase inhibitor KM-023 in healthy subjects

    Directory of Open Access Journals (Sweden)

    Cha YJ

    2014-09-01

    Full Text Available Yu-Jung Cha,1,* Kyoung Soo Lim,2,* Min-Kyu Park,1 Stephen Schneider,3 Brian Bray,3 Myung-Chol Kang,3 Jae-Yong Chung,1 Seo Hyun Yoon,1 Joo-Youn Cho,1 Kyung-Sang Yu11Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea; 2Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, South Korea; 3Kainos Medicine USA Inc., Morrisville, NC, USA *These authors contributed equally to this workBackground: KM-023 is a new second-generation nonnucleoside reverse-transcriptase inhibitor that is under development for the treatment of human immunodeficiency virus (HIV type 1 infection. Objective: This study determined KM-023 tolerability and pharmacokinetic characteristics in healthy subjects. Materials and methods: A randomized, double-blinded, placebo-controlled, dose-escalation study was conducted in 80 healthy South Korean male volunteers. The subjects were allocated to single- or multiple-dose (once daily for 7 days groups that received 75, 150, 300, or 600 mg drug or placebo in a 4:1 ratio. Safety and pharmacokinetic assessments were performed during the study. Plasma and urine concentrations were quantified using liquid chromatography–tandem mass spectrometry. Results: The average maximum concentration (Cmax and area under the concentration–time curve from time 0 to infinity (AUC∞ values of KM-023 for the 75–600 mg doses in the single-dose study ranged from 440.2 ng/mL to 1,245.4 ng/mL and 11,142.4 ng • h/mL to 33,705.6 ng • h/mL, respectively. Values of the mean Cmax at a steady state and AUC within the dosing interval ranged from 385.1 ng/mL to 1,096.7 ng/mL and 3,698.9 ng • h/mL to 10,232.6 ng • h/mL, respectively, following 75–600 mg doses in the multiple-dose study. Dose proportionality was not observed for KM-023. KM-023 showed a 0.6-fold accumulation after multiple doses in the 600

  5. Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

    Science.gov (United States)

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

    2013-05-01

    The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  6. Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects.

    Science.gov (United States)

    Chandra, Kumar P; Shiwalkar, Ajay; Kotecha, Jignesh; Thakkar, Purav; Srivastava, Ambrish; Chauthaiwale, Vijay; Sharma, Sanjay K; Cross, Maurice R; Dutt, Chaitanya

    2009-01-01

    Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic complications through a variety of mechanisms including endothelial dysfunction and structural abnormalities in the vasculature and myocardium. Reducing the AGEs burden and their ensuing pro-inflammatory, pro-oxidative and pro-coagulant effect with associated dysfunctional proteins in various target tissues may retard the progression of and even reverse diabetic macro- and microvascular complications. Pyridinium, 3-[[2-(methylsulfonyl) hydrazino] carbonyl]-1-[2-oxo-2-2-thienyl) ethyl]-chloride (TRC4186) has demonstrated AGE-breaking activities in in vitro experiments and improvement in the endothelial and myocardial function in animal models of diabetes mellitus with reduction of AGEs accumulation in tissues over time. The safety of TRC4186 has been established in in vitro and in vivo preclinical studies. Thus, this drug is being developed for the treatment of complications associated with diabetes. This investigation set out to evaluate the safety, tolerability and pharmacokinetics of TRC4186 in healthy human subjects after single and multiple ascending doses, fixed doses in elderly male and female subjects, and with food and different formulations of the compound. Four studies were conducted during phase I clinical development of TRC4186. These were: (i) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in healthy male subjects with doses of TRC4186 ranging from 250 to 2500 mg administered as an oral solution (total six doses); (ii) a randomized, double-blind, placebo-controlled, multiple-dose, dose-ascending study in healthy male subjects with three doses of TRC4186 ranging from 500 to 2000 mg twice daily for 6 days with a final single dose on day 7; (iii) a randomized, open-label, three-way crossover study to assess the effect of food (fasted vs fed) and formulation (solution vs tablet) with TRC4186 500 mg; (iv) a randomized, double

  7. Quantification of tissue inhibitor of metalloproteinases 2 in plasma from healthy donors and cancer patients

    DEFF Research Database (Denmark)

    Larsen, M. B.; Stephens, R. W.; Brünner, Nils

    2005-01-01

    Tissue inhibitor of metalloproteinases (TIMP)-2 is a highly conserved molecule, which binds both active and latent matrix metalloproteinase (MMP)-2. TIMP-2 is also involved in the activation of MMP-2 on the cell surface. A quantitative enzyme-linked immunosorbent assay (ELISA) was established...... and optimized for measurement of TIMP-2 in plasma. The capturing antibody in the ELISA was a monoclonal, while the detecting antibody was a chicken polyclonal antibody recognizing the native form of human TIMP-2. The levels of TIMP-2 were measured in ethylenediaminetetraacetic acid (EDTA) and citrate plasma...... from healthy donors. The median values were determined as 163 ng/ml (n = 186) with a range of 109-253 ng/ml for EDTA plasma and 139 ng/ml (n = 77) with a range of 95-223 ng/ml for citrate plasma. The TIMP-2 concentration in citrate plasma from 15 patients with advanced, stage IV breast cancer had...

  8. Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

    Science.gov (United States)

    Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

    2015-03-01

    Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

  9. Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

    Science.gov (United States)

    Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

    2017-02-01

    Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

  10. Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity.

    Science.gov (United States)

    Lackey, Denise E; Burk, David H; Ali, Mohamed R; Mostaedi, Rouzbeh; Smith, William H; Park, Jiyoung; Scherer, Philipp E; Seay, Shundra A; McCoin, Colin S; Bonaldo, Paolo; Adams, Sean H

    2014-02-01

    The extracellular matrix (ECM) plays an important role in the maintenance of white adipose tissue (WAT) architecture and function, and proper ECM remodeling is critical to support WAT malleability to accommodate changes in energy storage needs. Obesity and adipocyte hypertrophy place a strain on the ECM remodeling machinery, which may promote disordered ECM and altered tissue integrity and could promote proinflammatory and cell stress signals. To explore these questions, new methods were developed to quantify omental and subcutaneous WAT tensile strength and WAT collagen content by three-dimensional confocal imaging, using collagen VI knockout mice as a methods validation tool. These methods, combined with comprehensive measurement of WAT ECM proteolytic enzymes, transcript, and blood analyte analyses, were used to identify unique pathophenotypes of metabolic syndrome and type 2 diabetes mellitus in obese women, using multivariate statistical modeling and univariate comparisons with weight-matched healthy obese individuals. In addition to the expected differences in inflammation and glycemic control, approximately 20 ECM-related factors, including omental tensile strength, collagen, and enzyme transcripts, helped discriminate metabolically compromised obesity. This is consistent with the hypothesis that WAT ECM physiology is intimately linked to metabolic health in obese humans, and the studies provide new tools to explore this relationship.

  11. Mapping of NKp46+ cells in healthy human lymphoid and non-lymphoid tissues

    Directory of Open Access Journals (Sweden)

    Elena eTomasello

    2012-11-01

    Full Text Available Understanding Natural Killer (NK cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs expressing the retinoic acid receptor-related orphan receptor t (RORt transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORt+ILCs with a lineage-CD94-CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.

  12. Mapping of NKp46+ Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues

    Science.gov (United States)

    Tomasello, Elena; Yessaad, Nadia; Gregoire, Emilie; Hudspeth, Kelly; Luci, Carmelo; Mavilio, Domenico; Hardwigsen, Jean; Vivier, Eric

    2012-01-01

    Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs, and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORγt+ ILCs with a lineage−CD94−CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. PMID:23181063

  13. In vivo confocal microscopy of conjunctiva-associated lymphoid tissue in healthy humans.

    Science.gov (United States)

    Agnifili, Luca; Mastropasqua, Rodolfo; Fasanella, Vincenzo; Di Staso, Silvio; Mastropasqua, Alessandra; Brescia, Lorenza; Mastropasqua, Leonardo

    2014-07-29

    To investigate modifications with aging of the presence, distribution and morphologic features of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects using laser scanning in vivo confocal microscopy (IVCM). A total of 108 (age range, 17-75 years) subjects were enrolled. In vivo confocal microscopy of the tarsal and bulbar conjunctiva, and impression cytology (IC) with CD3 (intra-epithelial T-lymphocytes) and CD20 (intra-epithelial B-lymphocytes) antibody immunofluorescence staining were performed. The main outcomes were subepithelial lymphocyte density (LyD), follicular density (FD), and follicular area (FA). The secondary outcomes were follicular reflectivity (FR), and lymphocyte density (FLyD), and CD3 and CD20 positivity. Conjunctiva-associated lymphoid tissue was observed in all subjects (97% only superior and 3% in both superior and inferior tarsum). Lymphocyte density ranged from 7.8 to 165.8 cells/mm(2) (46.42 [18.37]; mean [SD]), FD from 0.5 to 19.4 follicles/mm(2) (5.3 [3.6]), and FA from 1110 to 96,280 mm(2) (26,440 [26,280]). All three parameters showed a highly significant inverse cubic relationship with age (P lymphoid structures. These modifications may account for the decrease of mucosal immune response and increase of ocular surface diseases in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  14. Tolerance and biochemical effects from intravenous injection of ioxaglate in healthy volunteers

    International Nuclear Information System (INIS)

    Nilsson, P.E.; Aspelin, P.; Nyman, U.; Hedner, U.; Malmoe Allmaenna Sjukhus

    1984-01-01

    The influence of intravenous injection of ioxaglate (Hexabrix, 320 mg I/ml) on various biochemical, coagulation and fibrinolytic parameters, fractionated plasma proteins, precordial ECG and blood pressure was prospectively and sequentially studied in 9 healthy volunteers. One ml/kg body weight of the contrast medium was injected within one minute into an antecubital vein. Small, but statistically significant, changes in some of the biochemical parameters were found during the observation period, 2 to 4 days. All values of the biochemical parameters were, however, within the normal reference range for each parameter. No significant alterations were seen in the coagulation parameters. Increased fibrinolysis was recorded in some subjects both before and after the injection. No fibrinolytic degradation products were found indicating that the fibrinolysis was nominal. No significant changes were observed in the fractionated plasma proteins. The heart rate decreased significantly 15 seconds after commencing the injection. No significant changes in blood pressure were recorded. Two participants became nauseated and one of them vomited during the injection. Apart from this, no adverse effects were noted. No clinically significant changes following the injections were found. (orig.)

  15. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects

    DEFF Research Database (Denmark)

    Hansen, K B; Vilsbøll, T; Bagger, J I

    2010-01-01

    The loss of incretin effect in patients with type 2 diabetes mellitus may be secondary to impaired glucose homeostasis. We investigated whether reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet in healthy young males...

  16. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the CGRP Binding Monoclonal Antibody LY2951742 (Galcanezumab in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    David Monteith

    2017-10-01

    Full Text Available Background: Calcitonin gene-related peptide (CGRP is pivotal in the pathophysiology of migraine headaches and represents a promising target for migraine treatment. The humanized monoclonal antibody galcanezumab (LY2951742 binds to CGRP and may be effective in migraine prophylaxis.Objectives: The primary objective was to evaluate the safety and tolerability of single and multiple doses of galcanezumab in humans. Secondary objectives included assessing the pharmacokinetics and evaluating target engagement.Methods: A double-blind, randomized, placebo-controlled study (NCT 01337596 with single escalating and multiple subcutaneous (SC doses of galcanezumab was performed in healthy male volunteers. Single doses of 1, 5, 25, 75, 200, and 600 mg of galcanezumab (n = 7/dose or placebo (n = 2/dose were injected SC in six consecutive cohorts of nine subjects each. One cohort of nine subjects received multiple (4 150 mg doses of galcanezumab or placebo every other week. Target engagement was evaluated by measuring inhibition of capsaicin-induced increase in dermal blood flow (DBF.Findings: Sixty-three subjects were randomized and included in the safety analyses. Galcanezumab was well tolerated in single doses (1–600 mg SC and consecutive doses (150 mg SC. There was no dose-dependent difference in type or frequency of treatment-emergent adverse events, and no clinically meaningful difference when compared with placebo. Pharmacokinetics were linear. Galcanezumab induced a robust, dose-dependent, and durable inhibition of capsaicin-induced increase in DBF, supporting the continued clinical development of galcanezumab for prophylaxis in migraine patients.

  17. Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects

    Directory of Open Access Journals (Sweden)

    Shen Z

    2017-07-01

    Full Text Available Zancong Shen,1 Michael Gillen,2 Jeffrey N Miner,1 Gail Bucci,1 David M Wilson,1 Jesse W Hall1 1Ardea Biosciences, Inc., San Diego, CA, 2AstraZeneca, Gaithersburg, MD, USA Purpose: Verinurad (RDEA3170 is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males.Subjects and methods: This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study. Panels of eight male subjects received a single oral dose of verinurad or placebo in either a fasted or fed state; panels of 10–12 male subjects received ascending doses of once-daily verinurad or placebo in a fasted state for 10 days. Serial blood and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse event (AE reports, laboratory tests, vital signs, and electrocardiograms (ECGs.Results: A total of 81 adult males completed the study. Following single doses of verinurad, maximum observed plasma concentration (Cmax and area under the plasma concentration–time curve (AUC increased in a dose-proportional manner; Cmax occurred at 0.5–0.75 hours and 1.25 hours in the fasted and fed states, respectively. Food decreased AUC by 23% and Cmax by 37%-53%. There was a modest accumulation of verinurad following multiple daily doses. Verinurad reduced serum urate levels by up to 62% (40 mg, single dose and 61% (10 mg, multiple dose. The increase in urinary excretion of uric acid was greatest in the first 6 hours after dosing and was still evident ≥24 hours for verinurad doses ≥2 mg. Verinurad was well tolerated at all doses. No serious AEs, severe AEs, discontinuations due to AEs, or clinically significant laboratory or ECG abnormalities were reported.Conclusion: Single and multiple doses of verinurad were well tolerated

  18. MRI Brain Images Healthy and Pathological Tissues Classification with the Aid of Improved Particle Swarm Optimization and Neural Network

    Science.gov (United States)

    Sheejakumari, V.; Sankara Gomathi, B.

    2015-01-01

    The advantages of magnetic resonance imaging (MRI) over other diagnostic imaging modalities are its higher spatial resolution and its better discrimination of soft tissue. In the previous tissues classification method, the healthy and pathological tissues are classified from the MRI brain images using HGANN. But the method lacks sensitivity and accuracy measures. The classification method is inadequate in its performance in terms of these two parameters. So, to avoid these drawbacks, a new classification method is proposed in this paper. Here, new tissues classification method is proposed with improved particle swarm optimization (IPSO) technique to classify the healthy and pathological tissues from the given MRI images. Our proposed classification method includes the same four stages, namely, tissue segmentation, feature extraction, heuristic feature selection, and tissue classification. The method is implemented and the results are analyzed in terms of various statistical performance measures. The results show the effectiveness of the proposed classification method in classifying the tissues and the achieved improvement in sensitivity and accuracy measures. Furthermore, the performance of the proposed technique is evaluated by comparing it with the other segmentation methods. PMID:25977706

  19. Tolerance doses of cutaneous and mucosal tissues in ring-necked parakeets (Psittacula krameri) for external beam megavoltage radiation.

    Science.gov (United States)

    Barron, Heather W; Roberts, Royce E; Latimer, Kenneth S; Hernandez-Divers, Stephen; Northrup, Nicole C

    2009-03-01

    Currently used dosages for external-beam megavoltage radiation therapy in birds have been extrapolated from mammalian patients and often appear to provide inadequate doses of radiation for effective tumor control. To determine the tolerance doses of cutaneous and mucosal tissues of normal birds in order to provide more effective radiation treatment for tumors that have been shown to be radiation responsive in other species, ingluvial mucosa and the skin over the ingluvies of 9 ring-necked parakeets (Psittacula krameri) were irradiated in 4-Gy fractions to a total dose of either 48, 60, or 72 Gy using an isocentric cobalt-60 teletherapy unit. Minimal radiation-induced epidermal changes were present in the high-dose group histologically. Neither dose-related acute nor chronic radiation effects could be detected in any group grossly in cutaneous or mucosal tissue over a 9-month period. Radiation doses of 72 Gy in 4-Gy fractions were well tolerated in the small number of ring-necked parakeets in this initial tolerance dose study.

  20. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves; Dose de tolerance a l'irradiation des tissus sains: les nerfs peripheriques

    Energy Technology Data Exchange (ETDEWEB)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G. [Departement de radiotherapie, institut Bergonie, centre regional de lutte contre le cancer, 33 - Bordeaux (France); Huchet, A.; Mamou, N. [Service d' oncologie medicale et de radiotherapie, CHU Saint-Andre, 33 - Bordeaux (France); Loiseau, H. [Service de neurochirurgie, CHU Pellegrin, 33 - Bordeaux (France)

    2010-07-15

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  1. HE4 Tissue Expression and Serum HE4 Levels in Healthy Individuals and Patients with Benign or Malignant Tumors

    DEFF Research Database (Denmark)

    Karlsen, Nikoline S; Karlsen, Mona A; Høgdall, Claus K

    2014-01-01

    , this review aims to systematically outline published results of HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors. Our findings suggest scientific basis for a potential diagnostic ability of HE4 in gynecologic cancer and lung cancer, and further...

  2. The effect of irradiance on the carbon balance and tissue characteristics of five herbaceous species differing in shade-tolerance.

    Science.gov (United States)

    Pons, Thijs L; Poorter, Hendrik

    2014-01-01

    The carbon balance is defined here as the partitioning of daily whole-plant gross CO2 assimilation (A) in C available for growth and C required for respiration (R). A scales positively with growth irradiance and there is evidence for an irradiance dependence of R as well. Here we ask if R as a fraction of A is also irradiance dependent, whether there are systematic differences in C-balance between shade-tolerant and shade-intolerant species, and what the causes could be. Growth, gas exchange, chemical composition and leaf structure were analyzed for two shade-tolerant and three shade-intolerant herbaceous species that were hydroponically grown in a growth room at five irradiances from 20 μmol m(-2) s(-1) (1.2 mol m(-2) day(-1)) to 500 μmol m(-2) s(-1) (30 mol m(-2) day(-1)). Growth analysis showed little difference between species in unit leaf rate (dry mass increase per unit leaf area) at low irradiance, but lower rates for the shade-tolerant species at high irradiance, mainly as a result of their lower light-saturated rate of photosynthesis. This resulted in lower relative growth rates in these conditions. Daily whole-plant R scaled with A in a very tight manner, giving a remarkably constant R/A ratio of around 0.3 for all but the lowest irradiance. Although some shade-intolerant species showed tendencies toward a higher R/A and inefficiencies in terms of carbon and nitrogen investment in their leaves, no conclusive evidence was found for systematic differences in C-balance between the shade-tolerant and intolerant species at the lowest irradiance. Leaf tissue of the shade-tolerant species was characterized by high dry matter percentages, C-concentration and construction costs, which could be associated with a better defense in shade environments where leaf longevity matters. We conclude that shade-intolerant species have a competitive advantage at high irradiance due to superior potential growth rates, but that shade-tolerance is not necessarily associated

  3. Preliminary study of tissue concentrations of penicillin after local administration into the guttural pouches in four healthy horses.

    Science.gov (United States)

    Kendall, A; Mayhew, I G; Petrovski, K

    2016-08-01

    Treatment of subclinical carriers of Streptococcus equi subsp. equi with a gelatine-penicillin formulation deposited in the guttural pouch has been empirically proposed, but data on local tissue penicillin concentrations after treatment are lacking. We analysed tissue levels of penicillin after administration into the guttural pouches of four healthy horses. Two horses received local treatment with gelatine-penicillin and two horses received local treatment with an intramammary formulation of penicillin. Tissues were harvested for analysis either 12 or 24 h later. Results indicate that local treatment may be effective, but more research on optimal drug formulations in a larger sample size is warranted. © 2016 Australian Veterinary Association.

  4. Gene Expression Profiles in Paired Gingival Biopsies from Periodontitis-Affected and Healthy Tissues Revealed by Massively Parallel Sequencing

    Science.gov (United States)

    Båge, Tove; Lagervall, Maria; Jansson, Leif; Lundeberg, Joakim; Yucel-Lindberg, Tülay

    2012-01-01

    Periodontitis is a chronic inflammatory disease affecting the soft tissue and bone that surrounds the teeth. Despite extensive research, distinctive genes responsible for the disease have not been identified. The objective of this study was to elucidate transcriptome changes in periodontitis, by investigating gene expression profiles in gingival tissue obtained from periodontitis-affected and healthy gingiva from the same patient, using RNA-sequencing. Gingival biopsies were obtained from a disease-affected and a healthy site from each of 10 individuals diagnosed with periodontitis. Enrichment analysis performed among uniquely expressed genes for the periodontitis-affected and healthy tissues revealed several regulated pathways indicative of inflammation for the periodontitis-affected condition. Hierarchical clustering of the sequenced biopsies demonstrated clustering according to the degree of inflammation, as observed histologically in the biopsies, rather than clustering at the individual level. Among the top 50 upregulated genes in periodontitis-affected tissues, we investigated two genes which have not previously been demonstrated to be involved in periodontitis. These included interferon regulatory factor 4 and chemokine (C-C motif) ligand 18, which were also expressed at the protein level in gingival biopsies from patients with periodontitis. In conclusion, this study provides a first step towards a quantitative comprehensive insight into the transcriptome changes in periodontitis. We demonstrate for the first time site-specific local variation in gene expression profiles of periodontitis-affected and healthy tissues obtained from patients with periodontitis, using RNA-seq. Further, we have identified novel genes expressed in periodontitis tissues, which may constitute potential therapeutic targets for future treatment strategies of periodontitis. PMID:23029519

  5. The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability.

    Science.gov (United States)

    Carhart-Harris, Robin L; Williams, Tim M; Sessa, Ben; Tyacke, Robin J; Rich, Ann S; Feilding, Amanda; Nutt, David J

    2011-11-01

    This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.

  6. Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects

    Directory of Open Access Journals (Sweden)

    Shin D

    2017-03-01

    Full Text Available Dongseong Shin,1 SeungHwan Lee,2 Sojeong Yi,2 Seo Hyun Yoon,2 Joo-Youn Cho,2 Mi Young Bahng,3 In-Jin Jang,2 Kyung-Sang Yu2 1Clinical Trials Center, Gachon University Gil Medical Center, Incheon, 2Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 3Department of Product Development, Dong-A ST, Seoul, Korea Objective: DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5 in the plasma and urine after administration of a single oral dose in healthy male subjects.Methods: A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP enzymes on the pharmacokinetics of DA-8031 was evaluated.Results: After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2–3 h and was eliminated with terminal elimination half-life of 17.9–28.7 h. The mean renal clearance was 3.7–5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20–80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized Cmax and AUC0–t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported.Conclusion: In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20

  7. Tolerance to low temperatures of Toxocara cati larvae in chicken muscle tissue

    DEFF Research Database (Denmark)

    Taira, Kensuke; Saitoh, Yasuhide; Okada, Natsuki

    2012-01-01

    Infectivity of Toxocara cati larvae in muscle tissue of chickens after storage at 4 degrees C and -25 degrees C was assessed in a mouse bioassay to provide information on the risk of meat-borne toxocarosis. Muscle tissue samples of 30-day old T. cati infections were stored at 4 degrees C for 14...

  8. Alendronate treatment alters bone tissues at multiple structural levels in healthy canine cortical bone.

    Science.gov (United States)

    Acevedo, Claire; Bale, Hrishikesh; Gludovatz, Bernd; Wat, Amy; Tang, Simon Y; Wang, Mingyue; Busse, Björn; Zimmermann, Elizabeth A; Schaible, Eric; Allen, Matthew R; Burr, David B; Ritchie, Robert O

    2015-12-01

    Bisphosphonates are widely used to treat osteoporosis, but have been associated with atypical femoral fractures (AFFs) in the long term, which raises a critical health problem for the aging population. Several clinical studies have suggested that the occurrence of AFFs may be related to the bisphosphonate-induced changes of bone turnover, but large discrepancies in the results of these studies indicate that the salient mechanisms responsible for any loss in fracture resistance are still unclear. Here the role of bisphosphonates is examined in terms of the potential deterioration in fracture resistance resulting from both intrinsic (plasticity) and extrinsic (shielding) toughening mechanisms, which operate over a wide range of length-scales. Specifically, we compare the mechanical properties of two groups of humeri from healthy beagles, one control group comprising eight females (oral doses of saline vehicle, 1 mL/kg/day, 3 years) and one treated group comprising nine females (oral doses of alendronate used to treat osteoporosis, 0.2mg/kg/day, 3 years). Our data demonstrate treatment-specific reorganization of bone tissue identified at multiple length-scales mainly through advanced synchrotron x-ray experiments. We confirm that bisphosphonate treatments can increase non-enzymatic collagen cross-linking at molecular scales, which critically restricts plasticity associated with fibrillar sliding, and hence intrinsic toughening, at nanoscales. We also observe changes in the intracortical architecture of treated bone at microscales, with partial filling of the Haversian canals and reduction of osteon number. We hypothesize that the reduced plasticity associated with BP treatments may induce an increase in microcrack accumulation and growth under cyclic daily loadings, and potentially increase the susceptibility of cortical bone to atypical (fatigue-like) fractures. Published by Elsevier Inc.

  9. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

    Science.gov (United States)

    Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

    2016-01-01

    Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin

  10. Improved classification and visualization of healthy and pathological hard dental tissues by modeling specular reflections in NIR hyperspectral images

    Science.gov (United States)

    Usenik, Peter; Bürmen, Miran; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

    2012-03-01

    Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots, which are difficult to diagnose. Near-infrared (NIR) hyperspectral imaging is a new promising technique for early detection of demineralization which can classify healthy and pathological dental tissues. However, due to non-ideal illumination of the tooth surface the hyperspectral images can exhibit specular reflections, in particular around the edges and the ridges of the teeth. These reflections significantly affect the performance of automated classification and visualization methods. Cross polarized imaging setup can effectively remove the specular reflections, however is due to the complexity and other imaging setup limitations not always possible. In this paper, we propose an alternative approach based on modeling the specular reflections of hard dental tissues, which significantly improves the classification accuracy in the presence of specular reflections. The method was evaluated on five extracted human teeth with corresponding gold standard for 6 different healthy and pathological hard dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized regions. Principal component analysis (PCA) was used for multivariate local modeling of healthy and pathological dental tissues. The classification was performed by employing multiple discriminant analysis. Based on the obtained results we believe the proposed method can be considered as an effective alternative to the complex cross polarized imaging setups.

  11. Sparing Healthy Tissue and Increasing Tumor Dose Using Bayesian Modeling of Geometric Uncertainties for Planning Target Volume Personalization

    International Nuclear Information System (INIS)

    Herschtal, Alan; Te Marvelde, Luc; Mengersen, Kerrie; Foroudi, Farshad; Eade, Thomas; Pham, Daniel; Caine, Hannah; Kron, Tomas

    2015-01-01

    Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predict future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes

  12. Pyrosequencing revealed shifts of prokaryotic communities between healthy and disease-like tissues of the Red Sea sponge Crella cyathophora

    KAUST Repository

    Gao, Zhao-Ming

    2015-06-11

    Sponge diseases have been widely reported, yet the causal factors and major pathogenic microbes remain elusive. In this study, two individuals of the sponge Crella cyathophora in total that showed similar disease-like characteristics were collected from two different locations along the Red Sea coast separated by more than 30 kilometers. The disease-like parts of the two individuals were both covered by green surfaces, and the body size was much smaller compared with adjacent healthy regions. Here, using high-throughput pyrosequencing technology, we investigated the prokaryotic communities in healthy and disease-like sponge tissues as well as adjacent seawater. Microbes in healthy tissues belonged mainly to the Proteobacteria, Cyanobacteria and Bacteroidetes, and were much more diverse at the phylum level than reported previously. Interestingly, the disease-like tissues from the two sponge individuals underwent shifts of prokaryotic communities and were both enriched with a novel clade affiliated with the phylum Verrucomicrobia, implying its intimate connection with the disease-like Red Sea sponge C. cyathophora. Enrichment of the phylum Verrucomicrobia was also considered to be correlated with the presence of algae assemblages forming the green surface of the disease-like sponge tissues. This finding represents an interesting case of sponge disease and is valuable for further study.

  13. High-throughput sequencing approach uncovers the miRNome of peritoneal endometriotic lesions and adjacent healthy tissues.

    Directory of Open Access Journals (Sweden)

    Merli Saare

    Full Text Available Accumulating data have shown the involvement of microRNAs (miRNAs in endometriosis pathogenesis. In this study, we used a novel approach to determine the endometriotic lesion-specific miRNAs by high-throughput small RNA sequencing of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissues together with eutopic endometria of the same patients. We found five miRNAs specific to epithelial cells--miR-34c, miR-449a, miR-200a, miR-200b and miR-141 showing significantly higher expression in peritoneal endometriotic lesions compared to healthy peritoneal tissues. We also determined the expression levels of miR-200 family target genes E-cadherin, ZEB1 and ZEB2 and found that the expression level of E-cadherin was significantly higher in endometriotic lesions compared to healthy tissues. Further evaluation verified that studied miRNAs could be used as diagnostic markers for confirming the presence of endometrial cells in endometriotic lesion biopsy samples. Furthermore, we demonstrated that the miRNA profile of peritoneal endometriotic lesion biopsies is largely masked by the surrounding peritoneal tissue, challenging the discovery of an accurate lesion-specific miRNA profile. Taken together, our findings indicate that only particular miRNAs with a significantly higher expression in endometriotic cells can be detected from lesion biopsies, and can serve as diagnostic markers for endometriosis.

  14. Sparing Healthy Tissue and Increasing Tumor Dose Using Bayesian Modeling of Geometric Uncertainties for Planning Target Volume Personalization

    Energy Technology Data Exchange (ETDEWEB)

    Herschtal, Alan, E-mail: Alan.Herschtal@petermac.org [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne (Australia); Te Marvelde, Luc [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne (Australia); Mengersen, Kerrie [School of Mathematical Sciences, Science and Engineering Faculty, Queensland University of Technology, Brisbane (Australia); Foroudi, Farshad [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Eade, Thomas [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Northern Clinical School, University of Sydney (Australia); Pham, Daniel [Department of Radiation Therapy, Peter MacCallum Cancer Centre, Melbourne (Australia); Caine, Hannah [Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards, Sydney (Australia); Kron, Tomas [The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne (Australia); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne (Australia)

    2015-06-01

    Objective: To develop a mathematical tool that can update a patient's planning target volume (PTV) partway through a course of radiation therapy to more precisely target the tumor for the remainder of treatment and reduce dose to surrounding healthy tissue. Methods and Materials: Daily on-board imaging was used to collect large datasets of displacements for patients undergoing external beam radiation therapy for solid tumors. Bayesian statistical modeling of these geometric uncertainties was used to optimally trade off between displacement data collected from previously treated patients and the progressively accumulating data from a patient currently partway through treatment, to optimally predict future displacements for that patient. These predictions were used to update the PTV position and margin width for the remainder of treatment, such that the clinical target volume (CTV) was more precisely targeted. Results: Software simulation of dose to CTV and normal tissue for 2 real prostate displacement datasets consisting of 146 and 290 patients treated with a minimum of 30 fractions each showed that re-evaluating the PTV position and margin width after 8 treatment fractions reduced healthy tissue dose by 19% and 17%, respectively, while maintaining CTV dose. Conclusion: Incorporating patient-specific displacement patterns from early in a course of treatment allows PTV adaptation for the remainder of treatment. This substantially reduces the dose to healthy tissues and thus can reduce radiation therapy–induced toxicities, improving patient outcomes.

  15. Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

    Science.gov (United States)

    Werner, Benjamin; Sottoriva, Andrea

    2018-06-01

    The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99)). In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88) in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.

  16. Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.

    Directory of Open Access Journals (Sweden)

    Benjamin Werner

    2018-06-01

    Full Text Available The immortal strand hypothesis poses that stem cells could produce differentiated progeny while conserving the original template strand, thus avoiding accumulating somatic mutations. However, quantitating the extent of non-random DNA strand segregation in human stem cells remains difficult in vivo. Here we show that the change of the mean and variance of the mutational burden with age in healthy human tissues allows estimating strand segregation probabilities and somatic mutation rates. We analysed deep sequencing data from healthy human colon, small intestine, liver, skin and brain. We found highly effective non-random DNA strand segregation in all adult tissues (mean strand segregation probability: 0.98, standard error bounds (0.97,0.99. In contrast, non-random strand segregation efficiency is reduced to 0.87 (0.78,0.88 in neural tissue during early development, suggesting stem cell pool expansions due to symmetric self-renewal. Healthy somatic mutation rates differed across tissue types, ranging from 3.5 × 10-9/bp/division in small intestine to 1.6 × 10-7/bp/division in skin.

  17. Radiation induced variation in potato for tolerance to salinity using tissue culture technique

    International Nuclear Information System (INIS)

    Sharabash, M.T.

    2001-01-01

    Meristem-tips of potato (Solanum tuberosum) cv. 'Diamant', obtained from tuber sprouts, were cultured on MS medium, and multiplied into plantlets through micropropagation. To induce variation for salt tolerance, the obtained plantlets were irradiated with 0, 20, and 40 Gy gamma rays at 27.7 rad/sec. Irradiated plantlets were cut into single nodes and cultured on MS medium, supplemented with 2000 and 4000 ppm NaCI. Salt tolerant plantlets were transferred for tuberization on MS liquid medium supplemented with the same concentration of NaCI. Micro-tubers, collected after 6 weeks of culture, had fresh weight between 0.03 to 0.3 g. Mini-tubers were obtained by planting micro-tubers in 25 cm pots under insect proof greenhouse. Mini-tuber number per plant ranged from 3 to 6, and the mini-tuber weight ranged from 0.5-3.0 g, depending upon the treatment. Further studies are in progress to produce conventional tubers under salinity stress from the promising variants, specially those tolerant to 4000 ppm, and to assure the stability of the obtained variants. (author)

  18. The effect of irradiance on the carbon balance and tissue characteristics of five herbaceous species differing in shade-tolerance

    Directory of Open Access Journals (Sweden)

    Thijs Leendert Pons

    2014-02-01

    Full Text Available Plant photosynthesis scales positively with growth irradiance. The carbon balance, defined here as the daily whole-plant gross CO2 assimilation (A partitioned in C available for growth and C required for respiration (R, is thus irradiance dependent. Here we ask if R as a fraction of A is also irradiance dependent, whether there are systematic differences in C-balance between shade-tolerant and shade-intolerant species, and what the causes could be. Growth, gas exchange, chemical composition and leaf structure were analyzed for two shade-tolerant and three shade-intolerant herbaceous species that were hydroponically grown in a growth room at five irradiances from 20 µmol m-2 s-1 (1.2 mol m-2 day-1 to 500 µmol m-2 s-1 (30 mol m-2 day-1. Growth analysis showed little difference between species in unit leaf rate (dry mass increase per unit leaf area at low irradiance, but lower rates for the shade-tolerant species at high irradiance, mainly as a result of their lower light saturated rate of photosynthesis. This resulted in lower relative growth rates in these conditions. Daily whole-plant R scaled with A in a very tight manner, giving a remarkably constant R/A ratio of around 0.3 for all but the lowest irradiance. Although some shade-intolerant species showed tendencies towards a higher R/A and inefficiencies in terms of carbon and nitrogen investment in their leaves, no conclusive evidence was found for systematic differences in C-balance between the shade-tolerant and intolerant species at the lowest irradiance. Leaf tissue of the shade-tolerant species was characterized by high dry matter percentages, C-concentration and construction costs, which could be associated with a better defense in shade environments where leaf longevity matters. We conclude that shade-intolerant species have a competitive advantage at high irradiance due to superior potential growth rates, but that shade-tolerance is not necessarily associated with a superior C

  19. Automated classification and visualization of healthy and pathological dental tissues based on near-infrared hyper-spectral imaging

    Science.gov (United States)

    Usenik, Peter; Bürmen, Miran; Vrtovec, Tomaž; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

    2011-03-01

    Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots which are difficult to diagnose. If detected early enough, such demineralization can be arrested and reversed by non-surgical means through well established dental treatments (fluoride therapy, anti-bacterial therapy, low intensity laser irradiation). Near-infrared (NIR) hyper-spectral imaging is a new promising technique for early detection of demineralization based on distinct spectral features of healthy and pathological dental tissues. In this study, we apply NIR hyper-spectral imaging to classify and visualize healthy and pathological dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized areas. For this purpose, a standardized teeth database was constructed consisting of 12 extracted human teeth with different degrees of natural dental lesions imaged by NIR hyper-spectral system, X-ray and digital color camera. The color and X-ray images of teeth were presented to a clinical expert for localization and classification of the dental tissues, thereby obtaining the gold standard. Principal component analysis was used for multivariate local modeling of healthy and pathological dental tissues. Finally, the dental tissues were classified by employing multiple discriminant analysis. High agreement was observed between the resulting classification and the gold standard with the classification sensitivity and specificity exceeding 85 % and 97 %, respectively. This study demonstrates that NIR hyper-spectral imaging has considerable diagnostic potential for imaging hard dental tissues.

  20. CHANGES IN TOOTH HARD TISSUE MINERALI-ZATION AND BLOOD RHEOLOGY IN HEALTHY ADOLESCENTS AND THOSE WITH THYROID DYSFUNCTION.

    Science.gov (United States)

    Beriashvili, S; Nikolaishvili, M; Mantskava, M; Momtsemlidze, N; Franchuk, K

    2016-11-01

    Thyroid dysfunction causes spreading and development of caries in the teeth and changes in periodontal tissues. In addition, it causes changes in peripheral blood flow and mineralization, local transcapillary metabolism causes changes in blood rheology. There are only few works in this direction and, therefore, the purpose of our research was to find out how the mineralization and the rheological properties of blood are changed in lesion of periodontal tissue on a background of thyroid dysfunction. Accordingly, the stomatological study was conducted in 75 adolescents aged 12-18 years by the standard method, recommended by the World Health Organization. According to the study, 45 patients out of them suffered from thyroid dysfunction, in particular from hypothyroidism. The comparator group consisted of 30 children of the same age without endocrine abnormalities. By the gained results it is noted that in spite of different type lesions due to dental caries, the caries incidence and intensiveness is higher in children with hypothyroidism as compared to healthy children. Decrease in saliva excretion rate and increase in oral fluid viscosity was found in children with thyroid and endocrine diseases as compared to healthy children. In children with endocrine disorders concurrent increase in calcium content (1,43±0,08 mmol/l) and decrease in inorganic phosphate concentrations (4,54±0,15 mmol/l) is reliably established. In children with thyroid disfunction and while periodontal tissue pathology, rheological features are disordered more dramatically than in healthy children. Therefore, it can be said that the changes in the adolescents' thyroid function is one of the reasons for formation of periodontal tissue diseases.Therefore, at detecting even the first signs of the periodontal tissue diseases, it is desirable in adolescents to assess the thyroid functional condition, since it will be the precondition for effective treatment and management of dental disease, in

  1. Simultaneous bone marrow and composite tissue transplantation in rats treated with nonmyeloablative conditioning promotes tolerance1

    Science.gov (United States)

    Xu, Hong; Ramsey, Deborah M.; Wu, Shengli; Bozulic, Larry D.; Ildstad, Suzanne T.

    2012-01-01

    Background Approaches to safely induce tolerance in vascularized composite allotransplantation (VCA) with chimerism through bone marrow transplantation (BMT) are currently being pursued. However, the VCA were historically performed sequentially after donor chimerism was established. Delayed VCA is not clinically applicable due to the time constraints associated with procurement from deceased donors. A more clinically relevant approach to perform both the BMT and VCA simultaneously was evaluated. Methods WF (RT1Au) rats were treated with a short course of immunosuppressive therapy (anti-αβ-TCR mAb, FK-506, and anti-lymphocyte serum). One day prior to BMT, rats were treated with varying doses of total body irradiation (TBI) followed by transplantation of heterotopic osteomyocutaneous flaps from hind limbs of ACI (RT1Aabl) rats. Results 80% of rats conditioned with 300 cGy TBI and 40% of rats receiving 400 cGy TBI accepted the VCA. Mixed chimerism was detected in peripheral blood at one month post-VCA, but chimerism was lost in all transplant recipients by 4 months. The majority of peripheral donor cells originated from the BMT and not the VCA. Acceptors of VCA were tolerant of a donor skin graft challenge and no anti-donor antibodies were detectable, suggesting a central deletional mechanism for tolerance. Regulatory T cells (Treg) from spleens of acceptors more potently suppressed lymphocyte proliferation than Treg from rejectors in the presence of donor stimulator cells. Conclusions These studies suggest that simultaneous BMT and VCA may establish indefinite allograft survival in rats through Treg-mediated suppression and thymic deletion of alloreactive T cells. PMID:23250336

  2. Normal tissue tolerance to external beam radiation therapy: Brain and hypophysis

    International Nuclear Information System (INIS)

    Haberer, S.; Assouline, A.; Mazeron, J.J.

    2010-01-01

    Anticancer treatments-induced central nervous system neurotoxicity has become a major problem in recent years. Real advances in therapeutic results for cancer treatments have improved patients survival. Nowadays, central nervous system radiation therapy is widely prescribed, both for palliative and curative treatments in the management of malignant or benign tumors. Recent data on tolerance of normal central nervous system to radiation therapy are reviewed here, early and delayed radiation-induced effects are described and dose recommendations are suggested for clinical practice. (authors)

  3. Reduced circulating stem cells associate with excess fasting and post-load NEFA exposure in healthy adults with normal glucose tolerance.

    Science.gov (United States)

    Fadini, Gian Paolo; Tura, Andrea; Pacini, Giovanni; Avogaro, Angelo; Vigili de Kreutzenberg, Saula

    2017-06-01

    Reduced levels of circulating stem cells (CSCs) predict cardiovascular events and death, but the factors underlying variability of CSCs in healthy adults are mostly unknown. Previous studies detected associations of CSCs with glucose tolerance or insulin resistance, while the role of fatty acids has been overlooked. We herein aimed to describe in better detail the metabolic abnormalities associated with a reduced CSC level. This was a cross-sectional study on 94 healthy male and female individuals with normal glucose tolerance, aged 18-65 years. All participants underwent an oral glucose tolerance test (OGTT) with blood samples collected at 0, 10, 20, 30, 60, 90 and 120 min. Mathematical models were applied to plasma glucose, insulin, C-peptide and non-esterified fatty acids (NEFA) concentrations. CSCs were defined as CD34 + or CD133 + . Participants (mean ± SEM age 43.8 ± 0.7; 41% males) were divided according to CSC levels below (low) or above (high) the median value and metabolic parameters were compared. There was no significant baseline difference between groups except for higher concentrations of fasting NEFA in subjects with low CSCs. Upon OGTT, individuals with low CSCs had higher area under curve (AUC) of NEFA (p glucose, insulin and C-peptide. Several insulin sensitivity and beta cell function indexes were not significantly different, except for a decrease in the disposition index (DI) in subjects with low CSCs. CSCs were associated with excess NEFA levels independently from age and DI. We show for the first time that, in healthy adults with normal glucose tolerance, low CSCs are strongly associated with excess NEFA exposure. The pathophysiological consequence of this association needs to be interpreted in view of the prognostic role of CSCs. Future studies should explore whether excess NEFA and low CSCs and are causally interconnected. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. WJD 5th Anniversary Special Issues(1): Insulin Benefits of healthy adipose tissue in the treatment of diabetes

    Institute of Scientific and Technical Information of China (English)

    Subhadra; C; Gunawardana

    2014-01-01

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin.Insulin deficiency is either absolute due to destruction or failure of pancreaticβcells,or relative due to decreased sensitivity of peripheral tissues to insulin.The primary lesion being related to insulin,treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin.These therapies have their own limitations and complications,some of which can be life-threatening.For example,exogenous insulin administration can lead to fatal hypoglycemic episodes;islet/pancreas transplantation requires life-long immunosuppressive therapy;and anti-diabetic drugs have dangerous side effects including edema,heart failure and lactic acidosis.Thus the need remains for better safer long term treatments for diabetes.The ultimate goal in treating diabetes is to re-establish glucose homeostasis,preferably through endogenously generated hormones.Recent studies increasingly show that extra-pancreatic hormones,particularly those arising from adipose tissue,can compensate for insulin,or entirely replace the function of insulin under appropriate circumstances.Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism.While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines,healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties,which can complement and/or compensate for the function of insulin.Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes,and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin.Although specific adipokines may correct diabetes,administration of individual adipokines still carries risks similar to those of insulin monotherapy.Thus a better approach is to

  5. Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis)

    Science.gov (United States)

    Honeyfield, D.C.; Ross, J.P.; Carbonneau, D.A.; Terrell, S.P.; Woodward, A.R.; Schoeb, T.R.; Perceval, H.F.; Hinterkopf, J.P.

    2008-01-01

    An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B"1) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. ?? Wildlife Disease Association 2008.

  6. Dissociation between peripheral blood chimerism and tolerance to hindlimb composite tissue transplants: preferential localization of chimerism in donor bone.

    Science.gov (United States)

    Rahhal, Dina N; Xu, Hong; Huang, Wei-Chao; Wu, Shengli; Wen, Yujie; Huang, Yiming; Ildstad, Suzanne T

    2009-09-27

    Mixed chimerism induces donor-specific tolerance to composite tissue allotransplants (CTAs). In the present studies, we used a nonmyeloablative conditioning approach to establish chimerism and promote CTA acceptance. Wistar Furth (RT1A(u)) rats were conditioned with 600 to 300 cGy total body irradiation (TBI, day-1), and 100 x 10(6) T-cell-depleted ACI (RT1A(abl)) bone marrow cells were transplanted on day 0, followed by a 11-day course of tacrolimus and one dose of antilymphocyte serum (day 10). Heterotopic osteomyocutaneous flap transplantation was performed 4 to 6 weeks after bone marrow transplantation. Mixed chimerism was initially achieved in almost all recipients, but long-term acceptance of CTA was only achieved in rats treated with 600 cGy TBI. When anti-alphabeta-T-cell receptor (TCR) monoclonal antibody (mAb) (day-3) was added into the regimens, donor chimerism was similar to recipients preconditioned without anti-alphabeta-TCR mAb. However, the long-term CTA survival was significantly improved in chimeras receiving more than or equal to 300 cGy TBI plus anti-alphabeta-TCR mAb. Higher levels of donor chimerism were associated with CTA acceptance. The majority of flap acceptors lost peripheral blood chimerism within 6 months. However, donor chimerism persisted in the transplanted bone at significantly higher levels compared with other hematopoietic compartments. The compartment donor chimerism may be responsible for the maintenance of tolerance to CTA. Long-term acceptors were tolerant to a donor skin graft challenge even in the absence of peripheral blood chimerism. Mixed chimerism established by nonmyeloablative conditioning induces long-term acceptance of CTA, which is associated with persistent chimerism preferentially in the transplanted donor bone.

  7. Salt Tolerant Mutants in Potato sp. Cara Induced by Gamma Irradiation and Tissue Culture Technique

    International Nuclear Information System (INIS)

    Sharabash, M.T.; Mohamed, A.A.; Ahmed, F.A.; Afifi, A.M.

    2003-01-01

    Sprouts of 2-3 cm length were cut off from potatoes cv. Cara tubers and sterilized. Apical meristemic tips were sown to produce virus free plantlets. After 6-8 weeks, the new plantlets became at 5-7cm heights. Micro-propagation was begun to obtain sufficient number of plantlets. Plantlets obtained from micro-propagation stage were divided into 3 groups to be exposed to 0.0,20 or 40Gy gamma rays. The dose rate was 27.7rad/sec. Irradiated and unirradiated plantlets were trimmed to be with 5-6 nodes and without leaves. They were transplanted onto 1/2MS [1] liquid medium supplemented with sodium chloride at different concentrations, i.e.,0.0, 2000 or 4000 ppm. Healthy plantlets were chosen, and all unfit ones were excluded. The plantlets were sub-cultured six times on the same fresh medium with the same concentrations of NaCI, with insisting to exclude all unfit plantlets. All maintained healthy plantlets, in the sixth vegetative generation (M 1 V 6 ), grown under salinity stress, whatever the concentration of NaCI, were considered as mutant lines

  8. Combined antibacterial effects of tissue-tolerable plasma and a modern conventional liquid antiseptic on chronic wound treatment.

    Science.gov (United States)

    Klebes, Martin; Ulrich, Christin; Kluschke, Franziska; Patzelt, Alexa; Vandersee, Staffan; Richter, Heike; Bob, Adrienne; von Hutten, Johanna; Krediet, Jorien T; Kramer, Axel; Lademann, Jürgen; Lange-Asschenfeld, Bernhard

    2015-05-01

    Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Regeneration and acclimatization of salt-tolerant arachis hypogaea plants through tissue culture

    International Nuclear Information System (INIS)

    Ghauri, E.G.

    2006-01-01

    Excised embryos of Arachis hypogaea were cultured on Murashige and Skoog's medium (MS medium) supplemented with different combinations of growth hormones. The highest frequency of callus proliferation (80%) was recorded on MS medium mixed with 1.0 mg/1 of 2,4-D and 0.5 mg/1 of BAP. These cultures were treated with 0.65 mg/l of trans-4-hydroxy-L-proline (HyP) a:1d various concentrations (0.1-0.5%) of NaCl. In all cases the presence of salt reduced the fresh mass of callus. Shoot regeneration in the cultures took place when transferred to MS medium supplemented with 1.0 mg/1 of kinetin (Kin) and 0.5 mg/1 of 6-benzyl aminopurine (BAP). Percentage of shoot regeneration decreased with the increase of NaCl (0.1- 0.5%) in the shoot regeneration medium. Root formation in these cultures took place when the cultures were nurtured on MS medium free of growth hormones. Regeneration, hardening and acclimatization of the salt tolerant plants was conducted. (author)

  10. The expression of syndecan-1, syndecan-4 and decorin in healthy human breast tissue during the menstrual cycle

    Directory of Open Access Journals (Sweden)

    Naessén Tord

    2010-04-01

    Full Text Available Abstract Background In order to unravel the interactions between the epithelium and the extra cellular matrix (ECM in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle. Methods Tissue from healthy women undergoing breast reduction plastic surgery was examined using immunohistochemistry (n = 38 and Real-Time RT-PCR (n = 20. Both parous and nulliparous women were eligible and the mean age of the women was 34(+/- 10 years with regular menstrual cycles (28 +/- 7 days. None of the women had used hormonal treatment the last three months. The women were randomized to needle biopsy two months before the operation in the follicular or luteal menstrual phase and for another biopsy at the operation in the opposite phase. Serum samples were obtained to characterize the menstrual phase. The Wilcoxon signed rank test and Mann Whitney test were used for statistical analyses. Results By real time-RT-PCR the gene signal for all three proteoglycans; decorin (p = 0.02 and syndecan-1 (p = 0.03 and syndecan-4 (p = 0.02 was significantly lower among parous women in the luteal phase than in the follicular phase. Immunohistochemistry confirmed the identification of the proteins but no significant difference between menstrual phases was observed. Serum samples verified the menstrual phase. Conclusions Our study shows, for the first time in the

  11. Associations of physical activity and inactivity with body tissue composition among healthy Polish women and women after mastectomy.

    Science.gov (United States)

    Czerniak, U; Demuth, A; Skrzypczak, M

    2014-10-01

    The aim of the study is to determine the relationship between physical activity and body composition among healthy women and women who have had mastectomy. This is in order to establish whether physical activity of women after breast cancer treatment improves composition and distribution of body mass components to a degree which will allow to achieve the body composition of healthy women. Research material consists of anthropometric measurements (body height, weight) of women and bioelectric impedance analysis (BIA) of body composition (using Akern - BIA 101 composition analyzer). Intensity of activity was assessed using the Physical Activity International Questionnaire. The sample consisted of 76 healthy women (active 44.74%, inactive 55.26%) and 70 females after mastectomy (54.29% and 45.71%, respectively). Mean chronological age of women after mastectomy was 53.40 years, SD=7.55, and of the healthy ones 52.38 years SD=11.01). A significant difference in body composition was noted among active and inactive women after mastectomy; namely the active females had lower weight (by approximately 12 kg), body mass index (BMI), level of fat mass (by approximately 8%) and (by approximately 5%) total body water. The active healthy women had 6% less fat mass, almost 4% more body water and 6% more fat free mass. Programmed physical activity undertaken by women after mastectomy is recommended and produces good results in the form of reduction of excessive body fat tissue. Through physical activity these women are able to achieve the same level of fat mass as healthy women. Copyright © 2014 Elsevier GmbH. All rights reserved.

  12. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast

    DEFF Research Database (Denmark)

    Nilsson, A.C.; Ostman, E.M.; Holst, Jens Juul

    2008-01-01

    Low-glycemic index (GI) foods and foods rich in whole grain are associated with reduced risk of type 2 diabetes and cardiovascular disease. We studied the effect of cereal-based bread evening meals (50 g available starch), varying in GI and content of indigestible carbohydrates, on glucose...... tolerance and related variables after a subsequent standardized breakfast in healthy subjects (n = 15). At breakfast, blood was sampled for 3 h for analysis of blood glucose, serum insulin, serum FFA, serum triacylglycerides, plasma glucagon, plasma gastric-inhibitory peptide, plasma glucagon-like peptide-1...... based bread (ordinary, high-amylose- or beta-glucan-rich genotypes) or an evening meal with white wheat flour bread (WWB) enriched with a mixture of barley fiber and resistant starch improved glucose tolerance at the subsequent breakfast compared with unsupplemented WWB (P

  13. Expression and biochemical characteristics of two different aldosterone receptors in both healthy and dilated cardiomyopathy dog heart tissue.

    Science.gov (United States)

    Reynoso Palomar, Alejandro R; Rodriguez Bravo, Moncerrat; Villa Mancera, Abel E; Mucha, Carlos J

    2017-03-01

    Recently, replicates of the aldosterone receptor expression have been done in healthy heart dog tissues through immunohistochemistry, showing an apparent heterogeneous distribution in the four chambers. Recent studies have also identified immediate effects of aldosterone, suggesting aldosterone also produces non-genomic effects caused by an unidentified receptor. In order to study the molecular and quantitative expression characteristics of aldosterone binding receptors in the canine heart, we conducted studies, using Western Blot, in the heart from both healthy animals and animals with dilated cardiomyopathy. The results show the presence and distribution of two aldosterone receptors; one of 110/120 kDa molecular weight, suggested as cytosolic/nuclear and the other of undetermined location with a 250 kDa molecular weight.

  14. Feasibility, tolerability and safety of pediatric hyperpolarized "1"2"9Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

    International Nuclear Information System (INIS)

    Walkup, Laura L.; Watters, Erin; Ruppert, Kai; Thomen, Robert P.; Woods, Jason C.; Akinyi, Teckla G.; Cleveland, Zackary I.; Clancy, John P.

    2016-01-01

    Hyperpolarized "1"2"9Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized "1"2"9Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent "1"2"9Xe MRI, receiving up to three doses of "1"2"9Xe gas prepared by either a commercially available or a homebuilt "1"2"9Xe polarizer. Subject heart rate and SpO_2 were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of "1"2"9Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO_2 (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO_2 values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following "1"2"9Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of "1"2"9Xe MRI has been assessed in a small group of children as young as 6 years. SpO_2 changes were consistent with the expected physiological effects of a short anoxic breath-hold, and other mild side effects were

  15. Feasibility, tolerability and safety of pediatric hyperpolarized {sup 129}Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Walkup, Laura L.; Watters, Erin; Ruppert, Kai [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Thomen, Robert P.; Woods, Jason C. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Washington University in St. Louis, Department of Physics, St. Louis, MO (United States); Akinyi, Teckla G.; Cleveland, Zackary I. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH (United States); Clancy, John P. [Cincinnati Children' s Hospital Medical Center, Division of Pulmonary Medicine, Cincinnati, OH (United States)

    2016-11-15

    Hyperpolarized {sup 129}Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized {sup 129}Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent {sup 129}Xe MRI, receiving up to three doses of {sup 129}Xe gas prepared by either a commercially available or a homebuilt {sup 129}Xe polarizer. Subject heart rate and SpO{sub 2} were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of {sup 129}Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO{sub 2} (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO{sub 2} values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following {sup 129}Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of {sup 129}Xe MRI has been assessed in a small group of children as young as 6 years. SpO{sub 2} changes were consistent with the expected physiological effects of a short anoxic breath

  16. Distinct Ezrin Truncations Differentiate Metastases in Sentinel Lymph Nodes from Unaffected Lymph Node Tissues, from Primary Breast Tumors, and from Healthy Glandular Breast Tissues

    Directory of Open Access Journals (Sweden)

    Claudia Röwer

    2018-02-01

    Full Text Available BACKGROUND: Lymph node metastasis status is a prognostic factor for further lymph node involvement and for patient survival in breast cancer patients. Frozen section analysis of lymph nodes is a reliable method for detection of macro-metastases. However, this method is far less effective in detecting micro-metastases, requesting improved diagnostic procedures. METHODS: We investigated expression and truncation of ezrin in (i sentinel lymph node metastases, (ii unaffected axillary lymph nodes, (iii primary breast tumors, and (iv healthy glandular breast tissues using 2D gel electrophoresis, SDS-PAGE, and mass spectrometry in addition to Western blotting. RESULTS: Full-length ezrin (E1; amino acids 1–586 is present in all four investigated tissues. Two truncated ezrin forms, one missing about the first hundred amino acids (E2a and the other lacking about 150 C-terminal amino acids (E2b were detectable in primary tumor tissues and in sentinel lymph node metastases but not in glandular tissues. Strikingly, an ezrin truncation (E3 which consists approximately of amino acids 238–586 was found strongly expressed in all sentinel lymph node metastases. Moreover, an N-terminal ezrin fragment (E4 that consists approximately of amino acids 1–273 was identified in sentinel lymph node metastases as well. CONCLUSIONS: We show for the first time the existence of tissue-dependent specific ezrin truncations. The distinguished strong Western blot staining of ezrin E3 in sentinel lymph node metastases underlines its capability to substantiate the occurrence of lymph node (micrometastases in breast cancer patients.

  17. Anthropometry, DXA and leptin reflect subcutaneous but not visceral abdominal adipose tissue by MRI in 197 healthy adolescents

    DEFF Research Database (Denmark)

    Tinggaard, Jeanette; Hagen, Casper P; Christensen, Anders Nymark

    2017-01-01

    Background Abdominal fat distribution is associated with the development of cardio-metabolic disease independently of body mass index (BMI). We assessed anthropometry, serum adipokines, and DXA as markers of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using...... to total abdominal volume. Results Girls had a higher SAT% than did boys in early and late puberty (16 vs. 13%, Pfat% (standard deviation score (SDS)), suprailiac skinfold...... magnetic resonance imaging (MRI). Methods We performed a cross-sectional study that included 197 healthy adolescents (114 boys) aged 10–15 years nested within a longitudinal population-based cohort. Clinical examination, blood sampling, DXA, and abdominal MRI were performed. SAT% and VAT% were adjusted...

  18. The tolerance of skin grafts to postoperative radiation therapy in patients with soft-tissue sarcoma

    International Nuclear Information System (INIS)

    Lawrence, W.T.; Zabell, A.; McDonald, H.D.

    1986-01-01

    During the last ten years at the National Cancer Institute, 11 patients have received 12 courses of postoperative adjuvant radiation therapy to skin grafts used for wound closure after the resection of soft-tissue sarcomas. The intervals between grafting and the initiation of radiation ranged between 3 and 20 weeks, and 4 patients received chemotherapy at the same time as their radiation. Ten of the 12 irradiated grafts remained intact after the completion of therapy. One graft had several small persistently ulcerated areas that required no further surgical treatment, and one graft required a musculocutaneous flap for reconstruction of a persistent large ulcer. Acute radiation effects on the grafted skin sometimes developed at slightly lower doses than usually seen with normal skin, but these acute effects necessitated a break in therapy on only five occasions. Concurrent chemotherapy and a relatively short interval between grafting and the initiation of radiation seemed to contribute to more severe radiation reactions. This experience indicates that postoperative adjuvant radiation therapy can be delivered to skin grafted areas without undue fear of complications, especially if the graft is allowed to heal adequately prior to initiating therapy and if chemotherapy is not given in conjunction with radiation

  19. Lymphoid tissue inducer cells: pivotal cells in the evolution of CD4 immunity and tolerance?

    Directory of Open Access Journals (Sweden)

    Peter John Lane

    2012-02-01

    Full Text Available Phylogeny suggests that the evolution of placentation in mammals was accompanied by substantial changes in the mammalian immune system: in particular lymph nodes and CD4 high affinity memory antibody responses co-evolved during the same period. Lymphoid tissue inducer cells (LTi are members of an emerging family of innate lymphoid cells (ILCs that are crucial for lymph node development, but our studies have indicated that they also play a pivotal role in the long-term maintenance of memory CD4 T cells in adult mammals through their expression of the tumor necrosis family members, OX40- and CD30-ligands. Additionally, our studies have shown that these two molecules are also key operators in CD4 effector function, as their absence obviates the need for the FoxP3-dependent regulatory T cells (Tregs that prevent CD4 driven autoimmune responses. In this perspective article, we summarize findings from our group over the last 10 years, and focus specifically on the role of LTi in thymus. We suggest that like memory CD4 T cells, LTi also play a role in the selection and maintenance of the Tregs that under normal circumstances are absolutely required to regulate CD4 effector cells.

  20. Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects.

    Science.gov (United States)

    Nirogi, Ramakrishna; Mudigonda, Koteshwara; Bhyrapuneni, Gopinadh; Muddana, Nageswara Rao; Goyal, Vinod Kumar; Pandey, Santosh Kumar; Palacharla, Raghava Choudary

    2018-05-01

    SUVN-502, a selective 5-HT6 receptor antagonist, was found to be active in preclinical models of cognitive deterioration suggesting a potential role in the treatment of dementia related to Alzheimer's disease. The objective of this study was to characterize the safety, tolerability and pharmacokinetics of SUVN-502 in healthy young adults and elderly subjects following single and multiple oral doses. Single doses (5, 15, 50, 100 and 200 mg SUVN-502) and multiple doses (50, 100 and 130 mg SUVN-502 once daily for 7 days) were evaluated in healthy young adults and multiple doses (50 and 100 mg SUVN-502 once daily for 14 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food, gender and age on SUVN-502 pharmacokinetics (100 mg single dose) was evaluated using an open-label, two-period, randomized, fed and fasted in a crossover design. SUVN-502 and M1 (major metabolite of SUVN-502) were monitored using validated analytical methods. SUVN-502 is safe and well tolerated up to the highest tested single dose of 200 mg in healthy young adults and multiple doses up to 130 mg for 7 days and 100 mg for 14 days in healthy young adults and elderly subjects, respectively. Exposures of SUVN-502 and M1 were more than dose-proportional over the evaluated dose range. Food and gender did not have a clinically meaningful effect on SUVN-502 exposure. The mean SUVN-502 total (AUC 0-∞ , and AUC 0-last ) and peak exposures (C max ) were 2.9- and 2.2-fold higher, respectively, in elderly subjects compared to young subjects. Steady-state was achieved for SUVN-502 and M1 within 7 days after once-daily dosing of SUVN-502. SUVN-502 exhibited an acceptable safety, tolerability and pharmacokinetic profile in healthy young adults and elderly subjects. Based on the above results, 50 and 100 mg once-daily doses of SUVN-502 were advanced to Phase 2 evaluation in patients with moderate AD.

  1. Serum glycated albumin is inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance.

    Directory of Open Access Journals (Sweden)

    Feifei Wang

    Full Text Available BACKGROUND: Recent studies have revealed that body mass index (BMI inversely influenced serum glycated albumin (GA, which may cause an underestimation of GA-monitored short-term hyperglycemic control. OBJECTIVE: This study was to investigate the association between anthropometric variables (BMI and waist circumference (W and accurate adiposity variables (percentage of body fat (%fat, fat mass, free fat mass (FFM, subcutaneous fat area (SFA, and visceral fat area (VFA with serum GA. DESIGN: A total of 2563 subjects (1037 men, 593 premenopausal women, and 933 postmenopausal women with normal glucose tolerance underwent bioelectrical impedance body fat content measurement and magnetic resonance imaging. Serum GA and absolute value of GA (aGA were measured by enzymatic assay. RESULTS: Compared to the BMI <25.0 kg/m(2 group, the BMI ≥25.0 kg/m(2 group had significantly higher fasting plasma glucose, glycated hemoglobin A1c, and body fat parameters including W, %fat, fat mass, FFM, SFA, and VFA, but significantly lower aGA, and GA in all the three sex- and menopause-stratified groups (all P<0.05. GA decreased with the increment of fat mass for all three groups (all P for trend <0.001. In the same BMI category, men and postmenopausal women with elevated %fat (men, ≥25%; women, ≥35% still had significantly lower GA than those with normal %fat (men, <25%; women, <35% (all P<0.05. Multiple stepwise regression showed that %fat, fat mass, and VFA were independently associated with GA. CONCLUSIONS: Serum GA was inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance.

  2. Effect of physical exercise on blood lipids and adipose tissue composition in young healthy men

    NARCIS (Netherlands)

    Danner, S. A.; Wieling, W.; Havekes, L.; Leuven, J. G.; Smit, E. M.; Dunning, A. J.

    1984-01-01

    In a prospective, controlled study, the influence of strenuous physical exercise on plasma total cholesterol, HDL cholesterol, apolipoprotein A-I, total triglycerides and fatty acid composition of adipose tissue was studied during 7 months of training in 15 senior oarsmen and 21 controls matched for

  3. 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...

  4. Time-dependent relation between smoking cessation and improved exercise tolerance in apparently healthy middle-age men and women.

    Science.gov (United States)

    Berkovitch, Anat; Kivity, Shaye; Klempfner, Robert; Segev, Shlomo; Milwidsky, Assi; Goldenberg, Ilan; Sidi, Yechezkel; Maor, Elad

    2015-06-01

    Smoking is an independent cardiovascular risk factor and correlates with reduced exercise tolerance. However, data on the time dependent effect of smoking cessation on exercise tolerance are limited. We investigated 17,115 men and women who were annually screened at the Institute for Medical Screening of the Chaim Sheba Medical Centre. All subjects had their smoking status documented and performed an exercise stress testing (EST) according to Bruce protocol at each visit. Subjects were divided at baseline into four groups: active smokers (N = 2858), recent quitters (smoking cessation ≤2 years before baseline EST; N = 861), remote quitters (smoking cessation >2 years before the baseline EST; N = 3856) and never smokers (N = 9810). Baseline and follow up EST duration were compared among the four groups. Recent quitters demonstrated a 2.4-fold improvement in their EST duration compared with active smokers (improvement of 24 ± 157 vs. 10 ± 157 s, respectively, p = 0.02). Multivariate logistic regression showed that recent quitters were 26% more likely to improve their exercise tolerance compared with active smokers (95% confidence interval (CI) 1.08-1.47, p = 0.003). Assessing smoking status as a time-dependent covariate during four consecutive visits demonstrated that recent quitters were 17% more likely to improve their exercise tolerance compared with active smokers (95% CI 1.02-1.34, p = 0.02), with a less pronounced benefit among remote quitters (hazard ratio = 1.11, 95% CI 1.02-1.21; p = 0.01). Smoking cessation is independently associated with improved exercise tolerance. The benefits of smoking cessation are evident within the first two years of abstinence. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. Influence of enrofloxacin traces in drinking water to doxycycline tissue pharmacokinetics in healthy and infected by Mycoplasma gallisepticum broiler chickens.

    Science.gov (United States)

    Gbylik-Sikorska, Malgorzata; Posyniak, Andrzej; Sniegocki, Tomasz; Sell, Bartosz; Gajda, Anna; Sawicka, Anna; Olszewska-Tomczyk, Monika; Bladek, Tomasz; Tomczyk, Grzegorz; Zmudzki, Jan

    2016-04-01

    Most of antibiotics, administrated in the treatment of poultry diseases are dissolved in drinking water, and it can lead to water supply systems contamination, especially when the regular cleaning is not using. This situation can lead to unconscious administration of low doses of antibiotics to untreated animals. The aim of this study was to clarify the impact of the exposure of enrofloxacin traces (500 μg l(-1)) to doxycycline pharmacokinetics in healthy and experimentally Mycoplasma gallisepticum infected broiler chickens., Two experimental groups, received of enrofloxacin in water and all groups, received 20 mg kg(-1) bw of doxycycline. The compounds concentrations in muscles and livers were determined by LC-MS/MS. The maximum drug tissue concentration (Cmax) of doxycycline was highest in liver obtained from infected chickens which, received enrofloxacin traces (ENR + DC/MG). It was about 40% higher than in healthy chickens from group I which received only doxycycline. It was found that the concentration-time curve AUC(0-t) values in group ENR + DC/MG were almost 75% higher than in the group (DC) and 35% higher than in group (ENR + DC) which also received enrofloxacin traces. The constant exposure of broiler chickens on enrofloxacin traces as well as infection, may significantly influenced on doxycycline tissue pharmacokinetic profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females.

    Science.gov (United States)

    Robinson, Lindsay J; Law, James M; Symonds, Michael E; Budge, Helen

    2016-04-01

    What is the central question of this study? Does psychological stress, which is known to promote cortisol secretion, simultaneously activate brown adipose tissue function in healthy adult females? What is the main finding and its importance? One explanation for the pronounced differences in brown adipose tissue function between individuals lies in their responsiveness to psychological stress and, as such, should be taken into account when examining its in vivo stimulation. Brown adipose tissue (BAT) has been implicated in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and is a potential therapeutic target. Brown adipose tissue can have a significant impact on energy balance and glucose homeostasis through the action of uncoupling protein 1, dissipating chemical energy as heat following neuroendocrine stimulation. We hypothesized that psychological stress, which is known to promote cortisol secretion, would simultaneously activate BAT at thermoneutrality. Brown adipose tissue activity was measured using infrared thermography to determine changes in the temperature of the skin overlying supraclavicular BAT (TSCR ). A mild psychological stress was induced in five healthy, lean, female, Caucasian volunteers using a short mental arithmetic (MA) test. The TSCR was compared with a repeated assessment, in which the MA test was replaced with a period of relaxation. Although MA did not elicit an acute stress response, anticipation of MA testing led to an increase in salivary cortisol, indicative of an anticipatory stress response, that was associated with a trend towards higher absolute and relative TSCR . A positive correlation between TSCR and cortisol was found during the anticipatory phase, a relationship that was enhanced by increased cortisol linked to MA. Our findings suggest that subtle changes in the level of psychological stress can stimulate BAT, findings that may account for the high variability and inconsistency in reported BAT

  7. Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.

    Science.gov (United States)

    Sarashina, Akiko; Koiwai, Kazuki; Seman, Leo J; Yamamura, Norio; Taniguchi, Atsushi; Negishi, Takahiro; Sesoko, Shogo; Woerle, Hans J; Dugi, Klaus A

    2013-01-01

    This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

  8. Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

    Science.gov (United States)

    Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

    2017-04-01

    A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

  9. Quantification of differences in the effective atomic numbers of healthy and cancerous tissues: A discussion in the context of diagnostics and dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, M. L. [School of Applied Sciences and Health Innovation Research Institute, RMIT University, Melbourne 3000 (Australia); Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne 3001 (Australia) and Medical Physics, WBRC, Alfred Hospital, Melbourne 3000 (Australia)

    2012-09-15

    Purpose: There are a range of genetic and nongenetic factors influencing the elemental composition of different human tissues. The elemental composition of cancerous tissues frequently differs from healthy tissue of the same organ, particularly in high-Z trace element concentrations. For this reason, one could suggest that this may be exploited in diagnostics and perhaps even influence dosimetry. Methods: In this work, for the first time, effective atomic numbers are computed for common cancerous and healthy tissues using a robust, energy-dependent approach between 10 keV and 100 MeV. These are then quantitatively compared within the context of diagnostics and dosimetry. Results: Differences between effective atomic numbers of healthy and diseased tissues are found to be typically less than 10%. Fibrotic tissues and calcifications of the breast exhibit substantial (tens to hundreds of percent) differences to healthy tissue. Expectedly, differences are most pronounced in the photoelectric regime and consequently most relevant for kV imaging/therapy and radionuclides with prominent low-energy peaks. Cancerous tissue of the testes and stomach have lower effective atomic numbers than corresponding healthy tissues, while diseased tissues of the other organ sites typically have higher values. Conclusions: As dose calculation approaches improve in accuracy, there may be an argument for the explicit inclusion of pathologies. This is more the case for breast, penile, prostate, nasopharyngeal, and stomach cancer, less so for testicular and kidney cancer. The calculated data suggest dual-energy computed tomography could potentially improve lesion identification in the aforementioned organs (with the exception of testicular cancer), with most import in breast imaging. Ultimately, however, the differences are very small. It is likely that the assumption of a generic 'tissue ramp' in planning will be sufficient for the foreseeable future, and that the Z differences do

  10. Quantification of differences in the effective atomic numbers of healthy and cancerous tissues: A discussion in the context of diagnostics and dosimetry

    International Nuclear Information System (INIS)

    Taylor, M. L.

    2012-01-01

    Purpose: There are a range of genetic and nongenetic factors influencing the elemental composition of different human tissues. The elemental composition of cancerous tissues frequently differs from healthy tissue of the same organ, particularly in high-Z trace element concentrations. For this reason, one could suggest that this may be exploited in diagnostics and perhaps even influence dosimetry. Methods: In this work, for the first time, effective atomic numbers are computed for common cancerous and healthy tissues using a robust, energy-dependent approach between 10 keV and 100 MeV. These are then quantitatively compared within the context of diagnostics and dosimetry. Results: Differences between effective atomic numbers of healthy and diseased tissues are found to be typically less than 10%. Fibrotic tissues and calcifications of the breast exhibit substantial (tens to hundreds of percent) differences to healthy tissue. Expectedly, differences are most pronounced in the photoelectric regime and consequently most relevant for kV imaging/therapy and radionuclides with prominent low-energy peaks. Cancerous tissue of the testes and stomach have lower effective atomic numbers than corresponding healthy tissues, while diseased tissues of the other organ sites typically have higher values. Conclusions: As dose calculation approaches improve in accuracy, there may be an argument for the explicit inclusion of pathologies. This is more the case for breast, penile, prostate, nasopharyngeal, and stomach cancer, less so for testicular and kidney cancer. The calculated data suggest dual-energy computed tomography could potentially improve lesion identification in the aforementioned organs (with the exception of testicular cancer), with most import in breast imaging. Ultimately, however, the differences are very small. It is likely that the assumption of a generic “tissue ramp” in planning will be sufficient for the foreseeable future, and that the Z differences do not

  11. Abdominal adipose tissue compartments vary with ethnicity in Asian neonates: Growing Up in Singapore Toward Healthy Outcomes birth cohort study.

    Science.gov (United States)

    Tint, Mya Thway; Fortier, Marielle V; Godfrey, Keith M; Shuter, Borys; Kapur, Jeevesh; Rajadurai, Victor S; Agarwal, Pratibha; Chinnadurai, Amutha; Niduvaje, Krishnamoorthy; Chan, Yiong-Huak; Aris, Izzuddin Bin Mohd; Soh, Shu-E; Yap, Fabian; Saw, Seang-Mei; Kramer, Michael S; Gluckman, Peter D; Chong, Yap-Seng; Lee, Yung-Seng

    2016-05-01

    A susceptibility to metabolic diseases is associated with abdominal adipose tissue distribution and varies between ethnic groups. The distribution of abdominal adipose tissue at birth may give insights into whether ethnicity-associated variations in metabolic risk originate partly in utero. We assessed the influence of ethnicity on abdominal adipose tissue compartments in Asian neonates in the Growing Up in Singapore Toward Healthy Outcomes mother-offspring cohort. MRI was performed at ≤2 wk after birth in 333 neonates born at ≥34 wk of gestation and with birth weights ≥2000 g. Abdominal superficial subcutaneous tissue (sSAT), deep subcutaneous tissue (dSAT), and internal adipose tissue (IAT) compartment volumes (absolute and as a percentage of the total abdominal volume) were quantified. In multivariate analyses that were controlled for sex, age, and parity, the absolute and percentage of dSAT and the percentage of sSAT (but not absolute sSAT) were greater, whereas absolute IAT (but not the percentage of IAT) was lower, in Indian neonates than in Chinese neonates. Compared with Chinese neonates, Malay neonates had greater percentages of sSAT and dSAT but similar percentages of IAT. Marginal structural model analyses largely confirmed the results on the basis of volume percentages with controlled direct effects of ethnicity on abdominal adipose tissue; dSAT was significantly greater (1.45 mL; 95% CI: 0.49, 2.41 mL, P = 0.003) in non-Chinese (Indian or Malay) neonates than in Chinese neonates. However, ethnic differences in sSAT and IAT were NS [3.06 mL (95% CI:-0.27, 6.39 mL; P = 0.0712) for sSAT and -1.30 mL (95% CI: -2.64, 0.04 mL; P = 0.057) for IAT in non-Chinese compared with Chinese neonates, respectively]. Indian and Malay neonates have a greater dSAT volume than do Chinese neonates. This finding supports the notion that in utero influences may contribute to higher cardiometabolic risk observed in Indian and Malay persons in our population. If such

  12. Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs : a blind, randomized, placebo-controlled study

    OpenAIRE

    Maina, Elisa; Pelst, Michael; Hesta, Myriam; Cox, Eric

    2017-01-01

    Background: Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healt...

  13. Fusidic acid suspension twice daily: a new treatment schedule for skin and soft tissue infection in children, with improved tolerability.

    Science.gov (United States)

    Török, Eva; Somogyi, Tihamér; Rutkai, Krisztina; Iglesias, Luis; Bielsa, Isabel

    2004-06-01

    This multicentre, randomized, double-blind, parallel group study aimed to compare a new regimen of fusidic acid suspension against a standard regimen in children with skin and soft tissue infections. Treatment groups were given either a new regimen of fusidic acid suspension (20 mg/kg divided b.i.d.) or a standard regimen (50 mg/kg divided t.i.d.), which were administered for 5 days in both groups and for a further 5 days if evidence of infection persisted. Assessment of those cured was carried out 14 days. Both regimens were effective. Cure was achieved in 194 (91.1%) of the 213 children given the new b.i.d. dosage and for 194 (89.4%) of the 217 children given the standard t.i.d. dosage (intention-to-treat population; p=0.72). Cure was maintained at the follow-up assessment for 94.8% (181 of 191) and 95.7% (180 of 188), respectively, of the children. Bacteriological cure of infections due to fusidic acid susceptible Staphylococcus aureus and/or group A beta-haemolytic streptococci, with elimination of pathogens, was achieved in all 121 (100%) children treated with the new b.i.d. regimen and in 123 (99.2%) of the 124 children treated with the standard TID regimen. The new twice-daily regimen had significantly better tolerance (p=0.025).

  14. A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers : A Double-Blind Sham-Controlled Crossover Study

    NARCIS (Netherlands)

    Kortekaas, R.; van Nierop, L.E.; Baas, V.G.; Konopka, K.H.; Harbers, M.; van der Hoeven, J.H.; van Wijhe, M.; Aleman, A.; Maurits, N.M.

    2013-01-01

    The 'complex neural pulse'(TM) (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a

  15. Intake of St John's wort improves the glucose tolerance in healthy subjects who ingest metformin compared with metformin alone

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Pedersen, Rasmus Steen; Damkier, Per

    2015-01-01

    AIMS: Our objective was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St John's wort and the antidiabetic drug metformin. METHODS: We performed an open cross-over study in 20 healthy male subjects, who received 1 g...

  16. Review of the efficacy and tolerability of the diclofenac epolamine topical patch 1.3% in patients with acute pain due to soft tissue injuries.

    Science.gov (United States)

    Kuehl, Kerry S

    2010-06-01

    The diclofenac epolamine topical patch 1.3% (DETP) was approved by the US Food and Drug Administration in January 2007 for the treatment of soft tissue injuries such as strains, sprains, and contusions, although it has been available for many years in >40 countries worldwide. The aim of this study was to review the efficacy and tolerability of the DETP in relieving acute pain caused by soft tissue injuries. The MEDLINE, Derwent Drug File, BIOSIS, and EMBASE databases were searched for literature published between 1984 and October 30, 2009, in any language, using the terms diclofenac epolamine patch, diclofenac hydroxyethylpyrrolidine patch, and FLECTOR Patch. Clinical studies of the efficacy and/or tolerability of the DETP in patients with acute pain due to soft tissue injuries or localized periarticular disorders were included. Efficacy studies that enrolled patients with other medical conditions were excluded, except for reports that focused on tolerability, which were included to supplement tolerability data. The bibliographies of included studies were reviewed manually for relevant articles based on inclusion and exclusion criteria, and the manufacturer was contacted for additional relevant postmarketing surveillance information and presentations from scientific meetings. The search identified 6 placebo-controlled clinical studies, 1 active-comparator-controlled clinical study, and 1 open-label comparator clinical study of the efficacy and tolerability of the DETP in patients with soft tissue injuries. Three studies reported on tolerability. Primary analyses among the 8 studies reported DETP-associated reductions in spontaneous pain from baseline, assessed using a visual analog scale, ranging from 26% to 88% on day 7 and 56% to 61% on day 14. The use of the DETP was associated with significantly greater reductions in pain scores compared with a placebo patch (2 studies) on day 7 (88% vs 74%; P = 0.001) and day 14 (56.5% vs 46.8%; P = 0.001) and compared with

  17. Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage.

    Directory of Open Access Journals (Sweden)

    Amilton M Fernandes

    Full Text Available Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM derived mesenchymal stem cells (MSCs from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin, ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.

  18. Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women.

    Science.gov (United States)

    Sieuwerts, Anieta M; De Napoli, Giuseppina; van Galen, Anne; Kloosterboer, Helenius J; de Weerd, Vanja; Zhang, Hong; Martens, John W M; Foekens, John A; De Geyter, Christian

    2011-12-01

    Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer-related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg norethisterone acetate [E2+NETA], 2.5mg tibolone [T] or [no HRT]. Except for [E2], which was only given to women after hysterectomy, the allocation to each of the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs putatively involved in breast cancer was prospectively determined in the biopsies of 6 women receiving [no HRT], 5 women receiving [E2], 5 women receiving [E2+NETA], and 6 receiving [T]. Using epithelial and endothelial markers genes, non-representative biopsies from 11 women were eliminated. Treatment of postmenopausal women with [E2+NETA] resulted in the highest number of differentially (pbreast tissue with a change in the expression of genes putatively involved in breast cancer. Our data suggest that normal mammary cells triggered by [E2+NETA] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. This feasibility study provides the basis for whole genome analyses to identify novel markers involved in increased breast cancer risk. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Noh, Yook-Hwan; Jin, Seok-Joon; Kim, Yo Han; Kim, Mi-Jo; Sung, Hyeryoung; Jang, Seong Bok; Lee, Sung Jae; Bae, Kyun-Seop; Lim, Hyeong-Seok

    2012-09-01

    To date, no definitive treatment of functional dyspepsia (FD) has been proven to be effective and reasonably well-tolerated. Proton pump inhibitors (PPIs) combined with prokinetic agents are considered an effective option. Revaprazan is a selective potassium-competitive acid blocker that reversibly inhibits gastric H(+)/K(+)-ATPase and shows effective acid suppression comparable to PPIs. Itopride is a prokinetic agent that has anticholinesterase activity as well as dopamine D(2) receptor antagonistic activity. For this reason, revaprazan and itopride have been prescribed for FD; however, no available studies have reported the pharmacokinetic interactions of these 2 drugs. The objective of this study was to compare the bioavailability and tolerability of revaprazan and itopride combination therapy to those of equally dosed monotherapies to acquire basic drug-drug interaction information about revaprazan. This multiple-dose, randomized crossover study was conducted in healthy male Korean subjects. Subjects received, in randomized sequence, a 7-day oral dose of revaprazan 200 mg once daily, itopride 50 mg TID, or both. Each treatment period was separated by a 7-day washout period. Blood samples were collected for up to 24 hours following the last dose at steady state, and drug concentrations were determined using validated LC/MS-MS. Pharmacokinetic properties were obtained using noncompartmental analysis. Drug tolerability was assessed throughout the study, using measurements of vital signs, clinical chemistry testing, and interviews. A total of 30 subjects were enrolled in the study. Among them, 28 subjects completed revaprazan treatment, and 27 completed the study (3 subjects were withdrawn). The geometric mean ratios (GMRs) (90% CI) of C(max,ss), and AUC(τ,ss) with revaprazan were 0.92 (0.84-1.00) and 0.96 (0.89-1.03), respectively. The GMRs of C(max,ss) and AUC(τ,ss) with itopride were 1.07 (0.96-1.20) and 1.12 (1.06-1.18), respectively. A total of 15 adverse

  20. Stem Cell Metabolism in Cancer and Healthy Tissues: Pyruvate in the Limelight

    Directory of Open Access Journals (Sweden)

    Cyril Corbet

    2018-01-01

    Full Text Available Normal and cancer stem cells (CSCs share the remarkable potential to self-renew and differentiate into many distinct cell types. Although most of the stem cells remain under quiescence to maintain their undifferentiated state, they can also undergo cell divisions as required to regulate tissue homeostasis. There is now a growing evidence that cell fate determination from stem cells implies a fine-tuned regulation of their energy balance and metabolic status. Stem cells can shift their metabolic substrate utilization, between glycolysis and mitochondrial oxidative metabolism, during specification and/or differentiation, as well as in order to adapt their microenvironmental niche. Pyruvate appears as a key metabolite since it is at the crossroads of cytoplasmic glycolysis and mitochondrial oxidative phosphorylation. This Review describes how metabolic reprogramming, focusing on pyruvate utilization, drives the fate of normal and CSCs by modulating their capacity for self-renewal, clonal expansion/differentiation, as well as metastatic potential and treatment resistance in cancer. This Review also explores potential therapeutic strategies to restore or manipulate stem cell function through the use of small molecules targeting the pyruvate metabolism.

  1. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    International Nuclear Information System (INIS)

    Deman, Pierre; Vautrin, Mathias; Edouard, Magali; Stupar, Vasile; Bobyk, Laure; Farion, Régine; Elleaume, Hélène; Rémy, Chantal; Barbier, Emmanuel L.; Estève, François; Adam, Jean-François

    2012-01-01

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm 3 volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm 3 volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  2. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Deman, Pierre [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Vautrin, Mathias [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); DOSIsoft, Cachan (France); Edouard, Magali [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Stupar, Vasile [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Bobyk, Laure; Farion, Regine [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Elleaume, Helene [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Remy, Chantal; Barbier, Emmanuel L. [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Esteve, Francois [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Adam, Jean-Francois, E-mail: adam@esrf.fr [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France)

    2012-03-15

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  3. Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing.

    Science.gov (United States)

    Lendeckel, Derik; Eymann, Christine; Emicke, Philipp; Daeschlein, Georg; Darm, Katrin; O'Neil, Serena; Beule, Achim G; von Woedtke, Thomas; Völker, Uwe; Weltmann, Klaus-Dieter; Jünger, Michael; Hosemann, Werner; Scharf, Christian

    2015-01-01

    The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine.

  4. Normal tissue tolerance to external beam radiation therapy: The stomach; Dose de tolerance a l'irradiation des tissus sains: l'estomac

    Energy Technology Data Exchange (ETDEWEB)

    Oberdiac, P. [Service de radiotherapie, hopital de Bellevue, CHU de Saint-Etienne, 42 - Saint-Etienne (France); Mineur, L. [Unite d' oncologie digestive et radiotherapie, institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  5. Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects.

    Science.gov (United States)

    Treanor, John; Nolan, Carrie; O'Brien, Diane; Burt, David; Lowell, George; Linden, Janine; Fries, Louis

    2006-01-16

    Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.

  6. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects.

    Science.gov (United States)

    la Porte, Charles; Voduc, Nha; Zhang, Guijun; Seguin, Isabelle; Tardiff, Danielle; Singhal, Neera; Cameron, D William

    2010-07-01

    Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol). This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels. Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.

  7. Safety and tolerability of a cell culture derived trivalent subunit inactivated influenza vaccine administered to healthy children and adolescents: A Phase III, randomized, multicenter, observer-blind study.

    Science.gov (United States)

    Nolan, Terry; Chotpitayasunondh, Tawee; Capeding, Maria Rosario; Carson, Simon; Senders, Shelly David; Jaehnig, Peter; de Rooij, Richard; Chandra, Richa

    2016-01-04

    Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictability of production to meet global demand. This study compared the safety and tolerability of TIVc with an egg-derived trivalent influenza vaccine (TIVf) in 4-17 yearolds. A Phase 3 observer blind, multicenter study enrolled 2055 healthy participants randomized 2:1 to receive either TIVc or TIVf, respectively (1372 TIVc and 683 TIVf evaluable subjects). Participants received one dose each on Days 1 and 28 (4-8 year-olds not previously vaccinated [NPV]) or one dose on Day 1 (4-8 and 9-17 yearolds previously vaccinated [PV]). Solicited adverse events (AEs) occurring within 7 days after each vaccination were assessed; participants were followed up for 6 months after their last dose for safety. Most solicited and unsolicited AEs were mild to moderate with vaccine-related SAEs were reported. TIVc and TIVf were similar in percentages of participants reporting solicited reactions in 4-8 years NPV group after the 1st dose: local reactions, TIVc: 48%, TIVf: 43%; systemic reactions, TIVc: 34%, TIVf: 32%; percentages were lower following the 2nd dose in TIVc; local reactions: TIVc: 40%; TIVf: 43%; systemic reactions: TIVc: 21%; TIVf: 22%. In 4-17 years PV group, solicited reactions were lower following TIVf, local reactions: TIVc: 53%; TIVf: 43%; systemic reactions: TIVc: 37%, TIVf: 30%. Injection-site pain was the most common solicited reaction, and was similar following TIVc and TIVf in 4-8 yearolds (TIVc: 56%; TIVf: 55%), and lower following TIVf in 9-17 years group (TIVc: 52%; TIVf: 42%). Reporting of unsolicited AEs was similar for TIVc and TIVf across the two age groups. TIVc was well tolerated and had a safety and reactogenicity profile similar to that of TIVf in healthy 4-17 yearolds (NCT01857206). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats

    Directory of Open Access Journals (Sweden)

    Karolline S. da Silva

    2017-09-01

    Full Text Available Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin in healthy rats, associated or not with N-acetylcysteine (NAC treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization.Methods: Male Wistar rats were intraperitoneally injected with control (C or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML and pyrraline (PYR were determined by LC/mass spectrometry (LC-MS/MS and ELISA.Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups.Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE

  9. The association of SNPs in Hsp90β gene 5' flanking region with thermo tolerance traits and tissue mRNA expression in two chicken breeds.

    Science.gov (United States)

    Chen, Zhuo-Yu; Gan, Jian-Kang; Xiao, Xiong; Jiang, Li-Yan; Zhang, Xi-Quan; Luo, Qing-Bin

    2013-09-01

    Thermo stress induces heat shock proteins (HSPs) expression and HSP90 family is one of them that has been reported to involve in cellular protection against heat stress. But whether there is any association of genetic variation in the Hsp90β gene in chicken with thermo tolerance is still unknown. Direct sequencing was used to detect possible SNPs in Hsp90β gene 5' flanking region in 3 chicken breeds (n = 663). Six mutations, among which 2 SNPs were chosen and genotypes were analyzed with PCR-RFLP method, were found in Hsp90β gene in these 3 chicken breeds. Association analysis indicated that SNP of C.-141G>A in the 5' flanking region of the Hsp90β gene in chicken had some effect on thermo tolerance traits, which may be a potential molecular marker of thermo tolerance, and the genotype GG was the thermo tolerance genotype. Hsp90β gene mRNA expression in different tissues detected by quantitative real-time PCR assay were demonstrated to be tissue dependent, implying that different tissues have distinct sensibilities to thermo stress. Besides, it was shown time specific and varieties differences. The expression of Hsp90β mRNA in Lingshan chickens in some tissues including heart, liver, brain and spleen were significantly higher or lower than that of White Recessive Rock (WRR). In this study, we presume that these mutations could be used in marker assisted selection for anti-heat stress chickens in our breeding program, and WRR were vulnerable to tropical thermo stress whereas Lingshan chickens were well adapted.

  10. Ageing and chronic intermittent hypoxia mimicking sleep apnea do not modify local brain tissue stiffness in healthy mice.

    Science.gov (United States)

    Jorba, Ignasi; Menal, Maria José; Torres, Marta; Gozal, David; Piñol-Ripoll, Gerard; Colell, Anna; Montserrat, Josep M; Navajas, Daniel; Farré, Ramon; Almendros, Isaac

    2017-07-01

    Recent evidence suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer´s disease (AD), with the latter promoting alterations in brain tissue stiffness, a feature of ageing. Here, we assessed the effects of age and intermittent hypoxia (IH) on brain tissue stiffness in a mouse model of OSA. Two-month-old and 18-month-old mice (N=10 each) were subjected to IH (20% O 2 40s - 6% O 2 20s) for 8 weeks (6h/day). Corresponding control groups for each age were kept under normoxic conditions in room air (RA). After sacrifice, the brain was excised and 200-micron coronal slices were cut with a vibratome. Local stiffness of the cortex and hippocampus were assessed in brain slices placed in an Atomic Force Microscope. For both brain regions, the Young's modulus (E) in each animal was computed as the average values from 9 force-indentation curves. Cortex E mean (±SE) values were 442±122Pa (RA) and 455±120 (IH) for young mice and 433±44 (RA) and 405±101 (IH) for old mice. Hippocampal E values were 376±62 (RA) and 474±94 (IH) for young mice and 486±93 (RA) and 521±210 (IH) for old mice. For both cortex and hippocampus, 2-way ANOVA indicated no statistically significant effects of age or challenge (IH vs. RA) on E values. Thus, neither chronic IH mimicking OSA nor ageing up to late middle age appear to modify local brain tissue stiffness in otherwise healthy mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: a phase I clinical trial.

    Science.gov (United States)

    Smilowitz, Jennifer T; Moya, Jackelyn; Breck, Melissa A; Cook, Chelsea; Fineberg, Annette; Angkustsiri, Kathleen; Underwood, Mark A

    2017-05-30

    Historically, bifidobacteria were the dominant intestinal bacteria in breastfed infants. Still abundant in infants in developing nations, levels of intestinal bifidobacteria are low among infants in developed nations. Recent studies have described an intimate relationship between human milk and a specific subspecies of Bifidobacterium, B. longum subsp. infantis (B. infantis), yet supplementation of breastfed, healthy, term infants with this organism, has not been reported. The IMPRINT Study, a Phase I clinical trial, was initiated to determine the safety and tolerability of supplementing breastfed infants with B. infantis (EVC001). Eighty mother-infant dyads were enrolled in either lactation support plus B. infantis supplementation (BiLS) or lactation support alone (LS). Starting with Day 7 postnatal, BiLS infants were fed 1.8-2.8 × 10 10  CFU B. infantis EVC001 daily in breast milk for 21 days. Mothers collected fecal samples, filled out health questionnaires, and kept daily logs about their infants' feeding and gastrointestinal symptoms from birth until Day 61 postnatal. Safety and tolerability were determined from maternal reports. There were no differences in the mean gestational age at birth, weight 1 and 2 months postnatal, and breast milk intake between groups. The mean Log 10 change in fecal Bifidobacterium from Day 6 to Day 28 was higher (p = 0.0002) for BiLS (6.6 ± 2.8 SD) than for LS infants (3.5 ± 3.5 SD). Daily stool number was higher (p jaundice, number of illnesses, sick doctor visits, or diagnoses of eczema were different for the groups at any point. The B. infantis EVC001 supplement was safely consumed and well-tolerated. Stools were fewer and better formed in infants in the BiLS group compared with LS group. Adverse events were those expected in healthy infants and not different between groups. ClinicalTrials.gov NCT02457338 . Registered May 27, 2015.

  12. Higher Ratio of Abdominal Subcutaneous to Visceral Adipose Tissue Related with Preservation of Islet β-Cell Function in Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Juan Liu

    2017-01-01

    Full Text Available Objective. To investigate the relationship between abdominal adipose tissue distribution, β-cell function, and insulin sensitivity (IS in a Chinese population. Methods. One hundred and eighty-eight healthy subjects (healthy group, 239 with normal glucose, and 1~4 abnormal metabolic traits (metabolic dysfunction group, MD group and 125 with hyperglycemia (hyperglycemia group were studied. HOMA-IR, HOMA-B, Matsuda index, early- (I0–30/G0–30 and late-phase (I30–120/G30–120 insulin responses and the corresponding disposition indexes (DI were calculated. The area of abdominal subcutaneous adipose tissue (ASAT and visceral adipose tissue (VAT was measured and the ratio of ASAT to VAT (SVR was calculated. Results. SVR was correlated positively with Matsuda index in healthy, MD, and hyperglycemia groups, and inversely with HOMA-IR. SVR positively related with both early- and late-phase DI in the healthy group only. In the healthy group, the hyperbolas of I0–30/G0–30 and I30–120/G30–120 versus Matsuda index in the highest quarter of SVR were significantly right shifted compared to those in the lowest (both P<0.05. Conclusions. In healthy adults, higher SVR was a protective factor for β-cell function and IS, while in those with glucometabolic abnormality, higher SVR contributed to a relative better IS, indicating SVR is possible to be an early predicator of type 2 diabetes development.

  13. Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome

    DEFF Research Database (Denmark)

    Leder, Lena; Kolehmainen, Marjukka; Narverud, Ingunn

    2016-01-01

    BACKGROUND: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism......-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. METHODS: A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study......, and the mRNA gene expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. RESULTS: The healthy ND significantly down-regulated the expression...

  14. A novel magnetic stimulator increases experimental pain tolerance in healthy volunteers - a double-blind sham-controlled crossover study.

    Directory of Open Access Journals (Sweden)

    Rudie Kortekaas

    Full Text Available UNLABELLED: The 'complex neural pulse'(TM (CNP is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF. A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. TRIAL REGISTRATION: Dutch Cochrane Centre NTR1093.

  15. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

    Science.gov (United States)

    Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

    2015-01-01

    In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin

  16. Waterlogging tolerance, tissue nitrogen and oxygen transport in the forage legume Melilotus siculus: a comparison of nodulated and nitrate-fed plants.

    Science.gov (United States)

    Konnerup, Dennis; Toro, Guillermo; Pedersen, Ole; Colmer, Timothy David

    2018-03-14

    Soil waterlogging adversely impacts most plants. Melilotus siculus is a waterlogging-tolerant annual forage legume, but data were lacking for the effects of root-zone hypoxia on nodulated plants reliant on N2 fixation. The aim was to compare the waterlogging tolerance and physiology of M. siculus reliant on N2 fixation or with access to NO3-. A factorial experiment imposed treatments of water level (drained or waterlogged), rhizobia (nil or inoculated) and mineral N supply (nil or 11 mm NO3-) for 21 d on plants in pots of vermiculite in a glasshouse. Nodulation, shoot and root growth and tissue N were determined. Porosity (gas volume per unit tissue volume) and respiration rates of root tissues and nodules, and O2 microelectrode profiling across nodules, were measured in a second experiment. Plants inoculated with the appropriate rhizobia, Ensifer (syn. Sinorhizobium) medicae, formed nodules. Nodulated plants grew as well as plants fed NO3-, both in drained and waterlogged conditions. The growth and total N content of nodulated plants (without any NO3- supplied) indicated N2 fixation. Respiration rates (mass basis) were highest in nodules and root tips and lowest in basal root tissues. Secondary aerenchyma (phellem) formed along basal root parts and a thin layer of this porous tissue also covered nodules, which together enhanced gas-phase diffusion of O2 to the nodules; O2 was below detection within the infected zone of the nodule interior. Melilotus siculus reliant on N2 fixation grew well both in drained and waterlogged conditions, and had similar tissue N concentrations. In waterlogged conditions the relatively high respiration rates of nodules must rely on O2 movement via the aerenchymatous phellem in hypocotyl, roots and the outer tissue layers of nodules.

  17. Tumor development in field-cancerized tissue is inhibited by a double application of Boron neutron capture therapy (BNCT) without exceeding radio-tolerance

    International Nuclear Information System (INIS)

    Monti Hughes, Andrea; Heber, Elisa M.; Itoiz, Maria E.; Molinari, Ana J.; Garabalino, Marcela A.; Trivillin, Veronica A.; Schwint, Amanda E.; Aromando, Romina F.

    2009-01-01

    Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of a 'single' application of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-1(Na 2 10 B 10 H 10 ) or (GB-10+BPA) to treat hamster cheek pouch tumors with no normal tissue radiotoxicity. Based on these results, we developed a model of precancerous tissue in the hamster cheek pouch for long-term studies. Employing this model we evaluated the long-term potential inhibitory effect on the development of second primary tumors from precancerous tissue and eventual radiotoxicity of a single application of BNCT mediated by BPA, GB-10 or (GB-10+BPA), in the RA-6. The clinical rationale of this study was to search for a BNCT protocol that is therapeutic for tumor, not radio-toxic for the normal tissue that lies in the neutron beam path, and exerts the desired inhibitory effect on the development of second primary tumors, without exceeding the radio-tolerance of precancerous tissue, the dose limiting tissue in this case. Second primary tumors that arise in precancerous tissue (also called locoregional recurrences) are a frequent cause of therapeutic failure in head and neck tumors. Aim: Evaluate the radiotoxicity and inhibitory effect of a 'double' application of the same BNCT protocols that were proved therapeutically successful for tumor and precancerous tissue, with a long term follow up (8 months). A 'double' application of BNCT is a potentially useful strategy for the treatment of tumors, in particular the larger ones, but the cost in terms of side-effects in dose-limiting tissues might preclude its application and requires cautious evaluation. Materials and methods: We performed a double application of 1) BPA-BNCT; 2) (GB

  18. Radioimmunoassay of human calcitonin in serum and tissue from healthy individuals and patients with medullary carcinoma of the thyroid gland

    International Nuclear Information System (INIS)

    Gautvik, K.M.; Normann, T.; Teig, V.; Wille, S.Oe.; Brennhovd, I.O.; Christensen, I.

    1976-01-01

    A specific radioimmunological method for measurement of immunoreactive calcitonin (iCT) in human serum and tissue is described. Of healthy individuals of both sexes, 85 % had measurable iCT in serum (mean, 0.23 ng/ml). Of 29 patients who had received treatment for medullary carcinoma of the thyroid gland (MCT), 19 had increased serum iCT (0-60 ng/ml to205 ng/ml). Elevated serum iCT was also found preoperatively in 2 MCT patients. Eleven of the patients with abnormal elevations of serum iCT were alive 4 to 13 years after the operation. Concentration of iCT in extracts from MCT varied from 0.5 to 540 ng/ml wet weight. The diagnostic value of this method and its importance for pre- and post-operative evaluation of these patients are improved by the use of selective venous catheterization in basal state and during stimulation of CT secretion. (Auth.)

  19. Dosimetric Comparison of Simulated Human Eye And Water Phantom in Investigation of Iodine Source Effects on Tumour And Healthy Tissues

    International Nuclear Information System (INIS)

    Sadi, A.S.; Masoudi, F.S. K.N.Toosi University of Technology

    2011-01-01

    For better clinical analysis in ophthalmic brachytherapy dosimetry, there is a need for the dose determination in different parts of the eye, so simulating the eye and defining the material of any parts of that, is helpful for better investigating dosimetry in human eye. However in brachytherapy dosimetry, it is common to consider the water phantom as human eye globe. In this work, a full human eye is simulated with MCNP-4C code by considering all parts of the eye like; lens, cornea, retina, choroid, sclera, anterior chamber, optic nerve, bulk of the eye comprising vitreous body and tumour. The average dose in different parts of this full model of human eye is determined and the results are compared with the dose calculated in water phantom. The central axes depth dose and the dose in whole of the tumour for these two simulated eye model are calculated too, and the results are compared. At long last, as the aim of this work is comparing the result of investigating dosimetry between two water phantom as human eye and simulated eye globe, the ratios of the absorbed dose by the healthy tissues to the absorbed dose by the tumour are calculated in these simulations and the comparison between results is done eventually.

  20. No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses.

    Directory of Open Access Journals (Sweden)

    Patricia L Hibberd

    Full Text Available Although Lactobacillus rhamnosus GG ATCC 53103 (LGG has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly.The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines.Fifteen elderly volunteers, aged 66-80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions.There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1-7 per volunteer, 39 (83% of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70% of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea, 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038 while there was no difference in other pro- or anti-inflammatory plasma cytokines.Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older.ClinicalTrials.gov NCT 01274598.

  1. [Observation on changes of oxygen partial pressure in the deep tissues along the large intestine meridian during acupuncture in healthy subjects].

    Science.gov (United States)

    Chen, Ming; Hu, Xiang-long; Wu, Zu-xing

    2010-06-01

    To observe changes of the partial oxygen pressure in the deep tissues along the Large Intestine Meridian (LIM) during acupuncture stimulation, so as to reveal the characteristics of energy metabolism in the tissues along the LIM. Thirty-one healthy volunteer subjects were enlisted in the present study. Partial oxygen pressure (POP) in the tissues (at a depth of about 1.5 cm) of acupoints Binao (LI 14), Shouwuli (LI 13), Shousanli (LI 10), 2 non-acupoints [the midpoints between Quchi (LI 11) and LI 14, and between Yangxi (LI 5) and LI 11) of the LIM, and 10 non-meridian points, 1.5-2.0 cm lateral and medial to each of the tested points of the LIM was detected before, during and after electroacupuncture (EA) stimulation of Hegu (LI 4) by using a tissue oxygen tension needle-like sensor. In normal condition, the POP values in the deep tissues along the LIM were significantly higher than those of the non-meridian control points on its bilateral sides. During and after EA of Hegu (LI 4), the POP levels decreased significantly in the deep tissues along the LIM in comparison with pre-EA (P 0.05). POP is significantly higher in the deep tissues along the LIM of healthy subjects under normal conditions, which can be downregulated by EA of Hegu (LI 4), suggesting an increase of both the utilization rate of oxygen and energy metabolism after EA.

  2. Differentiation between healthy thyroid remnants and tumor tissue after radioiodine therapy in patients with differentiated thyroid carcinoma using in-vitro phosphorus-31 magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Moka, D.; Dietlein, M.; Schicha, H.; Raffelt, K.; Hahn, J.

    2002-01-01

    Full text: In many tumors, tumor growth and spread is triggered by changes in cell membrane metabolism, which can lead to systemic alterations in levels of phospholipids. The aim of this study was to differentiate between healthy remnants of thyroid tissue and residual/recurrent tumor tissue or metastases in patients with thyroid carcinoma by measurement of plasma levels of various phospholipids. Phospholipid concentrations was measured by in-vitro phosphorus-31-magnetic resonance spectroscopy ( 31 P-MRS) in blood samples from 30 patients with thyroid cancer, who had been rendered hypothyroid in preparation for diagnostic/therapeutic administration of iodine-131. All patients were already thyroidectomized. 131 I-whole-body scintigraphy and measurements of thyroglobulin values in a 2-year-follow-up were used to distinguish between patients in remission, patients with only healthy thyroid remnants and patients with cancerous thyroid tissue and/or metastases. Significantly lower blood plasma levels of systemic sphingomyelin (0.33±0.06 vs. 0.46±0.03 (controls) mmol/l; p 31 P-MRS can be used to differentiate between the presence of tumor tissue, healthy remnants of thyroid tissue not requiring further treatment and remission in patients with thyroid cancer. In future, therefore, plasma 31 P-MRS could be developed as an additional diagnostic tool for the follow-up of differentiated thyroid cancer. (author)

  3. Influence of length of interval between pulses in PDR brachytherapy (PDRBT on value of Biologically Equivalent Dose (BED in healthy tissues

    Directory of Open Access Journals (Sweden)

    Tomasz Piotrowski

    2010-07-01

    Full Text Available Purpose: Different PDR treatment schemas are used in clinical practice, however optimal length of interval between pulses still remains unclear. The aim of this work was to compare value of BED doses measured in surrounded healthy tissues according to different intervals between pulses in PDRBT. Influence of doses optimization on BED values was analyzed.Material and methods: Fifty-one patients treated in Greater Poland Cancer Centre were qualified for calculations.Calculations of doses were made in 51 patients with head and neck cancer, brain tumor, breast cancer, sarcoma, penis cancer and rectal cancer. Doses were calculated with the use of PLATO planning system in chosen critical points in surrounded healthy tissues. For all treatment plans the doses were compared using Biologically Equivalent Dose formula.Three interval lengths (1, 2 and 4 hours between pulses were chosen for calculations. For statistical analysis Friedman ANOVA test and Kendall ratio were used.Results: The median value of BED in chosen critical points in healthy tissues was statistically related to the length of interval between PDR pulses and decreased exponentially with 1 hour interval to 4 hours (Kendall = from 0.48 to 1.0; p = from 0.002 to 0.00001.Conclusions: Prolongation of intervals between pulses in PDR brachytherapy was connected with lower values of BED doses in healthy tissues. It seems that longer intervals between pulses reduced the risk of late complications, but also decreased the tumour control. Furthermore, optimization influenced the increase of doses in healthy tissues.

  4. Normal tissue tolerance to external beam radiation therapy: Esophagus; Dose de tolerance a l'irradiation des tissus sains: l'oesophage

    Energy Technology Data Exchange (ETDEWEB)

    Bera, G.; Pointreau, Y. [Clinique d' oncologie-radiotherapie, centre Henry-S.-Kaplan, hopital Bretonneau, CHU de Tours, 37 - Tours (France); Denis, F.; Dupuis, O. [Centre Jean-Bernard, clinique Victor-Hugo, 72 - Le-Mans (France); Orain, I. [Service d' anatomie et cytologie pathologiques, hopital Trousseau, CHU de Tours, 37 - Tours (France); Crehange, G. [Departement de radiotherapie, centre Georges-Francois-Leclerc, 21 - Dijon (France)

    2010-07-15

    The esophagus is a musculo-membranous tube through which food passes from the pharynx to the stomach. Due to its anatomical location, it can be exposed to ionizing radiation in many external radiotherapy indications. Radiation-induced esophageal mucositis is clinically revealed by dysphagia and odynophagia, and usually begins 3 to 4 weeks after the start of radiation treatment. With the rise of multimodality treatments (e.g., concurrent chemoradiotherapy, dose escalation and accelerated fractionation schemes), esophageal toxicity has become a significant dose-limiting issue. Understanding the predictive factors of esophageal injury may improve the optimal delivery of treatment plans. It may help to minimize the risks, hence increasing the therapeutic ratio. Based on a large literature review, our study describes both early and late radiation-induced esophageal injuries and highlights some of the predictive factors for cervical and thoracic esophagus toxicity. These clinical and dosimetric parameters are numerous but none is consensual. The large number of dosimetric parameters strengthens the need of an overall analysis of the dose/volume histograms. The data provided is insufficient to recommend their routine use to prevent radiation-induced esophagitis. Defining guidelines for the tolerance of the esophagus to ionizing radiation remains essential for a safe and efficient treatment. (authors)

  5. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics

    Directory of Open Access Journals (Sweden)

    Qi Li

    2016-06-01

    Full Text Available Hyperlipidemia (HLP is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05 during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05 in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP.

  6. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  7. Knockout of Vasohibin-1 Gene in Mice Results in Healthy Longevity with Reduced Expression of Insulin Receptor, Insulin Receptor Substrate 1, and Insulin Receptor Substrate 2 in Their White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Eichi Takeda

    2017-01-01

    Full Text Available Vasohibin-1 (Vash1, originally isolated as an endothelium-derived angiogenesis inhibitor, has a characteristic of promoting stress tolerance in endothelial cells (ECs. We therefore speculated that the lack of the vash1 gene would result in a short lifespan. However, to our surprise, vash1−/− mice lived significantly longer with a milder senescence phenotype than wild-type (WT mice. We sought the cause of this healthy longevity and found that vash1−/− mice exhibited mild insulin resistance along with reduced expression of the insulin receptor (insr, insulin receptor substrate 1 (irs-1, and insulin receptor substrate 2 (irs-2 in their white adipose tissue (WAT but not in their liver or skeletal muscle. The expression of vash1 dominated in the WAT among those 3 organs. Importantly, vash1−/− mice did not develop diabetes even when fed a high-fat diet. These results indicate that the expression of vash1 was required for the normal insulin sensitivity of the WAT and that the target molecules for this activity were insr, irs1, and irs2. The lack of vash1 caused mild insulin resistance without the outbreak of overt diabetes and might contribute to healthy longevity.

  8. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

    Directory of Open Access Journals (Sweden)

    Park SI

    2015-02-01

    Full Text Available Sang-In Park,1,* Howard Lee,1,2,* Jaeseong Oh,1 Kyoung Soo Lim,3 In-Jin Jang,1 Jeong-Ae Kim,4 Jong Hyuk Jung,4 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Clinical Trials Center, Seoul National University Hospital, Seoul, 3Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, 4LG Life Sciences, Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Background: In type 2 diabetes mellitus, fixed-dose combination (FDC can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD, pharmacokinetic (PK, and tolerability profiles of gemigliptin and extended-release metformin (metformin XR between FDC and separate tablets.Methods: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1 and metformin XR (500 mg ×2 were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4 activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs of FDC to separate tablet formulations and their 90% confidence intervals (CIs were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study.Results: The plasma DPP-4 activity

  9. Comparison of the antiseptic efficacy of tissue-tolerable plasma and an octenidine hydrochloride-based wound antiseptic on human skin.

    Science.gov (United States)

    Lademann, J; Richter, H; Schanzer, S; Patzelt, A; Thiede, G; Kramer, A; Weltmann, K-D; Hartmann, B; Lange-Asschenfeldt, B

    2012-01-01

    Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area. Copyright © 2012 S. Karger AG, Basel.

  10. Environmental interaction, additive and non-additive genetic variability is involved in the expression of tissue and whole-plant heat tolerance in upland cotton (Gossypium hirsutum. L

    Directory of Open Access Journals (Sweden)

    Hafeez-ur-Rahman

    2006-01-01

    Full Text Available Heat tolerance is measured at tissue level by cellular membrane thermostability (CMT and at the whole plant level by the heat tolerance index (HTI. Eight upland cotton cultivars and 15 crosses were used to determine the type and extent of genetic variability associated with the expression of these traits between and within environments. Heat stress and non-stress conditions were used as the CMT environments and years for HTI. The wide variation in heterotic expression and combining ability effects observed for CMT and HTI suggest multigenic inheritance of these traits. Significant genetic variability across environments was evident but the traits were not highly heritable because of substantial environmental interaction. The available genetic variability included both additive and non-additive components, but the proportion of additive genetic variability was high for HTI. The parental cultivars CRIS-19 and CIM-448 were good donor parents for high CMT under heat-stressed conditions, and MNH-552 and N-Karishma under non-stressed conditions. Cultivar FH-634 was a good donor parent for HTI. The results show two types of general combining ability (GCA inheritance among high CMT parents: positive GCA inheritance expressed by CRIS-19 in the presence of heat stress and MNH-552 and N-Karishma in the absence of heat stress; and negative GCA inheritance expressed by FH-900 in the presence of heat stress. It was also evident that genes controlling high CMT in cultivar CRIS-19 were different from those present in the MNH-552, N-Karishma and FH-900 cultivars. Similarly, among high HTI parents, FH-634 showed positive and CIM-443 negative GCA inheritance. No significant relationship due to genetic causes existed between tissue and whole plant heat tolerance, diminishing the likelihood of simultaneous improvement and selection of the two traits.

  11. Normal tissue tolerance to external beam radiation therapy: Adult bone; Dose de tolerance a l'irradiation des tissus sains: l'os chez l'adulte

    Energy Technology Data Exchange (ETDEWEB)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G. [Departement de radiotherapie, Centre regional de lutte contre le cancer, institut Bergonie, 33 - Bordeaux (France); Huchet, A. [Departement de radiotherapie, hopital Saint-Andre, 33 - Bordeaux (France); Italiano, A. [Service d' oncologie medicale, Centre regional de lutte contre le cancer, institut Bergonie, 33 - Bordeaux (France)

    2010-07-15

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  12. Is the macromolecule signal tissue-specific in healthy human brain? A (1)H MRS study at 7 Tesla in the occipital lobe.

    Science.gov (United States)

    Schaller, Benoît; Xin, Lijing; Gruetter, Rolf

    2014-10-01

    The macromolecule signal plays a key role in the precision and the accuracy of the metabolite quantification in short-TE (1) H MR spectroscopy. Macromolecules have been reported at 1.5 Tesla (T) to depend on the cerebral studied region and to be age specific. As metabolite concentrations vary locally, information about the profile of the macromolecule signal in different tissues may be of crucial importance. The aim of this study was to investigate, at 7T for healthy subjects, the neurochemical profile differences provided by macromolecule signal measured in two different tissues in the occipital lobe, predominantly composed of white matter tissue or of grey matter tissue. White matter-rich macromolecule signal was relatively lower than the gray matter-rich macromolecule signal from 1.5 to 1.8 ppm and from 2.3 to 2.5 ppm with mean difference over these regions of 7% and 12% (relative to the reference peak at 0.9 ppm), respectively. The neurochemical profiles, when using either of the two macromolecule signals, were similar for 11 reliably quantified metabolites (CRLB occipital lobe at 7T in healthy human brain. Copyright © 2013 Wiley Periodicals, Inc.

  13. Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues

    Directory of Open Access Journals (Sweden)

    Jenny Chun-Yee Ng

    2015-10-01

    Full Text Available Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA or coral tumors are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch’s postulates in efforts to understand the etiology and progression of SGA.

  14. Risk assessment tool for incontinence-associated dermatitis in elderly patients combining tissue tolerance and perineal environment predictors: a prospective clinical study

    Directory of Open Access Journals (Sweden)

    Ichikawa-Shigeta Y

    2014-10-01

    Full Text Available Yoshie Ichikawa-Shigeta,1 Hiromi Sanada,2 Chizuko Konya,3 Saldy Yusuf,1 Supriadi,1 Junko Sugama11Department of Clinical Nursing, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan; 2Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; 3Department of Adult Nursing, Kanazawa Medical University, Ishikawa, JapanBackground: Elderly patients with incontinence are at risk of developing incontinence-associated dermatitis (IAD. Although perineal risk factors of IAD have been identified, the contribution of tissue tolerance to IAD remains poorly understood.Objective: This study aimed to identify predictors of IAD development in three categories of potential risk factors: perineal environment, tissue tolerance, and toileting ability.Methods: This was a prospective clinical study, conducted at a long-term medical facility in Japan between November 2011 and April 2012. The subjects were elderly female patients with urine and/or fecal incontinence, and constantly wearing absorbent products. The patients were monitored during 42 days for the onset of IAD and the emergence of potential risk factors of IAD related to tissue tolerance (skin hydration status, maceration, erythema index [EI], etc, perineal environment (urination, stool properties, etc, and toileting ability (mobility and cognitive awareness. The risk factors were identified by univariate and multiple logistic regression analysis. Receiver operating characteristic (ROC curve analysis was conducted to evaluate the predictive validity of the risk factors.Results: Among the 46 patients enrolled, IAD developed in 25 (54.3%. The factors significantly associated with IAD development were loose or liquid stools (odds ratio [OR]: 20.612, 95% confidence interval [CI]: 1.118–379.852, P=0.042, malodorous urine (OR: 37.094, 95% CI: 3.480–395.399, P=0.003, and EI ≥46 (OR: 35.191, 95% CI: 5

  15. Comparative Analyses of Tomato yellow leaf curl virus C4 Protein-Interacting Host Proteins in Healthy and Infected Tomato Tissues

    Directory of Open Access Journals (Sweden)

    Namgyu Kim

    2016-10-01

    Full Text Available Tomato yellow leaf curl virus (TYLCV, a member of the genus Begomovirus, is one of the most important viruses of cultivated tomatoes worldwide, mainly causing yellowing and curling of leaves with stunting in plants. TYLCV causes severe problems in sub-tropical and tropical countries, as well as in Korea. However, the mechanism of TYLCV infection remains unclear, although the function of each viral component has been identified. TYLCV C4 codes for a small protein involved in various cellular functions, including symptom determination, gene silencing, viral movement, and induction of the plant defense response. In this study, through yeast-two hybrid screenings, we identified TYLCV C4-interacting host proteins from both healthy and symptom-exhibiting tomato tissues, to determine the role of TYLCV C4 proteins in the infection processes. Comparative analyses of 28 proteins from healthy tissues and 36 from infected tissues showing interactions with TYLCV C4 indicated that TYLCV C4 mainly interacts with host proteins involved in translation, ubiquitination, and plant defense, and most interacting proteins differed between the two tissues but belong to similar molecular functional categories. Four proteins—two ribosomal proteins, S-adenosyl-L-homocysteine hydrolase, and 14-3-3 family protein—were detected in both tissues. Furthermore, the identified proteins in symptom-exhibiting tissues showed greater involvement in plant defenses. Some are key regulators, such as receptor-like kinases and pathogenesis-related proteins, of plant defenses. Thus, TYLCV C4 may contribute to the suppression of host defense during TYLCV infection and be involved in ubiquitination for viral infection.

  16. Differentiation of healthy and malignant tissue in colon cancer patients using optical spectroscopy: A tool for image-guided surgery

    NARCIS (Netherlands)

    Langhout, G.C.; Spliethoff, Jarich; Schmitz, S.J.; Aalbers, A.G.J.; van Velthuysen, M.L.; Hendriks, B.H.W.; Ruers, Theo J.M.; Kuhlmann, K.F.D.

    2015-01-01

    Background Surgery for colorectal cancer aims for complete tumor resection. Optical-based techniques can identify tumor and surrounding tissue through the tissue specific optical properties, absorption and scattering, which are both influenced by the biochemical and morphological composition of the

  17. Oxygen Mapping within Healthy and Acutely Infarcted Brain Tissue in Humans Using the NMR Relaxation of Lipids: A Proof-Of-Concept Translational Study.

    Science.gov (United States)

    Colliez, Florence; Safronova, Marta M; Magat, Julie; Joudiou, Nicolas; Peeters, André P; Jordan, Bénédicte F; Gallez, Bernard; Duprez, Thierry

    2015-01-01

    The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation ('Global T1' combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons ('Lipids T1') would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48-72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; pbrain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects.

  18. Assessment of the tolerability profile of an ophthalmic solution of 5% glycyrrhizin and copolymer PEG/PPG on healthy volunteers and evaluation of its efficacy in the treatment of moderate to severe blepharitis

    Directory of Open Access Journals (Sweden)

    Mencucci R

    2013-07-01

    Full Text Available Rita Mencucci, Eleonora Favuzza, Ugo MenchiniDepartment of Surgery and Translational Medicine – Eye Clinic, University of Florence, Florence, ItalyPurpose: To evaluate the tolerability on healthy volunteers and the efficacy on subjects affected by chronic moderate/severe blepharitis of a 5% glycyrrhizin and copolymer poly(ethylene glycol/poly(propylene glycol(PEG/PPG ophthalmic solution.Methods: The study was a randomized, controlled, open label, intra-patient monocentric study. It consisted of two different phases, the assessment of tolerability phase on 20 healthy volunteers, and the evaluation of the efficacy on 21 subjects affected by chronic moderate/severe blepharitis; the treatment period was 2 weeks, followed by 1-week of follow-up. In the efficacy phase, in both eyes, eyelid hygiene was also performed. At day 0, 3, 7, 14, and 21 a complete ophthalmological examination was performed. In the tolerability phase, signs of clinical toxicity were recorded and subject-reported symptoms were collected using a questionnaire. In the efficacy phase, global signs and symptoms of blepharitis scores were collected using standardized photographic scales and questionnaire. The statistical analysis was performed using the Wilcoxon signed-rank test. Results: No ocular signs of drug toxicity were reported. During the treatment period for tolerability phase, there were statistically significant higher scores of tearing and ocular discomfort in the tolerability study group versus the tolerability control group. In the efficacy phase, differences between global scores of the two groups were statistically significant at day 0 (score of the efficacy study group was higher than the efficacy control group; P = 0.005 and at day 21 (score of the efficacy study group was lower than the efficacy control group (P ≤ 0.001.The difference of global scores at day 3, 7, 14, and 21 versus day 0 was statistically significant in both groups. No serious adverse events

  19. Pharmacokinetics, safety, and tolerability of varenicline in healthy adolescent smokers: a multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

    Science.gov (United States)

    Faessel, Helene; Ravva, Patanjali; Williams, Kathryn

    2009-01-01

    Varenicline is approved as an aid to smoking cessation in adults aged > or =18 years. The goal of this study was to characterize the multiple-dose pharmacokinetics, safety, and tolerability of varenicline in adolescent smokers. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled healthy 12- to 16-year-old smokers (> or =3 cigarettes daily) into high-body-weight (>55 kg) and low-body-weight (daily. The apparent renal clearance (CL/F) and volume of distribution (V/F) of varenicline and the effect of body weight on these parameters were estimated using nonlinear mixed-effects modeling. The high-body-weight group consisted of 35 subjects (65.7% male; 77.1% white; mean age, 15.2 years). The low-body-weight group consisted of 37 subjects (37.8% male; 48.6% white; mean age, 14.3 years). The pharmacokinetic parameters of varenicline were dose proportional over the dose range from 0.5 to 2 mg/d. The CL/F for a 70-kg adolescent was 10.4 L/h, comparable to that in a 70-kg adult. The estimated varenicline V/F was decreased in individuals of small body size, thus predicting a varenicline C(max) approximately 30% greater in low-body-weight subjects than in high-body-weight subjects. In high-body-weight subjects, steady-state varenicline exposure, as represented by the AUC(0-24), was 197.0 ng . h/mL for varenicline 1 mg BID and 95.7 ng . h/mL for varenicline 0.5 mg BID, consistent with values reported previously in adult smokers at the equivalent doses. In low-body-weight subjects, varenicline exposure was 126.3 ng . h/mL for varenicline 0.5 mg BID and 60.1 ng . h/mL for varenicline 0.5 mg once daily, values at the lower end of the range observed previously in adults at doses of 1 mg BID and 0.5 mg BID, respectively. Among high-body-weight subjects, adverse events (AEs) were reported by 57.1% of subjects in both the high- and low-dose varenicline groups and by 14.3% of subjects in the placebo group; among low-body-weight subjects, AEs

  20. Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection.

    Science.gov (United States)

    Nations, Kari R; Bursi, Roberta; Dogterom, Peter; Ereshefsky, Larry; Gertsik, Lev; Mant, Tim; Schipper, Jacques

    2012-09-01

    A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials. Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population. Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently. Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted. This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study

  1. Rapid and Weight-Independent Improvement of Glucose Tolerance Induced by a Peptide Designed to Elicit Apoptosis in Adipose Tissue Endothelium

    Science.gov (United States)

    Kim, Dong-Hoon; Sartor, Maureen A.; Bain, James R.; Sandoval, Darleen; Stevens, Robert D.; Medvedovic, Mario; Newgard, Christopher B.; Woods, Stephen C.; Seeley, Randy J.

    2012-01-01

    A peptide designed to induce apoptosis of endothelium in white adipose tissue (WAT) decreases adiposity. The goal of this work is to determine whether targeting of WAT endothelium results in impaired glucose regulation as a result of impaired WAT function. Glucose tolerance tests were performed on days 2 and 3 of treatment with vehicle (HF-V) or proapoptotic peptide (HF-PP) and mice pair-fed to HF-PP (HF-PF) in obese mice on a high-fat diet (HFD). Serum metabolic variables, including lipid profile, adipokines, individual fatty acids, and acylcarnitines, were measured. Microarray analysis was performed in epididymal fat of lean or obese mice treated with vehicle or proapoptotic peptide (PP). PP rapidly and potently improved glucose tolerance of obese mice in a weight- and food intake–independent manner. Serum insulin and triglycerides were decreased in HF-PP relative to HF-V. Levels of fatty acids and acylcarnitines were distinctive in HF-PP compared with HF-V or HF-PF. Microarray analysis in AT revealed that pathways involved in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation were changed by exposure to HFD and were reversed by PP administration. These studies suggest a novel role of the AT vasculature in glucose homeostasis and lipid metabolism. PMID:22733798

  2. Abscisic acid synergizes with rosiglitazone to improve glucose tolerance, down-modulate macrophage accumulation in adipose tissue: possible action of the cAMP/PKA/PPAR γ axis

    Science.gov (United States)

    Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

    2010-01-01

    Background & Aims Abscisic acid (ABA) is effective in preventing insulin resistance and obesity-related inflammation through a PPAR γ-dependent mechanism. The objective of this study was to assess the efficacy ABA in improving glucose homeostasis and suppress inflammation when administered in combination with rosiglitazone (Ros) and to determine whether PPAR γ activation by ABA is initiated via cAMP/protein kinase A (PKA) signaling. Methods Obese db/db mice were fed high-fat diets containing 0, 10, or 70 mg/kg Ros with and without racemic ABA (100 mg/kg) for 60 days. Glucose tolerance and fasting insulin levels were assessed at 6 and 8 weeks, respectively, and adipose tissue macrophage (ATM) infiltration was examined by flow cytometry. Gene expression was examined on white adipose tissue (WAT) and stromal vascular cells (SVCs) cultured with ABA, Ros, or an ABA/Ros combination. Results Both Ros and ABA improved glucose tolerance, and ABA decreased plasma insulin levels while having no effect on Ros-induced weight gain. ABA in combination with low-dose Ros (10 mg/kg; Roslo) synergistically inhibited ATM infiltration. Treatment of SVCs with Ros, ABA or ABA/Ros suppressed expression of the M1 marker CCL17. ABA and Ros synergistically increased PPAR γ activity and pretreatment with a cAMP-inhibitor or a PKA-inhibitor abrogated ABA-induced PPAR γ activation. Conclusions ABA and Ros act synergistically to modulate PPAR γ activity and macrophage accumulation in WAT and ABA enhances PPAR γ activity through a membrane-initiated mechanism dependent on cAMP/PKA signaling. PMID:20207056

  3. The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers.

    Science.gov (United States)

    Durbin, Anna P; Wright, Peter F; Cox, Amber; Kagucia, Wangeci; Elwood, Daniel; Henderson, Susan; Wanionek, Kimberli; Speicher, Jim; Whitehead, Stephen S; Pletnev, Alexander G

    2013-11-19

    WNV has become the leading vector-borne cause of meningoencephalitis in the United States. Although the majority of WNV infections result in asymptomatic illness, approximately 20% of infections result in West Nile fever and 1% in West Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or flaccid paralysis. The elderly are at particular risk for WNND, with more than half the cases occurring in persons older than sixty years of age. There is no licensed treatment for WNND, nor is there any licensed vaccine for humans for the prevention of WNV infection. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a recombinant live attenuated WNV vaccine based on chimerization of the wild-type WNV NY99 genome with that of the live attenuated DENV-4 candidate vaccine rDEN4Δ30. The genes encoding the prM and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the resultant virus was designated rWN/DEN4Δ30. The vaccine was evaluated in healthy flavivirus-naïve adult volunteers age 18-50 years in two separate studies, both of which are reported here. The first study evaluated 10³ or 10⁴ PFU of the vaccine given as a single dose; the second study evaluated 10⁵ PFU of the vaccine given as two doses 6 months apart. The vaccine was well-tolerated and immunogenic at all three doses, inducing seroconversion to WNV NY99 in 74% (10³ PFU), 75% (10⁴ PFU), and 55% (10⁵ PFU) of subjects after a single dose. A second 10⁵ PFU dose of rWN/DEN4Δ30 given 6 months after the first dose increased the seroconversion rate 89%. Based on the encouraging results from these studies, further evaluation of the candidate vaccine in adults older than 50 years of age is planned. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

    Science.gov (United States)

    Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

    2015-01-01

    Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once

  5. Application of mutation breeding technique for producing NaCl tolerant plants of banana in tissue culture and greenhouse conditions

    International Nuclear Information System (INIS)

    Vedadi, C.; Rahimi, M.; Naserian, B.; Rahmani, E.; Neshan, N.

    2005-01-01

    Full text: To study of possibility to induce salt tolerant clones in banana by using mutation technique, an experiment was conducted with factorial (gamma irradiation and salt concentration factors) in a CRD design. In this research, plantlets of banana cv. Dwarf Cavendish were produced by subculture of irradiated shoot tips. It deserves to mention that consequent subculturing was aimed at getting rid of chimera. Next, these explants were transferred to MS medium containing 2.5 mg. l- 1 BAP and NaCl concentrations of 0, 6, 7, 8, 9 g.l -1 for 2 months .Then, living buds were transferred to medium without salt. After one month, we repeated the first stage. All living buds rooted and were transferred to potted soil. Acclimatized plants were irrigated weekly with above NaCl solution. Other irrigation was done with salt-free water. There was also a negative relation between salt concentration and survival - proliferation. In second salinity stress, salt had no significant difference on survival percentage. No-significant difference of effect salt on survival in second salinity stress was observed. (author)

  6. Detection of Acetaldehyde in the Esophageal Tissue among Healthy Male Subjects after Ethanol Drinking and Subsequent L-Cysteine Intake.

    Science.gov (United States)

    Okata, Hideki; Hatta, Waku; Iijima, Katsunori; Asanuma, Kiyotaka; Tsuruya, Atsuki; Asano, Naoki; Koike, Tomoyuki; Hamada, Shin; Nakayama, Toru; Masamune, Atsushi; Shimosegawa, Tooru

    2018-04-01

    Ethanol is oxidized by alcohol dehydrogenase to acetaldehyde, a recognized carcinogen for the esophagus. However, no previous study has measured the acetaldehyde levels in the esophageal tissue. L-cysteine has been shown to reduce the acetaldehyde levels in the saliva; however, it is unknown whether L-cysteine intake affects the acetaldehyde concentration in the esophageal tissue. The aim of this study was to measure the acetaldehyde concentration in the esophageal tissue after ethanol drinking and evaluate the effect of L-cysteine intake on the acetaldehyde levels in the esophagus. We enrolled 10 male subjects with active acetaldehyde dehydrogenase-2*1/*1 (ALDH2*1/*1) genotype and 10 male subjects with the inactive acetaldehyde dehydrogenase-2*1/*2 (ALDH2*1/*2) genotype, the mean ages of whom were 25.6 and 27.9 years, respectively. In this prospective, single-blind, placebo-controlled study using L-cysteine and placebo lozenges (first and second examination), saliva and blood were collected before and after ethanol drinking. Esophageal tissue was obtained by endoscopic biopsy at 60 minutes after drinking, and the acetaldehyde and ethanol concentrations were measured. The acetaldehyde concentration of the saliva was significantly lower in those taking L-cysteine than in those taking the placebo. Acetaldehyde in the esophageal tissue was detected only in those taking L-cysteine lozenges. There were no correlations between the acetaldehyde concentrations in the esophageal tissue and saliva or blood. In conclusion, we detected acetaldehyde in the human esophageal tissue after ethanol drinking. Unexpectedly, intake of L-cysteine lozenges appears to contribute to detection of acetaldehyde in the esophageal tissue.

  7. Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Pietsch, Hubertus [MR and CT Contrast Media Research, Bayer Pharma AG, Berlin (Germany); Lenhard, Diana Constanze [Charite, Institute of Vegetative Physiology, Berlin (Germany); Naganawa, Shinji [Nagoya University Graduate School of Medicine, Department of Radiology, Nagoya (Japan)

    2017-07-15

    Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. (orig.)

  8. Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue

    International Nuclear Information System (INIS)

    Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Pietsch, Hubertus; Lenhard, Diana Constanze; Naganawa, Shinji

    2017-01-01

    Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. (orig.)

  9. Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome

    DEFF Research Database (Denmark)

    Kolehmainen, Marjukka; Ulven, Stine M; Paananen, Jussi

    2015-01-01

    BACKGROUND: Previously, a healthy Nordic diet (ND) has been shown to have beneficial health effects close to those of Mediterranean diets. OBJECTIVE: The objective was to explore whether the ND has an impact on gene expression in abdominal subcutaneous adipose tissue (SAT) and whether changes...... in gene expression are associated with clinical and biochemical effects. DESIGN: Obese adults with features of the metabolic syndrome underwent an 18- to 24-wk randomized intervention study comparing the ND with the control diet (CD) (the SYSDIET study, carried out within Nordic Centre of Excellence...... sites for the nuclear transcription factor κB. CONCLUSION: A healthy Nordic diet reduces inflammatory gene expression in SAT compared with a control diet independently of body weight change in individuals with features of the metabolic syndrome. The study was registered at clinicaltrials.gov as NCT...

  10. Prospective Study Validating Inter- and Intraobserver Variability of Tissue Compliance Meter in Breast Tissue of Healthy Volunteers: Potential Implications for Patients With Radiation-Induced Fibrosis of the Breast

    International Nuclear Information System (INIS)

    Wernicke, A. Gabriella; Parashar, Bhupesh; Kulidzhanov, Fridon; Riley, Lillian; Christos, Paul J.; Fischer, Andrew; Nori, Dattatreyudu; Chao, K.S. Clifford

    2011-01-01

    Purpose: Accurate detection of radiation-induced fibrosis (RIF) is crucial in management of breast cancer survivors. Tissue compliance meter (TCM) has been validated in musculature. We validate TCM in healthy breast tissue with respect to interobserver and intraobserver variability before applying it in RIF. Methods and Materials: Three medical professionals obtained three consecutive TCM measurements in each of the four quadrants of the right and left breasts of 40 women with no breast disease or surgical intervention. The intraclass correlation coefficient (ICC) assessed interobserver variability. The paired t test and Pearson correlation coefficient (r) were used to assess intraobserver variability within each rater. Results: The median age was 45 years (range, 24-68 years). The median bra size was 35C (range, 32A-40DD). Of the participants, 27 were white (67%), 4 black (10%), 5 Asian (13%), and 4 Hispanic (10%). ICCs indicated excellent interrater reliability (low interobserver variability) among the three raters, by breast and quadrant (all ICC ≥0.99). The paired t test and Pearson correlation coefficient both indicated low intraobserver variability within each rater (right vs. left breast), stratified by quadrant (all r≥ 0.94, p < 0.0001). Conclusions: The interobserver and intraobserver variability is small using TCM in healthy mammary tissue. We are now embarking on a prospective study using TCM in women with breast cancer at risk of developing RIF that may guide early detection, timely therapeutic intervention, and assessment of success of therapy for RIF.

  11. PR-39, a porcine host defence peptide, is prominent in mucosa and lymphatic tissue of the respiratory tract in healthy pigs and pigs infected with Actinobacillus pleuropneumoniae.

    Science.gov (United States)

    Hennig-Pauka, Isabel; Koch, Rüdiger; Hoeltig, Doris; Gerlach, Gerald-F; Waldmann, Karl-Heinz; Blecha, Frank; Brauer, Carsten; Gasse, Hagen

    2012-09-28

    Host defence peptides are important components of mammalian innate immunity. We have previously shown that PR-39, a cathelicidin host defence peptide, is an important factor in porcine innate immune mechanisms as a first line of defence after infection with Actinobacillus pleuropneumoniae. PR-39 interacts with bacterial and mammalian cells and is involved in a variety of processes such as killing of bacteria and promotion of wound repair. In bronchoalveolar lavage fluid of infected pigs PR-39 concentrations are elevated during the chronic but not during the acute stage of infection when polymorphonuclear neutrophils (known as the major source of PR-39) are highly increased. Thus it was assumed, that the real impact of PR-39 during infection might not be reflected by its concentration in bronchoalveolar lavage fluid. Using immunohistochemistry this study demonstrates the actual distribution of PR-39 in tissue of the upper and lower respiratory tract of healthy pigs, and of pigs during the acute and chronic stage of experimental infection with Actinobacillus pleuropneumoniae.During the acute stage of infection PR-39 accumulated adjacent to blood vessels and within bronchi. Immune reactions were mainly localized in the cytoplasm of cells with morphological characteristics of polymorphonuclear neutrophils as well as in extracellular fluids. During the chronic stage of infection pigs lacked clinical signs and lung alterations were characterized by reparation and remodelling processes such as tissue sequestration and fibroblastic pleuritis with a high-grade accumulation of small PR-39-positive cells resembling polymorphonuclear neutrophils. In healthy pigs, PR-39 was homogenously expressed in large single cells within the alveoli resembling alveolar macrophages or type 2 pneumocytes. PR-39 was found in all tissue samples of the upper respiratory tract in healthy and diseased pigs. Within the tracheobronchial lymph nodes, PR-39 dominated in the cytoplasm and nuclei of

  12. A preliminary study of patient-specific mechanical properties of diabetic and healthy plantar soft tissue from gated magnetic resonance imaging.

    Science.gov (United States)

    Williams, Evan D; Stebbins, Michael J; Cavanagh, Peter R; Haynor, David R; Chu, Baocheng; Fassbind, Michael J; Isvilanonda, Vara; Ledoux, William R

    2017-07-01

    Foot loading rate, load magnitude, and the presence of diseases such as diabetes can all affect the mechanical properties of the plantar soft tissues of the human foot. The hydraulic plantar soft tissue reducer instrument was designed to gain insight into which variables are the most significant in determining these properties. It was used with gated magnetic resonance imaging to capture three-dimensional images of feet under dynamic loading conditions. Custom electronics controlled by LabVIEW software simultaneously recorded system pressure, which was then translated to applied force values based on calibration curves. Data were collected for two subjects, one without diabetes (Subject A) and one with diabetes (Subject B). For a 0.2-Hz loading rate, and strains 0.16, 0.18, 0.20, and 0.22, Subject A's average tangential heel pad stiffness was 10 N/mm and Subject B's was 24 N/mm. Maximum test loads were approximately 200 N. Loading rate and load magnitude limitations (both were lower than physiologic values) will continue to be addressed in the next version of the instrument. However, the current hydraulic plantar soft tissue reducer did produce a data set for healthy versus diabetic tissue stiffness that agrees with previous trends. These data are also being used to improve finite element analysis models of the foot as part of a related project.

  13. A diet enriched with Mugil cephalus processed roes modulates the tissue lipid profile in healthy rats: a biochemical and chemometric assessment.

    Science.gov (United States)

    Rosa, A; Atzeri, A; Putzu, D; Scano, P

    2016-01-01

    The effect of a diet enriched with mullet bottarga on the lipid profile (total lipids, total cholesterol, unsaturated fatty acids, α-tocopherol, and hydroperoxides) of plasma, liver, kidney, brain, and perirenal adipose tissues of healthy rats was investigated. Rats fed a 10% bottarga enriched-diet for 5 days showed body weights and tissue total lipid and cholesterol levels similar to those of animals fed control diet. Univariate and multivariate results showed that bottarga enriched-diet modified the fatty acid profile in all tissues, except brain. Significant increases of n-3 PUFA, particularly EPA, were observed together with a 20:4 n-6 decrease in plasma, liver, and kidney. Perirenal adipose tissue showed a fat accumulation that reflected the diet composition. The overall data suggest that mullet bottarga may be considered as a natural bioavailable source of n-3 PUFA and qualify it as a traditional food product with functional properties and a potential functional ingredient for preparation of n-3 PUFA enriched foods.

  14. A comparative study on the immunogenicity, safety and tolerance of purified duck embryo vaccine (PDEV) manufactured in India (Vaxirab) and Switzerland (Lyssavac-N): a randomized simulated post-exposure study in healthy volunteers.

    Science.gov (United States)

    Mahendra, Bangalore Jayakrishnappa; Madhusudana, Shampur Narayan; Ashwathnarayana, Doddabele Hanumanthaiah; Sampath, Gadey; datta, Soma Subhra; Sudarshan, Mysore Kalappa; Venkatesh, Gonibeedu Manjunatah; Muhamuda, Kader; Bilagumba, Gangaboraiah; Shamanna, Manjula

    2007-12-05

    Purified duck embryo vaccine (PDEV, Vaxirab) for rabies prophylaxis is now indigenously manufactured in India under technology transfer from Berna Biotech who made the original PDEV (Lyssavac). In the present study we have compared the two vaccines in terms of safety, immunogenicity and tolerance. The study was conducted in 220 adult healthy volunteers. It was observed that both vaccines produced neutralizing antibody titers (as determined by rapid fluorescent focus inhibition test, RFFIT) more than 0.5 IU/mL (minimum level for seroconversion) on all days tested but the titers on days 90 and 180 were significantly higher with Lyssavac. The adverse reactions produced were slightly more with Lysssavac but both vaccines were well tolerated. In conclusion, the indigenously produced PDEV (Vaxirab) was found to be equally safe and immunogenic as the original PDEV (Lyssavac) manufactured at Switzerland.

  15. Adipose tissue insulin receptor and glucose transporter 4 expression, and blood glucose and insulin responses during glucose tolerance tests in transition Holstein cows with different body condition.

    Science.gov (United States)

    Jaakson, H; Karis, P; Ling, K; Ilves-Luht, A; Samarütel, J; Henno, M; Jõudu, I; Waldmann, A; Reimann, E; Pärn, P; Bruckmaier, R M; Gross, J J; Kaart, T; Kass, M; Ots, M

    2018-01-01

    Glucose uptake in tissues is mediated by insulin receptor (INSR) and glucose transporter 4 (GLUT4). The aim of this study was to examine the effect of body condition during the dry period on adipose tissue mRNA and protein expression of INSR and GLUT4, and on the dynamics of glucose and insulin following the i.v. glucose tolerance test in Holstein cows 21 d before (d -21) and after (d 21) calving. Cows were grouped as body condition score (BCS) ≤3.0 (thin, T; n = 14), BCS = 3.25 to 3.5 (optimal, O; n = 14), and BCS ≥3.75 (overconditioned, OC; n = 14). Blood was analyzed for glucose, insulin, fatty acids, and β-hydroxybutyrate concentrations. Adipose tissue was analyzed for INSR and GLUT4 mRNA and protein concentrations. During the glucose tolerance test 0.15 g/kg of body weight glucose was infused; blood was collected at -5, 5, 10, 20, 30, 40, 50, and 60 min, and analyzed for glucose and insulin. On d -21 the area under the curve (AUC) of glucose was smallest in group T (1,512 ± 33.9 mg/dL × min) and largest in group OC (1,783 ± 33.9 mg/dL × min), and different between all groups. Basal insulin on d -21 was lowest in group T (13.9 ± 2.32 µU/mL), which was different from group OC (24.9 ± 2.32 µU/mL. On d -21 the smallest AUC 5-60 of insulin in group T (5,308 ± 1,214 µU/mL × min) differed from the largest AUC in group OC (10,867 ± 1,215 µU/mL × min). Time to reach basal concentration of insulin in group OC (113 ± 14.1 min) was longer compared with group T (45 ± 14.1). The INSR mRNA abundance on d 21 was higher compared with d -21 in groups T (d -21: 3.3 ± 0.44; d 21: 5.9 ± 0.44) and O (d -21: 3.7 ± 0.45; d 21: 4.7 ± 0.45). The extent of INSR protein expression on d -21 was highest in group T (7.3 ± 0.74 ng/mL), differing from group O (4.6 ± 0.73 ng/mL), which had the lowest expression. The amount of GLUT4 protein on d -21 was lowest in group OC (1.2 ± 0.14 ng/mL), different from group O (1.8 ± 0.14 ng/mL), which had the highest amount

  16. A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-11-15

    Preclinical work suggests that the metabotropic glutamate receptor subtype 5 (mGlu5) may represent a novel target to treat neuropsychiatric disorders, including alcohol use disorder and obesity. The goal of this first-in-man study was to evaluate the safety, tolerability and pharmacokinetics (PK) of GET 73 (PubChem SID: 329974174), a novel mGluR5 negative allosteric modulator. This was a double-blind, placebo-controlled, ascending dose, Phase I study conducted in healthy male volunteers in two experiments. GET 73 was administered as single ascending doses (N=48; Experiment 1; 10, 30, 100, 300, 450, 600-mg) or multiple ascending doses (N=32; Experiment 2; 100, 300, 450, 450-mg twice a day). Primary endpoints were the incidence of adverse events (AEs) among drug conditions and drug tolerability. The secondary endpoints were the PK parameters of GET 73 and its metabolite MET 2. Single GET 73 doses of up to 600-mg and repeated ascending doses of up to 450-mg twice/day were safe and well-tolerated. There were no serious or severe AEs. All AEs were mild or moderate in severity. Total GET 73 exposure increased with each increased GET 73 dose. A dose-related increase in mean maximum plasma drug concentration was observed after repeated dosing. Maximum plasma drug concentrations occurred between 0.5 and 2.05h after administration in all groups for both single and repeated doses. This first-in-human study indicates that GET 73, as single or multiple ascending doses, is safe and well-tolerated when administered to healthy male volunteers. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Mohs micrographic surgery in dermatofibrosarcoma protuberans allows tumour clearance with smaller margins and greater preservation of healthy tissue compared with conventional surgery: a study of 74 primary cases.

    Science.gov (United States)

    Serra-Guillén, C; Llombart, B; Nagore, E; Guillén, C; Requena, C; Traves, V; Kindem, S; Alcalá, R; Rivas, N; Sanmartín, O

    2015-01-01

    Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumour with aggressive local growth. Whether DFSP should be treated with conventional surgery (CS) or Mohs micrographic surgery (MMS) has long been a topic of debate. To calculate, in a large series of DFSP treated by MMS, the minimum margin that would have been needed to achieve complete clearance by CS. Secondly, to calculate the percentage of healthy tissue that was preserved by MMS rather than CS with 2- and 3-cm margins. The minimum margin was calculated by measuring the largest distance from the visible edge of the tumour to the edge of the definitive surgical defect. Tumour and surgical defect areas for hypothetical CS with 2- and 3-cm margins were calculated using AutoCAD for Windows. A mean minimum margin of 1·34 cm was required to achieve complete clearance for the 74 tumours analysed. The mean percentages of skin spared using MMS rather than CS with 2- and 3-cm margins were 49·4% and 67·9%, respectively. MMS can achieve tumour clearance with smaller margins and greater preservation of healthy tissue than CS. © 2014 British Association of Dermatologists.

  18. ADIPONECTIN AND C-REACTIVE PROTEIN RELATIONSHIP IN PLASMA AND ADIPOSE TISSUE (STUDY AMONG HEALTHY OBESE EGYPTIAN FEMALES)

    International Nuclear Information System (INIS)

    SOLIMAN, S.E.T.

    2008-01-01

    The adipokine, adiponectin inhibits vascular inflammation and acts as an endogenous modulator of obesity - linked diseases. High - sensitive C-reactive protein (hs-CRP) is recently debated as a risk factor and mediator for atherosclerosis. The present study investigated the association between adiponectin and hs-CRP in plasma and adipose tissue, and their relation to body composition and insulin sensitivity in a cohort of normal (30 subjects), obese (30 subjects) and morbidly - obese females (10 subjects). Messenger RNA (mRNA) expression of CRP and adiponectin in human adipose tissue were measured using real-time polymerase chain reaction. Plasma adiponectin and insulin were measured using radioimmunoassay methods, while, plasma hs-CRP was measured using ultrasensitive latex method.Results showed that adiponectin was negatively correlated with weight, BMI and insulin sensitivity index, and positively correlated with HDLc. The plasma hs-CRP levels were negatively correlated with plasma adiponectin. The plasma adiponectin levels being significantly lower and plasma hs-CRP being significantly higher in obese than normal females. Real- Time PCR analysis revealed the expression of CRP m-RNA in human adipose tissue and this was inversely correlated to adiponectin m RNA. These results suggest that elevation of CRP and reduction of adiponectin could emerge as mediators of atherogenesis and insulin resistance

  19. Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

    Science.gov (United States)

    Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

    2017-07-01

    Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

  20. Impact of physical inactivity on subcutaneous adipose tissue metabolism in healthy young male offspring of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Sonne, MP; Alibegovic, AC

    2010-01-01

    . The best known environmental modifiable risk factors for type 2 diabetes are obesity and a low level of habitual physical activity (1). Even though there is substantial evidence that a change toward a healthy lifestyle halts the progression of type 2 diabetes (2), certain groups, including first......OBJECTIVE Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study...... changes in CON subjects compared with FDR subjects. Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism. Type 2 diabetes is the product of a complex interplay between genetic susceptibility and environmental factors...

  1. Epithelial tissue hyperplasia induced by the RAF inhibitor PF-04880594 is attenuated by a clinically well-tolerated dose of the MEK inhibitor PD-0325901.

    Science.gov (United States)

    Torti, Vince R; Wojciechowicz, Donald; Hu, Wenyue; John-Baptiste, Annette; Evering, Winston; Troche, Gabriel; Marroquin, Lisa D; Smeal, Tod; Yamazaki, Shinji; Palmer, Cynthia L; Burns-Naas, Leigh Ann; Bagrodia, Shubha

    2012-10-01

    Clinical trials of selective RAF inhibitors in patients with melanoma tumors harboring activated BRAFV600E have produced very promising results, and a RAF inhibitor has been approved for treatment of advanced melanoma. However, about a third of patients developed resectable skin tumors during the course of trials. This is likely related to observations that RAF inhibitors activate extracellular signal-regulated kinase (ERK) signaling, stimulate proliferation, and induce epithelial hyperplasia in preclinical models. Because these findings raise safety concerns about RAF inhibitor development, we further investigated the underlying mechanisms. We showed that the RAF inhibitor PF-04880594 induces ERK phosphorylation and RAF dimerization in those epithelial tissues that undergo hyperplasia. Hyperplasia and ERK hyperphosphorylation are prevented by treatment with the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD-0325901 at exposures that extrapolate to clinically well-tolerated doses. To facilitate mechanistic and toxicologic studies, we developed a three-dimensional cell culture model of epithelial layering that recapitulated the RAF inhibitor-induced hyperplasia and reversal by MEK inhibitor in vitro. We also showed that PF-04880594 stimulates production of the inflammatory cytokine interleukin 8 in HL-60 cells, suggesting a possible mechanism for the skin flushing observed in dogs. The complete inhibition of hyperplasia by MEK inhibitor in epithelial tissues does not seem to reduce RAF inhibitor efficacy and, in fact, allows doubling of the PF-04880594 dose without toxicity usually associated with such doses. These findings indicated that combination treatment with MEK inhibitors might greatly increase the safety and therapeutic index of RAF inhibitors for the treatment of melanoma and other cancers. ©2012 AACR.

  2. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    Science.gov (United States)

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation. © 2016 Blackwell Verlag GmbH.

  3. Development of a tool-kit for the detection of healthy and injured cardiac tissue based on MR imaging

    Directory of Open Access Journals (Sweden)

    Westphal Philip

    2017-09-01

    Full Text Available Planning of interventions to treat cardiac arrhythmia requires a 3D patient specific model of the heart. Currently available commercial or free software dedicated to this task have important limitations for routinely use. Automatic algorithms are not robust enough while manual methods are time-consuming. Therefore, the project attempts to develop an optimal software tool. The heart model is generated from preoperative MR data-sets acquired with contrast agent and allows visualisation of damaged cardiac tissue. A requirement in the development of the software tool was the use of semi-automatic functions to be more robust. Once the patient image dataset has been loaded, the user selects a region of interest. Thresholding functions allow selecting the areas of high intensities which correspond to anatomical structures filled with contrast agent, namely cardiac cavities and blood vessels. Thereafter, the target-structure, for example the left ventricle, is coarsely selected by interactively outlining the gross shape. An active contour function adjusts automatically the initial contour to the image content. The result can still be manually improved using fast interaction tools. Finally, possible scar tissue located in the cavity muscle is automatically detected and visualized on the 3D heart model. The model is exported in format which is compatible with interventional devices at hospital. The evaluation of the software tool included two steps. Firstly, a comparison with two free software tools was performed on two image data sets of variable quality. Secondly, six scientists and physicians tested our tool and filled out a questionnaire. The performance of our software tool was visually judged more satisfactory than the free software, especially on the data set of lower quality. Professionals evaluated positively our functionalities regarding time taken, ease of use and quality of results. Improvements would consist in performing the planning based

  4. Safety, immunogenicity, and tolerability of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised, single-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Richmond, Peter C; Marshall, Helen S; Nissen, Michael D; Jiang, Qin; Jansen, Kathrin U; Garcés-Sánchez, Maria; Martinón-Torres, Federico; Beeslaar, Johannes; Szenborn, Leszek; Wysocki, Jacek; Eiden, Joseph; Harris, Shannon L; Jones, Thomas R; Perez, John L

    2012-08-01

    Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease, but a broadly protective vaccine is not currently licensed. A bivalent recombinant factor H-binding protein vaccine (recombinant lipoprotein 2086) has been developed to provide broad coverage against diverse invasive meningococcus serogroup B strains. Our aim was to test the immune response of this vaccine. This randomised, placebo-controlled trial enrolled healthy adolescents from 25 sites in Australia, Poland, and Spain. Exclusion criteria were previous invasive meningococcal disease or serogroup B vaccination, previous adverse reaction or known hypersensitivity to the vaccine, any significant comorbidities, and immunosuppressive therapy or receipt of blood products in the past 6 months. Participants were randomly assigned with a computerised block randomisation scheme to receive ascending doses of vaccine (60, 120, or 200 μg) or placebo at 0, 2, and 6 months. Principal investigators, participants and their guardians, and laboratory personnel were masked to the allocation; dispensing staff were not. Immunogenicity was measured by serum bactericidal assays using human complement (hSBA) against eight diverse meningococcus serogroup B strains. The co-primary endpoints were seroconversion for the two indicator strains (PMB1745 and PMB17) analysed by the Clopper-Pearson method. Local and systemic reactions and adverse events were recorded. The study is registered at ClinicalTrials.gov, number NCT00808028. 539 participants were enrolled and 511 received all three study vaccinations--116 in the placebo group, 21 in the 60 μg group, 191 in the 120 μg group, and 183 in the 200 μg group. The proportion of participants responding with an hSBA titre equal to or greater than the lower limit of quantitation of the hSBA assays (reciprcocal titres of 7 to 18, depending on test strain) was similar for the two largest doses and ranged from 75·6 to 100·0% for the 120 μg dose and 67·9 to

  5. Tissue Factor and Toll Like Receptor (TLR)4 in Hyperglycemia-Hyperinsulinemia: Effects in Healthy Subjects, and Type 1 and Type 2 Diabetes Mellitus

    Science.gov (United States)

    Singh, Anamika; Boden, Guenther; Rao, A. Koneti

    2015-01-01

    SUMMARY Background Diabetes mellitus (DM) patients have increased cardiovascular events. Blood tissue factor-procoagulant activity (TF-PCA), the initiating mechanism for blood coagulation, is elevated in DM. We have shown that hyperglycemia (HG), hyperinsulinemia (HI) and combined HG+HI (induced using 24 hr infusion clamps) increases TF-PCA in healthy and T2DM subjects, but not in T1DM subjects. The mechanisms for this are unknown. DM patients have elevated plasma lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 ligand. We postulated that TLR4 plays a role in modulating TF levels. Objectives and Methods We studied the effect of HG+HI on TLR4 and TF-PCA in vivo during 24 hr HG+HI infusion clamps in healthy subjects, and T1DM and T2DM subjects, and in vitro in blood. Results In vivo, in healthy subjects, 24 hr HG + HI infusion increased TLR4 6-fold, which correlated with TF-PCA (r= 0.91, p<0.0001). T2DM patients showed smaller increases in both. In T1DM subjects, TLR4 declined (50%, p<0.05) and correlated with TF-PCA (r=0.55; p<0.05). In vitro, HG (200 mg/dl added glucose) and HI (1-100 nM added insulin) increased TF-PCA in healthy subjects (~2-fold, 2-4 hr). Insulin inhibited by ~30% LPS-induced increase in TF-PCA and high glucose reversed it. TLR4 levels paralleled TF-PCA (r=0.71, p<0.0001); HG and HI increased TLR4 and insulin inhibited LPS-induced TLR4 increase. Conclusions This is first evidence that even in healthy subjects, HG of short duration increases TLR4 and TF-PCA, key players in inflammation and thrombosis. TLR4-TF interplay is strikingly different in non-diabetic, T1DM and T2DM subjects. PMID:25653143

  6. Safety and tolerability of tigecycline for the treatment of complicated skin and soft-tissue and intra-abdominal infections: an analysis based on five European observational studies.

    Science.gov (United States)

    Guirao, Xavier; Sánchez García, Miguel; Bassetti, Matteo; Bodmann, Klaus Friedrich; Dupont, Hervé; Montravers, Philippe; Heizmann, Wolfgang R; Capparella, Maria Rita; Simoneau, Damien; Eckmann, Christian

    2013-07-01

    Tigecycline is approved for the treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) in adults. In this analysis the safety and tolerability profile of tigecycline (used alone or in combination) for the treatment of patients with approved indications of cSSTI and cIAI were examined under real-life clinical conditions. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). A total of 254 cSSTI and 785 cIAI patients were included. The mean age was 63 years; 34.4% and 56.6% were in intensive care units, 90.9% and 88.1% had at least one comorbidity and mean Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the beginning of treatment were 15.0 ± 7.9 and 16.9 ± 7.6, respectively. Data on adverse events (AEs) were available for 198 cSSTI and 590 cIAI patients in three studies. Nausea and vomiting were reported in ≤ 2% of patients. The most common serious AEs were multi-organ failure (4.0% and 10.0% in cSSTI and cIAI patients, respectively) and sepsis (4.0% and 6.1%, respectively). Death was recorded for 24/254 (9.4%) cSSTI and 147/785 (18.7%) cIAI patients. Mortality rates were higher in the group with a baseline APACHE II score of >15 compared with those with a score of ≤ 15 (18.7% versus 3.5% for cSSTI patients and 23.8% versus 16.0% for cIAI patients). A similar trend was seen when cIAI patients were stratified by Sequential Organ Failure Assessment (SOFA) score. The safety and tolerability of tigecycline, alone and in combination, are consistent with the level of critical illness among patients in these real-life studies.

  7. Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome.

    Science.gov (United States)

    Kolehmainen, Marjukka; Ulven, Stine M; Paananen, Jussi; de Mello, Vanessa; Schwab, Ursula; Carlberg, Carsten; Myhrstad, Mari; Pihlajamäki, Jussi; Dungner, Elisabeth; Sjölin, Eva; Gunnarsdottir, Ingibjörg; Cloetens, Lieselotte; Landin-Olsson, Mona; Akesson, Björn; Rosqvist, Fredrik; Hukkanen, Janne; Herzig, Karl-Heinz; Dragsted, Lars O; Savolainen, Markku J; Brader, Lea; Hermansen, Kjeld; Risérus, Ulf; Thorsdottir, Inga; Poutanen, Kaisa S; Uusitupa, Matti; Arner, Peter; Dahlman, Ingrid

    2015-01-01

    Previously, a healthy Nordic diet (ND) has been shown to have beneficial health effects close to those of Mediterranean diets. The objective was to explore whether the ND has an impact on gene expression in abdominal subcutaneous adipose tissue (SAT) and whether changes in gene expression are associated with clinical and biochemical effects. Obese adults with features of the metabolic syndrome underwent an 18- to 24-wk randomized intervention study comparing the ND with the control diet (CD) (the SYSDIET study, carried out within Nordic Centre of Excellence of the Systems Biology in Controlled Dietary Interventions and Cohort Studies). The present study included participants from 3 Nordic SYSDIET centers [Kuopio (n = 20), Lund (n = 18), and Oulu (n = 18)] with a maximum weight change of ±4 kg, highly sensitive C-reactive protein concentration healthy Nordic diet reduces inflammatory gene expression in SAT compared with a control diet independently of body weight change in individuals with features of the metabolic syndrome. © 2015 American Society for Nutrition.

  8. Molecular characterization of Staphylococcus aureus isolates from skin and soft tissue infections samples and healthy carriers in the Central Slovenia region.

    Science.gov (United States)

    Svent-Kucina, Natasa; Pirs, Mateja; Kofol, Romina; Blagus, Rok; Smrke, Dragica Maja; Bilban, Marjan; Seme, Katja

    2016-04-01

    Staphylococcus aureus is among the most important human pathogens. It is associated with different infections and is a major cause of skin and soft tissue infections (SSTIs). The aim of our study was to compare S. aureus isolates associated with SSTIs with isolates obtained from healthy carriers in the Central Slovenia region in terms of antimicrobial susceptibility, genetic diversity by clonal complex (CC)/sequence type, spa type, and by toxin gene profiling. In total, 274 S. aureus isolates were collected prospectively by culturing wound samples from 461 SSTI patients and nasal samples from 451 healthy carriers. We have demonstrated high heterogeneity in terms of CCs and spa type in both groups of isolates. The main clone among SSTI strains was Panton-Valentine leukocidin gene (pvl) positive CC121, whereas the main clone among carrier strains was CC45 carrying a large range of toxin genes. The main spa type in both groups was t091. Pvl was more frequently present in SSTI strains (31.2% SSTI vs 3.6% carrier strains) and staphylococcal enterotoxin C was more frequently present in carrier strains (1.6% SSTI vs 17.0% carrier strains). We have also demonstrated that methicillin-resistant S. aureus was a rare cause (2.8%) of SSTIs in our region. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  9. Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study.

    Science.gov (United States)

    Shi, Shaojun; Liu, Yani; Wu, Jianhong; Li, Zhongfang; Zhao, Yan; Zhong, Dafang; Zeng, Fandian

    2010-10-01

    The proprietary formulation of fluoxetine hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. Pharmacokinetic studies investigating the bioequivalence of generic and branded formulations are needed to market generic fluoxetine in China. The aim of this study was to compare the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of fluoxetine hydrochloride 20 mg in a fasting, healthy Chinese male population. This 10-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test or reference formulation, followed by a 35-day washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties (including C(max), T(max), AUC(0-t), AUC(0-∞), and t(½)), blood samples were obtained over a 672-hour period after dosing. Plasma concentrations of fluoxetine and its active metabolite, norfluoxetine, were analyzed using a validated LC-MS/MS method. The formulations were to be considered bioequivalent if the ln-transformed ratios (test/ reference) of C(max) and AUC were within the predetermined bioequivalence range of 80% to 125%, as established by the US Food and Drug Administration, and if the P values were fasting, healthy Chinese male volunteers. Both formulations appeared to be well tolerated. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

  10. Implication of endothelial to mesenchymal cell transition in the development of healthy digestive tissue injury following radiotherapy

    International Nuclear Information System (INIS)

    Mintet, Elodie

    2015-01-01

    Fibrosis is identified as a chronic side effect occurring after radiotherapy for pelvic tumors in 5 to 10 % of patients. This pathological healing process is characterized by an accumulation of extracellular matrix synthesized by mesenchymal cells. Endothelial to mesenchymal transition (EndoMT), is a processes during which endothelial cells express mesenchymal markers in response to stress. EndoMT is identified as a new source of mesenchymal cells taking part to fibrosis development in patients suffering from inflammatory bowel diseases. Then, this study focused on the potential participation of EndoMT in radiation-induced intestinal fibrosis and tried to identify new therapeutics targets. Interestingly, our results showed for the first time EndoMT in rectal tissues from patients who developed radiation proctitis following radiotherapy. We used an in vivo approach to follow the mesenchymal cells having an endothelial origin in a mouse model expressing the GFP under the control of an endothelial promoter, Tie2 (Tie2-GFP). Thereby, our results confirmed the existence of radiation-induced EndoMT in our preclinical model of radiation proctitis. In vitro characterization showed that irradiation induced a modulation of the endothelial phenotype through a mesenchymal profile, a hallmark of EndoMT. This project also focused on a potential molecular actor, Hey2. In this context, we generated a transgenic mouse model in which Hey2 gene expression is repressed specifically in the endothelial compartment and observed a decrease in radiation-induced mucosal damages and EndoMT frequency. Consequently, inhibiting Hey2 expression could represent a new interesting therapeutic strategy. (author)

  11. Effects of dietary supplementation with EPA and/or α-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet.

    Science.gov (United States)

    Huerta, Ana E; Prieto-Hontoria, Pedro L; Fernández-Galilea, Marta; Escoté, Xavier; Martínez, J Alfredo; Moreno-Aliaga, María J

    2017-01-02

    In obesity, the increment of adiposity levels disrupts the whole body homeostasis, promoting an over production of oxidants and inflammatory mediators. The current study aimed to characterize the transcriptomic changes promoted by supplementation with eicosapentaenoic acid (EPA, 1.3 g/day), α-lipoic acid (0.3 g/day), or both (EPA + α-lipoic acid, 1.3 g/day + 0.3 g/day) in subcutaneous abdominal adipose tissue from overweight/obese healthy women, who followed a hypocaloric diet (30% of total energy expenditure) during ten weeks, by using a microarray approach. At the end of the intervention, a total of 33,297 genes were analyzed using Affymetrix GeneChip arrays. EPA promoted changes in extracellular matrix remodeling gene expression, besides a rise of genes associated with either chemotaxis or wound repair. α-Lipoic acid decreased expression of genes related with cell adhesion and inflammation. Furthermore, α-lipoic acid, especially in combination with EPA, upregulated the expression of genes associated with lipid catabolism while downregulated genes involved in lipids storage. Together, all these data suggest that some of the metabolic effects of EPA and α-lipoic acid could be related to their regulatory actions on adipose tissue metabolism. © 2016 BioFactors, 43(1):117-131, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  12. A system model of the effects of exercise on plasma Interleukin-6 dynamics in healthy individuals: Role of skeletal muscle and adipose tissue.

    Science.gov (United States)

    Morettini, Micaela; Palumbo, Maria Concetta; Sacchetti, Massimo; Castiglione, Filippo; Mazzà, Claudia

    2017-01-01

    Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (dynamics during exercise and post-exercise were consistent with literature data from exercise protocols differing in intensity, duration and modality. The model successfully emulated the physiological effects of exercise on plasma IL-6 levels and provided a reliable description of the role of skeletal muscle and adipose tissue on the dynamics of plasma IL-6. The system model here proposed is suitable to simulate IL-6 response to different exercise modalities. Its future integration with existing models of GLP-1-induced insulin secretion might provide a more reliable description of exercise's effects on glucose homeostasis and hence support the definition of more tailored interventions for the treatment of type 2 diabetes.

  13. Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

    Science.gov (United States)

    Sarsby, Joscelyn; Martin, Nicholas J.; Lalor, Patricia F.; Bunch, Josephine; Cooper, Helen J.

    2014-09-01

    Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

  14. Assessment of the short-term safety and tolerability of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii (PR 259 CT1) in healthy volunteers: a clinical phase I study.

    Science.gov (United States)

    Mesia, Kahunu; Cimanga, Kanyanga; Tona, Lutete; Mampunza, Ma Miezi; Ntamabyaliro, Nsengi; Muanda, Tsobo; Muyembe, Tamfum; Totté, Jozef; Mets, Tony; Pieters, Luc; Vlietinck, Arnold

    2011-01-01

    The aim of this study was to evaluate the short-term safety and tolerability of an antimalarial herbal medicinal product (PR 259 CT1) consisting of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii when given orally to healthy adult male volunteers. The amount of the major alkaloid strictosamide in the extract was determined by a validated HPLC method and was shown to be 5.6 %. The herbal preparation was formulated in a gelatine capsule form containing 500 mg of PCR 259 CT1. A sample of 15 healthy male volunteers, selected using the Lot Quality Assurance of Sampling (LQAS) method, was eligible for inclusion after fulfillment of the inclusion criteria and clinical examination by a physician. The volunteers were treated in an outpatient clinic with a drug regimen of two 500 mg capsules three times daily (each eight hours) for seven days, during meals. Safety and tolerability were monitored clinically, haematologically, biochemically and by electrocardiographic (ECG) examination at days 0, 1, 3, 7 and 14. Adverse effects were recorded by self-reporting of the participants or by detection of abnormalities in clinical examinations by a physician. The oral administration of PR 259 CT1 at high doses of 2 × 500 mg/capsule/day for 7 days was found to induce no significant changes in the concentration levels of all investigated haematological, biochemical, electrocardiogram and vital sign parameters and physical characteristics after 14 days of treatment compared to those seen in the baseline data. The concentration levels of all evaluated parameters were within the normal limits as reported in the literature. All adverse events noted were mild and self-resolving including increase of appetite (33 %), headache (20 %) and nausea (20 %). Other minor side effects were insomnia, somnolence and asthenia (7 %). Thus, PR 259 CT1 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II

  15. Antibody formation towards porcine tissue in patients implanted with crosslinked heart valves is directed to antigenic tissue proteins and αGal epitopes and is reduced in healthy vegetarian subjects.

    Science.gov (United States)

    Böer, Ulrike; Buettner, Falk F R; Schridde, Ariane; Klingenberg, Melanie; Sarikouch, Samir; Haverich, Axel; Wilhelmi, Mathias

    2017-03-01

    Glutaraldehyde-fixed porcine heart valves (ga-pV) are one of the most frequently used substitutes for insufficient aortic and pulmonary heart valves which, however, degenerate after 10-15 years. Yet, xeno-immunogenicity of ga-pV in humans including identification of immunogens still needs to be investigated. We here determined the immunogenicity of ga-pV in patients with respect to antibody formation, identity of immunogens and potential options to reduce antibody levels. Levels of tissue-specific and anti-αGal antibodies were determined retrospectively in patients who received ga-pV for 51 months (n=4), 25 months (n=6) or 5 months (n=4) and compared to age-matched untreated subjects (n=10) or younger subjects with or without vegetarian diet (n=12/15). Immunogenic proteins were investigated by Western blot approaches. Tissue-specific antibodies in patients were elevated after 5 (1.73-fold) and 25 (1.46-fold, both PVegetarian diet reduced significantly (0.63-fold, P<.01) the level of pre-formed αGal but not of tissue-specific antibodies. Immune response in patients towards ga-pV is induced by the porcine proteins albumin and collagen 6A1 as well as αGal epitopes, which seemed to be more sustained. In contrast, in healthy young subjects pre-formed anti-Gal antibodies were reduced by a meat-free nutrition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Echocardiographic Assessment of Left Ventricular Function in Healthy Horses and in Horses with Heart Disease Using Pulsed-Wave Tissue Doppler Imaging.

    Science.gov (United States)

    Koenig, T R; Mitchell, K J; Schwarzwald, C C

    2017-03-01

    Assessment of left ventricular (LV) function by tissue Doppler imaging (TDI) is not well established in horses with heart disease. To describe the use of pulsed-wave (PW) TDI for the assessment of LV function, establish reference intervals, investigate effects of mitral regurgitation (MR), aortic regurgitation (AR), and primary myocardial disease (MD), and provide proof of concept for the use of PW TDI in Warmblood horses with heart disease. Thirty healthy horses, 38 horses with MR, 25 with AR, 8 with MD. Echocardiograms were retrospectively analyzed. Reference intervals were calculated. PW TDI indices of healthy horses and horses with MR, AR, and MD were compared by one-way ANOVA and Dunnett's test. A complete set of PW TDI variables could be obtained in 94 of 101 horses. Variables corresponding to isovolumic intervals were most difficult to measure. Valvular regurgitation influenced variables describing isovolumic contraction and ejection. Horses with MD had significantly shortened ET m (-118.5 [-154.1 to -82.9] ms; mean difference [95% CI of difference of means]), increased PEP m /ET m (0.11 [0.05 to 0.17]), prolonged IMP m (0.28 [0.18 to 0.37]), increased S 1 (8.9 [5.2 to 12.6] cm/s), and decreased E 1 (-2.6 [-4.7 to -0.5] cm/s), E m (-14.2 [-19.9 to -8.5] cm/s), and E m /A m ratio (-1.6 [-2.6 to -0.6]). Pulsed-wave TDI might be useful for detection of LV dysfunction in horses with primary MD. The clinical value of TDI in horses with MR and AR remains uncertain. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. A link between expression level of long-non-coding RNA ZFAS1 in breast tissue of healthy women and obesity.

    Science.gov (United States)

    Mansoori, Yaser; Tabei, Mohammad Bagher; Askari, Alireza; Izadi, Pantea; Daraei, Abdolreza; Naghizadeh, Mohammad Mehdi; Zendehbad, Zahra; Bastami, Milad; Nariman-Saleh-Fam, Ziba; Mansoori, Hosein; Tavakkoly-Bazzaz, Javad

    2018-04-01

    Epidemiological and experimental literature indicates that the risk of breast cancer incidence is strongly linked to hormone-dependent factors, including reproductive history and obesity. However, the molecular mechanisms underlying the association between these factors and breast cancer risk are poorly understood. The aim of this study, therefore, was to determine whether obesity and reproductive history are associated with expression levels of two breast cancer-related long non-coding RNAs (lncRNAs), namely ZFAS1 and SRA1 in cancer-free breast tissues of women. In the current research, 145 healthy women were recruited, and the quantitative expression levels of the two lncRNAs were determined through qPCR assay after gathering the mammoplasty breast tissue samples. It was found that women with body mass index (BMI)≥30 kg/m 2 and BMI 25-29 kg/m 2 show a low expression of ZFAS1 compared to the BMI<25 kg/m 2 ( P=0.031 and P=0.027, respectively). Then, the correlation analysis disclosed a negative correlation of ZFAS1 low expression with increasing BMI (r=-0.194, P=0.019). Interestingly, this analysis demonstrated a negative correlation between low expression of the ZFAS1 and high BMI in women with menarche age below 14 (r=-221; P=0.028). Lastly, it was also revealed that there was a negative association of the low expression level of ZFAS1 with increasing BMI in women through regression models (B=-0.048, P=0.019). These findings suggest interesting clues about the links between high BMI and the expression levels of ZFAS1 in non-diseased breasts that may help us better understand the underlying mechanisms through which obesity contributes to breast carcinogenesis. However, such results need more validations in future research.

  18. Normal Tissue Complication Probability Estimation by the Lyman-Kutcher-Burman Method Does Not Accurately Predict Spinal Cord Tolerance to Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Daly, Megan E.; Luxton, Gary; Choi, Clara Y.H.; Gibbs, Iris C.; Chang, Steven D.; Adler, John R.; Soltys, Scott G.

    2012-01-01

    Purpose: To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear–quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS). Methods and Materials: From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18–30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8–30.9 Gy) and 22.0 Gy (range, 20.2–26.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD 50 , and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n. Results: In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy. Conclusions: The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP

  19. Efficiency Evaluation of Five-Phase Outer-Rotor Fault-Tolerant BLDC Drives under Healthy and Open-Circuit Faulty Conditions

    Directory of Open Access Journals (Sweden)

    ARASHLOO, R. S.

    2014-05-01

    Full Text Available Fault tolerant motor drives are an interesting subject for many applications such as automotive industries and wind power generation. Among different configurations of these systems, five-phase BLDC drives are gaining more importance which is because of their compactness and high efficiency. Due to replacement of field windings by permanent magnets in their rotor structure, the main sources of power losses in these drives are iron (core losses, copper (winding losses, and inverter unit (semiconductor losses. Although low amplitude of power losses in five-phase BLDC drives is an important aspect for many applications, but their efficiency under faulty conditions is not considered in previous studies. In this paper, the efficiency of an outer-rotor five phase BLDC drive is evaluated under normal and different faulty conditions. Open-circuit fault is considered for one, two adjacent and two non-adjacent faulty phases. Iron core losses are calculated via FEM simulations in Flux-Cedrat software, and moreover, inverter losses and winding copper losses are simulated in MATLAB� environment. Experimental evaluations are conducted to evaluate the efficiency of the entire BLDC drive which verifies the theoretical developments.

  20. Circulating and Tissue-Resident CD4+ T Cells With Reactivity to Intestinal Microbiota Are Abundant in Healthy Individuals and Function Is Altered During Inflammation.

    Science.gov (United States)

    Hegazy, Ahmed N; West, Nathaniel R; Stubbington, Michael J T; Wendt, Emily; Suijker, Kim I M; Datsi, Angeliki; This, Sebastien; Danne, Camille; Campion, Suzanne; Duncan, Sylvia H; Owens, Benjamin M J; Uhlig, Holm H; McMichael, Andrew; Bergthaler, Andreas; Teichmann, Sarah A; Keshav, Satish; Powrie, Fiona

    2017-11-01

    Interactions between commensal microbes and the immune system are tightly regulated and maintain intestinal homeostasis, but little is known about these interactions in humans. We investigated responses of human CD4 + T cells to the intestinal microbiota. We measured the abundance of T cells in circulation and intestinal tissues that respond to intestinal microbes and determined their clonal diversity. We also assessed their functional phenotypes and effects on intestinal resident cell populations, and studied alterations in microbe-reactive T cells in patients with chronic intestinal inflammation. We collected samples of peripheral blood mononuclear cells and intestinal tissues from healthy individuals (controls, n = 13-30) and patients with inflammatory bowel diseases (n = 119; 59 with ulcerative colitis and 60 with Crohn's disease). We used 2 independent assays (CD154 detection and carboxy-fluorescein succinimidyl ester dilution assays) and 9 intestinal bacterial species (Escherichia coli, Lactobacillus acidophilus, Bifidobacterium animalis subsp lactis, Faecalibacterium prausnitzii, Bacteroides vulgatus, Roseburia intestinalis, Ruminococcus obeum, Salmonella typhimurium, and Clostridium difficile) to quantify, expand, and characterize microbe-reactive CD4 + T cells. We sequenced T-cell receptor Vβ genes in expanded microbe-reactive T-cell lines to determine their clonal diversity. We examined the effects of microbe-reactive CD4 + T cells on intestinal stromal and epithelial cell lines. Cytokines, chemokines, and gene expression patterns were measured by flow cytometry and quantitative polymerase chain reaction. Circulating and gut-resident CD4 + T cells from controls responded to bacteria at frequencies of 40-4000 per million for each bacterial species tested. Microbiota-reactive CD4 + T cells were mainly of a memory phenotype, present in peripheral blood mononuclear cells and intestinal tissue, and had a diverse T-cell receptor Vβ repertoire. These

  1. A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.

    Science.gov (United States)

    Martinon-Torres, Federico; Gimenez-Sanchez, Francisco; Bernaola-Iturbe, Enrique; Diez-Domingo, Javier; Jiang, Qin; Perez, John L

    2014-09-08

    Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose. Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants. Copyright © 2014. Published by Elsevier Ltd.

  2. Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue

    International Nuclear Information System (INIS)

    Schwab, Felix; Schleede, Simone; Hahn, Dieter

    2013-01-01

    Purpose: An experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. Materials and Methods: Lungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. Results: In all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p = 0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p = 0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p = 0.03). Conclusion: The contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI. (orig.)

  3. Sex-related and tissue-specific effects of tobacco smoking on brain atrophy: assessment in a large longitudinal cohort of healthy elderly

    Directory of Open Access Journals (Sweden)

    Quentin eDuriez

    2014-11-01

    Full Text Available We investigated the cross-sectional and longitudinal effects of tobacco smoking on brain atrophy in a large cohort of healthy elderly participants (65 to 80 years. MRI was used for measuring whole brain (WB, gray matter (GM, white matter (WM, and hippocampus (HIP volumes at study entry time (baseline, N=1,451, and the annualized rates of variation of these volumes using a 4-year follow-up MRI in a subpart of the cohort (N=1,111. Effects of smoking status (never, former, or current smoker at study entry and of lifetime tobacco consumption on these brain phenotypes were studied using sex-stratified AN(COVAs, including other health parameters as covariates. At baseline, male current smokers had lower GM, while female current smokers had lower WM. In addition, female former smokers exhibited reduced baseline HIP, the reduction being correlated with lifetime tobacco consumption. Longitudinal analyses demonstrated that current smokers, whether men or women, had larger annualized rates of HIP atrophy, as compared to either current or former smokers, independent of their lifetime consumption of tobacco. There was no effect of smoking on the annualized rate of WM loss. In all cases, measured sizes of these tobacco-smoking effects were of the same order of magnitude than those of age, and larger than effect sizes of any other covariate. These results demonstrate gender- and tissue specific effects of tobacco smoking on brain atrophy. They indicate that tobacco smoking is a major factor of brain aging, with notable effects on the hippocampus annualized-rate of atrophy after the age of 65.

  4. Jelly-type carbohydrate supplement in healthy subjects suppresses the catabolism of adipose tissue and muscle protein and improves their satisfactions

    Directory of Open Access Journals (Sweden)

    Takuro Oyama

    2018-06-01

    Full Text Available Summary: Background & aims: Many studies have reported the effects of preoperative clear fluid carbohydrate supplements; however, few studies have reported the effects of preoperative jelly-type carbohydrate supplements. This study aimed to assess the effect of a jelly-type oral nutritional supplement (ONS on metabolism, redox balance by using various surrogate markers and to evaluate its excretion from the stomach. Methods: This study was conducted according to a crossover design. Participants underwent a control experiment whereby they fasted after dinner and only ingested water until the experiment. The remaining participants underwent an ONS experiment whereby they ingested 400 g of ONS before bed and another 400 g at 7:00 am. Blood samples were collected at 9:00 am. After a break of at least 24 h, participants underwent the alternate experiment. Results: Thirty minutes after intake of jelly, the gastric antrum appeared flat (the same result as that at baseline on ultrasonography. The ONS group showed significantly lower serum free fatty acid levels (100 μEq/L, p = 0.027, vs. 327 μEq/L, n = 6, total ketone bodies levels, 3-MH/creatinine levels, and oxidative stress surrogate markers. Serum insulin levels were significantly higher and participant's satisfaction was improved in the ONS group. Conclusions: We have the limitations of our methodologies as surrogate markers, compared with direct measurement of lipolysis, proteolysis and redox balance regulation. But Jelly-type ONS suppresses the catabolism of adipose tissue and muscle protein, decreases oxidative stress and improves patient satisfaction in healthy participants, without any increased risk of aspiration. Keywords: Crossover design, Jelly-type oral nutritional supplement, Metabolism, Antioxidation, ERAS

  5. Association of Maternal Vitamin D Status with Glucose Tolerance and Caesarean Section in a Multi-Ethnic Asian Cohort: The Growing Up in Singapore Towards Healthy Outcomes Study.

    Science.gov (United States)

    Loy, See Ling; Lek, Ngee; Yap, Fabian; Soh, Shu E; Padmapriya, Natarajan; Tan, Kok Hian; Biswas, Arijit; Yeo, George Seow Heong; Kwek, Kenneth; Gluckman, Peter D; Godfrey, Keith M; Saw, Seang Mei; Müller-Riemenschneider, Falk; Chong, Yap-Seng; Chong, Mary Foong-Fong; Chan, Jerry Kok Yen

    2015-01-01

    Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26-28 weeks' gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section. In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73). 25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency

  6. Association of Maternal Vitamin D Status with Glucose Tolerance and Caesarean Section in a Multi-Ethnic Asian Cohort: The Growing Up in Singapore Towards Healthy Outcomes Study.

    Directory of Open Access Journals (Sweden)

    See Ling Loy

    Full Text Available Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD with gestational diabetes mellitus (GDM and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO study.Plasma 25OHD concentrations, fasting glucose (FG and 2-hour postprandial glucose (2HPPG concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26-28 weeks' gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section.In total, 388 (41.3% women had 25OHD inadequacy. Of these, 131 (33.8%, 155 (39.9% and 102 (26.3% were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI = 0.01, 0.14, but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR = 1.39, 95% CI = 0.95, 2.05 was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33, while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43 and Indian women (OR = 2.41, 95% CI = 1.01, 5.73.25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency

  7. Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.

    Science.gov (United States)

    Vesikari, Timo; Wysocki, Jacek; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert E; York, Laura J; Perez, John L

    2016-06-01

    Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. Healthy adolescents aged ≥11 to B proteins different from the vaccine antigens. Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270

  8. Healthy Places for Healthy People

    Science.gov (United States)

    Describes the Healthy Places for Healthy People technical assistance program that helps communities create walkable, healthy, economically vibrant places by engaging with local health care facility partners

  9. Crafting tolerance

    DEFF Research Database (Denmark)

    Kirchner, Antje; Freitag, Markus; Rapp, Carolin

    2011-01-01

    Ongoing changes in social structures, orientation, and value systems confront us with the growing necessity to address and understand transforming patterns of tolerance as well as specific aspects, such as social tolerance. Based on hierarchical analyses of the latest World Values Survey (2005......–08) and national statistics for 28 countries, we assess both individual and contextual aspects that influence an individual's perception of different social groupings. Using a social tolerance index that captures personal attitudes toward these groupings, we present an institutional theory of social tolerance. Our...

  10. The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice

    DEFF Research Database (Denmark)

    Sylow, Lykke; Long, Jonathan; Lokurkar, Isha A

    2016-01-01

    Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia (CML). In this study we identify dasatinib as a potent inducer of PGC-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal ......, dasatinib significantly impaired glucose tolerance in obese, but not lean mice. As far as we are aware, this is the first study to show that dasatinib regulates PGC-1α and causes glucose intolerance in obese mice. This should be considered in the treatment of CML....

  11. Maintaining Healthy Skin -- Part 2

    Science.gov (United States)

    ... and SCI • Depression and SCI • Taking Care of Pressure Sores • Maintaining Healthy Skin (Part I) • Maintaining Healthy Skin ( ... For information on establishing skin tolerance, see our “Pressure Sores” pamphlet.) Pressure releases in a wheelchair can be ...

  12. Induction of abiotic stress tolerance in plants by endophytic microbes.

    Science.gov (United States)

    Lata, R; Chowdhury, S; Gond, S K; White, J F

    2018-04-01

    Endophytes are micro-organisms including bacteria and fungi that survive within healthy plant tissues and promote plant growth under stress. This review focuses on the potential of endophytic microbes that induce abiotic stress tolerance in plants. How endophytes promote plant growth under stressful conditions, like drought and heat, high salinity and poor nutrient availability will be discussed. The molecular mechanisms for increasing stress tolerance in plants by endophytes include induction of plant stress genes as well as biomolecules like reactive oxygen species scavengers. This review may help in the development of biotechnological applications of endophytic microbes in plant growth promotion and crop improvement under abiotic stress conditions. Increasing human populations demand more crop yield for food security while crop production is adversely affected by abiotic stresses like drought, salinity and high temperature. Development of stress tolerance in plants is a strategy to cope with the negative effects of adverse environmental conditions. Endophytes are well recognized for plant growth promotion and production of natural compounds. The property of endophytes to induce stress tolerance in plants can be applied to increase crop yields. With this review, we intend to promote application of endophytes in biotechnology and genetic engineering for the development of stress-tolerant plants. © 2018 The Society for Applied Microbiology.

  13. NMR-metabolomics profiling of mammary gland secretory tissue and milk serum in two goat breeds with different levels of tolerance to seasonal weight loss.

    Science.gov (United States)

    Palma, Mariana; Hernández-Castellano, Lorenzo E; Castro, Noemí; Arguëllo, Anastasio; Capote, Juan; Matzapetakis, Manolis; de Almeida, André Martinho

    2016-06-21

    Goats are of special importance in the Mediterranean and tropical regions for producing a variety of dairy products. The scarcity of pastures during the dry season leads to seasonal weight loss (SWL), which affects milk production. In this work, we studied the effect of feed-restriction on two dairy goat breeds, with different tolerance levels to SWL: the Majorera breed (tolerant) and the Palmera breed (susceptible). Nuclear magnetic resonance (NMR) was used to compare the metabolome of an aqueous fraction of the mammary gland and milk serum from both breeds. Goats in mid-lactation were divided by breed, and each in two feed-regime groups: the control group and the restricted-fed group (to achieve 15-20% reduction of body weight at the end of the experiment). Milk and mammary gland samples were collected at the end of the experimental period (23rd day). (1)H NMR spectra were collected from the aqueous extract of the mammary gland biopsies and the milk serum. Profiling analysis has led to the identification of 46 metabolites in the aqueous extract of the mammary gland. Lactose, glutamate, glycine and lactate were found to be the most abundant. Analysis of milk serum allowed the identification of 50 metabolites, the most abundant being lactose, citrate and creatine. Significant differences were observed, in mammary gland biopsies and milk serum, between control and restricted-fed groups in both breeds, albeit with no differences between the breeds. Variations seem to be related to metabolism adaptation to the low-energy diet and are indicative of breed-specific microflora. Milk serum showed more metabolites varying between control and restricted groups, than the mammary gland. The Majorera breed also showed more variations than the Palmera breed in milk samples, which could be an indication of a prompt adaptation to SWL by the Majorera breed.

  14. Eating Healthy

    Science.gov (United States)

    ... There is much we can do to promote healthy eating habits. Together we can prevent or delay onset of diabetes, obesity and other chronic conditions and diseases. Benefits Helps maintain a healthy weight A healthy weight reduces risk of chronic ...

  15. Toxicokinetics of fumonisin B1 in turkey poults and tissue persistence after exposure to a diet containing the maximum European tolerance for fumonisins in avian feeds.

    Science.gov (United States)

    Tardieu, Didier; Bailly, Jean-Denis; Skiba, Fabien; Grosjean, François; Guerre, Philippe

    2008-09-01

    The kinetic of fumonisin B1 (FB1) after a single IV and oral dose, and FB1 persistence in tissue were investigated in turkey poults by HPLC after purification of samples on columns. After IV administration (single-dose: 10mg FB1/kg bw), serum concentration-time curves were best described by a three-compartment open model. Elimination half-life and mean residence time of FB1 were 85 and 52min, respectively. After oral administration (single-dose: 100mg FB1/kg bw) bioavailability was 3.2%; elimination half-life and mean residence time were 214 and 408min, respectively. Clearance of FB1 was 7.6 and 7.5ml/min/kg for IV and oral administration, respectively. Twenty-four hours after the administration of FB1 by the intravenous route, liver and kidney contained the highest levels of FB1 in tissues, level in muscle was low or below the limit of detection (LD, 13microg/kg). The persistence of FB1 in tissue was also studied after administration for 9 weeks of a feed that contained 5, 10 and 20mg FB1+FB2/kg diet. Eight hours after the last intake of 20mg FB1+FB2/kg feed (maximum recommended concentration of fumonisins established by the EU for avian feed), hepatic and renal FB1 concentrations were 119 and 22microg/kg, level in muscles was below the LD.

  16. Immunogenicity and tolerability of inactivated flu vaccine In high risk and healthy children Inmunogenicidad y tolerancia de la vacuna inactivada anti-influenza en niños en alto riesgo y en controles sanos

    Directory of Open Access Journals (Sweden)

    Maria Luisa Avila Aguero

    2007-08-01

    Full Text Available We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe® in 154 children between 6 and 36 months of age at high risk of influenza- related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP. The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications.Se realizó un estudio clínico abierto para evaluar la inmunogenícidad y la seguridad de la vacuna inactivada anti-influenza, Imovax Gripe®, en 154 niños entre 6 y 36 meses de edad con alto riesgo de complicaciones ligadas a la influenza, y en un grupo de referencia de 64 niños sanos. El estudio fue

  17. Abscisic acid synergizes with rosiglitazone to improve glucose tolerance and down-modulate macrophage accumulation in adipose tissue: possible action of the cAMP/PKA/PPAR γ axis.

    Science.gov (United States)

    Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

    2010-10-01

    Abscisic acid (ABA) is effective in preventing insulin resistance and obesity-related inflammation through a PPAR γ-dependent mechanism. The objective of this study was to assess the efficacy ABA in improving glucose homeostasis and suppress inflammation when administered in combination with rosiglitazone (Ros) and to determine whether PPAR γ activation by ABA is initiated via cAMP/protein kinase A (PKA) signaling. Obese db/db mice were fed high-fat diets containing 0, 10, or 70 mg/kg Ros with and without racemic ABA (100 mg/kg) for 60 days. Glucose tolerance and fasting insulin levels were assessed at 6 and 8 weeks, respectively, and adipose tissue macrophage (ATM) infiltration was examined by flow cytometry. Gene expression was examined on white adipose tissue (WAT) and stromal vascular cells (SVCs) cultured with ABA, Ros, or an ABA/Ros combination. Both Ros and ABA improved glucose tolerance, and ABA decreased plasma insulin levels while having no effect on Ros-induced weight gain. ABA in combination with low-dose Ros (10 mg/kg; Roslo) synergistically inhibited ATM infiltration. Treatment of SVCs with Ros, ABA or ABA/Ros suppressed expression of the M1 marker CCL17. ABA and Ros synergistically increased PPAR γ activity and pretreatment with a cAMP-inhibitor or a PKA-inhibitor abrogated ABA-induced PPAR γ activation. ABA and Ros act synergistically to modulate PPAR γ activity and macrophage accumulation in WAT and ABA enhances PPAR γ activity through a membrane-initiated mechanism dependent on cAMP/PKA signaling. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  18. Evaluation of healthy muscle tissue by strain and shear wave elastography – Dependency on depth and ROI position in relation to underlying bone

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Carlsen, Jonathan Frederik; Christiansen, Iben Riishede

    2016-01-01

    and methods: Ten healthy volunteers (five males and five females) had their biceps brachii, gastrocnemius, and quadriceps muscle examined with strain- and shear wave elastography at three different depths and in regions located above bone and beside bone. Strain ratios were averaged from cine-loops of 10 s...

  19. Om tolerance

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2007-01-01

    Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik.......Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik....

  20. Ayurvedic Amalaki Rasayana promotes improved stress tolerance

    Indian Academy of Sciences (India)

    Ayurvedic Amalaki Rasayana promotes improved stress tolerance and thus ... and some otheringredients, and is used for general good health and healthy aging. ... Wild-type larvae/flies rearedon AR-supplemented food survived the various ...

  1. Assessment of tissue oxygen saturation during a vascular occlusion test using near-infrared spectroscopy: the role of probe spacing and measurement site studied in healthy volunteers

    NARCIS (Netherlands)

    Bezemer, R.; Lima, A.; Myers, D.; Klijn, E.; Heger, M.; Goedhart, P.T.; Bakker, J.; Ince, C.

    2009-01-01

    INTRODUCTION: To assess potential metabolic and microcirculatory alterations in critically ill patients, near-infrared spectroscopy (NIRS) has been used, in combination with a vascular occlusion test (VOT), for the non-invasive measurement of tissue oxygen saturation (StO2), oxygen consumption, and

  2. Efficacy and tolerability of a new ibuprofen 200mg plaster in patients with acute sports-related traumatic blunt soft tissue injury/contusion.

    Science.gov (United States)

    Predel, Hans-Georg; Giannetti, Bruno; Connolly, Mark P; Lewis, Fraser; Bhatt, Aomesh

    2018-01-01

    Ibuprofen is used for the treatment of non-serious pain. This study assessed the efficacy and safety of a new ibuprofen plaster for the treatment of pain associated with acute sports impact injuries/contusions. In this randomised, double-blind, multi-centre, placebo controlled, parallel group study, adults (n = 130; 18-58 years of age) diagnosed with acute sports-related blunt soft tissue injury/contusion were randomized to receive either ibuprofen 200 mg plaster or placebo plaster. Plasters were administered once daily for five consecutive days. The primary assessment was area under the visual analogue scale (VAS) of pain on movement (POM) over 0 to three days (VAS AUC 0-3d ). Other endpoints included algometry AUC from 0 to three days (AUC 0-3d ) and 0 to five days (AUC 0-5d ), to evaluate improvement of sensitivity at the injured site, and patient and investigator global assessment of efficacy. Safety was monitored throughout the study. The ibuprofen plaster resulted in superior reduction in AUC 0-3d compared with placebo; the Least Squares (LS) mean difference was 662.82 mm*h in favour of the ibuprofen 200mg plaster (P = 0.0011). The greater improvement in VAS AUC of POM was also observed after 12 h, 24 h, and five days of therapy. Tenderness also significantly improved with the ibuprofen plaster compared with placebo; LS mean difference in algometry/tenderness AUC 0-3d was 1.87 N/cm 2 *d and AUC 0-5d was 1.87 N/cm 2 *d (P values ≤0.0004). At all study timepoints, a greater percentage of patients and investigators rated the effectiveness of the ibuprofen 200 mg plaster as good/excellent than the placebo plaster. Treatment-emergent adverse events for the ibuprofen plaster were few (≤1.5%) and were mild in severity. The results of this study indicate 200 mg plaster is effective and safe for the treatment of pain due to acute sports-related traumatic blunt soft tissue injury/contusion in adults.

  3. Towards Tolerance

    NARCIS (Netherlands)

    Lisette Kuyper; Jurjen Iedema; Saskia Keuzenkamp

    2013-01-01

    Across Europe, public attitudes towards lesbian, gay and bisexual (LGB) individuals range from broad tolerance to widespread rejection. Attitudes towards homosexuality are more than mere individual opinions, but form part of the social and political structures which foster or hinder the equality

  4. Intolerant tolerance.

    Science.gov (United States)

    Khushf, G

    1994-04-01

    The Hyde Amendment and Roman Catholic attempts to put restrictions on Title X funding have been criticized for being intolerant. However, such criticism fails to appreciate that there are two competing notions of tolerance, one focusing on the limits of state force and accepting pluralism as unavoidable, and the other focusing on the limits of knowledge and advancing pluralism as a good. These two types of tolerance, illustrated in the writings of John Locke and J.S. Mill, each involve an intolerance. In a pluralistic context where the free exercise of religion is respected, John Locke's account of tolerance is preferable. However, it (in a reconstructed form) leads to a minimal state. Positive entitlements to benefits like artificial contraception or nontherapeutic abortions can legitimately be resisted, because an intolerance has already been shown with respect to those that consider the benefit immoral, since their resources have been coopted by taxation to advance an end that is contrary to their own. There is a sliding scale from tolerance (viewed as forbearance) to the affirmation of communal integrity, and this scale maps on to the continuum from negative to positive rights.

  5. Tissue persistence of fumonisin B1 in ducks and after exposure to a diet containing the maximum European tolerance for fumonisins in avian feeds.

    Science.gov (United States)

    Tardieu, Didier; Bailly, Jean-Denis; Benlashehr, Imad; Auby, Alienor; Jouglar, Jean-Yves; Guerre, Philippe

    2009-12-10

    Toxicity and persistence of fumonisin B1 (FB1) in liver, kidney and muscle were investigated in ducks fed 5, 10 and 20mg FB1+FB2/kg feed during force-feeding. Mortality and signs of toxicity were only obtained with 20mg/kg, whereas an increased Sa/So ratio was observed from 5mg/kg on. Persistence of FB1 was only found in liver (16 and 20 microg FB1/kg liver in ducks fed 10 and 20 mg FB1+FB2/kg feed, respectively). Toxicokinetic studies were conducted by the intravenous route (IV, single dose: 10mg FB1/kg body weight) and the oral route (single dose: 100mg FB1/kg body weight), in growing ducks and in ducks during force-feeding. After IV administration, serum concentration-time curves were described by a two-compartment open model. Elimination half-life and mean residence time of FB1 were 26 and 24 min, respectively, clearance was 19.3 ml/min/kg. After oral administration, bioavailability, elimination half-life, mean residence time and clearance varied during force-feeding and growth from 2-2.3%, 71-80 min, 200-188 min, 16.7-17 ml/min/kg, respectively. Taken together these results demonstrate that the risk of persistence of FB1 in ducks after force-feeding is very low, Sa/So being a good biomarker which increases before signs of toxicity and risk of persistence of FB1 in tissue (limit of detection 13 microg/kg).

  6. External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Sminia, Peter, E-mail: p.sminia@vumc.nl [Department of Radiation Oncology, Radiobiology Section, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, Amsterdam (Netherlands); Mayer, Ramona [EBG MedAustron GmbH., Viktor Kaplan-Strasse 2, A-2700, Wiener Neustadt (Austria)

    2012-04-05

    Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis), to obtain information on the tolerance dose and treatment volume of normal human brain tissue. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2{sub cumulative}). Analysis shows that the EQD2{sub cumulative} increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT) to LINAC-based stereotactic radiosurgery (SRS). The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. Following conventional re-irradiation, radiation-induced normal brain tissue necrosis occurred beyond an EQD2{sub cumulative} around 100 Gy. With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated. Despite the dose escalation, no increase in late normal tissue toxicity was reported. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials.

  7. External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain

    Directory of Open Access Journals (Sweden)

    Peter Sminia

    2012-04-01

    Full Text Available Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis, to obtain information on the tolerance dose and treatment volume of normal human brain tissue. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2cumulative. Analysis shows that the EQD2cumulative increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT to LINAC-based stereotactic radiosurgery (SRS. The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. Following conventional re-irradiation, radiation-induced normal brain tissue necrosis occurred beyond an EQD2cumulative around 100 Gy. With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated. Despite the dose escalation, no increase in late normal tissue toxicity was reported. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials.

  8. Healthy Living

    Science.gov (United States)

    ... Health Menu Topics Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The Natural World Games ... Lessons Topics Expand Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The Natural World Games ...

  9. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals 

    DEFF Research Database (Denmark)

    Sheldrick, A; Camara, S; Ilieva, M

    2017-01-01

    The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence...... and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8±5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant...... medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample...

  10. The CT (Hounsfield unit) number of brain tissue in healthy infants. A new reliable method for detection of possible degenerative disease.

    Science.gov (United States)

    Boris, P; Bundgaard, F; Olsen, A

    1987-01-01

    It is difficult to correlate CT Hounsfield unit (H. U.) numbers from one CT investigation to another and from one CT scanner to another, especially when dealing with small changes in the brain substance, as in degenerative brain diseases in children. By subtracting the mean value of cerebrospinal fluid (CSF) from the mean value of grey and white matter, it is possible to remove most of the errors due, for example, to maladjustments, short and long-term drift, X-ray fan, and detector asymmetry. Measurements of white and grey matter using these methods showed CT H. U. numbers changing from 15 H. U. to 22 H. U. in white matter and 23 H. U. to 30 H. U. in grey matter in 86 healthy infants aged 0-5 years. In all measurements, the difference between grey and white matter was exactly 8 H. U. The method has proven to be highly accurate and reproducible.

  11. Salt Tolerance

    OpenAIRE

    Xiong, Liming; Zhu, Jian-Kang

    2002-01-01

    Studying salt stress is an important means to the understanding of plant ion homeostasis and osmo-balance. Salt stress research also benefits agriculture because soil salinity significantly limits plant productivity on agricultural lands. Decades of physiological and molecular studies have generated a large body of literature regarding potential salt tolerance determinants. Recent advances in applying molecular genetic analysis and genomics tools in the model plant Arabidopsis thaliana are sh...

  12. Infectious Tolerance

    OpenAIRE

    Jonuleit, Helmut; Schmitt, Edgar; Kakirman, Hacer; Stassen, Michael; Knop, Jürgen; Enk, Alexander H.

    2002-01-01

    Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, ...

  13. Infectious Tolerance

    Science.gov (United States)

    Jonuleit, Helmut; Schmitt, Edgar; Kakirman, Hacer; Stassen, Michael; Knop, Jürgen; Enk, Alexander H.

    2002-01-01

    Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, freshly isolated CD4+ T helper (Th) cells. This infectious suppressive activity, transferred from CD25+ Treg cells via cell contact, is cell contact–independent and partially mediated by soluble transforming growth factor (TGF)-β. The induction of suppressive properties in conventional CD4+ Th cells represents a mechanism underlying the phenomenon of infectious tolerance. This explains previously published conflicting data on the role of TGF-β in CD25+ Treg cell–induced immunosuppression. PMID:12119350

  14. Healthy Weight

    Science.gov (United States)

    ... such diets limit your nutritional intake, can be unhealthy, and tend to fail in the long run. The key to achieving and maintaining a healthy weight isn't about short-term dietary changes. It's about a lifestyle that includes healthy eating, regular physical activity, and ...

  15. 68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

    International Nuclear Information System (INIS)

    Kroiss, A.; Putzer, D.; Decristoforo, C.; Uprimny, C.; Warwitz, B.; Nilica, B.; Gabriel, M.; Kendler, D.; Waitz, D.; Virgolini, I.J.; Widmann, G.

    2013-01-01

    We wanted to establish the range of 68 Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 68 Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUV max (mean ± standard deviation) values of 68 Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV max (p max between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p max for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p 68 Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV max can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUV max , except in liver metastases of patients with NET. (orig.)

  16. {sup 68}Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kroiss, A.; Putzer, D.; Decristoforo, C.; Uprimny, C.; Warwitz, B.; Nilica, B.; Gabriel, M.; Kendler, D.; Waitz, D.; Virgolini, I.J. [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Widmann, G. [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-04-15

    We wanted to establish the range of {sup 68}Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 {sup 68}Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUV{sub max} (mean {+-} standard deviation) values of {sup 68}Ga-DOTA-TOC were 29.8 {+-} 16.5 in 162 liver metastases, 19.8 {+-} 18.8 in 89 bone metastases and 34.6 {+-} 17.1 in 43 pancreatic NET (33.6 {+-} 14.3 in 30 tumours of the uncinate process and 36.3 {+-} 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV{sub max} (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV{sub max} between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV{sub max} for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001). {sup 68}Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV{sub max} can offer important clinical

  17. Healthy Places

    Centers for Disease Control (CDC) Podcasts

    Every person has a stake in environmental public health. As the environment deteriorates, so does the physical and mental health of the people within it. Healthy places are those designed and built to improve the quality of life for all people who live, work, worship, learn, and play within their borders -- where every person is free to make choices amid a variety of healthy, available, accessible, and affordable options. The CDC recognizes significant health issues and places that are vital in developing the Healthy Places program and provides examples in this report.

  18. Healthy Schools

    Science.gov (United States)

    ... Nutrition Facts School Meals Smart Snacks Celebrations & Rewards Food and Beverage Marketing Water Access Healthy Eating Learning Opportunities Staff ... Services Acute & Emergency Care Care Coordination Chronic Disease Management Family Engagement Chronic ... Allergies Oral Health Local School Wellness Policy Whole ...

  19. Pharmacokinetic and tolerability of i.m. disodium clodronate 200 mg/lidocaine 1%, given twice monthly, in comparison with i.m. disodium clodronate 100 mg/lidocaine 1%, given weekly, in healthy postmenopausal female patients.

    Science.gov (United States)

    Radicioni, Milko; Cremonesi, Giovanni; Baraldi, Enrica; Leuratti, Chiara; Mariotti, Fabrizia

    2013-04-01

    Clodronate is a bisphosphonate effective in the prevention and treatment of osteoporosis in postmenopausal women. Non-adherence to bisphosphonates, however, is a major issue in clinical practice. Simplifying dose regimens may increase compliance. To assess bioequivalence between an intramuscular (i.m.) clodronate 200 mg/lidocaine 1% twice-a-month formulation and a clodronate 100 mg/lidocaine 1% weekly formulation in 32 postmenopausal women. In this double-blind, randomized, two-way crossover study, test and reference formulations were administered in single dose, with a 2-week wash-out between administrations. The primary endpoint was clodronic acid cumulative excretion in the first 24 hours after injection (Xu0-24h). Cumulative excretion in the 72 hours post-dose (Xu0-72h) and maximum excretion rate (Ratemax) were also evaluated. Bioequivalence was assumed if the 90% confidence intervals (CIs) of the geometric means ratios of the dose-normalized parameters were within the 80.00 - 125.00% range. Local tolerability was evaluated. Mean Xu0-24h values were 114.03 ±23.13 mg and 55.22 ±9.73 mg for clodronate 200 mg and 100 mg. The 90% CIs for dose-normalized Xu0-24h, Xu0-72h and Ratemax ere 95 -110%, 94 -107% and 95 - 113%. Local tolerability of both treatments was good. The differences in pain intensity between formulations were not sigificantly different at most assessment times. Headache was the only treatment-related adverse event. Bioequivalence of the two formulations was confirmed in terms of dose-normalized rate and amount of clodronic acid excretion. This result, together with the favorable tolerability of the novel 200 mg formulation, suggests the possibility of reducing the number of i.m. administrations from once-a-week to twice-a-month.

  20. Repressive Tolerance

    DEFF Research Database (Denmark)

    Pedersen, Morten Jarlbæk

    2017-01-01

    Consultation of organised interests and others when drafting laws is often seen as an important source of both input and output legitimacy. But whereas the input side of the equation stems from the very process of listening to societal actors, output legitimacy can only be strengthened if consult......Consultation of organised interests and others when drafting laws is often seen as an important source of both input and output legitimacy. But whereas the input side of the equation stems from the very process of listening to societal actors, output legitimacy can only be strengthened...... a substantial effect on the substance of laws – shows that there is a great difference in the amenability of different branches of government but that, in general, authorities do not listen much despite a very strong consultation institution and tradition. A suggestion for an explanation could be pointing...... to an administrative culture of repressive tolerance of organised interests: authorities listen but only reacts in a very limited sense. This bears in it the risk of jeopardising the knowledge transfer from societal actors to administrative ditto thus harming the consultation institutions’ potential for strengthening...

  1. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers.

    Science.gov (United States)

    Chowdhury, Abeed H; Cox, Eleanor F; Francis, Susan T; Lobo, Dileep N

    2012-07-01

    We compared the effects of intravenous infusions of 0.9% saline ([Cl] 154 mmol/L) and Plasma-Lyte 148 ([Cl] 98 mmol/L, Baxter Healthcare) on renal blood flow velocity and perfusion in humans using magnetic resonance imaging (MRI). Animal experiments suggest that hyperchloremia resulting from 0.9% saline infusion may affect renal hemodynamics adversely, a phenomenon not studied in humans. Twelve healthy adult male subjects received 2-L intravenous infusions over 1 hour of 0.9% saline or Plasma-Lyte 148 in a randomized, double-blind manner. Crossover studies were performed 7 to 10 days apart. MRI scanning proceeded for 90 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled and weight recorded hourly for 4 hours. Sustained hyperchloremia was seen with saline but not with Plasma-Lyte 148 (P Blood volume changes were identical (P = 0.867), but there was greater expansion of the extravascular fluid volume after saline (P = 0.029). There was a significant reduction in mean renal artery flow velocity (P = 0.045) and renal cortical tissue perfusion (P = 0.008) from baseline after saline, but not after Plasma-Lyte 148. There was no difference in concentrations of urinary neutrophil gelatinase-associated lipocalin after the 2 infusions (P = 0.917). This is the first human study to demonstrate that intravenous infusion of 0.9% saline results in reductions in renal blood flow velocity and renal cortical tissue perfusion. This has implications for intravenous fluid therapy in perioperative and critically ill patients. NCT01087853.

  2. Random lasing in human tissues

    International Nuclear Information System (INIS)

    Polson, Randal C.; Vardeny, Z. Valy

    2004-01-01

    A random collection of scatterers in a gain medium can produce coherent laser emission lines dubbed 'random lasing'. We show that biological tissues, including human tissues, can support coherent random lasing when infiltrated with a concentrated laser dye solution. To extract a typical random resonator size within the tissue we average the power Fourier transform of random laser spectra collected from many excitation locations in the tissue; we verified this procedure by a computer simulation. Surprisingly, we found that malignant tissues show many more laser lines compared to healthy tissues taken from the same organ. Consequently, the obtained typical random resonator was found to be different for healthy and cancerous tissues, and this may lead to a technique for separating malignant from healthy tissues for diagnostic imaging

  3. A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.

    Science.gov (United States)

    Palmer, Melissa; Jennings, Lee; Silberg, Debra G; Bliss, Caleb; Martin, Patrick

    2018-03-16

    Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat. Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids. All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 μmol (standard deviation [SD] 468.965) with volixibat and 224.75 μmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990

  4. Healthy Places

    Centers for Disease Control (CDC) Podcasts

    2007-04-10

    Every person has a stake in environmental public health. As the environment deteriorates, so does the physical and mental health of the people within it. Healthy places are those designed and built to improve the quality of life for all people who live, work, worship, learn, and play within their borders -- where every person is free to make choices amid a variety of healthy, available, accessible, and affordable options. The CDC recognizes significant health issues and places that are vital in developing the Healthy Places program and provides examples in this report.  Created: 4/10/2007 by CDC National Center for Environmental Health.   Date Released: 4/13/2007.

  5. A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.

    Science.gov (United States)

    Struys, Michel M R F; Valk, Beatrijs I; Eleveld, Douglas J; Absalom, Anthony R; Meyer, Peter; Meier, Sascha; den Daas, Izaak; Chou, Thomas; van Amsterdam, Kai; Campagna, Jason A; Sweeney, Steven P

    2017-07-01

    Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new "soft" etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships. Sixty subjects were divided into 10 cohorts and received an increasing, single bolus of either ABP-700 or placebo. Safety was assessed by clinical laboratory evaluations, infusion-site reactions, continuous monitoring of vital signs, physical examination, adverse event monitoring, and adrenocorticotropic hormone stimulation testing. Clinical effects were assessed with modified observer's assessment of alertness/sedation and Bispectral Index monitoring. Pharmacokinetic parameters were calculated. Stopping criteria were met at 1.00 mg/kg dose. No serious adverse events were reported. Adverse events were dose-dependent and comprised involuntary muscle movement, tachycardia, and ventilatory effects. Adrenocorticotropic hormone stimulation evoked a physiologic cortisol response in all subjects, no different from placebo. Pharmacokinetics were dose-proportional. A three-compartment pharmacokinetic model described the data well. A rapid onset of anesthesia/sedation after bolus administration and also a rapid recovery were observed. A quantitative concentration-effect relationship was described for the modified observer's assessment of alertness/sedation and Bispectral Index. This first-in-human study of ABP-700 shows that ABP-700 was safe and well tolerated after single-bolus injections up to 1.00 mg/kg. Bolus doses of 0.25 and 0.35 mg/kg were found to provide the most beneficial clinical effect versus side-effect profile.

  6. Healthy living

    Science.gov (United States)

    ... living URL of this page: //medlineplus.gov/ency/article/002393.htm Healthy living To use the sharing features on this page, please enable JavaScript. Good health habits can allow you to avoid illness and improve your quality of life. The following steps will help you ...

  7. Intracranial CSF flow on cine-MR. 2. Qualitative analysis in CSF dynamics by MR signal ratio of CSF to fat tissue in healthy subjects and patients with aqueduct stenosis

    International Nuclear Information System (INIS)

    Kadowaki, Chikafusa; Hara, Mitsuhiro; Takeuchi, Kazuo; Saito, Isamu

    1994-01-01

    Changes in MR signal intensities (SIs) of CSF and relative MR signal ratios (SRs) of intraventricular CSF to fat tissue were evaluated in 5 healthy adults on cine MR images during a cardiac cycle in a study of normal intracranial CSF dynamics. The altered patterns of MR SIs and SRs in 6 patients with aqueduct stenosis were compared with normal CSF flow patterns in a demonstration of CSF dynamics changes. MR SIs of CSF within the ventricles were measured on each cine image obtained by cardiac gated, multiframe, cine MR imaging. Chronological changes in MR SIs and SRs during a cardiac cycle were compared with the actual CSF flow visualized on real cine images. In normal CSF circulation, MR SIs of CSF within the ventricles were reduced quickly following an R-wave on ECG to 15% of the R-R interval, after which SIs fluctuated slightly. These changes in MR SIs of CSF could only be related to the pulsatile CSF flow through the foramen of Monro into the anterior part of the third ventricle during early cardiac systole. MR SRs of CSF to fat tissue fluctuated according to the actual CSF flow within the ventricles during a cardiac cycle. MR SRs in the third ventricle decreased to 20-30% of the R-R interval following the R-wave due to downward CSF flow during early cardiac systole, and decreased again from late cardiac systole to diastole due to caudal CSF flow in the third ventricle. In the fourth ventricle, MR SRs of CSF decreased to 60-80% of the R-R interval because of the CSF flow through the aqueduct during cardiac diastole. In patients with aqueduct stenosis, MR SRs of CSF within the ventricles fluctuated randomly, and the amplitude of MR SRs was also greater than in subjects with a patent aqueduct. These changes were identified as turbulence and stagnation due to obstruction in the CSF pathway. Analysis of chronological changes in MR signal ratios of CSF to fat is useful in demonstrating the pathophysiologic features of intracranial CSF dynamics. (author) 52 refs

  8. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals - a proof of concept study.

    Science.gov (United States)

    Sheldrick, A; Camara, S; Ilieva, M; Riederer, P; Michel, T M

    2017-10-01

    The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8±5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant treatment and overall age 84.3±5 years versus 14 unaffected subjects at age 70.3±13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample size in this proof of concept study corroborates data from previous studies, which show that treatment with antidepressants mediates alterations in neuroplasticity via the action of NTF. However, more research using post-mortem brain tissue with larger samples needs to be carried out as well as longitudinal studies to further verify these results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. The tissue injury and repair in cancer radiotherapy. A concept of tissue architecture and radio sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

    1975-06-01

    One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed.

  10. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

    Science.gov (United States)

    Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

    2016-05-05

    In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. Published by Elsevier Ltd.

  11. Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study.

    Science.gov (United States)

    Santolaya, María Elena; O'Ryan, Miguel L; Valenzuela, María Teresa; Prado, Valeria; Vergara, Rodrigo; Muñoz, Alma; Toneatto, Daniela; Graña, Gabriela; Wang, Huajun; Clemens, Ralf; Dull, Peter M

    2012-02-18

    Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents. We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713. Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (pvaccine-related serious adverse events were reported and no significant safety signals were identified. On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against

  12. Teaching Tolerance? Associational Diversity and Tolerance Formation

    DEFF Research Database (Denmark)

    Rapp, Carolin; Freitag, Markus

    2015-01-01

    , a closer look is taken at how associational diversity relates to the formation of tolerance and the importance of associations as schools of tolerance are evaluated. The main theoretical argument follows contact theory, wherein regular and enduring contact in diverse settings reduces prejudice and thereby...

  13. Effects of whole grain rye, with and without resistant starch type 2 supplementation, on glucose tolerance, gut hormones, inflammation and appetite regulation in an 11-14.5 hour perspective; a randomized controlled study in healthy subjects.

    Science.gov (United States)

    Sandberg, Jonna C; Björck, Inger M E; Nilsson, Anne C

    2017-04-21

    The prevalence of obesity is increasing worldwide and prevention is needed. Whole grain has shown potential to lower the risk of obesity, cardiovascular disease and type 2 diabetes. One possible mechanism behind the benefits of whole grain is the gut fermentation of dietary fiber (DF), e.g. non-starch polysaccharides and resistant starch (RS), in whole grain. The purpose of the study is to investigate the effect of whole grain rye-based products on glucose- and appetite regulation. Twenty-one healthy subjects were provided four rye-based evening test meals in a crossover overnight study design. The test evening meals consisted of either whole grain rye flour bread (RFB) or a 1:1 ratio of whole grain rye flour and rye kernels bread (RFB/RKB), with or without added resistant starch (+RS). White wheat flour bread (WWB) was used as reference evening meal. Blood glucose, insulin, PYY, FFA, IL-6 as well as breath H 2 and subjective rating of appetite were measured the following morning at fasting and repeatedly up to 3.5 h after a standardized breakfast consisting of WWB. Ad libitum energy intake was determined at lunch, 14.5 h after evening test and reference meals, respectively. The evening meal with RFB/RKB + RS decreased postprandial glucose- and insulin responses (iAUC) (P appetite regulation in a semi-acute perspective. Meanwhile, RFB and RFB/RKB improved subjective appetite ratings. The effects probably emanate from gut fermentation events. The study was registered at: ClinicalTrials.gov, register number NCT02347293 ( www.clinicaltrials.gov/ct2/show/NCT02347293 ). Registered 15 January 2015.

  14. Lactose tolerance tests

    Science.gov (United States)

    Hydrogen breath test for lactose tolerance ... Two common methods include: Lactose tolerance blood test Hydrogen breath test The hydrogen breath test is the preferred method. It measures the amount of hydrogen ...

  15. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms...... or interpretations of recognition and toleration are considered, confusing and problematic uses of the terms are noted, and the compatibility of toleration and recognition is discussed. The article argues that there is a range of legitimate and importantly different conceptions of both toleration and recognition...

  16. Fault Tolerant Feedback Control

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Niemann, H.

    2001-01-01

    An architecture for fault tolerant feedback controllers based on the Youla parameterization is suggested. It is shown that the Youla parameterization will give a residual vector directly in connection with the fault diagnosis part of the fault tolerant feedback controller. It turns out...... that there is a separation be-tween the feedback controller and the fault tolerant part. The closed loop feedback properties are handled by the nominal feedback controller and the fault tolerant part is handled by the design of the Youla parameter. The design of the fault tolerant part will not affect the design...... of the nominal feedback con-troller....

  17. Anhydrobiosis and Freezing-Tolerance

    DEFF Research Database (Denmark)

    McGill, Lorraine; Shannon, Adam; Pisani, Davide

    2015-01-01

    Anhydrobiotic animals can survive the loss of both free and bound water from their cells. While in this state they are also resistant to freezing. This physiology adapts anhydrobiotes to harsh environments and it aids their dispersal. Panagrolaimus davidi, a bacterial feeding anhydrobiotic nematode...... Panagrolaimus strains from tropical, temperate, continental and polar habitats and we analysed their phylogenetic relationships. We found that several other Panagrolaimus isolates can also survive freezing when fully hydrated and that tissue extracts from these freezing-tolerant nematodes can inhibit the growth...

  18. Healthy food trends -- flaxseeds

    Science.gov (United States)

    ... seeds; Healthy food trends - linseeds; Healthy snacks - flaxseeds; Healthy diet - flaxseeds; Wellness - flaxseeds ... of nutrition and dietetics: dietary fatty acids for healthy adults. J Acad Nutr Diet . 2014;114(1):136-153. PMID: 24342605 www. ...

  19. Healthy Cooking Techniques

    Science.gov (United States)

    Healthy Lifestyle Nutrition and healthy eating Healthy-cooking techniques capture the flavor and nutrients of food without extra fat or salt. By Mayo Clinic Staff Healthy cooking doesn't mean that ...

  20. Mast cell degranulation breaks peripheral tolerance.

    Science.gov (United States)

    de Vries, V C; Wasiuk, A; Bennett, K A; Benson, M J; Elgueta, R; Waldschmidt, T J; Noelle, R J

    2009-10-01

    Mast cells (MC) have been shown to mediate regulatory T-cell (T(reg))-dependent, peripheral allograft tolerance in both skin and cardiac transplants. Furthermore, T(reg) have been implicated in mitigating IgE-mediated MC degranulation, establishing a dynamic, reciprocal relationship between MC and T(reg) in controlling inflammation. In an allograft tolerance model, it is now shown that intragraft or systemic MC degranulation results in the transient loss of T(reg) suppressor activities with the acute, T-cell dependent rejection of established, tolerant allografts. Upon degranulation, MC mediators can be found in the skin, T(reg) rapidly leave the graft, MC accumulate in the regional lymph node and the T(reg) are impaired in the expression of suppressor molecules. Such a dramatic reversal of T(reg) function and tissue distribution by MC degranulation underscores how allergy may causes the transient breakdown of peripheral tolerance and episodes of acute T-cell inflammation.

  1. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2004-01-01

    BackgroundDimensioning and TolerancingTolerance Format and Decimal PlacesConverting Plus/Minus Dimensions and Tolerances into Equal Bilaterally Toleranced DimensionsVariation and Sources of VariationTolerance AnalysisWorst-case Tolerance StackupsStatistical Tolerance StackupsGeometric Dimensioning and Tolerancing (GD&T)Converting Plus/Minus Tolerancing to Positional Tolerancing and Projected Tolerance ZonesDiametral and Radial Tolerance StackupsSpecifying Material Condition Modifiers and Their Effect on Tolerance Stackups The Tolerance Stackup SketchThe Tolerance Stackup Report FormTolerance S

  2. How Does Physical Activity Help Build Healthy Bones?

    Science.gov (United States)

    ... Share Facebook Twitter Pinterest Email Print How does physical activity help build healthy bones? Bones are living tissue. Weight-bearing physical activity causes new bone tissue to form, and this ...

  3. Activation of natural killer T cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via the IL-4/STAT6 signaling axis in obesity

    NARCIS (Netherlands)

    Ji, Yewei; Sun, Shengyi; Xu, Aimin; Yang, Liu; Bhargava, Prerna; Lam, Karen S.; Gao, Bin; Lee, Chih-Hao; Kersten, Sander; Qi, Ling

    2012-01-01

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type-1

  4. Activation of natural killer T Cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signalling axis in obesity

    NARCIS (Netherlands)

    Ji, Y.; Sun, S.; Xu, Aimin; Bhargava, P.; Yang, Liu; Lam, K.S.L.; Gao, Bin; Lee, Chih-Hao; Kersten, A.H.; Qi, L.

    2012-01-01

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type

  5. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2013-01-01

    Under conditions of pluralism different cultures, interests or values can come into conflict, which raises the problem of how to secure peaceful co-existence. The idea of toleration historically emerged as an answer to this problem. Recently Rainer Forst has argued that toleration should not just...... be based on a modus vivendi designed to secure peaceful co-existence, but should be based on moral reasons. Forst therefore advances what he calls the ‘respect conception’ of toleration as an in itself morally desirable type of relationship, which is furthermore the only conception of toleration...... that avoids various so-called ‘paradoxes of toleration’. The paper first examines whether Forst’s respect conception can be applied descriptively to distinguish between actual patterns of behaviour and classify different acts of toleration. Then the focus is shifted to toleration out of respect as a normative...

  6. Tolerance in Drosophila

    OpenAIRE

    Atkinson, Nigel S.

    2009-01-01

    The set of genes that underlie ethanol tolerance (inducible resistance) are likely to overlap with the set of genes responsible for ethanol addiction. Whereas addiction is difficult to recognize in simple model systems, behavioral tolerance is readily identifiable and can be induced in large populations of animals. Thus, tolerance lends itself to analysis in model systems with powerful genetics. Drosophila melanogaster has been used by a variety of laboratories for the identification of genes...

  7. System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

    Science.gov (United States)

    Kologrivova, I V; Suslova, T E; Koshel'skaya, O A; Vinnitskaya, I V; Trubacheva, O A

    2014-03-01

    The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

  8. The tissue injury and repair in cancer radiotherapy

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju

    1975-01-01

    One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed. (author)

  9. Six Different Fat Tolerance Tests in Young, Healthy Subjects

    DEFF Research Database (Denmark)

    Rasmussen, Ole Winther; Lauszus, Finn Friis

    2016-01-01

    ) was dtermined for the postprandial values. Results: The meals with six types of butters had similar postprandial response even if the saturated fat content varied with 50%.Gender significantly affected the TG responses, as time to pesk was 90 minutes in women and 180 min in men. Postprandial AUC was higherwith...

  10. Healthy Family 2009: Assuring Healthy Aging

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Healthy Family 2009 Assuring Healthy Aging Past Issues / Winter 2009 ... for steady, modest loss. Seek emotional support from family and friends. Expect setbacks; forgive yourself. Make physical ...

  11. Compromise and Toleration

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature, justifi...... in compromise are more stringent than those for being tolerated. Still, the limits of compromise cannot be drawn to narrowly if it is to remain its value as a form of agreement that respects and embodies the differences of opinion in society.......Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature......, justification, and limits of compromise if we see it merely as a matter of toleration. While toleration is mainly a matter of accepting citizens' equal right to co-existence as subjects to law, political compromise includes the parties in making law – it makes them co-authors of law. Toleration entails...

  12. Tolerances in micro manufacturing

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Zhang, Yang; Islam, Aminul

    This paper describes a method for analysis of tolerances in micro manufacturing. It proposes a mapping oftolerances to dimensions and compares this with current available international standards. The analysisdocuments that tolerances are not scaled down as the absolute dimension. In practice...

  13. Fault tolerant computing systems

    International Nuclear Information System (INIS)

    Randell, B.

    1981-01-01

    Fault tolerance involves the provision of strategies for error detection damage assessment, fault treatment and error recovery. A survey is given of the different sorts of strategies used in highly reliable computing systems, together with an outline of recent research on the problems of providing fault tolerance in parallel and distributed computing systems. (orig.)

  14. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    be based on a modus vivendi designed to secure peaceful co-existence, but should be based on moral reasons. Forst therefore advances what he calls the ‘respect conception’ of toleration as an in itself morally desirable type of relationship, which is furthermore the only conception of toleration...

  15. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms or inter...

  16. Remember Tolerance Differently

    DEFF Research Database (Denmark)

    Tønder, Lars

    2012-01-01

    This essay questions the linear conception of history which often accompanies the way contemporary democratic theory tends to disavow tolerance's discontinuities and remainders. In the spirit of Foucault's genealogy of descent, the idea is to develop a new sense of tolerance's history, not by inv......This essay questions the linear conception of history which often accompanies the way contemporary democratic theory tends to disavow tolerance's discontinuities and remainders. In the spirit of Foucault's genealogy of descent, the idea is to develop a new sense of tolerance's history......, not by invoking a critique external to contemporary democratic theory, but by witnessing the history of tolerance paraliptically, with an eye to what it obscures and yet presupposes....

  17. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Science.gov (United States)

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  18. Healthy Sleep Habits

    Science.gov (United States)

    ... Sleep Apnea Testing CPAP Healthy Sleep Habits Healthy Sleep Habits Your behaviors during the day, and especially ... team at an AASM accredited sleep center . Quick Sleep Tips Follow these tips to establish healthy sleep ...

  19. Healthy Pets and People

    Science.gov (United States)

    ... prevent the spread of germs between pets and people. Keep pets and their supplies out of the kitchen, and ... a local wildlife rehabilitation facility. More Information Healthy Pets Healthy People Clean Hands Save Lives! Stay Healthy at Animal ...

  20. Thalassemia: Healthy Living

    Science.gov (United States)

    ... Thalassemia” More What can a person living with thalassemia do to stay healthy? A healthy lifestyle is ... disorder”, as well as making healthy choices. Managing Thalassemia Thalassemia is a treatable disorder that can be ...

  1. Healthy food trends - kale

    Science.gov (United States)

    Healthy food trends - borecole; Healthy snacks - kale; Weight loss - kale; Healthy diet - kale; Wellness - kale ... Kale is full of vitamins and minerals, including: Vitamin A Vitamin C Vitamin K If you take ...

  2. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  3. An abnormal carbohydrate tolerance in acromegaly

    International Nuclear Information System (INIS)

    Qi Jinwu

    1988-01-01

    An abnormal secretion of plasma human growth hormore (hGH) and insulin in 67 acromegalic patients had been previously treated by external pituitary radiation were studied. All subjects, following an overnight fast, a standard 100 g oral glucose tolerance test, were performed and venous blood samples were taken at 0, 30, 60, 120 and 180 min. They were measured for blood glucose, plasma insulin and hGH. The results of this study have shown that, of the 67 subjects, 23 cases had an abnormal glucose tolerance(34.32%). Diabetes was detected in 17 cases (23.37%) and 6 patients had decreased glucose tolerance(8.69%). In all, hGH levels were consistantly above 5 ng/ml and were not suppressed after an oral glucose load. In these patients, however, about one-third had abnormal glucose tolerance. Low plasma insulin response to glucose and that of the releasing were evident in them than the normal glucose tolerance and a healthy control group. In addition, the mechanism of the abnormal secretion of hGH and insulin were disscussed

  4. Critical temperature: A quantitative method of assessing cold tolerance

    Science.gov (United States)

    D.H. DeHayes; M.W., Jr. Williams

    1989-01-01

    Critical temperature (Tc), defined as the highest temperature at which freezing injury to plant tissues can be detected, provides a biologically meaningful and statistically defined assessment of the relative cold tolerance of plant tissues. A method is described for calculating critical temperatures in laboratory freezing studies that use...

  5. A Multirelational Account of Toleration

    DEFF Research Database (Denmark)

    Ferretti, Maria Paola; Lægaard, Sune

    2013-01-01

    Toleration classically denotes a relation between two agents that is characterised by three components: objection, power, and acceptance overriding the objection. Against recent claims that classical toleration is not applicable in liberal democracies and that toleration must therefore either be ...

  6. 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.

  7. State, religion and toleration

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2009-01-01

    Contribution to Religion and State - From separation to cooperation? Legal-philosophical reflections for a de-secularized world. (IVR Cracow Special Workshop). Eds. Bart. C. Labuschagne & Ari M. Solon. Abstract: Toleration is indeed a complex phenomenon. A discussion of the concept will have...... to underline not only the broadmindedness and liberty of individuals or of groups, but also the relevant distinctions and arguments in political philosophy, epistemology, philosophy of religion and philosophical anthropology and their connection with educational issues. Through a discussion of these relations......, the essay argues three theses: (1) Toleration is not reducible to an ethics of spiritual freedom. (2) Toleration is not neutral to fanatism. (3) Toleration involves esteem for the person....

  8. Have a Healthy Pregnancy

    Science.gov (United States)

    ... important that you: Don’t smoke or drink alcohol. Eat healthy foods and get enough folic acid. Stay active. Take ... Learn more: Pregnant? Don’t Smoke! Quit Smoking Alcohol Use in Pregnancy Next ... 7 of 11 sections Take Action: Eat Healthy and Stay Active Eat healthy foods. Making healthy food choices during pregnancy can help ...

  9. A Theory of Tolerance

    OpenAIRE

    Corneo, Giacomo; Jeanne, Olivier

    2006-01-01

    We develop an economic theory of tolerance where styles of behaviour are invested with symbolic value. Value systems are endogenous and taught by parents to their children. In conjunction with actual behaviour, value systems determine the esteem enjoyed by individuals. Intolerant individuals have all symbolic value invested in a single style of behaviour, whereas tolerant people have diversified values. The proposed model identifies a link between the unpredictability of children's lifestyles...

  10. Tolerance doses for treatment planning

    International Nuclear Information System (INIS)

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD 5 ) or 50% (TD 50 ) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs

  11. CYCLOXYDIM-TOLERANT MAIZE – BREEDERS STANDPOINT

    Directory of Open Access Journals (Sweden)

    G. Bekavac

    2008-09-01

    Full Text Available Cycloxydim-Tolerant Maize (CTM was developed by researches at the University of Minnesota. CTM plants were regenerated from tissue culture selected for callus growth in the presence of cycloxydim, and the resulting plants were shown to contain a nuclear mutation, expressed as a single, partially dominant gene (known as Acc1 that conferred tolerance to the herbicide. Cycloxydim is a systemic herbicide for post emergence application in dicot crops to selectively control grass weeds. Corn, like most grasses is susceptible to cycloxydim due to inhibited acetyl-coenzyimeA carboxylaze enzyme activity. There are two key benefits of this technology: first, cycloxydim applications in CTM hybrids can be delayed until the weed spectrum and population density exceed agro-economic threshold; second, cycloxydim can be applied at either stage of plant development with no effect on basic agronomic traits, compared to non treated plants. Nevertheless, this type of tolerance requires 2 genes to be fully effective, i.e. gene must be present in both inbred parents to provide complete tolerance in the resulting hybrid. Such type of tolerance doubles the chances for yield drag and doubles the number of inbred conversions needed. This also limits germplasm integration and increases time lag in developing hybrids. Despite these difficulties, many seed companies introduce tolerance to cycloxydim into their commercial inbreds, and many of them have already commercialized CTM hybrids. Finally, it came as a logical question what is more important – hybrid performance or new trait? Critical to the success of this technology has been yield performance of CTM hybrids. At the same time, performance and herbicide tolerance do not exclude each other and can surely co-exist. To be accepted, this coexistence must secure high profitability to corn producers. However, CTM hybrids will not replace conventional ones on a large scale, but could be used as a specific tool, or could

  12. Role of adenosine receptors in caffeine tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, S.G.; Mante, S.; Minneman, K.P. (Emory Univ. School of Medicine, Atlanta, GA (USA))

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity.

  13. Role of adenosine receptors in caffeine tolerance

    International Nuclear Information System (INIS)

    Holtzman, S.G.; Mante, S.; Minneman, K.P.

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity

  14. Salt tolerance in wheat - an overview. (abstract)

    International Nuclear Information System (INIS)

    Ashraf, M.

    2005-01-01

    Considerable efforts have been made during the past few years to overcome the problem of salinity through the development of salt tolerant lines of important crop species using screening, breeding and molecular biology techniques. In view of considerable importance of spring wheat as a major staple food crop of many countries, plant scientists have directed there attention to identify and develop salt tolerant genotypes that can be of direct use on salt-affected soils. Although considerable progress in understanding individual phenomenon and genes involved in plant response to salinity stress has been made over the past few years, underlying physiological mechanisms producing salt tolerant plants is still unclear. It has been suggested that salt tolerance of plants could be improved by defining genes or characters. Twenty years ago, it was suggested that genes located on the D genome of bread wheat confer salinity tolerance to hexaploid wheat by reducing Na/sup +/ accumulation in the leaf tissue and increasing discrimination in favour of K/sup +/. However, recently, low Na/sup +/ accumulation and high K/sup +/Na/sup +/ discrimination, of similar magnitude to bread wheat, in several selections of durum wheat has been observed, supporting the notion that salt tolerance is controlled by multiple genes, which are distributed throughout the entire set of chromosomes. In addition, various physiological selection criteria such as compatible osmolytes (glycinebetaine, proline, trehalose, mannitol etc.), antioxidants, carbon discrimination, high K/sup +//Na/sup +/ ratio etc. have been discussed. Although tolerance to salinity is known to have a multigenic inheritance, mediated by a large number of genes, knowledge of heritability and the genetic mode of salinity tolerance is still lacking because few studies have yet been conducted in these areas. Indeed, genetic information is lagging behind the physiological information. Modern methods such as recombinant DNA technology

  15. A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Morris Peter E

    2012-02-01

    Full Text Available Abstract Background The tissue factor (TF-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS. Methods This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO2/FiO2 ≤ 300 mm. Eighteen patients (6 per cohort were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters. Results Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population. Conclusions Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS. Trial registration ClinicalTrials.gov: NCT01438853

  16. 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...

  17. Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG

    DEFF Research Database (Denmark)

    Støy, Julie; Kampmann, Ulla; Mengel, Annette

    2015-01-01

    BACKGROUND: CD300LG rs72836561 (c.313C>T, p.Arg82Cys) has in genetic-epidemiological studies been associated with the lipoprotein abnormalities of the metabolic syndrome. CD300LG belongs to the CD300-family of membrane-bound molecules which have the ability to recognize and interact with extracel......BACKGROUND: CD300LG rs72836561 (c.313C>T, p.Arg82Cys) has in genetic-epidemiological studies been associated with the lipoprotein abnormalities of the metabolic syndrome. CD300LG belongs to the CD300-family of membrane-bound molecules which have the ability to recognize and interact...... with extracellular lipids. We tested whether this specific polymorphism results in abnormal lipid accumulation in skeletal muscle and liver and other indices of metabolic dysfunction. METHODS: 40 healthy men with a mean age of 55 years were characterized metabolically including assessment of insulin sensitivity...

  18. Systematic optimization of multiplex zymography protocol to detect active cathepsins K, L, S, and V in healthy and diseased tissue: compromise among limits of detection, reduced time, and resources.

    Science.gov (United States)

    Dumas, Jerald E; Platt, Manu O

    2013-07-01

    Cysteine cathepsins are a family of proteases identified in cancer, atherosclerosis, osteoporosis, arthritis, and a number of other diseases. As this number continues to rise, so does the need for low cost, broad use quantitative assays to detect their activity and can be translated to the clinic in the hospital or in low resource settings. Multiplex cathepsin zymography is one such assay that detects subnanomolar levels of active cathepsins K, L, S, and V in cell or tissue preparations observed as clear bands of proteolytic activity after gelatin substrate SDS-PAGE with conditions optimal for cathepsin renaturing and activity. Densitometric analysis of the zymogram provides quantitative information from this low cost assay. After systematic modifications to optimize cathepsin zymography, we describe reduced electrophoresis time from 2 h to 10 min, incubation assay time from overnight to 4 h, and reduced minimal tissue protein necessary while maintaining sensitive detection limits; an evaluation of the pros and cons of each modification is also included. We further describe image acquisition by Smartphone camera, export to Matlab, and densitometric analysis code to quantify and report cathepsin activity, adding portability and replacing large scale, darkbox imaging equipment that could be cost prohibitive in limited resource settings.

  19. Systematic optimization of multiplex zymography protocol to detect active cathepsins K, L, S, and V in healthy and diseased tissue: compromise between limits of detection, reduced time, and resources

    Science.gov (United States)

    Dumas, Jerald E.; Platt, Manu O.

    2013-01-01

    Cysteine cathepsins are a family of proteases identified in cancer, atherosclerosis, osteoporosis, arthritis and a number of other diseases. As this number continues to rise, so does the need for low cost, broad use quantitative assays to detect their activity and can be translated to the clinic in the hospital or in low resource settings. Multiplex cathepsin zymography is one such assay that detects subnanomolar levels of active cathepsins K, L, S, and V in cell or tissue preparations observed as cleared bands of proteolytic activity after gelatin substrate SDS-PAGE with conditions optimal for cathepsin renaturing and activity. Densitometric analysis of the zymogram provides quantitative information from this low cost assay. After systematic modifications to optimize cathepsin zymography, we describe reduced electrophoresis time from 2 hours to 10 minutes, incubation assay time from overnight to 4 hours, and reduced minimal tissue protein necessary while maintaining sensitive detection limits; an evaluation of the pros and cons of each modification is also included. We further describe image acquisition by smartphone camera, export to Matlab, and densitometric analysis code to quantify and report cathepsin activity, adding portability and replacing large scale, darkbox imaging equipment that could be cost prohibitive in limited resource settings. PMID:23532386

  20. Abnormal glucose tolerance and lipid abnormalities in Indian ...

    African Journals Online (AJOL)

    Glucose tolerance and lipid levels in a random sample of 103 Indian patients (96 males and 7 females) with coronary artery disease (CAD) aged between 20 and 55 years were compared with those in a healthy Indian control group matched as regards age and sex. Previous episodes of myocardial infarction were taken as ...

  1. Escaping the tolerance trap

    International Nuclear Information System (INIS)

    Hammoudeh, S.; Madan, V.

    1994-01-01

    In order to examine the implications of the weakening of OPEC's responsiveness in adjusting its production levels, this paper explicitly incorporates rigidity in the quantity adjustment mechanism, thereby extending previous research which assumed smooth quantity adjustments. The rigidity is manifested in a tolerance range for the discrepancy between the declared target price and that of the market. This environment gives rise to a 'tolerance trap' which impedes the convergence process and inevitably brings the market to a standstill before its reaches the targeted price and revenue objectives. OPEC's reaction to the standstill has important implications for the achievement of the target-based equilibrium and for the potential collapse of the market price. This paper examines OPEC's policy options in the tolerance trap and reveals that the optional policy in order to break this impasse and move closer to the equilibrium point is gradually to reduce output and not to flood the market. (Author)

  2. Tolerance to exercise intensity modulates pleasure when exercising in music: The upsides of acoustic energy for High Tolerant individuals.

    Directory of Open Access Journals (Sweden)

    Mauraine Carlier

    Full Text Available Moderate physical activity can be experienced by some as pleasurable and by others as discouraging. This may be why many people lack sufficient motivation to participate in the recommended 150 minutes of moderately intense exercise per week. In the present study, we assessed how pleasure and enjoyment were modulated differently by one's tolerance to self-paced physical activity. Sixty-three healthy individuals were allocated to three independent experimental conditions: a resting condition (watching TV, a cycling in silence condition, and a cycling in music condition. The tolerance threshold was assessed using the PRETIE-Questionnaire. Physical activity consisted in cycling during 30 minutes, at an intensity perceived as "somewhat difficult" on the Ratings of Perceived Exertion Scale. While controlling for self-reported physical activity level, results revealed that for the same perception of exertion and a similar level of enjoyment, the High Tolerance group produced more power output than the Low Tolerance group. There was a positive effect of music for High Tolerant individuals only, with music inducing greater power output and more pleasure. There was an effect of music on heart rate frequency in the Low Tolerant individuals without benefits in power output or pleasure. Our results suggest that for Low Tolerant individuals, energizing environments can interfere with the promised (positive distracting effects of music. Hence, tolerance to physical effort must be taken into account to conceive training sessions that seek to use distracting methods as means to sustain pleasurable exercising over time.

  3. Tolerance to exercise intensity modulates pleasure when exercising in music: The upsides of acoustic energy for High Tolerant individuals.

    Science.gov (United States)

    Carlier, Mauraine; Delevoye-Turrell, Yvonne

    2017-01-01

    Moderate physical activity can be experienced by some as pleasurable and by others as discouraging. This may be why many people lack sufficient motivation to participate in the recommended 150 minutes of moderately intense exercise per week. In the present study, we assessed how pleasure and enjoyment were modulated differently by one's tolerance to self-paced physical activity. Sixty-three healthy individuals were allocated to three independent experimental conditions: a resting condition (watching TV), a cycling in silence condition, and a cycling in music condition. The tolerance threshold was assessed using the PRETIE-Questionnaire. Physical activity consisted in cycling during 30 minutes, at an intensity perceived as "somewhat difficult" on the Ratings of Perceived Exertion Scale. While controlling for self-reported physical activity level, results revealed that for the same perception of exertion and a similar level of enjoyment, the High Tolerance group produced more power output than the Low Tolerance group. There was a positive effect of music for High Tolerant individuals only, with music inducing greater power output and more pleasure. There was an effect of music on heart rate frequency in the Low Tolerant individuals without benefits in power output or pleasure. Our results suggest that for Low Tolerant individuals, energizing environments can interfere with the promised (positive) distracting effects of music. Hence, tolerance to physical effort must be taken into account to conceive training sessions that seek to use distracting methods as means to sustain pleasurable exercising over time.

  4. Fault tolerant linear actuator

    Science.gov (United States)

    Tesar, Delbert

    2004-09-14

    In varying embodiments, the fault tolerant linear actuator of the present invention is a new and improved linear actuator with fault tolerance and positional control that may incorporate velocity summing, force summing, or a combination of the two. In one embodiment, the invention offers a velocity summing arrangement with a differential gear between two prime movers driving a cage, which then drives a linear spindle screw transmission. Other embodiments feature two prime movers driving separate linear spindle screw transmissions, one internal and one external, in a totally concentric and compact integrated module.

  5. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  6. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  7. Healthy Watersheds Protection

    Science.gov (United States)

    ... for restoring areas with degraded water quality, as well as protecting healthy waters from emerging problems before expensive damages occur. ... exclusively on restoring impaired waters, EPA created the Healthy ... more emphasis to proactively protecting high quality waters, following the ...

  8. Tips for Healthy Voices

    Science.gov (United States)

    ... prevent voice problems and maintain a healthy voice: Drink water (stay well hydrated): Keeping your body well hydrated by drinking plenty of water each day (6-8 glasses) is essential to maintaining a healthy voice. The ...

  9. Tissue types (image)

    Science.gov (United States)

    ... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

  10. NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity

    Directory of Open Access Journals (Sweden)

    Karen Nørgaard Nielsen

    2018-05-01

    Full Text Available Objective: The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society. We speculate that nicotinamide adenine dinucleotide (NAD+ biosynthesis exemplifies this concept. Indeed NAD+/NADH metabolism in fat tissue has been previously linked with obesity, yet whether it plays a causal role in diet-induced adiposity is unknown. Here we investigated how the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT supports adipose plasticity and the pathological progression to obesity. Methods: We utilized a newly generated Nampt loss-of-function model to investigate the tissue-specific and systemic metabolic consequences of adipose NAD+ deficiency. Energy expenditure, glycemic control, tissue structure, and gene expression were assessed in the contexts of a high dietary fat burden as well as the transition back to normal chow diet. Results: Fat-specific Nampt knockout (FANKO mice were completely resistant to high fat diet (HFD-induced obesity. This was driven in part by reduced food intake. Furthermore, HFD-fed FANKO mice were unable to undergo healthy expansion of adipose tissue mass, and adipose depots were rendered fibrotic with markedly reduced mitochondrial respiratory capacity. Yet, surprisingly, HFD-fed FANKO mice exhibited improved glucose tolerance compared to control littermates. Removing the HFD burden largely reversed adipose fibrosis and dysfunction in FANKO animals whereas the improved glucose tolerance persisted. Conclusions: These findings indicate that adipose NAMPT plays an essential role in

  11. Toleration, Groups, and Multiculturalism

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    have the ability to interfere with the group’s activities, an object of dislike or disapproval, an agent enjoying non-interference or a moral patient. This means that 'toleration of groups' can mean quite different things depending on the exact meaning of 'group' in relation to each component...

  12. Fault Tolerant Control Systems

    DEFF Research Database (Denmark)

    Bøgh, S. A.

    This thesis considered the development of fault tolerant control systems. The focus was on the category of automated processes that do not necessarily comprise a high number of identical sensors and actuators to maintain safe operation, but still have a potential for improving immunity to component...

  13. Toleration and its enemies

    DEFF Research Database (Denmark)

    Jarvad, Ib Martin

    2010-01-01

    After a presentation of the development of freedom of expression in Danish constitutional law, to freedom of the press in European human rights law - the Jersild case- to a right to mock and ridicule other faiths in recent Danish practice, the essay of Locke on toleration is examined, its...

  14. A little toleration, please

    Science.gov (United States)

    McKnight, C.

    2000-01-01

    Value pluralism does not imply relativism or subjectivism about values. What it does is allow respect for an at least limited toleration of values with which one may profoundly disagree. Thus a doctor can respect the autonomy of a patient whose values he does not share. Key Words: Pluralism • multiculturalism • relativism • subjectivism • patient autonomy PMID:11129842

  15. Cancerous tissue mapping from random lasing emission spectra

    International Nuclear Information System (INIS)

    Polson, R C; Vardeny, Z V

    2010-01-01

    Random lasing emission spectra have been collected from both healthy and cancerous tissues. The two types of tissue with optical gain have different light scattering properties as obtained from an average power Fourier transform of their random lasing emission spectra. The difference in the power Fourier transform leads to a contrast between cancerous and benign tissues, which is utilized for tissue mapping of healthy and cancerous regions of patients

  16. Deconstructing tolerance with clobazam

    Science.gov (United States)

    Wechsler, Robert T.; Sankar, Raman; Montouris, Georgia D.; White, H. Steve; Cloyd, James C.; Kane, Mary Clare; Peng, Guangbin; Tworek, David M.; Shen, Vivienne; Isojarvi, Jouko

    2016-01-01

    Objective: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Methods: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg−1·d−1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg−1·d−1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Results: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Conclusions: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. ClinicalTrials.gov identifier: NCT00518713 and NCT01160770. Classification of evidence: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. PMID:27683846

  17. ADOLESCENTS’ HEALTHY EATING

    DEFF Research Database (Denmark)

    Pedersen, Susanne

    understanding of adolescent healthy eating. Based on this, the thesis presents three research questions which are investigated in three research papers. The research questions are: 1. Which roles do parents and adolescents have in healthy eating socialisation? 2. How does the social influence from parents...... and family members’ roles regarding healthy eating socialisation is underexposed, the study aimed at exploring adolescents’ and parents’ awareness of and involvement in healthy eating and investigated how they related it to their roles in the healthy eating socialisation taking place within the family...... or a cooperative one helping parents. Parents initiated dialogues with family members about healthy eating and felt responsible as role models often fulfilling the adolescents’ demands and acknowledging their help. The findings confirm that parents still have the upper hand, when it comes to healthy eating...

  18. Induction of nitrate tolerance is not a useful treatment in cluster headache

    DEFF Research Database (Denmark)

    Christiansen, I; Iversen, Helle Klingenberg; Olesen, J

    2000-01-01

    UNLABELLED: The aims of the present study were to investigate whether induction of nitrate tolerance is a useful treatment in cluster headache and to correlate any changes in attack frequency of cluster headache and nitrate-induced headache to the vascular adaptation during continuous nitrate...... attacks and interval headaches over time. RESULTS: Tolerance was complete within 24 h in the middle cerebral arteries and after 7 days in the symptomatic temporal artery, while tolerance of the radial artery was not observed within this period. The time profiles of tolerance were almost identical...... to the time profiles observed in healthy subjects. A close temporal association between the disappearance of nitrate-induced headache and tolerance of the temporal artery was observed but tolerance had no effect on cluster headache attack frequency. CONCLUSIONS: Induction of tolerance to nitrates cannot...

  19. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

  20. Study of calcium-dependent lead-tolerance on plants differing in their level of Ca-deficiency tolerance

    International Nuclear Information System (INIS)

    Antosiewicz, Danuta Maria

    2005-01-01

    The main aim of the study was to determine the role of calcium in the amelioration of lead toxic effects in plants with accordingly high/low level of Pb-tolerance and high/low Ca-deficiency tolerance. The study was performed on maize, rye, tomato and mustard. Plants were cultivated in modified Knop's solution. They were subjected to Ca-deficiency, and to lead nitrate administered in the presence of four calcium nitrate concentrations 3.0, 2.4, 1.2, 0.3 mM. Lead-tolerance and tolerance to Ca-deficiency were determined, as were concentration of the studied elements in plant tissues, and the Pb deposition pattern at the ultrastructural level (electron microscopy study, X-ray microanalysis). In all studied plants, lead toxicity increased as medium calcium content decreased, however, only in the Ca-deficiency sensitive mustard with low Pb-tolerance was it accompanied by a rise in tissue lead concentration. In contrast, lead root and shoot levels did not increase in the highly Ca-deficiency tolerant tomato, mustard and rye with high Pb-tolerance irrespective of the Ca 2+ regimens applied. Thus, in these plants, lead's unfavourable effects resulted only from the higher toxicity of the same amount of lead in tissues at low calcium in the medium. Of particular relevance is the finding by electron microscopy and X-ray microanalysis, that under low calcium in both highly Ca-deficiency tolerant and Ca-deficiency sensitive plants, less efficient Pb 2+ detoxification was accompanied by the restriction of the formation of large lead deposits in cell walls. Obtained results are novel in demonstrating calcium involvement in the lead deposition in the cell wall, thus in the regulation of the internal lead detoxification. - Calcium regulated lead deposition in cell walls of plants

  1. Relatively lower body mass index is associated with an excess of severe truncal asymmetry in healthy adolescents: Do white adipose tissue, leptin, hypothalamus and sympathetic nervous system influence truncal growth asymmetry?

    Directory of Open Access Journals (Sweden)

    Triantafyllopoulos Georgios

    2009-06-01

    Full Text Available Abstract Background In healthy adolescents normal back shape asymmetry, here termed truncal asymmetry (TA, is evaluated by higher and lower subsets of BMI. The study was initiated after research on girls with adolescent idiopathic scoliosis (AIS showed that higher and lower BMI subsets discriminated patterns of skeletal maturation and asymmetry unexplained by existing theories of pathogenesis leading to a new interpretation which has therapeutic implications (double neuro-osseous theory. Methods 5953 adolescents age 11–17 years (boys 2939, girls 3014 were examined in a school screening program in two standard positions, standing forward bending (FB and sitting FB. The sitting FB position is thought to reveal intrinsic TA free from back humps induced by any leg-length inequality. TA was measured in both positions using a Pruijs scoliometer as angle of trunk inclinations (ATIs across the back at each of three spinal regions, thoracic, thoracolumbar and lumbar. Abnormality of ATIs was defined as being outside 2 standard deviations for each age group, gender, position and spinal region, and termed severe TA. Results In the sitting FB position after correcting for age,relatively lower BMIs are statistically associated with a greater number of severe TAs than with relatively higher BMIs in both girls (thoracolumbar region and boys (thoracolumbar and lumbar regions. The relative frequency of severe TAs is significantly higher in girls than boys for each of the right thoracic (56.76% and thoracolumbar (58.82% regions (p = 0.006, 0.006, respectively. After correcting for age, smaller BMIs are associated with more severe TAs in boys and girls. Discussion BMI is a surrogate measure for body fat and circulating leptin levels. The finding that girls with relatively lower BMI have significantly later menarche, and a significant excess of TAs, suggests a relation to energy homeostasis through the hypothalamus. The hypothesis we suggest for the pathogenesis

  2. Heat tolerance in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari

    As a consequence of global climate change, heat stress together with other abiotic stresses will remain an important determinant of future food security. Wheat (Triticum aestivum L.) is the third most important crop of the world feeding one third of the world population. Being a crop of temperate...... climate, wheat is sensitive to heat stress. We need to understand how our crops will perform in these changing climatic conditions and how we can develop varieties, which are more tolerant. The PhD study focussed on understanding heat tolerance in wheat with a combined approach of plant physiology...... and quantitative genetics in particular, plant phenotyping based quantitative trait loci (QTL) discovery for a physiological trait under heat stress. Chlorophyll a fluorescence trait, Fv/Fm was used as a phenotyping tool, as it reflects the effect of heat stress on maximum photochemical efficiency of photosystem...

  3. A randomized, controlled, double-blind crossover study on the effects of 1-L infusions of 6% hydroxyethyl starch suspended in 0.9% saline (voluven) and a balanced solution (Plasma Volume Redibag) on blood volume, renal blood flow velocity, and renal cortical tissue perfusion in healthy volunteers.

    Science.gov (United States)

    Chowdhury, Abeed H; Cox, Eleanor F; Francis, Susan T; Lobo, Dileep N

    2014-05-01

    We compared the effects of intravenous administration of 6% hydroxyethyl starch (maize-derived) in 0.9% saline (Voluven; Fresenius Kabi, Runcorn, United Kingdom) and a "balanced" preparation of 6% hydroxyethyl starch (potato-derived) [Plasma Volume Redibag (PVR); Baxter Healthcare, Thetford, United Kingdom] on renal blood flow velocity and renal cortical tissue perfusion in humans using magnetic resonance imaging. Hyperchloremia resulting from 0.9% saline infusion may adversely affect renal hemodynamics when compared with balanced crystalloids. This phenomenon has not been studied with colloids. Twelve healthy adult male subjects received 1-L intravenous infusions of Voluven or PVR over 30 minutes in a randomized, double-blind manner, with crossover studies 7 to 10 days later. Magnetic resonance imaging proceeded for 60 minutes after commencement of infusion to measure renal artery blood flow velocity and renal cortical perfusion. Blood was sampled, and weight was recorded at 0, 30, 60, 120, 180, and 240 minutes. Mean peak serum chloride concentrations were 108 and 106 mmol/L, respectively, after Voluven and PVR infusion (P = 0.032). Changes in blood volume (P = 0.867), strong ion difference (P = 0.219), and mean renal artery flow velocity (P = 0.319) were similar. However, there was a significant increase in mean renal cortical tissue perfusion after PVR when compared with Voluven (P = 0.033). There was no difference in urinary neutrophil gelatinase-associated liopcalin to creatinine ratios after the infusion (P = 0.164). There was no difference in the blood volume-expanding properties of the 2 preparations of 6% hydroxyethyl starch. The balanced starch produced an increase in renal cortical tissue perfusion, a phenomenon not seen with starch in 0.9% saline.

  4. Socially-Tolerable Discrimination

    OpenAIRE

    Amegashie, J. Atsu

    2008-01-01

    History is replete with overt discrimination on the basis of race, gender, age, citizenship, ethnicity, marital status, academic performance, health status, volume of market transactions, religion, sexual orientation, etc. However, these forms of discrimination are not equally tolerable. For example, discrimination based on immutable or prohibitively unalterable characteristics such as race, gender, or ethnicity is much less acceptable. Why? I develop a simple rent-seeking model of conflict w...

  5. Liver tissue tolerance for irradiation : Experimental and clinical investigations

    NARCIS (Netherlands)

    Cromheecke, M; Konings, AWT; Szabo, BG; Hoekstra, HJ

    2000-01-01

    Radiation treatment of the liver for malignant disease has gained renewed interest due to newly developed treatment modalities. Still limited specific knowledge is available concerning liver damage following irradiation. Inconsistencies between reported animal experimental studies are largely due to

  6. Tolerance of normal tissues to radiation therapy: Ear

    International Nuclear Information System (INIS)

    Fleury, B.; Lapeyre, M.

    2010-01-01

    The main objective of this work was to describe, based on a literature survey, the radiation-induced toxicity of the ear and to try to establish the limiting dose. The limiting toxicity was the sensorineural hearing loss. A dose-effect relationship has been described by several authors. Thirty to 40% of patients who are irradiated for head and neck cancer are concerned, but the intensity of the hearing loss tends to depend on the exact localisation of the primary tumour: nasopharyngeal irradiations, paranasal sinusal and parotid irradiation are at greater risk of complication. High frequencies are more vulnerable than the lower ones. Age of patients, as well as baseline hearing abilities, deeply influence the issue. As far as possible, the dose to the inner ear (the cochlea more precisely) should be kept under 40 Gy. In case of association with other causes of toxicity (such as age, low baseline value, association to cisplatin), this dose should be as low as possible. Should carcinologic constraints lead to toxic doses, then patients should be properly informed. (authors)

  7. Normal tissue tolerance to external beam radiation therapy: Skin

    International Nuclear Information System (INIS)

    Ginot, A.; Doyen, J.; Hannoun-Levi, J.M.; Courdi, A.

    2010-01-01

    Acute skin toxicity is frequent during radiation therapy and can lead to temporary arrest of the treatment. Chronic toxicity can occur and conduct to cosmetic problems. Alopecia is the most frequent toxicity concerning hair and is most of the time reversible. Several factors linked to patients influence skin toxicity, such as under-nutrition, old age, obesity, smoking, skin diseases, autoimmune diseases, failure of DNA reparation. Skin, hair and nail toxicities depend also on radiation schedule. Acute toxicity is greater when dose per fraction increases. Chronic and acute toxicities are more often when total dose increases. Under 45 Gy, the risk of severe skin toxicity is low, and begins above 50 Gy. Skin toxicity depends also on the duration of radiotherapy and split course schedules are associated with less toxicities. Irradiation surface seems to influence skin toxicity but interaction is more complex. Reirradiation is often feasible in case of cancer recurrence but with a risk of grade 3-4 toxicity above all in head and neck cancer. The benefit/risk ratio has to be always precisely evaluated. Permanent alopecia is correlated with the follicle dose. Modern techniques of radiation therapy allow to spare skin. (authors)

  8. Normal tissue tolerance to external beam radiation therapy: Ovaries

    International Nuclear Information System (INIS)

    Gross, E.; Champetier, C.; Zaccariotto, A.; Duberge, T.; Guerder, C.; Pointreau, Y.; Ortholan, C.; Chauvet, B.

    2010-01-01

    Clinical situations requiring protections of ovaries are mainly paediatric irradiations and pre-menopausal pelvic irradiations. The main complication of ovarian irradiation is the induced castration. Ovaries are extremely radiosensitive organs with strong interpersonal variations. The castrative effect of irradiation depends mainly on two factors: patient's age and the dose delivered to ovaries. The surgical technique of ovarian transposition allows to minimize the dose received by ovaries by taking them away, out of irradiation fields; the aim is to exclude them from the volume receiving 5 Gy or more, and if possible from those receiving 2 Gy. This technique becomes integrated into a multidisciplinary approach of conservation of fertility for patients exposed to other cytotoxic treatments. (authors)

  9. [Healthy Cities projects].

    Science.gov (United States)

    Takano, Takehito

    2002-05-01

    This is a review article on "Healthy Cities". The Healthy Cities programme has been developed by the World Health Organization (WHO) to tackle urban health and environmental issues in a broad way. It is a kind of comprehensive policy package to carry out individual projects and activities effectively and efficiently. Its key aspects include healthy public policy, vision sharing, high political commitment, establishment of structural organization, strategic health planning, intersectoral collaboration, community participation, setting approach, development of supportive environment for health, formation of city health profile, national and international networking, participatory research, periodic monitoring and evaluation, and mechanisms for sustainability of projects. The present paper covered the Healthy Cities concept and approaches, rapid urbanization in the world, developments of WHO Healthy Cities, Healthy Cities developments in the Western Pacific Region, the health promotion viewpoint, and roles of research.

  10. Are there healthy obese?

    Science.gov (United States)

    Griera Borrás, José Luis; Contreras Gilbert, José

    2014-01-01

    It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  11. Serum progranulin concentrations are not responsive during oral lipid tolerance test and oral glucose tolerance test.

    Science.gov (United States)

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2015-07-01

    The postprandial regulation of progranulin by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of progranulin in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn at 0 hours (h) (fasting) and at 2, 4, and 6 h in OLTT or 1 and 2 h in OGTT. A novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of progranulin were measured by enzyme-linked immunosorbent assay (ELISA). Circulating progranulin levels remained unchanged during OLTT and OGTT. Fasting progranulin levels ranged between 31.3±8.7 and 40.6±7.7 ng/ml and were not different in subgroups addressing BMI, gender, family history, smoking habits, and hormonal contraception. There was a reciprocal correlation of progranulin with HDL (negative) and LDL cholesterol levels (positive). In healthy adults, fasting and postprandial circulating progranulin levels are not different in BMI subgroups. Oral uptake of carbohydrates and lipids does not influence circulating progranulin levels in a short-term manner. A postprandial and short-term regulation of this adipokine is absent, at least in healthy subjects. There is a negative correlation of progranulin with HDL cholesterol, but a positive correlation with LDL cholesterol. This reciprocal association might be of physiological importance for an individual's atherosclerotic risk. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Sex differences and plasticity in dehydration tolerance: insight from a tropical liverwort

    OpenAIRE

    Marks, Rose A.; Burton, James F.; McLetchie, D. Nicholas

    2016-01-01

    Background and Aims Adaptations allowing plants to cope with drying are particularly relevant in the light of predicted climate change. Dehydration tolerance (DhT, also dehydration-tolerant) is one such adaptation enabling tissue to survive substantial drying. A great deal of work has been conducted on highly DhT species. However, bryophytes showing less intense and variable DhT are understudied, despite the potential for these species to provide an informative link between highly tolerant an...

  13. Preclinical investigation of tolerance and antitumour activity of new fluorodeoxyglucose-coupled chlorambucil alkylating agents.

    Science.gov (United States)

    Miot-Noirault, Elisabeth; Reux, Bastien; Debiton, Eric; Madelmont, Jean-Claude; Chezal, Jean-Michel; Coudert, Pascal; Weber, Valérie

    2011-06-01

    Our strategy is to increase drug accumulation in target tumour cells using specific "vectors" tailored to neoplastic tissue characteristics, which ideally are not found in healthy tissues. The aim of this work was to use 2-fluoro-2-deoxyglucose (FDG) as a drug carrier, in view of its well-known accumulation by most primary and disseminated human tumours. We had previously selected two FDG-cytotoxic conjugates of chlorambucil (CLB), i.e. compounds 21a and 40a, on the basis of their in vitro profiles. Here we investigated the antitumour profile and tolerance of these compounds in vitro and in vivo in two murine cell lines of solid tumours. In vitro, we found that micromolar concentrations of compounds 21a and 40a inhibited proliferation of B16F0 and CT-26 cell lines. Interestingly, compounds 21a and 40a were found to act at different levels in the cell cycle: S and subG1 accumulation for 21a and G2 accumulation for 40a. In vivo, a single-dose-finding study to select the Maximum Tolerated Dose (MTD) by the intraperitoneal route (IP) showed that the two peracetylated glucoconjugates of CLB were less toxic than CLB itself. When given to tumour-bearing mice (melanoma and colon carcinoma models), according to a "q4d × 3" schedule (i.e., three doses at 4-day intervals) both compounds demonstrated a promising antitumour activity, with Log Cell Kill (LCK) values higher than 1.3 in both B16F0 and CT-26 models. Hence compounds 21a and 40a are good candidates for further works to develop new highly active antineoplastic compounds.

  14. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    Xu Feng; Wen Ting; Lu Tianjian; Seffen Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great problem for burn patients. Thus, it is of great importance to quantify the thermal damage in skin tissue. In this paper, the available models and experimental methods for quantification of thermal damage in skin tissue are discussed.

  15. Active and Healthy Schools

    Science.gov (United States)

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  16. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  17. Making Healthy Choices Easier

    DEFF Research Database (Denmark)

    Guldborg Hansen, Pelle; Skov, Laurits Rohden; Lund Skov, Katrine

    2016-01-01

    . However, integration and testing of the nudge approach as part of more comprehensive public health strategies aimed at making healthy choices easier is being threatened by inadequate understandings of its scientific character, relationship with regulation and its ethical implications. This article reviews...... working with or incorporating the nudge approach into programs or policies aimed at making healthy choices easier...

  18. A personalized healthy workplace

    NARCIS (Netherlands)

    Timmer, Justin

    2017-01-01

    In February 2017, seven partners signed a contract to collaborate on a project called the Healthy Workplace. Measuremen, Menzis, Health2Work, ENGIE, Planon, and Hanzehogeschool Groningen are dedicated to make the regular workplace a healthy workplace. Health is of primary importance for both the

  19. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    徐峰; 文婷; 卢天健; Seffen; Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great...

  20. Phenylalanine kinetics in human adipose tissue.

    OpenAIRE

    Coppack, S W; Persson, M; Miles, J M

    1996-01-01

    Very little is known about the regulation of protein metabolism in adipose tissue. In this study systemic, adipose tissue, and forearm phenylalanine kinetics were determined in healthy postabsorptive volunteers before and during a 2-h glucose infusion (7 mg.kg-1.min-1). [3H]Phenylalanine was infused and blood was sampled from a radial artery, a subcutaneous abdominal vein, and a deep forearm vein. Adipose tissue and forearm blood flow were measured with 133Xe and plethysmography, respectively...

  1. Fault Tolerant Computer Architecture

    CERN Document Server

    Sorin, Daniel

    2009-01-01

    For many years, most computer architects have pursued one primary goal: performance. Architects have translated the ever-increasing abundance of ever-faster transistors provided by Moore's law into remarkable increases in performance. Recently, however, the bounty provided by Moore's law has been accompanied by several challenges that have arisen as devices have become smaller, including a decrease in dependability due to physical faults. In this book, we focus on the dependability challenge and the fault tolerance solutions that architects are developing to overcome it. The two main purposes

  2. Toleration, Synthesis or Replacement?

    DEFF Research Database (Denmark)

    Holtermann, Jakob v. H.; Madsen, Mikael Rask

    2016-01-01

    , in order to answer is not yet another partisan suggestion, but rather an attempt at making intelligible both the oppositions and the possibilities of synthesis between normative and empirical approaches to law. Based on our assessment and rational reconstruction of current arguments and positions, we...... therefore outline a taxonomy consisting of the following three basic, ideal-types in terms of the epistemological understanding of the interface of law and empirical studies: toleration, synthesis and replacement. This tripartite model proves useful with a view to teasing out and better articulating...

  3. Aerobic Exercise Training Improves Orthostatic Tolerance in Aging Humans.

    Science.gov (United States)

    Xu, Diqun; Wang, Hong; Chen, Shande; Ross, Sarah; Liu, Howe; Olivencia-Yurvati, Albert; Raven, Peter B; Shi, Xiangrong

    2017-04-01

    This study was designed to test the hypothesis that aerobic exercise training of the elderly will increase aerobic fitness without compromising orthostatic tolerance (OT). Eight healthy sedentary volunteers (67.0 ± 1.7 yr old, four women) participated in 1 yr of endurance exercise training (stationary bicycle and/or treadmill) program at the individuals' 65%-75% of HRpeak. Peak O2 uptake (V˙O2peak) and HRpeak were determined by a maximal exercise stress test using a bicycle ergometer. Carotid baroreceptor reflex (CBR) control of HR and mean arterial pressure (MAP) were assessed by a neck pressure-neck suction protocol. Each subject's maximal gain (Gmax), or sensitivity, of the CBR function curves were derived from fitting their reflex HR and MAP responses to the corresponding neck pressure-neck suction stimuli using a logistic function curve. The subjects' OT was assessed using lower-body negative pressure (LBNP) graded to -50 mm Hg; the sum of the product of LBNP intensity and time (mm Hg·min) was calculated as the cumulative stress index. Training increased V˙O2peak (before vs after: 22.8 ± 0.92 vs 27.9 ± 1.33 mL·min·kg, P stress index was increased from 767 ± 68 mm Hg·min pretraining to 946 ± 44 mm Hg·min posttraining (P Aerobic exercise training improved the aerobic fitness and OT in elderly subjects. An improved OT is likely associated with an enhanced CBR function that has been reset to better maintain cerebral perfusion and cerebral tissue oxygenation during LBNP.

  4. Radiation therapy tolerance doses for treatment planning

    International Nuclear Information System (INIS)

    Lyman, J.T.

    1987-01-01

    To adequately plan acceptable dose distributions for radiation therapy treatments it is necessary to ensure that normal structures do not receive unacceptable doses. Acceptable doses are generally those that are below a stated tolerance dose for development of some level of complication. To support the work sponsored by the National Cancer Institute, data for the tolerance of normal tissues or organs to low-LET radiation has been compiled from a number of sources. These tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD 5 ) or 50% (TD 50 ) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represent doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same end point. 20 refs., 1 fig., 1 tab

  5. Ethnopoly promotes tolerance

    CERN Document Server

    CERN Bulletin

    2010-01-01

    On Friday 23 April, 225 primary school children from the eight schools in Meyrin-Cointrin and their accompanying adults took part in a big game of Ethnopoly. Private individuals, associations, administrations, shopkeepers and CERN all opened their doors to them to talk about their countries, their customs and what they are doing to promote tolerance and integration.   The CERN stand set up at ForumMeyrin for the Ethnopoly game. Scurrying from one place to another, the 10 and 11 year olds were made aware of the rich cultural diversity of their commune, which is home to 130 different nationalities. Physicists and engineers from CERN took up residence in the Forum Meyrin for the day in order to talk to the children about the advantages of international collaboration, a subject dear to the Organization's heart. They welcomed around fifty children in the course of the day, conveying to them a message of tolerance: despite their differences, the 10,000 scientists and other members of the CERN...

  6. Chitinase Activity in Healthy and Sclerotium rolfsii Infected Peanut

    Directory of Open Access Journals (Sweden)

    ENDANG PUDJIHARTATI

    2006-06-01

    Full Text Available The objectives of this experiment were to analyze the endo- or exo-chitinase activities of healthy and Sclerotium rolfsii infected peanuts. The experiment analyzed 24 different peanut genotypes. Results of the experiment showed chromogenic dimer was the most suitable substrate for analysing chitinase activities. Both endo- and exo-chitinases activities were detected in leaf, stem, and crown tissues. Increased in chitinase activities were detected in S. rolfsii infected peanut tissues than in healthy plant. Regression analysis showed negative slope between disease intensity and chitinase activity in S. rolfsii infected peanut tissue (R2= 0.45.

  7. Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

    Science.gov (United States)

    Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

    2011-01-01

    OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

  8. Fault-tolerant computing systems

    International Nuclear Information System (INIS)

    Dal Cin, M.; Hohl, W.

    1991-01-01

    Tests, Diagnosis and Fault Treatment were chosen as the guiding themes of the conference. However, the scope of the conference included reliability, availability, safety and security issues in software and hardware systems as well. The sessions were organized for the conference which was completed by an industrial presentation: Keynote Address, Reconfiguration and Recover, System Level Diagnosis, Voting and Agreement, Testing, Fault-Tolerant Circuits, Array Testing, Modelling, Applied Fault Tolerance, Fault-Tolerant Arrays and Systems, Interconnection Networks, Fault-Tolerant Software. One paper has been indexed separately in the database. (orig./HP)

  9. Commercialization of radiation tolerant camera

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Bum; Choi, Young Soo; Kim, Sun Ku; Lee, Jong Min; Cha, Bung Hun; Lee, Nam Ho; Byun, Eiy Gyo; Yoo, Seun Wook; Choi, Bum Ki; Yoon, Sung Up; Kim, Hyun Gun; Sin, Jeong Hun; So, Suk Il

    1999-12-01

    In this project, radiation tolerant camera which tolerates 10{sup 6} - 10{sup 8} rad total dose is developed. In order to develop radiation tolerant camera, radiation effect of camera components was examined and evaluated, and camera configuration was studied. By the result of evaluation, the components were decided and design was performed. Vidicon tube was selected to use by image sensor and non-browning optics and camera driving circuit were applied. The controller needed for CCTV camera system, lens, light, pan/tilt controller, was designed by the concept of remote control. And two type of radiation tolerant camera were fabricated consider to use in underwater environment or normal environment. (author)

  10. Commercialization of radiation tolerant camera

    International Nuclear Information System (INIS)

    Lee, Yong Bum; Choi, Young Soo; Kim, Sun Ku; Lee, Jong Min; Cha, Bung Hun; Lee, Nam Ho; Byun, Eiy Gyo; Yoo, Seun Wook; Choi, Bum Ki; Yoon, Sung Up; Kim, Hyun Gun; Sin, Jeong Hun; So, Suk Il

    1999-12-01

    In this project, radiation tolerant camera which tolerates 10 6 - 10 8 rad total dose is developed. In order to develop radiation tolerant camera, radiation effect of camera components was examined and evaluated, and camera configuration was studied. By the result of evaluation, the components were decided and design was performed. Vidicon tube was selected to use by image sensor and non-browning optics and camera driving circuit were applied. The controller needed for CCTV camera system, lens, light, pan/tilt controller, was designed by the concept of remote control. And two type of radiation tolerant camera were fabricated consider to use in underwater environment or normal environment. (author)

  11. Overexpression of AtSTO1 leads to improved salt tolerance in Populus tremula × P. alba

    Science.gov (United States)

    Shaneka S. Lawson; Charles H. Michler

    2014-01-01

    One of the major abiotic stress conditions limiting healthy growth of trees is salinity stress. The use of gene manipulation for increased tolerance to abiotic stress has been successful in many plant species. Overexpression of the Arabidopsis SALT TOLERANT1 (STO1) gene leads to increased concentrations of 9-cis-epoxycarotenoid dioxygenase3, a vital...

  12. Chitin Scaffolds in Tissue Engineering

    Science.gov (United States)

    Jayakumar, Rangasamy; Chennazhi, Krishna Prasad; Srinivasan, Sowmya; Nair, Shantikumar V.; Furuike, Tetsuya; Tamura, Hiroshi

    2011-01-01

    Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine. PMID:21673928

  13. Disparities -- Healthy People 2020

    Science.gov (United States)

    ... health based on their racial or ethnic group; religion; socioeconomic status; gender; age; mental health; cognitive, sensory, ... Contact Us Site Map Accessibility Privacy Policy Disclaimers Freedom of Information Act Healthy People 2010 Archive Nondiscrimination ...

  14. Jaundice in Healthy Newborns

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Jaundice in Healthy Newborns KidsHealth / For Parents / Jaundice in ... within a few days of birth. Types of Jaundice The most common types of jaundice are: Physiological ( ...

  15. Healthy Living after Stroke

    Science.gov (United States)

    ... Nutrition Cooking for Health Food for Thought: Heart-healthy Diet is Also Good For Your Brain Physical Activity Get Moving and Boost Your Brain Power Understanding Risky Conditions Converging Risk Factors for Stroke ...

  16. Healthy Skin Matters

    Science.gov (United States)

    ... skin. If you’re helping out in the kitchen, make sure you use hot pads or wear ... in humans, plants, and animals, while others are essential for a healthy life. Propionibacterium acnes (P. acnes) ( ...

  17. Healthy Lifestyle: Women's Health

    Science.gov (United States)

    ... maintain a healthy weight. Try brisk walking, jogging, biking, swimming or water aerobics. If you're a ... as dancing and gardening, also can improve your health. Whatever you choose, take time to warm up ...

  18. Healthy Ride Trip Data

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A dataset that shows trips taken using the Healthy Ride system by quarter. The dataset includes bike number, membership type, trip start and end timestamp, and...

  19. Healthy Conflict Management

    OpenAIRE

    Brower, Naomi

    2012-01-01

    Without healthy conflict management skills, conflict can often escalate or intensify over time. This fact sheet gives tips on utilizing key negotiation skills to help individuals effectively address and cope with conflict and potentially build stronger relationships with others.

  20. Healthy lifestyle in teachers

    OpenAIRE

    Pirzadeh, Asiyeh; Sharifirad, Gholamreza; Kamran, Aziz

    2012-01-01

    Introduction: The role of individual healthy behaviors like physical activity, nutrition and stress management on reduction of rate of disease mortality and morbidity is well known. The aim of this study is to determine healthy life style in teachers employed in district No.4 in Isfahan, Iran, in 2010. Materials and Methods: The participants of this cross-sectional study were 96 teachers in district No. 4, selected via random sampling method. The data collection was performed using a question...

  1. Salt Tolerance in Soybean

    Institute of Scientific and Technical Information of China (English)

    Tsui-Hung Phang; Guihua Shao; Hon-Ming Lam

    2008-01-01

    Soybean is an Important cash crop and its productivity is significantly hampered by salt stress. High salt Imposes negative impacts on growth, nodulation, agronomy traits, seed quality and quantity, and thus reduces the yield of soybean. To cope with salt stress, soybean has developed several tolerance mechanisms, including: (I) maintenance of ion homeostasis; (ii) adjustment in response to osmotic stress; (iii) restoration of osmotic balance; and (iv) other metabolic and structural adaptations. The regulatory network for abiotic stress responses in higher plants has been studied extensively in model plants such as Arabidopsis thaliana. Some homologous components involved in salt stress responses have been identified in soybean. In this review, we tried to integrate the relevant works on soybean and proposes a working model to descdbe Its salt stress responses at the molecular level.

  2. Delay tolerant networks

    CERN Document Server

    Gao, Longxiang; Luan, Tom H

    2015-01-01

    This brief presents emerging and promising communication methods for network reliability via delay tolerant networks (DTNs). Different from traditional networks, DTNs possess unique features, such as long latency and unstable network topology. As a result, DTNs can be widely applied to critical applications, such as space communications, disaster rescue, and battlefield communications. The brief provides a complete investigation of DTNs and their current applications, from an overview to the latest development in the area. The core issue of data forward in DTNs is tackled, including the importance of social characteristics, which is an essential feature if the mobile devices are used for human communication. Security and privacy issues in DTNs are discussed, and future work is also discussed.

  3. Shaping tolerant attitudes towards immigrants

    DEFF Research Database (Denmark)

    Rapp, Carolin

    2017-01-01

    This article contributes to the ongoing discussion on how tolerance may be fostered in Western European countries and to the question of how contextual factors such as welfare state expenditures may contribute to this formation. Tolerance is understood as a basic democratic principle that helps c...

  4. Legal Quality, Inequality, and Tolerance

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    Previous findings suggest that income inequality leads to lower legal quality. This paper argues that voters' tolerance of inequality exerts an additional influence. Empirical findings suggest that inequality leads to lower legal quality due to its effect on trust while the tolerance of inequality...

  5. Legal Quality, Inequality, and Tolerance

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    Previous findings suggest that income inequality leads to lower legal quality. This paper argues that voters' tolerance of inequality exerts an additional influence. Empirical findings suggest that inequality leads to lower legal quality due to its effect on trust while the tolerance of inequality...

  6. Tolerance Issue in Kazakh Culture

    Science.gov (United States)

    Aubakirova, Saltanat S.; Ismagambetova, Zukhra N.; Karabayeva, Aliya G.; Rysbekova, Shamshiya S.; Mirzabekova, Alma Sh.

    2016-01-01

    In this article the authors reveal the basic cultural mechanisms that influence the formation of the tolerance strategy in Kazakh and Kazakhstan society, show its basic directions, as well as its importance for the modern Kazakhstan society and the formation of intercultural communication with foreign countries. Tolerance is a necessary element of…

  7. Tolerance-Based Feature Transforms

    NARCIS (Netherlands)

    Reniers, Dennie; Telea, Alexandru

    2007-01-01

    Tolerance-based feature transforms (TFTs) assign to each pixel in an image not only the nearest feature pixels on the boundary (origins), but all origins from the minimum distance up to a user-defined tolerance. In this paper, we compare four simple-to-implement methods for computing TFTs on binary

  8. Aluminum-Tolerant Pisolithus Ectomycorrhizas Confer Increased Growth, Mineral Nutrition, and Metal Tolerance to Eucalyptus in Acidic Mine Spoil

    Directory of Open Access Journals (Sweden)

    Louise Egerton-Warburton

    2015-01-01

    Full Text Available Ectomycorrhizal fungi (ECM may increase the tolerance of their host plants to Al toxicity by immobilizing Al in fungal tissues and/or improving plant mineral nutrition. Although these benefits have been demonstrated in in vitro (pure culture or short-term nutrient solution (hydroponic experiments, fewer studies have examined these benefits in the field. This study examined the growth, mineral nutrition, and Al levels in two Eucalyptus species inoculated with three Pisolithus ecotypes that varied in Al tolerance (in vitro and grown in mine spoil in the greenhouse and field. All three ecotypes of Pisolithus improved Eucalyptus growth and increased host plant tolerance to Al in comparison to noninoculated plants. However, large variations in plant growth and mineral nutrition were detected among the Pisolithus-inoculated plants; these differences were largely explained by the functional properties of the Pisolithus inoculum. Seedlings inoculated with the most Al-tolerant Pisolithus inoculum showed significantly higher levels of N, P, Ca, Mg, and K and lower levels of Al than seedlings inoculated with Al-sensitive ecotypes of Pisolithus. These findings indicate an agreement between the fungal tolerance to Al in vitro and performance in symbiosis, indicating that both ECM-mediated mineral nutrient acquisition and Al accumulation are important in increasing the host plant Al tolerance.

  9. Extraintestinal heterotopic gastric tissue simulating acute appendicitis

    Institute of Scientific and Technical Information of China (English)

    Elizabeth Bender; Steven P Schmidt

    2008-01-01

    We describe the case of a 68-year-old otherwise healthy male who presented to our emergency room with signs and symptoms of acute appendicitis. Exploratory surgery revealed a normal appendix. Further examination revealed an enlarged lymph node-like mass of tissue near the appendix, in the ileocecal mesentery. This mass was removed and was found to be inflamed heterotopic gastric tissue. Although reports of heterotopic gastric tissue in the literature are common, we believe that this case represents the first report of inflamed heterotopic gastric tissue simulating appendicitis.

  10. Analysis of tooth tissues using Raman spectroscopy

    International Nuclear Information System (INIS)

    Timchenko, E.V.; Timchenko, P.E.; Kulabukhova, A.Yu.; Volova, L.T.; Rosenbaum, A.Yu.

    2016-01-01

    The results of experimental studies of healthy tooth tissue and tooth tissues during caries disease are presented. Features of Raman spectrum of tooth tissues during caries disease are obtained: the main changes are detected at wavenumbers 956 cm -1 .1069 cm -1 . corresponding to phosphates. and 1241 cm -1 . 1660 cm -1 . corresponding to collagen III and collagen I. respectively. Were introduced criteria allowing to detect caries and to identify weakening of tooth tissues. preceding the caries. The reliability of research results is confirmed by scanning electron microscopy. (paper)

  11. Regulatory dendritic cells for promotion of liver transplant operational tolerance: Rationale for a clinical trial and accompanying mechanistic studies.

    Science.gov (United States)

    Thomson, Angus W; Humar, Abhinav; Lakkis, Fadi G; Metes, Diana M

    2018-05-01

    Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8 + memory T cell responses in the early post-transplant period. Based on these observations, and in view of the critical need to reduce patient dependence on non-specific IS agents that predispose to cardiometabolic side effects and renal insufficiency, we will conduct a first-in-human safety and preliminary efficacy study of donor-derived DCreg infusion to achieve early (18 months post-transplant) complete IS withdrawal in low-risk, living donor liver transplant recipients receiving standard-of-care IS (mycophenolate mofetil, tacrolimus and steroids). We will test the hypothesis that, although donor-derived DCreg are short-lived, they will induce robust donor-specific T cell hyporesponsiveness. We will examine immunological mechanisms by sequential analysis of blood and tissue samples, incorporating cutting-edge technologies. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  12. Healthy human gut phageome.

    Science.gov (United States)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

  13. 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

  14. Impact of a high intensity training program on glucose tolerance in people with multiple sclerosis

    OpenAIRE

    Patyn, Cédric

    2014-01-01

    Abstract Background: Recent research reported a higher prevalence of impaired glucose tolerance (IGT) in MS patients than in healthy people. The influence of high intensity exercise on IGT in MS was never investigated before. Objective: To investigate the effect of high intensity aerobic interval (HIIT) or continuous endurance (CT) training, both in combination with resistance training, on glucose tolerance muscle strength and body composition. Methods: 34 subjects were randomly as...

  15. Strain-time cell death threshold for skeletal muscle in a tissue-engineered model system for deep tissue injury

    NARCIS (Netherlands)

    Gefen, A.; Nierop, van B.J.; Bader, D.L.; Oomens, C.W.J.

    2008-01-01

    Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained deformation of muscle tissue overlying bony prominences. In order to understand the etiology of DTI, it is essential to determine the tolerance of muscle cells to large mechanical strains. In this study, a new

  16. Tolerance and chimerism.

    Science.gov (United States)

    Kolb, Hans-Jochem; Guenther, Wolfgang; Gyurkocza, Boglarka; Hoetzl, Florian; Simoes, Belinda; Falk, Christine; Schleuning, Michael; Ledderose, Georg

    2003-05-15

    Stem-cell transplantation from human leukocyte antigen (HLA)-haploidentical family members carries a high risk of rejection and graft-versus-host disease (GVHD) if donor and recipient differ by more than one HLA antigen. The authors have developed treatment protocols from studies in dog leukocyte antigen-haploidentical dogs that prevent rejection and modify GVHD to the extent that patients with aggressive hematologic neoplasia can be treated with success. Principal improvements have been achieved in the use of cyclophosphamide and total-body irradiation for conditioning and T-cell depletion for prevention of GVHD. More recently, the combination of marrow and CD6-depleted mobilized donor blood cells (MDBC) has been introduced for HLA-haploidentical transplantation on the basis that CD6-depleted MDBC contain immunoregulatory cells besides stem cells and natural killer cells. Clinical results are reported on 36 patients with high-risk hematologic neoplasia. The results encourage the use of HLA-haploidentical stem-cell transplantation at an earlier stage of the disease. This method could also be of use for tolerance induction in organ transplantation.

  17. [Healthy obesity? Why the adiposity paradox is only seemingly paradox].

    Science.gov (United States)

    Ströhle, Alexander; Worm, Nicolai

    2014-02-01

    The health consequences of being overweight have been discussed controversially. Indeed, from a metabolic point of view, overweight and obese people are quite heterogenous. The body mass index (BMI) is not suitable to predict health oriented outcomes on an individual level without taking into account further parameters such as waist circumference, blood pressure, serum glucose, serum lipids, and physical fitness. The BMI does not distinguish between metabolically healthy and metabolically unhealthy. Of upmost importance for health consequences of obesity is body fat distribution. Two types of principally different fat distribution can be identified: abdominal and gluteofemoral fat. Waist circumference and hip circumference can be utilized to distinguish between those two types. People with accumulation of body fat in the abdominal region have a markedly higher risk of developing type-2-diabetes and cardiovascular disease. Moreover, their total mortality is increased. On the other hand, waist circumference is not sufficiently capable of indicating individual risk. Instead, the amount of visceral fat is believed to be a primary risk factor because of its metabolic characteristics (i. e. increased lipolysis, diabetogenic and atherogenic adipokine profile). Recent findings point to visceral fat being more an indicator of the parallel accumulation of fat deposits in organs placed in the abdomen. The accumulation of lipids in tissues not primary intended for fat storage is called,,ectopic fat". It can be found in muscle, liver, pancreas, and kidney. The fattening of those organs is now considered to have the key role in the pathogenesis of type-2-diabetes. The pathophysiological effects of ectopic fat and the associated metabolic derangements can solve the conflicting findings concerning health consequences of BMI--at least in part. Moreover, these findings may have therapeutic consequences. The reduction of ectopic fat as well as the modification of its metabolic

  18. Healthy Buildings '88

    International Nuclear Information System (INIS)

    Berglund, B.; Lindvall, T.; Maansson, L.G.

    1988-06-01

    The Healthy Buildings '88 Conference focuses on the technical solutions and functional requirements contributing to Healthy Buildings for people to live and work in. The main object of the Conference is to give architects, consultants, real-estate owners and manufacturers of building materials recommendations on choice of materials and choice of systems and on how to combine materials and systems. The program includes overview lectures, plenary symposia with invited speakers, workshops, poster presentations and an exhibition of scientific, educational and technical material. One part of the conference is devoted to the problem of radon in residential buildings

  19. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2011-01-01

    Use Tolerance Analysis Techniques to Avoid Design, Quality, and Manufacturing Problems Before They Happen Often overlooked and misunderstood, tolerance analysis is a critical part of improving products and their design processes. Because all manufactured products are subject to variation, it is crucial that designers predict and understand how these changes can affect form, fit, and function of parts and assemblies--and then communicate their findings effectively. Written by one of the developers of ASME Y14.5 and other geometric dimension and tolerancing (GD&T) standards, Mechanical Tolerance

  20. Advanced cloud fault tolerance system

    Science.gov (United States)

    Sumangali, K.; Benny, Niketa

    2017-11-01

    Cloud computing has become a prevalent on-demand service on the internet to store, manage and process data. A pitfall that accompanies cloud computing is the failures that can be encountered in the cloud. To overcome these failures, we require a fault tolerance mechanism to abstract faults from users. We have proposed a fault tolerant architecture, which is a combination of proactive and reactive fault tolerance. This architecture essentially increases the reliability and the availability of the cloud. In the future, we would like to compare evaluations of our proposed architecture with existing architectures and further improve it.

  1. Peripheral tissue oximetry

    DEFF Research Database (Denmark)

    Hyttel-Sorensen, Simon; Hessel, Trine Witzner; Greisen, Gorm

    2014-01-01

    Estimation of regional tissue oxygenation (rStO2) by near infrared spectroscopy enables non-invasive end-organ oxygen balance monitoring and could be a valuable tool in intensive care. However, the diverse absolute values and dynamics of different devices, and overall poor repeatability of measur......Estimation of regional tissue oxygenation (rStO2) by near infrared spectroscopy enables non-invasive end-organ oxygen balance monitoring and could be a valuable tool in intensive care. However, the diverse absolute values and dynamics of different devices, and overall poor repeatability......, and response to changing oxygenation by the down slope of rStO2 during vascular occlusion in the respective arm. 10 healthy adults, 21-29 years old, with double skinfolds on the forearm less than 10 mm participated. The median rStO2 was 70.7% (interquartile range (IQR) 7.7%), 68.4% (IQR 8.4%), and 64.6% (IQR 4...

  2. Terahertz pulsed imaging of freshly excised human colonic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Caroline B; Gibson, Adam P [Department of Medical Physics and Bioengineering, University College London, London, WC1E 6BT (United Kingdom); Fitzgerald, Anthony; Wallace, Vincent P [School of Physics, University of Western Australia, Crawley 6009 (Australia); Reese, George; Tekkis, Paris [Division of Surgery, Chelsea and Westminster Campus, Imperial College London, London (United Kingdom); Goldin, Robert [Centre for Pathology, Imperial College London, St Mary' s Campus, London (United Kingdom); O' Kelly, P S [TeraView Ltd, Platinum Building, St John' s Innovation Park, Cowley Road, Cambridge, CB4 0WS (United Kingdom); Pickwell-MacPherson, Emma, E-mail: c.reid@medphys.ucl.ac.uk [Department of Electronic Engineering, Chinese University of Hong Kong, Shatin, NT (Hong Kong)

    2011-07-21

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  3. Terahertz pulsed imaging of freshly excised human colonic tissues

    International Nuclear Information System (INIS)

    Reid, Caroline B; Gibson, Adam P; Fitzgerald, Anthony; Wallace, Vincent P; Reese, George; Tekkis, Paris; Goldin, Robert; O'Kelly, P S; Pickwell-MacPherson, Emma

    2011-01-01

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption.

  4. Tolerance to and cross tolerance between ethanol and nicotine.

    Science.gov (United States)

    Collins, A C; Burch, J B; de Fiebre, C M; Marks, M J

    1988-02-01

    Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.

  5. Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Pedersen, Susanne Brix; Frøkiær, Hanne

    2004-01-01

    antibody response in the offspring, bat in this case in the absence of oral tolerance. This indicates that, under certain conditions, factors involved in spontaneous antibody production can be transmitted from mother to offspring. Understanding the immune response to soya protein ingested under healthy...... by ELISA, and to the presence of oral tolerance detected as a suppressed antibody and cell-proliferation response upon immunisation with soya protein. F0 mice generated soya-specific antibodies, while oral tolerance to the same soya proteins was also clearly induced. When F0 dams were transferred to soya...

  6. Healthy lifestyle in teachers.

    Science.gov (United States)

    Pirzadeh, Asiyeh; Sharifirad, Gholamreza; Kamran, Aziz

    2012-01-01

    The role of individual healthy behaviors like physical activity, nutrition and stress management on reduction of rate of disease mortality and morbidity is well known. The aim of this study is to determine healthy life style in teachers employed in district No.4 in Isfahan, Iran, in 2010. The participants of this cross-sectional study were 96 teachers in district No. 4, selected via random sampling method. The data collection was performed using a questionnaire including demographic healthy lifestyle questions. Analysis of the data was performed through Software SPSS version 18. The mean age of the subjects was 40.26 ± 6.05 years and, BMI mean was 25.08 ± 3.20. 96.8% of them were married and 3.1% also were single. 1% of the teachers had a weak lifestyle, 13.5%had moderate, 85.4% had a good lifestyle. In terms of nutrition, 2% of the teachers had a weak lifestyle, 23% moderate, 74% good. 76% in terms of physical activity, 29.2% smoking and 21.9% stress had a weak lifestyle. According to the results, planning for teachers in school for receiving information about healthy lifestyle is important.

  7. Healthy Eating for Women

    Science.gov (United States)

    ... and beverages, such as some yogurts and juices. Foods and Beverages to Limit To keep weight in check at ... helps with weight control, muscle strength and stress management. Reviewed April 2018 Tags Food Health Nutrition Wellness Dietary Guidelines and MyPlate Healthy ...

  8. Many Healthy Returns

    Centers for Disease Control (CDC) Podcasts

    International travel is usually very safe but there are things you should do to stay safe and healthy. Experts show you how to avoid problems when visiting developing nations. This includes being cautious about the food you eat and the water you drink, and to be aware of vehicles and road conditions to prevent problems.

  9. Eating Healthy for Two

    Science.gov (United States)

    You are what you eat—and so is your baby. In addition to being smokefree, eating well during pregnancy is one of the best and most important things you can do for yourself and your baby. But healthy “eating for two” is more than just eating more.

  10. Accident tolerant fuel analysis

    International Nuclear Information System (INIS)

    2014-01-01

    Safety is central to the design, licensing, operation, and economics of Nuclear Power Plants (NPPs). Consequently, the ability to better characterize and quantify safety margin holds the key to improved decision making about light water reactor design, operation, and plant life extension. A systematic approach to characterization of safety margins and the subsequent margins management options represents a vital input to the licensee and regulatory analysis and decision making that will be involved. The purpose of the Risk Informed Safety Margin Characterization (RISMC) Pathway research and development (R&D) is to support plant decisions for risk-informed margins management by improving economics and reliability, and sustaining safety, of current NPPs. Goals of the RISMC Pathway are twofold: (1) Develop and demonstrate a risk-assessment method coupled to safety margin quantification that can be used by NPP decision makers as part of their margin recovery strategies. (2) Create an advanced ''RISMC toolkit'' that enables more accurate representation of NPP safety margin. In order to carry out the R&D needed for the Pathway, the Idaho National Laboratory is performing a series of case studies that will explore methods- and tools-development issues, in addition to being of current interest in their own right. One such study is a comparative analysis of safety margins of plants using different fuel cladding types: specifically, a comparison between current-technology Zircaloy cladding and a notional ''accident-tolerant'' (e.g., SiC-based) cladding. The present report begins the process of applying capabilities that are still under development to the problem of assessing new fuel designs. The approach and lessons learned from this case study will be included in future Technical Basis Guides produced by the RISMC Pathway. These guides will be the mechanism for developing the specifications for RISMC tools and for defining how plant

  11. Regurgitation in healthy and non healthy infants

    Directory of Open Access Journals (Sweden)

    Cavallo Luciano

    2009-12-01

    Full Text Available Abstract Uncomplicate regurgitation in otherwise healthy infants is not a disease. It consists of milk flow from mouth during or after feeding. Common causes include overfeeding, air swallowed during feeding, crying or coughing; physical exam is normal and weight gain is adequate. History and physical exam are diagnostic, and conservative therapy is recommended. Pathologic gastroesophageal reflux or gastroesophageal reflux disease refers to infants with regurgitation and vomiting associated with poor weight gain, respiratory symptoms, esophagitis. Reflux episodes occur most often during transient relaxations of the lower esophageal sphincter unaccompanied by swallowing, which permit gastric content to flow into the esophagus. A minor proportion of reflux episodes occurs when the lower esophageal sphincter fails to increase pressure during a sudden increase in intraabdominal pressure or when lower esophageal sphincter resting pressure is chronically reduced. Alterations in several protective mechanisms allow physiologic reflux to become gastroesophageal reflux disease; diagnostic approach is both clinical and instrumental: radiological series are useful to exclude anatomic abnormalities; pH-testing evaluates the quantity, frequency and duration of the acid reflux episodes; endoscopy and biopsy are performed in the case of esophagitis. Therapy with H2 receptor antagonists and proton pump inhibitors are suggested.

  12. Tolerance of retroperitoneal structures to intraoperative radiation

    International Nuclear Information System (INIS)

    Sindelar, W.F.; Tepper, J.; Travis, E.L.; Terrill, R.

    1982-01-01

    In conjunction with the clinical development of intraoperative radiotherapy, a study was undertaken in dogs to define the tolerance of normal anatomic structures in the retroperitoneum to radiation delivered during operation. Twenty adult dogs were subjected to laparotomy and intraoperative 11 MeV electron irradiation in single doses ranging from 0.to 5000 rad. Animals were followed regularly with clinical observation, blood count, serum chemistries, pyelography, and angiography. Animals were sacrificed and autopsied at regular intervals up to 12 months following treatment to assess radiation-induced complications or tissue damage. Irradiation field in all dogs consisted of a 4 X 15 cm rectangle extending in the retroperitoneum from the level of the renal vessels to the bifurcation of aorta and vena cava. The field included aorta, vena cava, inferior portion of left kidney, and distal portion of left ureter. No complications or histologic changes occurred in any animal given doses of 2000 rad, with a follow-up in excess of 18 months. A dose of 3000 rad was well tolerated, except for left ureteral occlusion in one animal. Mild vascular fibrosis was present inthe aorta and vena cava, and significant ureteral fibrosis developed by six months after doses of 4000 or 5000 rad. All animals that received 5000 rad died of radiation-related complications, including ureteral obstruction and rectal perforation. It was concluded that major vessels tolerate intraoperative irradiation well up to and including 3000 rad and that no clinically significant vascular problems develop after 4000 and 5000 rad, although some fibrosis does occur. The ureter and kidney appear to be the most radiosensitive structures inthe retroperitoneum, showing progressive changes at 300 rad or greater and showing the potential for serious complications after doses of 4000 rad or more

  13. TEMPERATURE TOLERANCES AND OSMOREGULATION IN ...

    African Journals Online (AJOL)

    The salinity and temperature tolerances of some burrowiq bivalves which oc:eur ... Along most of the estuary the salinity normally remains close to that of seawater (35'/.) ...... grapsoid crabs, Hemigrapsus nudus and Hemigrapsus oregonensis.

  14. TOLERANCE OF Abelmoschus esculentus (L

    African Journals Online (AJOL)

    Cletus

    Key word: - Tolerance, diesel oil, polluted soil, Abelmoschus esculentus. INTRODUCTION ... errors -of the mean values were calculated for the replicate readings and data .... African Schools and Colleges, 2nd Ed. University Press Limited ...

  15. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  16. Heavy metal pollutant tolerance of Azolla pinnata

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, A.; Jana, S.

    1986-01-01

    The effects of Hg, As, Pb, Cu, Cd, and Cr (1,2 and 5 mg L/sup -1/ each) on Azolla pinnata R. Br. were analyzed. The treatments (2 and 5 mg L/sup -1/) of the heavy metal pollutants decreased Hill activity, chlorophyll, protein and dry wt, and increased tissue permeability over control values. The effects were most pronounced with the treatment of 5 mg L/sup -1/. The harmful effects of the metals were, in general, found by the treatments in the order: Cd > Hg > Cu > As > Pb > Cr. There was no significant change in these parameters at 1 mg L/sup -1/ of the metals over control. Thus Azolla pinnata shows tolerance to the heavy metals tested up to 1 mg L/sup -1/ each.

  17. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  18. Women’s G Tolerance

    Science.gov (United States)

    1986-08-01

    for the groups matched by age (70 pairs), weight sickness, uncomfortable feelings of distension in arms (26 pairs), and act~vity status (84 pairs...mass-spring-damper) s ,stem Straining G tolerance, being dpendent on skeletal having a resonant frequency above about I Hz. As muscular strength and...of the women’s G tolerance stud\\ scclic variations in muscular strength and endurance. was below 0.1 Hz (11), the production of any significant

  19. Fault-tolerant rotary actuator

    Science.gov (United States)

    Tesar, Delbert

    2006-10-17

    A fault-tolerant actuator module, in a single containment shell, containing two actuator subsystems that are either asymmetrically or symmetrically laid out is provided. Fault tolerance in the actuators of the present invention is achieved by the employment of dual sets of equal resources. Dual resources are integrated into single modules, with each having the external appearance and functionality of a single set of resources.

  20. Behavioral Tolerance to Anticholinergic Agents

    Science.gov (United States)

    1986-11-20

    Medicine , 47, 137-141. 7. Kurtz, P.J. (1977) Behavioral and biochemical effects of the carbamate insecticide, mobam. Pharmacology Biochemistry & Behavior...tolerance to marihuana in rats. Pharmacology Biochemistry and Behavior, 1, 73-76. 43 40. Olson, J. and Carder, B. (1974) Behavioral tolerance to... marihuana as a function of amount of prior training. Pharmacology Biochemistry and Behavior, 2, 243-247. 41. Sidman, M. (1960) Tactics of Scientific

  1. Transplantation tolerance after total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Strober, S.; Slavin, S.; Fuks, Z.; Kaplan, H.S.; Gottlieb, M.; Bieber, C.; Hoppe, R.T.; Grumet, F.C.

    1979-03-01

    We have presented an animal model of tissue transplantation tolerance using the unusual effects of TLI on the immune system. The application of TLI to bone marrow and whole-organ transplantation in humans merits further study, since TLI offers several advantages over presently used therapeutic modalities. Current regimens used to prepare patients for marrow transplantation are lethal in the absence of allogeneic marrow engraftment, and marrow donors are restricted to HLA-matched siblings due to the danger of GHVD. On the other hand, TLI is a nonlethal procedure that has been used successfully in animals to transplant allogeneic marrow from unmatched donors without the development of GHVD. Thus, TLI might allow for marrow transplantation in all patients with a single sibling, whereas conventional procedures are feasible in only one of four such cases (probability of finding a single HLA-matched sibling). In addition, the induction of transplantation tolerance with TLI would obviate the requirement for the use of maintenance immunosuppressive drugs after whole-organ transplantation. Systemic infections associated with the use of these drugs currently account for the majority of deaths in heart transplant patients. Serious infectious complications associated with TLI are rare; thus this therapeutic regimen may offer considerable improvement in the long-term survival of organ graft recipients as compared to that presently obtained with immunosuppressive drugs.

  2. Rothmund-Thomson syndrome and tolerance of chemoradiotherapy

    International Nuclear Information System (INIS)

    Borg, M.F.; Olver, I.N.; Hill, M.P.

    1998-01-01

    Rothmund-Thomson syndrome (RTS) is a rare disorder with a predisposition for cutaneous and non-cutaneous malignancy. It is speculated that ultraviolet (UV) sensitivity and deficient DNA repair may account for this predisposition and influence the tolerance of chemoradiotherapeutic management. A case is reported of the management of an RTS patient with squamous cell carcinoma of the tongue who demonstrated increased radiosensitivity and tissue intolerance to chemotherapy. Copyright (1998) Blackwell Science Pty Ltd

  3. Dendritic cells in oral tolerance in the gut.

    Science.gov (United States)

    Rescigno, Maria

    2011-09-01

    Oral tolerance is a process that allows generation of systemic unresponsiveness to food antigens. Hence if the same antigen is introduced systemically even under immunogenic conditions it does not induce immune responsiveness. Dendritic cells (DCs) have been identified as essential players in this process. DCs in the gut are located in a strategic position as they can interact directly with luminal antigens or indirectly after their transcytosis across epithelial cells. DCs can then migrate to associated lymphoid tissues to induce tolerance. Antigen presenting cells in the gut are specialized in function and have divided their labour so that there are cells capable to migrate to the draining mesenteric lymph node for induction of T regulatory cells, while other subsets are resident and are required to enforce tolerance locally in the gut after food antigen exposure. In this review, I shall summarize the characteristics of antigen presenting cells in the gut and their involvement in oral tolerance induction. In addition, I will also emphasize that tolerance to food allergens may be contributed by plasmacytoid DCs in the liver that participate to the elimination or anergy of allergen-specific CD8 T cells. Hence specialized functions are associated to different subsets of antigen presenting cells and different organs. © 2011 Blackwell Publishing Ltd.

  4. Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test

    Directory of Open Access Journals (Sweden)

    Rohit Babbar

    2018-03-01

    Full Text Available IntroductionImpaired glucose tolerance (IGT is diagnosed by a standardized oral glucose tolerance test (OGTT. However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state.MethodsGiven a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA, proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1 year.ResultsThe most accurate prediction of IGT was reached with the recursive partitioning method (accuracy = 0.78. For all classifiers, mean accuracy was 0.73 ± 0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77.ConclusionMachine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a

  5. Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema : The RENEW Randomized Clinical Trial

    NARCIS (Netherlands)

    Sciurba, Frank C.; Criner, Gerard J.; Strange, Charlie; Shah, Pallav L.; Michaud, Gaetane; Connolly, Timothy A.; Deslee, Gaetan; Tillis, William P.; Delage, Antoine; Marquette, Charles-Hugo; Krishna, Ganesh; Kalhan, Ravi; Ferguson, J. Scott; Jantz, Michael; Maldonado, Fabien; McKenna, Robert; Majid, Adnan; Rai, Navdeep; Gay, Steven; Dransfield, Mark T.; Angel, Luis; Maxfield, Roger; Herth, Felix J. F.; Wahidi, Momen M.; Mehta, Atul; Slebos, Dirk-Jan

    2016-01-01

    IMPORTANCE Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE To determine the effectiveness and safety of

  6. Healthy eating at school

    DEFF Research Database (Denmark)

    Bruselius-Jensen, Maria Louisa; Egberg Mikkelsen, Bent

    ". This paper highlights the role that the organisation of food provision plays by comparing the attitudes of students towards in-school food provision as opposed to out-of-school provision where food is provided by outside caterers. Schools having internal food production and schools having external food...... operated catering seems to have a negative effect on the social and cultural structures and functions related to the meal during lunchtime. Having meals in schools where external caterers are employed is experienced as an individual act by the students in comparison with schools having internal catering......Unhealthy eating are common among adolescents and the school is a well suited setting for promoting healthy eating. For the school to play a role here, however an environment must be created, in which the school and the students develop a sense of ownership for a healthy food and nutrition "regime...

  7. : Healthy lifestyles’ promotion

    OpenAIRE

    Fernández Gómez, Erika; Díaz-Campo, Jesús

    2014-01-01

    International audience; The goal of this research was to analyse the advertising of food broadcast by the two Spanish private thematic channels aimed at children with more audience in Spain (Neox and Boing). A content analysis was made in order to study the commercials showed during the hours of children’s enhanced protection established by the normative of this country. The paper presents the increasing concern about kids´ obesity and the role of food industry. Healthy lifestyles are promote...

  8. Some like it healthy

    DEFF Research Database (Denmark)

    Contini, Caterina; Casini, Leonardo; Stancu, Violeta

    2015-01-01

    Authorising new health claims in Europe will favour the diffusion on the market of a greater number of foods with health claims. This scenario presents new opportunities to promote healthy food choices and launches new challenges to define strategies aimed at promoting products on the market...... sensitive of health claims and to characterise them with respect to the rest of the population. The results supply insights for the development of more targeted health promotion campaigns, as well as for actions in food marketing....

  9. Many Healthy Returns

    Centers for Disease Control (CDC) Podcasts

    2010-02-08

    International travel is usually very safe but there are things you should do to stay safe and healthy. Experts show you how to avoid problems when visiting developing nations. This includes being cautious about the food you eat and the water you drink, and to be aware of vehicles and road conditions to prevent problems.  Created: 2/8/2010 by National Center for Emerging and Zoonotic Infectious Disease (NCEZID).   Date Released: 2/8/2010.

  10. Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

    Science.gov (United States)

    Nel, Annalene M; Coplan, Paul; Smythe, Shanique C; McCord, Karen; Mitchnick, Mark; Kaptur, Paulina E; Romano, Joseph

    2010-11-01

    To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice daily on Days 2-9. Pharmacokinetics of dapivirine were assessed in plasma on Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory tests (hematology, clinical chemistry, and urinalysis), physical examinations, and assessment of adverse events. Plasma concentrations of dapivirine increased over time with gel dose and were greater on Day 10 (C(max) 31 to 471 pg/ml) than Day 1 (C(max) 23 to 80 pg/ml). T(max) was 10-12 h on Day 1, and 9 h on Day 10. Concentrations in CVF generally increased with dose but were highly variable among participants. Mean peak values ranged from 4.6-8.3 × 10(6) pg/ml on Day 1 and from 2.3-20.7 × 10(6) pg/ml on Day 10 across dose groups. Dapivirine was detectable in all tissue biopsies on Day 10 at concentrations of 1.0-356 × 10(3) pg/mg. Dapivirine was widely distributed throughout the lower genital tract with low systemic absorption when administered in a vaginal gel formulation for 10 consecutive days. The gel was safe and well tolerated.

  11. Genetics of healthy aging and longevity.

    Science.gov (United States)

    Brooks-Wilson, Angela R

    2013-12-01

    Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and

  12. Empowering a healthy practice environment.

    Science.gov (United States)

    Kushner, Jodi; Ruffin, Tasha

    2015-03-01

    This article provides frontline nurses a tool kit so they can advocate a healthy practice environment. The healthy nurse, healthy work hours, job satisfaction, adequate sleep, power naps at work, and balancing family/work are discussed. The overweight nurse, nurse fatigue, compassion fatigue, shift work sleep disorder, and role strain are discussed as barriers to a healthy practice environment. Case reports with analysis and recommendations are discussed to overcome these barriers. Resources are presented for frontline nurses to develop a tool kit for transforming their environment to a healthy practice environment and to empower them to become healthy nurses. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 75 FR 29908 - Prothioconazole; Pesticide Tolerances

    Science.gov (United States)

    2010-05-28

    .... The straw numerical value (5 ppm) is matched between the U.S. and Codex. The tolerance definition for... lower (0.07 ppm) than the recommended U.S. group tolerance. The 0.07 ppm value is the current U.S. tolerance value for wheat, but will be replaced by the cereal grain group tolerance. Canada does not...

  14. 78 FR 40027 - Novaluron; Pesticide Tolerances

    Science.gov (United States)

    2013-07-03

    ...). This regulation additionally deletes the time- limited tolerance for strawberry, as that tolerance..., pears, potatoes, strawberries, and tomatoes and utilized estimates for PCT for recently registered uses... deletes the time-limited tolerance for strawberry, as that tolerance expired on December 31, 2011. VI...

  15. Microsurgical Composite Tissue Transplantation

    Science.gov (United States)

    Serafin, Donald; Georgiade, Nicholas G.

    1978-01-01

    Since 1974, 69 patients with extensive defects have undergone reconstruction by microsurgical composite tissue transplantation. Using this method, donor composite tissue is isolated on its blood supply, removed to a distant recipient site, and the continuity of blood flow re-established by microvascular anastomoses. In this series, 56 patients (81%) were completely successful. There have been eight (12%) failures, primarily in the extremities. There have been five (7%) partial successes, (i.e., a microvascular flap in which a portion was lost requiring a secondary procedure such as a split thickness graft). In those patients with a severely injured lower extremity, the failure rate was the greatest. Most of these were arterial (six of seven). These failures occurred early in the series and were thought to be related to a severely damaged recipient vasculature. This problem has been circumvented by an autogenous interpositional vein graft, permitting more mobility of flap placement. In the upper extremity, all but one case were successful. Early motion was permitted, preventing joint capsular contractures and loss of function. Twenty-three cases in the head and neck region were successful (one partial success). This included two composite rib grafts to the mandible. Prolonged delays in reconstruction following extirpation of a malignancy were avoided. A rapid return to society following complete reconstruction was ensured. Nine patients presented for reconstruction of the breast and thorax following radical mastectomy. All were successfully reconstructed with this new technique except one patient. Its many advantages include immediate reconstruction without delayed procedures and no secondary deformity of the donor site. Healthy, well vascularized tissue can now be transferred to a previously irradiated area with no tissue loss. This new method offers many advantages to older methods of reconstruction. Length of hospital stay and immobilization are reduced. The

  16. Healthy ageing - from molecules to hormesis

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2012-01-01

    Ageing can be understood at various levels, from evolutionary and biological levels to psychological and sociological levels. At the molecular biological level ageing is characterized by the stochastic occurrence and progressive accumulation of molecular damage. Failure of homeodynamics, increased...... molecular heterogeneity, altered cellular functioning and reduced stress tolerance are the determinants of health status, probability of diseases and the duration of survival. The inefficiency and imperfection of the maintenance and repair systems underlie the biological basis of ageing. Two major issues...... life style alterations are examples of ageing interventions. A promising healthy-ageing approach is that of hormesis by strengthening the homeodynamic ability of self-maintenance through transient and repetitive mild stress-inducing hormetins. Achieving the goal of extended health-span will depend...

  17. Dynamics of personal development on healthy students

    Directory of Open Access Journals (Sweden)

    I.E. Kramida

    2013-04-01

    Full Text Available The aim is to study the effectiveness of different physical training for the relatively healthy students. The study involved 1004 students. The directions of development of the students' positive personal qualities. Found that the positive development of personality of students observed mostly on the first and third year than in the second. Could not find significant differences between the growth estimates of development of personality traits of students in classes in the sample program and the program specializations. Found that the rate of development of students' personality traits minor: the average growth estimates for core positive personal qualities for 3 years does not exceed 10% of the maximum possible level. Recommended in the classroom more emphasis on developing positive personality traits. It is shown that special attention should be paid to the development of emotional stability of students and their tolerance towards other people.

  18. Healthy Bones Matter

    Science.gov (United States)

    ... Also, women generally have less bone tissue than men. So, it’s especially important for girls to build up their bone “bank account” during their teenage years by exercising regularly and getting enough calcium and vitamin D. What to do for strong bones—today and tomorrow Osteoporosis is usually a ...

  19. Gene expression of Lactobacillus plantarum and the commensal microbiota in the ileum of healthy and early SIV-infected rhesus macaques

    Science.gov (United States)

    Golomb, Benjamin L.; Hirao, Lauren A.; Dandekar, Satya; Marco, Maria L.

    2016-01-01

    Chronic HIV infection results in impairment of gut-associated lymphoid tissue leading to systemic immune activation. We previously showed that in early SIV-infected rhesus macaques intestinal dysfunction is initiated with the induction of the IL-1β pathway in the small intestine and reversed by treatment with an exogenous Lactobacillus plantarum strain. Here, we provide evidence that the transcriptomes of L. plantarum and ileal microbiota are not altered shortly after SIV infection. L. plantarum adapts to the small intestine by expressing genes required for tolerating oxidative stress, modifying cell surface composition, and consumption of host glycans. The ileal microbiota of L. plantarum-containing healthy and SIV+ rhesus macaques also transcribed genes for host glycan metabolism as well as for cobalamin biosynthesis. Expression of these pathways by bacteria were proposed but not previously demonstrated in the mammalian small intestine. PMID:27102350

  20. [Prevalence of postpartum impaired glucose tolerance after gestational diabetes].

    Science.gov (United States)

    Romero Gutiérrez, Gustavo; Macias Rocha, Ana Laura; Puente Alvarez, Erika Isela

    2012-10-01

    gestational diabetes mellitus (GDM) affects 2 to 10% of pregnancies and it has been postulated as a variant of type 2 diabetes mellitus (DM2) because they share a similar pathophysioiogy. Approximately in 90% the carbohydrate intolerance resolves after pregnancy, however after 5 to 16 years after delivery women will have a risk of 17 to 63% to the development of type 2 diabetes mellitus. to determine the frequency of postpartum impaired glucose tolerance in women with previous GDM. 125 patients with diagnosis of GMD were included, general data were captured, type of control during pregnancy and complications occurred. The women were instructed to undergo a postpartum oral glucose tolerance test of 75 g and 2 h, 6 weeks after their delivery date and they were classified into five groups: normal patients, type 2 diabetes mellitus, impaired glucose tolerance, impaired fasting glucose and combined both. after follow up 13 women (10.4%) were diagnosed as DM2; 14 patients (11.2%) were classified as glucose intolerance; 16 (12.8%) were catalogued with impaired fasting glucose; 6 (4.8%) had both disorders; and 76 (60.8%) were diagnosed as healthy women. the detection with a postpartum oral glucose tolerance test is necessary for the identification of the various types of disorders of the carbohydrate metabolism including DM2.

  1. Bioactive glass in tissue engineering

    Science.gov (United States)

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  2. Healthy Swimming/Recreational Water

    Science.gov (United States)

    ... Medical Professionals En Español Publications, Data, & Statistics Healthy Swimming Resources Health Promotion Materials Find Your State Training & ... Announcements Outbreak Response Toolkits CDC at Work: Healthy Swimming Fast Facts Index of Water-Related Topics Model ...

  3. Healthy Eating and Academic Achievement

    Centers for Disease Control (CDC) Podcasts

    This podcast highlights the evidence that supports the link between healthy eating and improved academic achievement. It also identifies a few actions to support a healthy school nutrition environment to improve academic achievement.

  4. Healthy Habits Can Lengthen Life

    Science.gov (United States)

    ... 2018 Print this issue Health Capsule Healthy Habits Can Lengthen Life Send us your comments Physical activity is one of five healthy lifestyle factors that can lower your risk for several diseases and lengthen ...

  5. Glucose in vaginal secretions before and after oral glucose tolerance testing in women with and without recurrent vulvovaginal candidiasis.

    Science.gov (United States)

    Ehrström, Sophia; Yu, Anna; Rylander, Eva

    2006-12-01

    To measure the change of glucose in vaginal secretions during glucose tolerance testing in women with recurrent vulvovaginal candidiasis and in healthy control subjects. Thirty-eight women with recurrent vulvovaginal candidiasis and 45 healthy, age-matched controls completed a health questionnaire regarding general and gynecologic health and food and alcohol habits. They all underwent an oral glucose tolerance test and a vaginal examination. Vaginal secretion was collected from the proximal part of the vagina. Glucose in plasma and in vaginal secretions were measured at fasting and after 2 hours and analyzed with the hexokinase method. A sample size analysis showed that the number of subjects included in the study was sufficient for a beta value of 0.80, at the significance level of alpha=.05, at a difference in glucose in vaginal secretions of 30% after oral glucose tolerance test. In healthy women, the median level of glucose in vaginal secretions was 5.2 mM before and 3.7 mM after oral glucose tolerance test, and plasma glucose was 5.0 mM before and 5.8 mM after oral glucose tolerance test. No significant difference was seen regarding change of glucose level in vaginal secretions and plasma glucose after testing, compared with before oral glucose tolerance testing. There were no differences between women with recurrent vulvovaginal candidiasis and control subjects regarding change in glucose level in vaginal secretions or in plasma during oral glucose tolerance test. II-2.

  6. Contraction-mediated glucose uptake is increased in men with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Skov-Jensen, Camilla; Skovbro, Mette; Flint, Anne

    2007-01-01

    stimulation alone and with superimposed exercise. Patients with type 2 diabetes, subjects with impaired glucose tolerance (IGT), healthy controls, and endurance-trained subjects were studied. The groups were matched for age and lean body mass (LBM), and differed in peak oxygen uptake (VO2 peak), body fat...

  7. B cells in operational tolerance.

    Science.gov (United States)

    Chesneau, M; Danger, R; Soulillou, J-P; Brouard, S

    2018-02-16

    Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunosuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal. This review summarizes studies that suggest a role for B cells as biomarkers of operational tolerance and discusses the use of B cells as a predictive tool for immunologic risk. Copyright © 2018. Published by Elsevier Inc.

  8. Immune tolerance in radiation chimeras

    International Nuclear Information System (INIS)

    Awaya, Kazuhiko; Kuniki, Hiromichi; Neki, Miyuki

    1978-01-01

    Establishment of immune tolerance in radiation chimeras and the mechanism of maintaining it were discussed from certain points. Semiallogeneic radiation chimeras are mostly of long-living, and the hematopoietic organ of this individual consists mainly of the cells derived from the marrow donor, i. e., F 1 -type cells. F 1 -type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F 1 -skin graft maintains to be fresh as long as the host is alive, showing immune tolerance effective through its life. In establishment and maintenance of this immune tolerance, the suppressing mechanism of host-type or F 1 -type seems to be involved. The allogeneic radiation chimera has very poor long-survival rate compared with that of the semiallogeneic radiation chimera. To raise this survival rate, efforts are now being made from the immunological point of view. (Ueda, J.)

  9. [Food additives and healthiness].

    Science.gov (United States)

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  10. Aim For a Healthy Weight

    Science.gov (United States)

    ... out of your control, you can make positive lifestyle changes to lose weight and to maintain a healthy weight. These include a healthy eating plan and being more physically active. Take the Challenge When it comes to aiming for a healthy ...

  11. Maintaining Healthy Skin -- Part 1

    Science.gov (United States)

    ... with no breaks in the surface. It is warm (not hot or red) and neither dry and flaky nor moist and wrinkled. Healthy skin is a mirror of a healthy body. How to take care of your skin NUTRITION: To keep your skin healthy, eat a well- ...

  12. Methods to establish flaw tolerances

    International Nuclear Information System (INIS)

    Varga, T.

    1978-01-01

    Three conventional methods used to establish flaw tolerances are compared with new approaches using fracture mechanics. The conventional methods are those based on (a) non-destructive testing methods; (b) fabrication and quality assurance experience; and (c) service and damage experience. Pre-requisites of fracture mechanics methods are outlined, and summaries given of linear elastic mechanics (LEFM) and elastoplastic fracture mechanics (EPFM). The latter includes discussion of C.O.D.(crack opening displacement), the J-integral and equivalent energy. Proposals are made for establishing flaw tolerances. (U.K.)

  13. Tolerating extremism : to what extent should intolerance be tolerated?

    NARCIS (Netherlands)

    Guiora, Amos Neuser

    2013-01-01

    In discussing extremism, the key questions are: to whom is a duty owed and what are the limits of intolerance that are to be tolerated? Answering these questions requires examining limits and rights; analyzing them in the context of extremism is the ‘core’ of this book. While freedom of speech and

  14. [Healthy school environments].

    Science.gov (United States)

    Quintero-Corzo, Josefina; Munévar-Molina, Raúl A; Munévar-Quintero, Fabio I

    2015-04-01

    Objective To determine factors that characterizes school environments and their relationship with student learning, welfare and health. Method This is a case study supported by a comprehensive qualitative paradigm applied to classroom ecology. The fieldwork was carried out in six public schools for students in economic strata one and two that use computers in virtual classrooms. The information was collected through field journals, film recordings, observation, and recordings of interviews. The information was analyzed by categories in open general and focused cycles. Results The virtual era has enriched the debate about the importance of the environment in pedagogical processes. Nonetheless, the emergence of new diseases is a risk which students are exposed to. Pollution and overcrowding factors prevail in traditional classroom activities, while in the computer rooms the environment is healthier. Hence the need to incorporate these issues into the curriculum reforms and action plans to guide healthy living of schoolchildren and their families. Despite budget constraints, innovative ideas and projects were found. Schools have developed free preventive and corrective strategies such as workshops, talks and lectures by invited specialists, trainees, and students writing theses. They have also introduced controlled Internet access. Conclusion The educational community understands that the concept of health is at the heart of a comprehensive concept of education. In addition, classroom ecology has determining implications for learning and living together in pleasant and healthy environments that are incorporated into institutional educational projects.

  15. Tolerance of snakes to hypergravity

    Science.gov (United States)

    Lillywhite, H. B.; Ballard, R. E.; Hargens, A. R.

    1996-01-01

    Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.

  16. Assessing Your Board's Risk Tolerance

    Science.gov (United States)

    Griswold, John S.; Jarvis, William F.

    2014-01-01

    In the wake of the financial crisis, trustees of many endowed nonprofit institutions realized that their portfolio was riskier than they thought and their own ability to tolerate loss wasn't as strong as they imagined. What can board and investment committee members do to improve their ability to assess their--and their institution's--capacity for…

  17. Toleration, Multiculturalism and Mistaken Belief

    Science.gov (United States)

    Standish, Paul

    2006-01-01

    Doubts have been expressed about the virtue of toleration, especially in view of what some have seen as its complicity with a morality of anything goes. More rigorous arguments have been provided by Peter Gardner and Harvey Siegel against the relativism evident in certain versions of multiculturalism and in the new religious studies. This article…

  18. A safety and pharmacokinetic trial assessing delivery of dapivirine from a vaginal ring in healthy women.

    Science.gov (United States)

    Nel, Annalene; Haazen, Wouter; Nuttall, Jeremy; Romano, Joseph; Rosenberg, Zeda; van Niekerk, Neliëtte

    2014-06-19

    Women-initiated HIV-prevention products are urgently needed. To address this need, a trial was conducted to assess the safety and pharmacokinetics of a silicone elastomer matrix vaginal ring containing 25 mg of the antiretroviral drug dapivirine when used continuously for 28 consecutive days. A double-blind, randomized, placebo-controlled trial was conducted in 16 healthy, HIV-negative women, 18-40 years of age, who were randomized 1:1 to use either the active or matching placebo ring for 28 days. Participants were followed during and for 28 days after ring use for safety and pharmacokinetic evaluations. The dapivirine vaginal ring was safe and well tolerated with no differences in safety endpoints between the active and placebo ring. The concentration-time plots of dapivirine in vaginal fluid were indicative of a sustained release of dapivirine over the 28 days of use. Dapivirine vaginal fluid concentrations were highest near the ring, followed by the cervix and introïtus (mean Cmax of 80, 67 and 31 μg/g, respectively). Vaginal fluid concentrations of dapivirine on the day of ring removal (day 28) at all three collection sites exceeded by more than 3900-fold the IC99 for dapivirine in a tissue explant infection model. Plasma dapivirine concentrations were low (dapivirine vaginal ring has a safety and pharmacokinetic profile that supports its use as a sustained-release topical microbicide for HIV-1 prevention in women.

  19. The effects of the CXCR2 antagonist, MK-7123, on bone marrow functions in healthy subjects.

    Science.gov (United States)

    Hastrup, Nina; Khalilieh, Sauzanne; Dale, David C; Hanson, Lars G; Magnusson, Peter; Tzontcheva, Anjela; Tseng, Jack; Huyck, Susan; Rosenberg, Elizabeth; Krogsgaard, Kim

    2015-04-01

    The CXCR2 antagonist MK-7123 causes dose-dependent reductions in absolute neutrophil counts (ANC) and decreases neutrophil tissue responses, but its effects on bone marrow functions are not yet known. We conducted a double-blind, randomized study in 18 healthy subjects comparing the effects of either MK-7123 (30mg, po, daily for 28days) or placebo on peripheral blood counts and bone marrow myeloid cell populations. MK-7123 caused a reversible decrease (approximately 50%) in the ANC as demonstrated on days 1 and 28, the first and last days of the treatment period. Bone marrow aspirate smears and biopsy imprints did not differ in the proportion of mature neutrophils in pretreatment, day 28, day 56 or placebo samples. There were no treatment effects on biopsy or aspirate clot cellularity, myeloid to erythroid or myeloid post-mitotic to mitotic ratios; flow-cytometric analyses of aspirate cells; or bone marrow fat to cell balance as assessed by MRI. MK-7123 was generally well tolerated with neutropenia being the most common adverse event; however, there were no clinical symptoms associated with decreased ANCs. These findings indicate that the CXCR2 antagonist MK-7123 causes rapidly reversible decrease in the ANC without measurable myelosuppressive effects. The results support the development of CXCR2 antagonists as potentially useful anti-inflammatory agents, primarily interrupting neutrophil trafficking. Copyright © 2015. Published by Elsevier Ltd.

  20. Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.

    Science.gov (United States)

    Erol, Onur; Özel, Mustafa Kemal; Ellidağ, Hamit Yaşar; Toptaş, Tayfun; Derbent, Aysel Uysal; Yılmaz, Necat

    2017-07-01

    The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

  1. The Muscle Metabolome Differs between Healthy and Frail Older Adults.

    Science.gov (United States)

    Fazelzadeh, Parastoo; Hangelbroek, Roland W J; Tieland, Michael; de Groot, Lisette C P G M; Verdijk, Lex B; van Loon, Luc J C; Smilde, Age K; Alves, Rodrigo D A M; Vervoort, Jacques; Müller, Michael; van Duynhoven, John P M; Boekschoten, Mark V

    2016-02-05

    Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects, and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference group. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies.

  2. Mixed Connective Tissue Disease

    Science.gov (United States)

    Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...

  3. Undifferentiated Connective Tissue Disease

    Science.gov (United States)

    ... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

  4. Soft Tissue Sarcoma

    Science.gov (United States)

    ... muscles, tendons, fat, and blood vessels. Soft tissue sarcoma is a cancer of these soft tissues. There ... have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove ...

  5. Comparative study of SOS2 and a novel PMP3-1 gene expression in two sunflower (Helianthus annuus L.) lines differing in salt tolerance.

    Science.gov (United States)

    Saadia, Mubshara; Jamil, Amer; Ashraf, Muhammad; Akram, Nudrat Aisha

    2013-06-01

    Gene expression pattern of two important regulatory proteins, salt overly sensitive 2 (SOS2) and plasma membrane protein 3-1 (PMP3-1), involved in ion homeostasis, was analyzed in two salinity-contrasting sunflower (Helianthus annuus L.) lines, Hysun-38 (salt tolerant) and S-278 (moderately salt tolerant). The pattern was studied at selected time intervals (24 h) under 150 mM NaCl treatment. Using reverse transcription PCR, SOS2 gene fragment was obtained from young leaf and root tissues of opposing lines while that for PMP3-1 was obtained only from young root tissues. Both tolerant and moderately tolerant lines showed a gradual increase in SOS2 expression in sunflower root tissues. Leaf tissues showed the gradually increasing pattern of SOS2 expression in tolerant plants as compared to that for moderately tolerant ones that showed a relatively lower level of expression for this gene. We found the highest level of PMP 3-1 expression in the roots of tolerant sunflower line at 6 and 12 h postsalinity treatment. The moderately tolerant line showed higher expression of PMP3-1 at 12 and 24 h after salt treatment. Overall, the expression of genes for both the regulator proteins varied significantly in the two sunflower lines differing in salinity tolerance.

  6. Traction force microscopy of engineered cardiac tissues.

    Science.gov (United States)

    Pasqualini, Francesco Silvio; Agarwal, Ashutosh; O'Connor, Blakely Bussie; Liu, Qihan; Sheehy, Sean P; Parker, Kevin Kit

    2018-01-01

    Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.

  7. Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

  8. Physiological determinants of human acute hypoxia tolerance.

    Science.gov (United States)

    2013-11-01

    AbstractIntroduction. We investigated possible physiological determinants of variability in hypoxia tolerance in subjects given a 5-minute normobaric exposure to 25,000 ft equivalent. Physiological tolerance to hypoxia was defined as the magnitude of...

  9. Persistence and drug tolerance in pathogenic yeast

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2017-01-01

    In this review, we briefly summarize the current understanding of how fungal pathogens can persist antifungal treatment without heritable resistance mutations by forming tolerant persister cells. Fungal infections tolerant to antifungal treatment have become a major medical problem. One mechanism...

  10. Drought and submergence tolerance in plants

    Energy Technology Data Exchange (ETDEWEB)

    Du, Hewei; Zhou, Yufan; Oksenberg, Nir; Ronald, Pamela

    2017-11-14

    The invention provides methods of genetically modified plants to increase tolerance to drought and/or submergence. The invention additionally provides plants having increased drought and/or submergence tolerance engineered using such methods.

  11. Urbanism, Migration, and Tolerance: A Reassessment.

    Science.gov (United States)

    Wilson, Thomas C.

    1991-01-01

    Urbanism's impact on the personality may be stronger than previously thought. Finds that urban residence has a strong positive effect on tolerance. Migration also promotes tolerance, regardless of the size of the destination community. (DM)

  12. Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance.

    Science.gov (United States)

    Honkala, Sanna M; Motiani, Kumail K; Eskelinen, Jari-Joonas; Savolainen, Anna; Saunavaara, Virva; Virtanen, Kirsi A; Löyttyniemi, Eliisa; Kapanen, Jukka; Knuuti, Juhani; Kalliokoski, Kari K; Hannukainen, Jarna C

    2017-07-01

    Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). A total of 28 healthy men (body mass index = 20.7-30.0 kg·m, age = 40-55 yr) and 16 men with DGT (body mass index = 23.8-33.5 kg·m, age = 43-53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by H-MRS. At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = -42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (-5%) and PAT (-6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC.

  13. Diminished interferon-gamma production and responsiveness after endotoxin administration to healthy humans

    NARCIS (Netherlands)

    Weijer, Sebastiaan; Lauw, Fanny N.; Branger, Judith; van den Blink, Bernt; van der Poll, Tom

    2002-01-01

    To obtain insight in the capacity of the lipopolysaccharide (LPS)-tolerant host to produce interferon (IFN)-gamma and to respond to this cytokine, whole blood was obtained from healthy humans before and 4 h after intravenous injection of LPS (4 ng/kg) and stimulated ex vivo. LPS exposure in vivo

  14. Methadone Recycling Sustains Drug Reservoir in Tissue.

    Science.gov (United States)

    Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie; Schiesser, William E; Boston, Raymond C

    2015-09-01

    We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels. We studied a random sample of six opioid-naïve healthy subjects. We performed a clinical trial simulation in silico using pharmacokinetic modeling. We found a large tissue store of methadone content whose size was much larger than methadone's size in plasma in response to a single oral dose of methadone 10 mg. The tissue store measured 13-17 mg. This finding could only be explained by the contemporaneous storage of methadone in tissue with dose recycling. We found that methadone recycles 2-5 times through an inaccessible extravascular compartment (IAC), from an accessible plasma-containing compartment (AC), before exiting irreversibly. We estimate the rate of accumulation (or storage) of methadone in tissue was 0.029-7.29 mg/h. We predict 39 ± 13% to 83 ± 6% of methadone's tissue stores "spillover" into the circulation. Our results indicate that there exists a large quantifiable tissue store of methadone in humans. Our results support the notion that methadone in humans undergoes tissue uptake, storage, release into the circulation, reuptake from the circulation, and re-release into the circulation, and that spillover of methadone from tissue stores, in part, maintain plasma methadone levels in humans.

  15. 75 FR 17566 - Flutolanil; Pesticide Tolerances

    Science.gov (United States)

    2010-04-07

    ... ppm, and the greater tolerance value is needed to accommodate indirect residues from soybean..., and soybean hay at 2.5 ppm are being revoked since the same tolerance values are being established...; Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This...

  16. 77 FR 49732 - Cyprodinil; Pesticide Tolerances

    Science.gov (United States)

    2012-08-17

    .../puree (1x) and lemon/lime juice (1x) were used to modify the tolerance values. iii. Cancer. Based on the... the tolerance necessitate a higher value. Additionally, Codex has an established MRL on grape at 3 ppm...; Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This...

  17. 15 CFR 750.11 - Shipping tolerances.

    Science.gov (United States)

    2010-01-01

    ... in the ECCN applicable to your item reads “ $ value” or “in $ value”, there is no shipping tolerance... is no shipping tolerance with respect to the number of units. However, the value of all of your... shipping tolerance on this license because the items are controlled by an ECCN where “$ value” is the...

  18. 78 FR 18511 - Thiamethoxam; Pesticide Tolerances

    Science.gov (United States)

    2013-03-27

    ... Health Risk Assessment of New Uses on Strawberry, Pistachio, and Citrus; New Tolerance for Tea; and... Uses on Strawberry, Pistachio, and Citrus; New Tolerance for Tea; and Revised PHI and Tolerance for... ``Clothianidin--Aggregate Human Health Risk Assessment of New Uses on Strawberry, Pistachio, and Citrus; New...

  19. 77 FR 28493 - Propylene Oxide; Tolerance Actions

    Science.gov (United States)

    2012-05-15

    .... SUMMARY: EPA is establishing the tree nut crop group tolerance and separate tolerances on pistachio and...; nut, tree, group 14; and pistachio; and in 40 CFR 180.491(a)(2) tolerances for propylene chlorohydrin at 10.0 ppm on nut, pine; nut, tree, group 14; and pistachio. Also, in accordance with current Agency...

  20. 75 FR 26673 - Clethodim; Pesticide Tolerances

    Science.gov (United States)

    2010-05-12

    ... regulation establishes tolerances for residues of clethodim in or on the raw agricultural commodity artichoke... clethodim, in or on the raw agricultural commodity artichoke, globe at 1.3 parts per million (ppm... bushberry subgroup 13-07B tolerance from 3.0 ppm to 0.20 ppm and the globe artichoke tolerance from 1.3 ppm...