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Sample records for cells preserves function

  1. Ebselen Preserves Tissue-Engineered Cell Sheets and their Stem Cells in Hypothermic Conditions.

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    Katori, Ryosuke; Hayashi, Ryuhei; Kobayashi, Yuki; Kobayashi, Eiji; Nishida, Kohji

    2016-12-14

    Clinical trials have been performed using autologous tissue-engineered epithelial cell sheets for corneal regenerative medicine. To improve stem cell-based therapy for convenient clinical practice, new techniques are required for preserving reconstructed tissues and their stem/progenitor cells until they are ready for use. In the present study, we screened potential preservative agents and developed a novel medium for preserving the cell sheets and their stem/progenitor cells; the effects were evaluated with a luciferase-based viability assay. Nrf2 activators, specifically ebselen, could maintain high ATP levels during preservation. Ebselen also showed a strong influence on maintenance of the viability, morphology, and stem cell function of the cell sheets preserved under hypothermia by protecting them from reactive oxygen species-induced damage. Furthermore, ebselen drastically improved the preservation performance of human cornea tissues and their stem cells. Therefore, ebselen shows good potential as a useful preservation agent in regenerative medicine as well as in cornea transplantation.

  2. Small amounts of tissue preserve pancreatic function: Long-term follow-up study of middle-segment preserving pancreatectomy.

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    Lu, Zipeng; Yin, Jie; Wei, Jishu; Dai, Cuncai; Wu, Junli; Gao, Wentao; Xu, Qing; Dai, Hao; Li, Qiang; Guo, Feng; Chen, Jianmin; Xi, Chunhua; Wu, Pengfei; Zhang, Kai; Jiang, Kuirong; Miao, Yi

    2016-11-01

    Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear.The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP.From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires.Our case series included 3 women and 2 men, with median age of 50 (37-81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250-615) min and 800 (400-5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4 preoperatively euglycemic

  3. Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

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    Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

    2017-01-01

    Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

  4. Supercooling as a viable non-freezing cell preservation method of rat hepatocytes.

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    O Berk Usta

    Full Text Available Supercooling preservation holds the potential to drastically extend the preservation time of organs, tissues and engineered tissue products, and fragile cell types that do not lend themselves well to cryopreservation or vitrification. Here, we investigate the effects of supercooling preservation (SCP at -4(oC on primary rat hepatocytes stored in cryovials and compare its success (high viability and good functional characteristics to that of static cold storage (CS at +4(oC and cryopreservation. We consider two prominent preservation solutions a Hypothermosol (HTS-FRS and b University of Wisconsin solution (UW and a range of preservation temperatures (-4 to -10 (oC. We find that there exists an optimum temperature (-4(oC for SCP of rat hepatocytes which yields the highest viability; at this temperature HTS-FRS significantly outperforms UW solution in terms of viability and functional characteristics (secretions and enzymatic activity in suspension and plate culture. With the HTS-FRS solution we show that the cells can be stored for up to a week with high viability (~56%; moreover we also show that the preservation can be performed in large batches (50 million cells with equal or better viability and no loss of functionality as compared to smaller batches (1.5 million cells performed in cryovials.

  5. Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea.

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    Nottage, Kerri A; Ware, Russell E; Winter, Bryan; Smeltzer, Matthew; Wang, Winfred C; Hankins, Jane S; Dertinger, Stephen D; Shulkin, Barry; Aygun, Banu

    2014-11-01

    More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function. Children with SCA enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE-NCT00305175) underwent clinical evaluations including Tc(99) m liver-spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake, Hydroxyurea at MTD is associated with preserved or improved splenic filtrative function, with 33% demonstrating LS scan uptake after 3 yrs. Younger age, higher %HbF, and baseline splenic function are associated with a favorable outcome. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. The time has come to test the beta cell preserving effects of exercise in patients with new onset type 1 diabetes

    DEFF Research Database (Denmark)

    Narendran, Parth; Solomon, Thomas; Kennedy, Amy

    2015-01-01

    Type 1 diabetes is characterised by immune-mediated destruction of insulin-producing beta cells. Significant beta cell function is usually present at the time of diagnosis with type 1 diabetes, and preservation of this function has important clinical benefits. The last 30 years have seen a number...... for physical exercise as a therapy for the preservation of beta cell function in patients with newly diagnosed type 1 diabetes. We highlight possible mechanisms by which exercise could preserve beta cell function and then present evidence from other models of diabetes that demonstrate that exercise preserves...... beta cell function. We conclude by proposing that there is now a need for studies to explore whether exercise can preserve beta cell in patients newly diagnosed with type 1 diabetes....

  7. Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction.

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    Sharp, Thomas E; Schena, Giana J; Hobby, Alexander R; Starosta, Timothy; Berretta, Remus M; Wallner, Markus; Borghetti, Giulia; Gross, Polina; Yu, Daohai; Johnson, Jaslyn; Feldsott, Eric; Trappanese, Danielle M; Toib, Amir; Rabinowitz, Joseph E; George, Jon C; Kubo, Hajime; Mohsin, Sadia; Houser, Steven R

    2017-11-10

    Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×10 7 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU + cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve

  8. Functional Nerve Preservation in Extracranial Head and Neck Schwannoma Surgery.

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    Ijichi, Kei; Kawakita, Daisuke; Maseki, Shinichiro; Beppu, Shintaro; Takano, Gaku; Murakami, Shingo

    2016-05-01

    A schwannoma is an uncommon, benign neurogenic tumor of Schwann cells. Tumor enucleation is the recommended surgical method to preserve function of the original nerve, although enucleation does not guarantee completely intact nerve function after the operation. To establish a strategy for functional preservation in extracranial head and neck schwannoma treatment by using an electromyographic (EMG) system during tumor resection. A retrospective cohort study was conducted of 15 patients who underwent surgery for removal of schwannoma tumors between April 1, 2006, and March 31, 2015, at an academic tertiary referral center. Data analysis was conducted from April 3, 2006, to September 15, 2015. Neurogenic tumors were diagnosed according to preoperative findings, and during surgery tumors were exposed and given EMG-controlled electrical stimulation to analyze their origins. In motor nerve cases, the electrical activity of the muscle was measured and recorded by EMG. The tumor was then enucleated by incision along tumor fibers mapped using EMG stimulation. If a nerve bundle was visible, we incised along there and enucleated the tumor. A strategy using electrical stimulation to improve preservation of nerve function in extracranial head and neck schwannoma operations. Frequency and duration of postoperative neurologic complications associated with functional preservation surgery with tumor enucleation was evaluated using EMG monitoring according to tumor origin. Of the 15 patients with extracranial schwannoma, 9 (60%) were women (mean [SD] age, 36.3 [15.3] years). All 15 patients underwent surgery using a transcervical approach. The most common nerves of origin were the vagus nerve and the sympathetic chain. In sensory or sympathetic nerve cases, the EMG response was absent. Two of 5 patients with vagus schwannoma had postoperative temporary vocal nerve palsy. These symptoms showed improvement after 1 year. There was no tumor recurrence during the follow-up period in any

  9. Elastin overexpression by cell-based gene therapy preserves matrix and prevents cardiac dilation

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    Li, Shu-Hong; Sun, Zhuo; Guo, Lily; Han, Mihan; Wood, Michael F G; Ghosh, Nirmalya; Alex Vitkin, I; Weisel, Richard D; Li, Ren-Ke

    2012-01-01

    After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re-establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full-length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs). In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity (by birefringence of polarized light; P elastin showed the greatest functional improvement (P elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell-based gene therapy provides a new approach to cardiac regeneration. PMID:22435995

  10. Preservation of Ejaculatory and Erectile Function after Radical Cystectomy for Urothelial Malignancy

    International Nuclear Information System (INIS)

    Salem, H.K.

    2005-01-01

    Treating cancer patients, sexual issues should not be forgotten. With increasing survival from urologic cancer, quality of life and quality of sexuality have became very important targets in treating those patients. Fertility to those patients who desire fatherhood is sometimes more important than cancer morbidity, especially young patients in the rural areas in our country, to the extent that they may refuse the operation. We describe a new technique to preserve the erectile function and antegrade ejaculation after radical cystectomy. Patients and Methods: Seven potent men with a median age of 40 years (range 35-50) presented with invasive transitional cell carcinoma (TCC) of the lateral or the anterior bladder wall. All patients wished to preserve the ejaculatory function and fertility potential. We described the surgical technique of nerve sparing radical cystectomy with preservation of the vas deferens, seminal vesicles, whole prostate and neurovascular bundles. The follow up period ranged from six months to three years (mean 20 months) to assess recurrence, erectile function and ejaculatory function. Erectile function is normal in all patients with satisfactory sexual intercourse. Antegrade ejaculation was documented in six cases. One of them fathered a child. No local or distant recurrence was detected in the seven patients at the last follow-up. The technique of radical cystectomy (with preservation of the vas deferens, whole prostate and seminal vesicle) is a good option in selected young men with bladder carcinoma in whom preservation of fertility is desirable

  11. Donor Satellite Cell Engraftment is Significantly Augmented When the Host Niche is Preserved and Endogenous Satellite Cells are Incapacitated

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    Boldrin, Luisa; Neal, Alice; Zammit, Peter S; Muntoni, Francesco; Morgan, Jennifer E

    2012-01-01

    Stem cell transplantation is already in clinical practice for certain genetic diseases and is a promising therapy for dystrophic muscle. We used the mdx mouse model of Duchenne muscular dystrophy to investigate the effect of the host satellite cell niche on the contribution of donor muscle stem cells (satellite cells) to muscle regeneration. We found that incapacitation of the host satellite cells and preservation of the muscle niche promote donor satellite cell contribution to muscle regeneration and functional reconstitution of the satellite cell compartment. But, if the host niche is not promptly refilled, or is filled by competent host satellite cells, it becomes nonfunctional and donor engraftment is negligible. Application of this regimen to aged host muscles also promotes efficient regeneration from aged donor satellite cells. In contrast, if the niche is destroyed, yet host satellite cells remain proliferation-competent, donor-derived engraftment is trivial. Thus preservation of the satellite cell niche, concomitant with functional impairment of the majority of satellite cells within dystrophic human muscles, may improve the efficiency of stem cell therapy. Stem Cells2012;30:1971–1984 PMID:22730231

  12. In vitro effects of preservative-free and preserved prostaglandin analogs on primary cultured human conjunctival fibroblast cells.

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    Kim, Eun Joo; Kim, Yeoun-Hee; Kang, Sun-Hee; Lee, Kyoo Won; Park, Young Jeung

    2013-12-01

    Long-term use of topical medication is needed for glaucoma treatment. One of the most commonly prescribed classes of hypotensive agents are prostaglandin analogs (PGs) used as both first-line monotherapy; as well as in combination therapy with other hypotensive agents. Several side effects of eye drops can be caused by preservatives. The purpose of this study was to evaluate the effects of PGs with varying concentrations of benzalkonium chloride (BAC), alternative preservatives, or no preservatives on human conjunctival fibroblast cells. Primary human conjunctival fibroblast cells were used in these experiments. Cells were exposed to the following drugs: BAC at different concentrations, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), tafluprost 0.0015% with/without 0.001% BAC and travoprost 0.004% (with 0.001% Polyquad) for 15 and 30 minutes. Cell cytotoxicity was evaluated by phase-contrast microscopy to monitor morphological changes of cells, Counting Kit-8 (CCK-8) assay to cell viability, and fluorescent activated cell sorting (FACS) analysis to measure apoptosis. BAC caused cell shrinkage and detachment from the plate in a dose-dependent manner. Morphological changes were observed in cells treated with bimatoprost 0.01% and latanoprost 0.005%. However, mild cell shrinkage was noted in cells treated with tafluprost 0.0015%, while a non-toxic effect was noted with travoprost 0.004% and preservative-free tafluprost 0.0015%. CCK-8 assay and FACS analysis showed all groups had a significantly decreased cell viability and higher apoptosis rate compared with the control group. However, travoprost 0.004% and preservative-free tafluprost 0.0015% showed lower cytotoxicity and apoptosis rate than other drugs. This in vitro study revealed that BAC-induced cytotoxicity is dose-dependent, although it is important to emphasize that the clinical significance of toxicity differences observed among the different PGs formulations has not yet been firmly

  13. Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling

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    John eHarrell

    2015-12-01

    Full Text Available Data indicate endothelium-dependent dilation (EDD may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS and cyclooxygenase (COX toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh in younger (27±1 yr obese (n=29 and lean (n=46 humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of L-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC. Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS. ΔFVC to ACh was similar between groups. After L-NMMA, ΔFVC to ACh was greater in obese adults (p<0.05. There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction.

  14. Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation

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    Limesand, Kirsten H.; Avila, Jennifer L.; Victory, Kerton; Chang, Hui-Hua; Shin, Yoon Joo; Grundmann, Oliver; Klein, Rob R.

    2010-01-01

    Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.

  15. [Valuation and prospect of function preserving gastrectomy].

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    Wang, Shuchang; Yu, Site; Xu, Jia; Zhao, Gang

    2017-10-25

    Preserving gastric function and improving quality of life (QOL) is the tendency of surgery for early gastric cancer. Function preserving gastrectomy (FPG) is applied to modify the extent of surgery and to achieve better quality of life at the premise of radical resection. Pylorus-preserving gastrectomy is the most favorable approach of FPG with oncological safety, which can improve nutritional status and QOL via preserving pylorus and vagal nerve. Proximal gastrectomy is widely accepted as FPG for early upper 1/3 gastric cancer. However, the most optimal way of anastomosis is not yet solved. Sentinel node navigation is currently the most accurate approach for intraoperative diagnosis of lymph node metastasis, which stimulates the development of many kinds of FPG procedures for individual treatment. Nevertheless, more efforts should be made to reduce false negative rate of sentinel node biopsy. Herein we discuss the valuation and prospect of FPG.

  16. Comparative in vitro toxicology study of travoprost polyquad-preserved, travoprost BAK-preserved, and latanoprost BAK-preserved ophthalmic solutions on human conjunctival epithelial cells.

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    Brignole-Baudouin, Françoise; Riancho, Luisa; Liang, Hong; Baudouin, Christophe

    2011-11-01

    To compare the toxicological profile of a new formulation of travoprost 0.004% ophthalmic solution (travoprost PQ), containing the preservative polyquaternium-1(PQ, polyquad), with the commercially available formulation of benzalkonium chloride (BAK)-preserved travoprost 0.004% ophthalmic solution (travoprost BAK) and BAK-preserved latanoprost 0.005% ophthalmic solution (latanoprost BAK). Human conjunctival epithelial cells were incubated with phosphate-buffered saline (PBS), BAK 0.015%, BAK 0.020%, PQ 0.001%, travoprost PQ preserved with PQ 0.001%, travoprost preserved with BAK 0.015%, or latanoprost preserved with BAK 0.020%. Six toxicological assays were used to assess: cell viability (neutral red, Alamar blue), apoptosis (YO-PRO-1, Hoechst 33342), and oxidative stress (H(2)DCF-DA, hydroethidine). Apoptosis and oxidative stress were each reported according to cell viability as observed with neutral red and Alamar blue for a total of 10 analyses per treatment depending on the cell viability test used to interpret apoptosis and oxidative stress responses. There were no significant differences in toxicity between cells exposed to PBS and cells exposed to travoprost PQ (10/10 analyses) or PQ 0.001% (9/10 analyses). Ten out of 10 analyses revealed that travoprost PQ produced significantly less cytotoxicity than latanoprost BAK (p solution in 9 of 10 analyses (p < 0.0001). A panel of in vitro toxicity analyses supports the safety of travoprost PQ. Travoprost PQ may be better for ocular surface health than BAK-preserved formulations of latanoprost or travoprost but clinical studies are required to validate these comparisons.

  17. Preserving human cells for regenerative, reproductive, and transfusion medicine.

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    Asghar, Waseem; El Assal, Rami; Shafiee, Hadi; Anchan, Raymond M; Demirci, Utkan

    2014-07-01

    Cell cryopreservation maintains cellular life at sub-zero temperatures by slowing down biochemical processes. Various cell types are routinely cryopreserved in modern reproductive, regenerative, and transfusion medicine. Current cell cryopreservation methods involve freezing (slow/rapid) or vitrifying cells in the presence of a cryoprotective agent (CPA). Although these methods are clinically utilized, cryo-injury due to ice crystals, osmotic shock, and CPA toxicity cause loss of cell viability and function. Recent approaches using minimum volume vitrification provide alternatives to the conventional cryopreservation methods. Minimum volume vitrification provides ultra-high cooling and rewarming rates that enable preserving cells without ice crystal formation. Herein, we review recent advances in cell cryopreservation technology and provide examples of techniques that are utilized in oocyte, stem cell, and red blood cell cryopreservation. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Endothelial cell preservation at hypothermic to normothermic conditions using clinical and experimental organ preservation solutions

    NARCIS (Netherlands)

    Post, Ivo C. J. H.; de Boon, Wadim M. I.; Heger, Michal; van Wijk, Albert C. W. A.; Kroon, Jeffrey; van Buul, Jaap D.; van Gulik, Thomas M.

    2013-01-01

    Endothelial barrier function is pivotal for the outcome of organ transplantation. Since hypothermic preservation (gold standard) is associated with cold-induced endothelial damage, endothelial barrier function may benefit from organ preservation at warmer temperatures. We therefore assessed

  19. Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function

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    Catalina Carrasco-Pozo

    2017-01-01

    Full Text Available Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

  20. Cytotoxicity of ophthalmic solutions with and without preservatives to human corneal endothelial cells, epithelial cells and conjunctival epithelial cells.

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    Ayaki, Masahiko; Yaguchi, Shigeo; Iwasawa, Atsuo; Koide, Ryohei

    2008-08-01

    The cytotoxicity of a range of commercial ophthalmic solutions in the presence and absence of preservatives was assessed in human corneal endothelial cells (HCECs), corneal epithelia and conjunctival epithelia using in vitro techniques. Cell survival was measured using the WST-1 assay for endothelial cells and the MTT assay for epithelial cells. Commercially available timolol, carteolol, cromoglicate, diclofenac, bromfenac and hyaluronic acid ophthalmic solutions were assessed for cytotoxicity in the presence and absence of preservatives. The preservatives benzalkonium, chlorobutanol and polysorbate were also tested. The survival of cells exposed to test ophthalmic solutions was expressed as a percentage of cell survival in the control solution (distilled water added to media) after 48 h exposure. HCEC survival was 20-30% in ophthalmic solutions diluted 10-fold. The survival of HCEC was significantly greater in all solutions in the absence of preservative than in the presence of preservative. The survival of corneal and conjunctival epithelia was consistent with that of HCECs for all test ophthalmic solutions. The preservatives polysorbate and benzalkonium were highly cytotoxic with cell survival decreasing to 20% at the concentration estimated in commercial ophthalmic solutions. By comparison, the survival of cells exposed to chlorobutanol was 80% or greater. The cytotoxicity of ophthalmic solutions to HCEC, corneal epithelia and conjunctival epithelia decreased in the absence of preservative.

  1. Preservation of Antigen-Specific Functions of αβ T Cells and B Cells Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy.

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    Li Pira, Giuseppina; Di Cecca, Stefano; Biagini, Simone; Girolami, Elia; Cicchetti, Elisabetta; Bertaina, Valentina; Quintarelli, Concetta; Caruana, Ignazio; Lucarelli, Barbarella; Merli, Pietro; Pagliara, Daria; Brescia, Letizia Pomponia; Bertaina, Alice; Montanari, Mauro; Locatelli, Franco

    2017-01-01

    Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification.

  2. Preservation of Antigen-Specific Functions of αβ T Cells and B Cells Removed from Hematopoietic Stem Cell Transplants Suggests Their Use As an Alternative Cell Source for Advanced Manipulation and Adoptive Immunotherapy

    Science.gov (United States)

    Li Pira, Giuseppina; Di Cecca, Stefano; Biagini, Simone; Girolami, Elia; Cicchetti, Elisabetta; Bertaina, Valentina; Quintarelli, Concetta; Caruana, Ignazio; Lucarelli, Barbarella; Merli, Pietro; Pagliara, Daria; Brescia, Letizia Pomponia; Bertaina, Alice; Montanari, Mauro; Locatelli, Franco

    2017-01-01

    Hematopoietic stem cell transplantation is standard therapy for numerous hematological diseases. The use of haploidentical donors, sharing half of the HLA alleles with the recipient, has facilitated the use of this procedure as patients can rely on availability of a haploidentical donor within their family. Since HLA disparity increases the risk of graft-versus-host disease, T-cell depletion has been used to remove alloreactive lymphocytes from the graft. Selective removal of αβ T cells, which encompass the alloreactive repertoire, combined with removal of B cells to prevent EBV-related lymphoproliferative disease, proved safe and effective in clinical studies. Depleted αβ T cells and B cells are generally discarded as by-products. Considering the possible use of donor T cells for donor lymphocyte infusions or for generation of pathogen-specific T cells as mediators of graft-versus-infection effect, we tested whether cells in the discarded fractions were functionally intact. Response to alloantigens and to viral antigens comparable to that of unmanipulated cells indicated a functional integrity of αβ T cells, in spite of the manipulation used for their depletion. Furthermore, B cells proved to be efficient antigen-presenting cells, indicating that antigen uptake, processing, and presentation were fully preserved. Therefore, we propose that separated αβ T lymphocytes could be employed for obtaining pathogen-specific T cells, applying available methods for positive selection, which eventually leads to indirect allodepletion. In addition, these functional T cells could undergo additional manipulation, such as direct allodepletion or genetic modification. PMID:28386262

  3. Evolution of natural agents: preservation, advance, and emergence of functional information

    OpenAIRE

    Sharov, Alexei A.

    2016-01-01

    Biological evolution is often viewed narrowly as a change of morphology or allele frequency in a sequence of generations. Here I pursue an alternative informational concept of evolution, as preservation, advance, and emergence of functional information in natural agents. Functional information is a network of signs (e.g., memory, transient messengers, and external signs) that are used by agents to preserve and regulate their functions. Functional information is preserved in evolution via comp...

  4. Function-preserving surgery for rectal cancer

    International Nuclear Information System (INIS)

    Moriya, Yoshihiro

    2006-01-01

    When total mesorectal excision (TME) is accurately performed, dysfunction, theoretically, does not occur. However, there are differences among individuals in the running patterns and the volumes of nerve fibers, and if obesity or a narrow pelvis is present, nerve identification is difficult. Currently, the rate of urinary dysfunction after rectal surgery ranges from 33% to 70%. Many factors other than nerve preservation play a role in minor incontinence. Male sexual function shows impotence rates ranging from 20% to 46%, while 20%-60% of potent patients are unable to ejaculate. In women, information on sexual function is not easily obtained, and there are more unknown aspects than in men. As urinary, sexual, and defecation dysfunction due to adjuvant radiotherapy have been reported to occur at a high frequency, the creation of a protocol that enables analysis of long-term functional outcome will be essential for future clinical trials. In the treatment of rectal cancer, surgeon-related factors are extremely important, not only in achieving local control but also in preserving function. This article reviews findings from recent studies investigating urinary, sexual, and defecation dysfunction after rectal cancer surgery and discusses questions to be studied in the future. (author)

  5. Should deciduous teeth be preserved in adult patients? How about stem cells? Is it reasonable to preserve them?

    Directory of Open Access Journals (Sweden)

    Alberto Consolaro

    2016-04-01

    Full Text Available Abstract When seeking orthodontic treatment, many adolescents and adult patients present with deciduous teeth. Naturally, deciduous teeth will inevitably undergo exfoliation at the expected time or at a later time. Apoptosis is the biological trigger of root resorption. In adult patients, deciduous teeth should not be preserved, as they promote: infraocclusion, traumatic occlusion, occlusal trauma, diastemata and size as well as morphology discrepancy malocclusion. Orthodontic movement speeds root resorption up, and so do restoring or recontouring deciduous teeth in order to establish esthetics and function. Deciduous teeth cells are dying as a result of apoptosis, and their regeneration potential, which allows them to act as stem cells, is limited. On the contrary, adult teeth cells have a greater proliferative potential. All kinds of stem cell therapies are laboratory investigative non authorized trials.

  6. Intrasplenic masses of ``preserved`` functioning splenic tissue in sickle cell disease: correlation of imaging findings (CT, ultrasound, MRI, and nuclear scintigraphy)

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Berdon, W.E. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Haller, J.O. [Department of Radiology, SUNY Downstate Medical Center, Brooklyn, New York (United States); Ruzal-Shapiro, C. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Hurlet-Jenson, A. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, New York (United States)

    1996-09-01

    Purpose. We studied six patients with sickle cell disease (SSD), five homozygous for sickle cell anemia and one with sickle beta-thalassemia, in whom rounded intrasplenic masses proved to be preserved functioning splenic tissue. Materials and methods. Available images including computed tomography, ultrasonography, bone scans (Tc-99m MDP), liver spleen scans (Tc-99m sulfur colloid), and MRI were evaluated. Results. The masses were low density on CT (in an otherwise calcified spleen), hypoechoic relative to the echogenic spleen on US, and had the imaging characteristics of normal spleen on MRI. They failed to accumulate Tc-99m MDP but did demonstrate uptake of Tc-99m sulfur colloid. Conclusion. In a patient with SSD and intrasplenic masses, proper correlation of multiple imaging modalities will establish the diagnosis of functioning splenic tissue and avoid mistaken diagnosis of splenic abscess or infarction. (orig.). With 2 figs., 1 tab.

  7. Intrasplenic masses of ''preserved'' functioning splenic tissue in sickle cell disease: correlation of imaging findings (CT, ultrasound, MRI, and nuclear scintigraphy)

    International Nuclear Information System (INIS)

    Levin, T.L.; Berdon, W.E.; Haller, J.O.; Ruzal-Shapiro, C.; Hurlet-Jenson, A.

    1996-01-01

    Purpose. We studied six patients with sickle cell disease (SSD), five homozygous for sickle cell anemia and one with sickle beta-thalassemia, in whom rounded intrasplenic masses proved to be preserved functioning splenic tissue. Materials and methods. Available images including computed tomography, ultrasonography, bone scans (Tc-99m MDP), liver spleen scans (Tc-99m sulfur colloid), and MRI were evaluated. Results. The masses were low density on CT (in an otherwise calcified spleen), hypoechoic relative to the echogenic spleen on US, and had the imaging characteristics of normal spleen on MRI. They failed to accumulate Tc-99m MDP but did demonstrate uptake of Tc-99m sulfur colloid. Conclusion. In a patient with SSD and intrasplenic masses, proper correlation of multiple imaging modalities will establish the diagnosis of functioning splenic tissue and avoid mistaken diagnosis of splenic abscess or infarction. (orig.). With 2 figs., 1 tab

  8. Enzymes and membrane proteins of ADSOL-preserved red blood cells

    Directory of Open Access Journals (Sweden)

    Maria Sueli Soares Leonart

    2000-03-01

    Full Text Available CONTEXT: The preservative solution ADSOL (adenine, dextrose, sorbitol, sodium chloride and mannitol maintains red cell viability for blood trans-fusion for 6 weeks. It would be useful to know about its preservation qualities over longer periods. OBJECTIVE: To determine some red cell biochemical parameters for peri-ods of up to 14 weeks in order to determine whether the red cell metabo-lism integrity would justify further studies aiming at increasing red cell preservation and viability. DESIGN: Biochemical evaluation designed to study red cell preservation. SETTING: São Paulo University erythrocyte metabolism referral center. SAMPLE: Six normal blood donors from the University Hospital of the Universidade Federal do Paraná, Curitiba, Brazil. MAIN MEASUREMENTS: Weekly assay of erythrocyte adenosine-5´-triphosphate (ATP, 2,3-diphosphoglycerate (2,3DPG, hexokinase (HX, phosphofructokinase (PFK, pyruvate kinase (PK, glucose-6-phosphate dehydrogenase (G-6-PD, 6-phosphogluconic dehydrogenase (6-PGD, glyceraldehyde-3-phosphate dehydrogenase (GAPD, glutathione reduc-tase (GR, glutathione peroxidase (GSHPx, plasma sodium and potas-sium, blood pH, and membrane proteins of red cells preserved in ADSOL were studied during storage for 14 weeks storage. RESULTS: During ADSOL preservation, erythrocyte ATP concentration decreased 60% after 5 weeks, and 90% after 10 weeks; the pH fell from 6.8 to 6.4 by the 14th week. 2,3-DPG concentration was stable during the first week, but fell 90% after 3 weeks and was exhausted after 5 weeks. By the end of the 5th week, an activity decrease of 16-30% for Hx, GAPD, GR, G-6-PD and 6-PGD, 35% for PFK and GSHPx, and 45% for PK were observed. Thereafter, a uniform 10% decay was observed for all enzymes up to the 14th week. The red blood cell membrane pro-teins did not show significant alterations in polyacrylamide gel electro-phoresis (SDS-PAGE during the 14 weeks. CONCLUSION: Although the blood viability was shown to be poor

  9. Transportable, small high-pressure preservation vessel for cells

    International Nuclear Information System (INIS)

    Kamimura, N; Sotome, S; Shimizu, A; Nakajima, K; Yoshimura, Y

    2010-01-01

    We have previously reported that the survival rate of astrocytes increases under high-pressure conditions at 4 0 C. However, pressure vessels generally have numerous problems for use in cell preservation and transportation: (1) they cannot be readily separated from the pressurizing pump in the pressurized state; (2) they are typically heavy and expensive due the use of materials such as stainless steel; and (3) it is difficult to regulate pressurization rate with hand pumps. Therefore, we developed a transportable high-pressure system suitable for cell preservation under high-pressure conditions. This high-pressure vessel has the following characteristics: (1) it can be easily separated from the pressurizing pump due to the use of a cock-type stop valve; (2) it is small and compact, is made of PEEK and weighs less than 200 g; and (3) pressurization rate is regulated by an electric pump instead of a hand pump. Using this transportable high-pressure vessel for cell preservation, we found that astrocytes can survive for 4 days at 1.6 MPa and 4 0 C.

  10. Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves β-cell mass and function in ZDF rats.

    Science.gov (United States)

    Mahadevan, Jana; Parazzoli, Susan; Oseid, Elizabeth; Hertzel, Ann V; Bernlohr, David A; Vallerie, Sara N; Liu, Chang-qin; Lopez, Melissa; Harmon, Jamie S; Robertson, R Paul

    2013-10-01

    We reported earlier that β-cell-specific overexpression of glutathione peroxidase (GPx)-1 significantly ameliorated hyperglycemia in diabetic db/db mice and prevented glucotoxicity-induced deterioration of β-cell mass and function. We have now ascertained whether early treatment of Zucker diabetic fatty (ZDF) rats with ebselen, an oral GPx mimetic, will prevent β-cell deterioration. No other antihyperglycemic treatment was given. Ebselen ameliorated fasting hyperglycemia, sustained nonfasting insulin levels, lowered nonfasting glucose levels, and lowered HbA1c levels with no effects on body weight. Ebselen doubled β-cell mass, prevented apoptosis, prevented expression of oxidative stress markers, and enhanced intranuclear localization of pancreatic and duodenal homeobox (Pdx)-1 and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA), two critical insulin transcription factors. Minimal β-cell replication was observed in both groups. These findings indicate that prevention of oxidative stress is the mechanism whereby ebselen prevents apoptosis and preserves intranuclear Pdx-1 and MafA, which, in turn, is a likely explanation for the beneficial effects of ebselen on β-cell mass and function. Since ebselen is an oral antioxidant currently used in clinical trials, it is a novel therapeutic candidate to ameliorate fasting hyperglycemia and further deterioration of β-cell mass and function in humans undergoing the onset of type 2 diabetes.

  11. Novel Cell Preservation Technique to Extend Bovine In Vitro White Blood Cell Viability.

    Directory of Open Access Journals (Sweden)

    Emilie L Laurin

    Full Text Available Although cell-mediated immunity based diagnostics can be integral assays for early detection of various diseases of dairy cows, processing of blood samples for these tests is time-sensitive, often within 24 hours of collection, to maintain white blood cell viability. Therefore, to improve utility and practicality of such assays, the objective of this study was to assess the use of a novel white blood cell preservation technology in whole bovine blood. Blood samples from ten healthy cows were each divided into an unpreserved control sample and a test sample preserved with commercially-available cell transport medium. Samples were maintained at room temperature and stimulated with the mitogens pokeweed and concanavalinA, as well as with interleukin-12 p40. Stimulation was completed on days 1, 5, and 8 post-sampling. Viability of white blood cells was assessed through interferon gamma production determined with a commercial enzyme linked immunosorbent assay. In addition, mononuclear cell viability was assessed with propidium iodide flow cytometry. Greater interferon gamma production was observed on days 5 and 8 post-collection in preserved samples, with both pokeweed and concanavalinA stimulating positive interferon gamma production on day 5 post-collection. A greater proportion of the amount of interferon gamma produced on day 1 continued to be produced on days 5 and 8 post-collection with concanavalinA stimulation (with or without interleukin 12 as compared to pokeweed stimulation. Additionally, viable mononuclear cells were still present at eight days post-collection, with a higher mean proportion detected at days 5 and 8 in all stimulated preserved samples. This practical and simple method to extend in vitro white blood cell viability could benefit the efficient utilization of cell-based blood tests in ruminants.

  12. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T

    2015-01-01

    to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ2 protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby...

  13. In vitro cytotoxicity of chemical preservatives on human fibroblast cells

    Directory of Open Access Journals (Sweden)

    Daniel Gonsales Spindola

    2018-05-01

    Full Text Available ABSTRACT Preservatives are widely used substances that are commonly added to various cosmetic and pharmaceutical products to prevent or inhibit microbial growth. In this study, we compared the in vitro cytotoxicity of different types of currently used preservatives, including methylparaben, imidazolidinyl urea (IMU, and sodium benzoate, using the human newborn fibroblast cell line CCD1072Sk. Of the tested preservatives, only IMU induced a reduction in cell viability, as shown using the MTT assay and propidium iodide staining (IMU>methylparaben>sodium benzoate. IMU was shown to promote homeostatic alterations potentially related to the initiation of programed cell death, such as decreased mitochondrial membrane potential and caspase-3 activation, in the treated cells. Methylparaben and sodium benzoate were shown to have a very low cytotoxic activity. Taken together, our results suggest that IMU induces programed cell death in human fibroblasts by a canonical intrinsic pathway via mitochondrial perturbation and subsequent release of proapoptotic factors.

  14. Will Incremental Hemodialysis Preserve Residual Function and Improve Patient Survival?

    Science.gov (United States)

    Davenport, Andrew

    2015-01-01

    The progressive loss of residual renal function in peritoneal dialysis patients is associated with increased mortality. It has been suggested that incremental dialysis may help preserve residual renal function and improve patient survival. Residual renal function depends upon both patient related and dialysis associated factors. Maintaining patients in an over-hydrated state may be associated with better preservation of residual renal function but any benefit comes with a significant risk of cardiovascular consequences. Notably, it is only observational studies that have reported an association between dialysis patient survival and residual renal function; causality has not been established for dialysis patient survival. The tenuous connections between residual renal function and outcomes and between incremental hemodialysis and residual renal function should temper our enthusiasm for interventions in this area. PMID:25385441

  15. Cytotoxicity and mutagenicity of opthalmic solution preservatives and UVA radiation in L5178Y cells

    International Nuclear Information System (INIS)

    Withrow, T.J.; Brown, N.T.; Hitchins, V.M.; Strickland, A.G.

    1989-01-01

    Four preservatives used in ophthalmic solutions were tested for toxic and mutagenic potential in mouse lymphoma cells with and without exposure of cells to ultraviolet A (UVA) radiation. The preservatives tested were benzalkonium chloride (BAK), chlorhexidine, thimerosal and ethylenediaminetetraacetic acid (EDTA). Cell survival and mutagenesis were measured using the L5178Y mouse lymphoma (TK +/- ) system. Cells were exposed to varying amounts of preservatives for 1 h at 37 0 C, and aliquots irradiated with UVA radiation (during exposure to preservative). Cells were then assayed for survival, and mutagenesis at the thymidine kinase (TK) locus. In concentrations commonly found in ophthalmic solutions, BAK, chlorhexidine, and thimerosal were toxic to cells, and thimerosal was slightly mutagenic. When cells were exposed to preservative and UVA radiation, chlorhexidine was mutagenic and the mutagenic activity of thimerosal was enhanced. (author)

  16. Cytotoxicity and mutagenicity of opthalmic solution preservatives and UVA radiation in L5178Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Withrow, T.J.; Brown, N.T.; Hitchins, V.M.; Strickland, A.G. (Food and Drug Administration, Rockville, MD (USA). Center for Devices and Radiological Health)

    1989-09-01

    Four preservatives used in ophthalmic solutions were tested for toxic and mutagenic potential in mouse lymphoma cells with and without exposure of cells to ultraviolet A (UVA) radiation. The preservatives tested were benzalkonium chloride (BAK), chlorhexidine, thimerosal and ethylenediaminetetraacetic acid (EDTA). Cell survival and mutagenesis were measured using the L5178Y mouse lymphoma (TK{sup +/-}) system. Cells were exposed to varying amounts of preservatives for 1 h at 37{sup 0}C, and aliquots irradiated with UVA radiation (during exposure to preservative). Cells were then assayed for survival, and mutagenesis at the thymidine kinase (TK) locus. In concentrations commonly found in ophthalmic solutions, BAK, chlorhexidine, and thimerosal were toxic to cells, and thimerosal was slightly mutagenic. When cells were exposed to preservative and UVA radiation, chlorhexidine was mutagenic and the mutagenic activity of thimerosal was enhanced. (author).

  17. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

    Science.gov (United States)

    Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

    2015-01-01

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  18. The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

    Science.gov (United States)

    Mavrommatis, Evangelos; Shioura, Krystyna M; Los, Tamara; Goldspink, Paul H

    2013-09-01

    Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

  19. Preservation of Bone-Marrow Cells, Leucocytes and Platelets at Low Temperatures. A Review

    Energy Technology Data Exchange (ETDEWEB)

    Ashwood-Smith, M. J. [Medical Research Council, Radiobiological Research Unit, Harwell, Berks. (United Kingdom)

    1969-07-15

    The basic principles of cryobiology are discussed and applications of these principles by numerous workers in attempts to preserve marrow cells, leucocytes and platelets at low temperatures are reviewed. It is concluded that: (1) Lymphocytes from animals and man can be stored for long periods of time at low temperatures when cooled slowly in 10-15% DMSO or glycerol and thawed rapidly. Recovery figures are high and function is intact and unaltered. DMSO is probably a better preservative than glycerol, and storage life at -196 Degree-Sign C is probably indefinite for all practical purposes. Other leucocytes can be stored with similar techniques but recoveries after freezing and thawing are probably lower than with lymphocytes. (2) Bone-marrow cells of several animals including mouse, rabbit and dog can be preserved at -196 Degree-Sign C, probably indefinitely, and similar procedures to those used for lymphocytes give the best results. The comprehensive studies of Lewis and Trobaugh indicate that under carefully controlled conditions 95% of the stem cells in mouse marrow are viable after freezing and thawing. Opinions are divided over the efficacy of the two preservatives, DMSO and glycerol, but in view of the well documented accounts of the lack of toxicity of glycerol it would seem advisable for the moment to use this agent with all human marrow samples. The usefulness of PVP as a preservative for marrow is still to be resolved. Human marrow after freezing and thawing probably behaves in a similar manner to mouse marrow both in vitro and in vivo. However, it would be wise to consider that there might be differences which could cause wrong assessments of freezing procedures. (3) Platelet preservation, clinically perhaps the most useful procedure discussed in this review, is still to a large extent in the experimental stage. Much work has been done but even the best methods available permit relatively low recoveries of viable platelets. Preservation of human platelets

  20. Toxicity of cosmetic preservatives on human ocular surface and adnexal cells.

    Science.gov (United States)

    Chen, Xiaomin; Sullivan, David A; Sullivan, Amy Gallant; Kam, Wendy R; Liu, Yang

    2018-05-01

    Cosmetic products, such as mascara, eye shadow, eyeliner and eye makeup remover are used extensively to highlight the eyes or clean the eyelids, and typically contain preservatives to prevent microbial growth. These preservatives include benzalkonium chloride (BAK) and formaldehyde (FA)-releasing preservatives. We hypothesize that these preservatives, at concentrations (BAK = 1 mg/ml; FA = 0.74 mg/ml) approved for consumer use, are toxic to human ocular surface and adnexal cells. Accordingly, we tested the influence of BAK and FA on the morphology, survival, and proliferation and signaling ability of immortalized human meibomian gland (iHMGECs), corneal (iHCECs) and conjunctival (iHConjECs) epithelial cells. iHMGECs, iHCECs and iHConjECs were cultured with different concentrations of BAK (5 μg/ml to 0.005 μg/ml) or FA (1 mg/ml to 1 μg/ml) under basal, proliferating or differentiating conditions up to 7 days. We used low BAK levels, because we found that 0.5 mg/ml and 50 μg/ml BAK killed iHMGECs within 1 day after a 15 min exposure. Experimental procedures included analyses of cell appearance, cell number, and neutral lipid content (LipidTox), lysosome accumulation (LysoTracker) and AKT signaling in all 3 cell types. Our results demonstrate that BAK and FA cause dose-dependent changes in the morphology, survival, proliferation and AKT signaling of iHMGECs, iHCECs and iHConjECs. Many of the concentrations tested induced cell atrophy, poor adherence, decreased proliferation and death, after 5 days of exposure. Cellular signaling, as indicated by AKT phosphorylation after 15 (FA) or 30 (BAK) minutes of treatment, was also reduced in a dose-dependent fashion in all 3 cell types, irrespective of whether cells had been cultured under proliferating or differentiating conditions. Our results support our hypothesis and demonstrate that the cosmetic preservatives, BAK and FA, exert many toxic effects on cells of the ocular surface and adnexa

  1. Evolution of natural agents: preservation, advance, and emergence of functional information.

    Science.gov (United States)

    Sharov, Alexei A

    2016-04-01

    Biological evolution is often viewed narrowly as a change of morphology or allele frequency in a sequence of generations. Here I pursue an alternative informational concept of evolution, as preservation, advance, and emergence of functional information in natural agents. Functional information is a network of signs (e.g., memory, transient messengers, and external signs) that are used by agents to preserve and regulate their functions. Functional information is preserved in evolution via complex interplay of copying and construction processes: the digital components are copied, whereas interpreting subagents together with scaffolds, tools, and resources, are constructed. Some of these processes are simple and invariant, whereas others are complex and contextual. Advance of functional information includes improvement and modification of already existing functions. Although the genome information may change passively and randomly, the interpretation is active and guided by the logic of agent behavior and embryonic development. Emergence of new functions is based on the reinterpretation of already existing information, when old tools, resources, and control algorithms are adopted for novel functions. Evolution of functional information progressed from protosemiosis, where signs correspond directly to actions, to eusemiosis, where agents associate signs with objects. Language is the most advanced form of eusemiosis, where the knowledge of objects and models is communicated between agents.

  2. Impact of aging on antigen presentation cell function of dendritic cells.

    Science.gov (United States)

    Wong, Christine; Goldstein, Daniel R

    2013-08-01

    Older people exhibit increased mortality to infections and cancer as compared to younger people, indicating that aging impairs immunity. Dendritic cells (DCs) are key for bridging the innate and adaptive arms of the immune system by priming antigen specific T cells. Discerning how aging impacts DC function to initiate adaptive immune responses is of great biomedical importance as this could lead to the development of novel therapeutics to enhance immunity with aging. This review details reports indicating that aging impairs the antigen presenting function of DCs but highlights other studies indicating preserved DC function with aging. How aging impacts antigen presentation by DCs is complex and without a clear unifying biological underpinning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. The Consequence of Delayed Fixation on Subsequent Preservation of Urine Cells

    Directory of Open Access Journals (Sweden)

    Hussain G. Ahmed,

    2011-01-01

    Full Text Available Objectives: Degenerative changes caused by delays in urine preservation contribute to false-negative and false-positive interpretation of urothelial disease in cytology. The aim of this study is to assess whether the delay of fixation of urine samples makes any significant difference to urine cytology and morphology, and the limit of acceptability of delay for routine use in the hospital laboratory.Methods: Three cell collection fluids were evaluated by analyzing the preservation and degeneration of cells in urine samples. In this study, 50 voided urine specimens were taken at random from females complaining of vaginal discharge. Each specimen was divided into three sterile containers. The first was immediately centrifugated and the deposit was smeared onto a cleaned micro slide and immediately fixed into 95�0ethyl alcohol for 15 minutes. The remaining two were prepared in the same manner, however, the second after two hours of collection and the third after four hours of collection. The degree of degeneration and thus the preservation were assessed by a table of chosen criteria, then ranked and analyzed using Friedman's nonparametric test, atp=0.05.Results: The results showed a significant difference between the preservation and the delay in urine fixation, p<0.0001.Conclusion: Any delay in fixation of urine specimen for cytology affects the preservation of cells, which may result in miss diagnosis. It is recommended that urine samples for cytology should be fixed immediately after collection.

  4. On Fréchet theorem in the set of measure preserving functions over the unit interval

    Directory of Open Access Journals (Sweden)

    So-Hsiang Chou

    1990-01-01

    Full Text Available In this paper, we study the Fréchet theorem in the set of measure preserving functions over the unit interval and show that any measure preserving function on [0,1] can be approximated by a sequence of measure preserving piecewise linear continuous functions almost everywhere. Some application is included.

  5. Neural Stem Cell-Preserving External-Beam Radiotherapy of Central Nervous System Malignancies

    International Nuclear Information System (INIS)

    Barani, Igor J.; Cuttino, Laurie W.; Benedict, Stanley H.; Todor, Dorin; Bump, Edward A.; Wu Yan; Chung, Theodore D.; Broaddus, William C.; Lin, Peck-Sun

    2007-01-01

    Purpose: Recent discoveries have implicated neural stem cells (NSC) as the source of plasticity and repair in the mature mammalian brain. Treatment-induced NSC dysfunction may lead to observed toxicity. This study evaluates the feasibility of NSC-preserving external beam radiotherapy. Methods and Materials: A single computed tomography (CT) dataset depicting a right periventricular lesion was used in this study as this location reflects the most problematic geometric arrangement with respect to NSC preservation. Conventional and NSC preserving radiotherapy (RT) plans were generated for the same lesion using two clinical scenarios: cerebral metastatic disease and primary high-grade glioma. Disease-specific target volumes were used. Metastatic disease was conventionally treated with whole-brain radiotherapy (WBRT) to 3,750 cGy (15 fractions) followed by a single stereotactic radiosurgery (SRS) boost of 1,800 cGy to gross disease only. High-grade glioma was treated with conventional opposed lateral and anterior superior oblique beams to 4,600 cGy (23 fractions) followed by a 1,400 cGy (7 fractions) boost. NSC preservation was achieved in both scenarios with inverse-planned intensity modulated radiotherapy (IMRT). Results: Cumulative dose reductions of 65% (metastatic disease) and 25% (high-grade glioma) to the total volume of the intracranial NSC compartments were achieved with NSC-preserving IMRT plans. The reduction of entry and exit dose to NSC niches located contralateral to the target contributed most to NSC preservation. Conclusions: Neural stem cells preservation with current external beam radiotherapy techniques is achievable in context of both metastatic brain disease and high-grade glioma, even when the target is located adjacent to a stem cell compartment. Further investigation with clinical trials is warranted to evaluate whether NSC preservation will result in reduced toxicity

  6. Design of Connectivity Preserving Flocking Using Control Lyapunov Function

    Directory of Open Access Journals (Sweden)

    Bayu Erfianto

    2016-01-01

    Full Text Available This paper investigates cooperative flocking control design with connectivity preserving mechanism. During flocking, interagent distance is measured to determine communication topology of the flocks. Then, cooperative flocking motion is built based on cooperative artificial potential field with connectivity preserving mechanism to achieve the common flocking objective. The flocking control input is then obtained by deriving cooperative artificial potential field using control Lyapunov function. As a result, we prove that our flocking protocol establishes group stabilization and the communication topology of multiagent flocking is always connected.

  7. High-Yield Purification, Preservation, and Serial Transplantation of Human Satellite Cells

    Directory of Open Access Journals (Sweden)

    Steven M. Garcia

    2018-03-01

    Full Text Available Summary: Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs. : Garcia and colleagues report methods for efficient purification of satellite cells from human skeletal muscle. They use their approaches to demonstrate stem cell functions of endogenous satellite cells and to make human satellite cells accessible for sharing among researchers. Keywords: human satellite cell purification, serial transplantation, satellite cell cryopreservation

  8. Preserving Functional Lung Using Perfusion Imaging and Intensity-Modulated Radiation Therapy for Advanced-Stage Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Shioyama, Yoshiyuki; Jang, Si Young; Liu, H. Helen; Guerrero, Thomas; Wang, Xuanmin; Gayed, Isis W.; Erwin, William D.; Liao, Zhongxing; Chang, Joe Y.; Jeter, Melenda; Yaremko, Brian P.; Borghero, Yerko O.; Cox, James D.; Komaki, Ritsuko; Mohan, Radhe

    2007-01-01

    Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients

  9. [Fertility preservation in boys: spermatogonial stem cell transplantation and testicular grafting].

    Science.gov (United States)

    Goossens, E; Tournaye, H

    2013-09-01

    Spermatogonial stem cells (SSC) are the founder cells of spermatogenesis and are responsible for the lifelong production of spermatozoa. The cryopreservation and transplantation of these cells has been proposed as a fertility preservation strategy for young boys at risk for stem cell loss, i.e. patients undergoing chemotherapy for cancer or as a conditioning treatment for bone marrow transplantation. To prevent lifelong sterility in boys, two fertility restoration strategies are being developed: the injection of SSC and the grafting of testicular tissue containing SSC. Depending on the disease of the patient one of these two approaches will be applicable. Grafting has the advantage that SSC can reside within their natural niche, preserving the interactions between germ cells and their supporting cells and may therefore be regarded as the first choice strategy. However, in cases where the risk for malignant contamination of the testicular tissue is real, e.g. leukemia, transplantation of SSC by injection is preferable over grafting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Bacterial cell wall preservation during organic matter diagenesis in sediments off Peru

    DEFF Research Database (Denmark)

    Lomstein, Bente Aagaard; Niggemann, Jutta; Jørgensen, Bo Barker

    BACTERIAL CELL WALL PRESERVATION DURING ORGANIC MATTER DIAGENESIS IN SEDIMENTS OFF PERU The spatial distribution of total hydrolysable amino acids, total hydrolysable amino sugars and amino acid enantiomers (D- and L-forms) were investigated in surface sediments at 20 stations in the Peru margin: 9......°45 S - 13º32 S. The objective of this study was to assess the preservation of bacterial cell walls during diagenesis of organic matter. Bacterial cell walls were traced by analysis of biomarkers uniquely produced by bacteria (D-amino acids and muramic acid). The diagenetic status of the sediments......:00 Presentation is given by student: No...

  11. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses

    Science.gov (United States)

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Dolores Ledesma, Maria; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria

    2016-01-01

    Summary The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases. PMID:26299452

  12. Hemodynamics, functional state of endothelium and renal function, platelets depending on the body mass index in patients with chronic heart failure and preserved systolic function

    Directory of Open Access Journals (Sweden)

    Kushnir Yu.

    2014-03-01

    Full Text Available The aim of the study was to evaluate hemodynamics, endothelium function of kidneys and platelets depending on the body mass index (BMI in patients with chronic heart failure (CHF and preserved systolic function. 42 patients (mean age - 76,690,83 years with CHF II-III FC NYHA with preserved systolic function (LVEF>45% were enrolled. Echocardiography was performed, endothelial function, serum creatinine levels and microalbuminuria were determined in patients. BMI and glomerulation filtration rate were calculated by formulas. The morphological and functional status of platelets was estimated by electronic microscopy. It was defined that increased BMI in patients with CHF and preserved systolic function determines the structural and functional changes of the myocardium and leads to the endothelial and renal functional changes. An increased risk of thrombogenesis was established in patients with overweight and obesity.

  13. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kover, Karen, E-mail: kkover@cmh.edu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Tasch, James; Hager, Melissa [Kansas City University Medical Biosciences, Kansas City, MO (United States); Clements, Mark; Moore, Wayne V. [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States)

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  14. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    International Nuclear Information System (INIS)

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-01-01

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H 2 O 2 assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H 2 O 2 levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced TXNIP

  15. DNA preservation in silk.

    Science.gov (United States)

    Liu, Yawen; Zheng, Zhaozhu; Gong, He; Liu, Meng; Guo, Shaozhe; Li, Gang; Wang, Xiaoqin; Kaplan, David L

    2017-06-27

    The structure of DNA is susceptible to alterations at high temperature and on changing pH, irradiation and exposure to DNase. Options to protect and preserve DNA during storage are important for applications in genetic diagnosis, identity authentication, drug development and bioresearch. In the present study, the stability of total DNA purified from human dermal fibroblast cells, as well as that of plasmid DNA, was studied in silk protein materials. The DNA/silk mixtures were stabilized on filter paper (silk/DNA + filter) or filter paper pre-coated with silk and treated with methanol (silk/DNA + PT-filter) as a route to practical utility. After air-drying and water extraction, 50-70% of the DNA and silk could be retrieved and showed a single band on electrophoretic gels. 6% silk/DNA + PT-filter samples provided improved stability in comparison with 3% silk/DNA + filter samples and DNA + filter samples for DNA preservation, with ∼40% of the band intensity remaining at 37 °C after 40 days and ∼10% after exposure to UV light for 10 hours. Quantitative analysis using the PicoGreen assay confirmed the results. The use of Tris/borate/EDTA (TBE) buffer enhanced the preservation and/or extraction of the DNA. The DNA extracted after storage maintained integrity and function based on serving as a functional template for PCR amplification of the gene for zinc finger protein 750 (ZNF750) and for transgene expression of red fluorescence protein (dsRed) in HEK293 cells. The high molecular weight and high content of a crystalline beta-sheet structure formed on the coated surfaces likely accounted for the preservation effects observed for the silk/DNA + PT-filter samples. Although similar preservation effects were also obtained for lyophilized silk/DNA samples, the rapid and simple processing available with the silk-DNA-filter membrane system makes it appealing for future applications.

  16. Perforator plus flaps: Optimizing results while preserving function and esthesis

    Directory of Open Access Journals (Sweden)

    Mehrotra Sandeep

    2010-01-01

    Full Text Available Background: The tenuous blood supply of traditional flaps for wound cover combined with collateral damage by sacrifice of functional muscle, truncal vessels, or nerves has been the bane of reconstructive procedures. The concept of perforator plus flaps employs dual vascular supply to flaps. By safeguarding perforators along with supply from its base, robust flaps can be raised in diverse situations. This is achieved while limiting collateral damage and preserving nerves, vessels, and functioning muscle with better function and aesthesis. Materials and Methods: The perforator plus concept was applied in seven different clinical situations. Functional muscle and fasciocutaneous flaps were employed in five and adipofascial flaps in two cases, primarily involving lower extremity defects and back. Adipofascial perforator plus flaps were employed to provide cover for tibial fracture in one patients and chronic venous ulcer in another. Results: All flaps survived without any loss and provided long-term stable cover, both over soft tissue and bone. Functional preservation was achieved in all cases where muscle flaps were employed with no clinical evidence of loss of power. There was no sensory loss or significant oedema in or distal to the flap in both cases where neurovascular continuity was preserved during flap elevation. Fracture union and consolidation were satisfactory. One patient had minimal graft loss over fascia which required application of stored grafts with subsequent take. No patient required re-operation. Conclusions: Perforator plus concept is holistic and applicable to most flap types in varied situations. It permits the exercise of many locoregional flap options while limiting collateral functional damage. Aesthetic considerations are also addressed while raising adipofascial flaps because of no appreciable donor defects. With quick operating times and low failure risk, these flaps can be a better substitute to traditional flaps and at

  17. Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells.

    Science.gov (United States)

    Ammar, David A; Kahook, Malik Y

    2011-01-01

    We investigated the potential short and long-term effects in cultured human trabecular meshwork (TM) cells of various topical glaucoma formulations containing different preservatives. We tested the fixed combination medications 0.004% travoprost plus 0.5% timolol preserved with either 0.015% benzalkonium chloride (BAK; DuoTrav®), or with 0.001% polyquad (PQ; DuoTrav(®) BAK-free); and 0.005% latanoprost plus 0.5% timolol preserved with 0.020% BAK (Xalacom(®)). Also tested was a range of BAK concentrations (0.001%-0.020%) in balanced salt solution (BSS). Cells were treated for 25 min at 37 °C with solutions diluted 1:10 and 1:100 to mimic the reduced penetration of topical preparations to the anterior chamber. The percentage of live cells was determined immediately after treatment through the uptake of the fluorescent vital dye calcein-AM. To determine any long-term effects, we assayed release of matrix metalloproteinase 9 (MMP-9) and apoptosis 24 h after treatments. BAK demonstrated a dose-dependent reduction in TM cell viability, ranging from 71±5% live cells at 0.001% BAK (diluted 1:10) to 33±3% live cells at 0.020% BAK (diluted 1:10). Travoprost (0.004%) plus 0.5% timolol preserved with 0.015% BAK had statistically fewer live TM cells (79±7%) than the same preparation preserved with 0.001% polyquad® (PQ; 93±1%; p<0.001). Latanoprost plus timolol preserved with 0.020% BAK (29±9% live cells) was similar to the 0.020% BAK (33±3%) treatment. However, travoprost plus timolol preserved in 0.015% BAK had significantly more live cells (83±12%) than the 1:10 dilution of 0.015% BAK (49±10%). We also found 0.020% BAK (diluted 1:100) resulted in elevated levels of extracellular MMP-9 at 24 h. These results demonstrate that the substitution of the preservative BAK from topical ophthalmic drugs results in greater in vitro viability of TM cells. Travoprost with timolol, but not latanoprost with timolol, countered some of the toxic BAK effects. BAK treatment

  18. Unstable volatility functions: the break preserving local linear estimator

    DEFF Research Database (Denmark)

    Casas, Isabel; Gijbels, Irene

    The objective of this paper is to introduce the break preserving local linear (BPLL) estimator for the estimation of unstable volatility functions. Breaks in the structure of the conditional mean and/or the volatility functions are common in Finance. Markov switching models (Hamilton, 1989......) and threshold models (Lin and Terasvirta, 1994) are amongst the most popular models to describe the behaviour of data with structural breaks. The local linear (LL) estimator is not consistent at points where the volatility function has a break and it may even report negative values for finite samples...

  19. Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.

    Directory of Open Access Journals (Sweden)

    Georgia Perganta

    Full Text Available Autosomal dominant optic atrophy (ADOA is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies.

  20. Neuropsychological Impairment in Detoxified Alcohol-Dependent Subjects with Preserved Psychosocial Functioning

    Directory of Open Access Journals (Sweden)

    Catherine Martelli

    2017-09-01

    Full Text Available BackgroundChronic alcoholism and its related cognitive impairments are associated with increased social, relational, and professional deficits which have a variable overall impact on social integration. These impairments are known to have varying severities and have rarely been studied among healthy alcohol-dependent subjects with preserved psychosocial functioning. Thus, the objective of this study is to describe neuropsychological performance in this particular population.MethodTwenty-nine socially adjusted alcohol-dependent men, hospitalized for a first or second withdrawal and abstinent for 3 weeks minimum, were compared to 29 healthy non-alcoholic controls. All subjects underwent clinical and psychiatric examination, neuropsychological tests of memory (M, working memory (WM, and executive functions (EF. Comparisons were performed using Student’s t-tests or Mann–Whitney U tests.ResultsNo group differences were found on the Self-Reported Social Adjustment Scale (SAS-SR or in the Mini-Mental State Examination. Compared to controls, patients had greater episodic, spatial, and WM deficits as well as slightly altered executive functions. In contrast, their executive functions (spontaneous flexibility, criteria generation, rule maintenance, and inhibitory control were relatively preserved.ConclusionOur sample of socially and professionally integrated alcoholic patients shows fewer cognitive deficits than described in previous studies. Our results suggest that early on, alcohol-dependent subjects develop compensatory adaptation processes to preserve social function and adaptation. Minor cognitive impairments should be screened early in the disease to integrate cognitive interventions into the health-care plan to thus eventually prevent further socio-professional marginalization.

  1. Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis.

    Science.gov (United States)

    Abdelsamed, Hossam A; Moustaki, Ardiana; Fan, Yiping; Dogra, Pranay; Ghoneim, Hazem E; Zebley, Caitlin C; Triplett, Brandon M; Sekaly, Rafick-Pierre; Youngblood, Ben

    2017-06-05

    Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T EM ), and longer-lived central memory (T CM ) and stem cell memory (T SCM ) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T CM and T SCM memory cells resulted in phenotypic conversion into T EM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T EM -associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells. © 2017 Abdelsamed et al.

  2. Prognostic implications of left ventricular diastolic dysfunction with preserved systolic function following acute myocardial infarction

    DEFF Research Database (Denmark)

    Poulsen, S H; Møller, J E; Nørager, B

    2001-01-01

    of the mitral and pulmonary venous flow, and the propagation velocity of early mitral flow by color M-mode Doppler echocardiography in 183 consecutive patients at day 5-7 following their first acute MI. Patients were classified into four groups: group A: preserved LV systolic and diastolic function (n = 73......%) and D (38%) compared to A (2%) (p class >or=II (p = 0.006), and age (0.008) as predictors of cardiac death or readmission due to heart failure. The presence of LV diastolic dysfunction with preserved......The contribution of diastolic dysfunction in patients with preserved left ventricular (LV) systolic function to impaired functional status and cardiac mortality in myocardial infarction (MI) is unknown. In the present study, assessment of LV diastolic function was performed by Doppler analysis...

  3. Functional imaging in bulk tissue specimens using optical emission tomography: fluorescence preservation during optical clearing

    International Nuclear Information System (INIS)

    Sakhalkar, H S; Dewhirst, M; Oliver, T; Cao, Y; Oldham, M

    2007-01-01

    Optical emission computed tomography (optical-ECT) is a technique for imaging the three-dimensional (3D) distribution of fluorescent probes in biological tissue specimens with high contrast and spatial resolution. In optical-ECT, functional information can be imaged by (i) systemic application of functional labels (e.g. fluorophore labelled proteins) and/or (ii) endogenous expression of fluorescent reporter proteins (e.g. red fluorescent protein (RFP), green fluorescent protein (GFP)) in vivo. An essential prerequisite for optical-ECT is optical clearing, a procedure where tissue specimens are made transparent to light by sequential perfusion with fixing, dehydrating and clearing agents. In this study, we investigate clearing protocols involving a selection of common fixing (4% buffered paraformaldehyde (PFA), methanol and ethanol), dehydrating (methanol and ethanol) and clearing agents (methyl salicylate and benzyl-alcohol-benzyl-benzoate (BABB)) in order to determine a 'fluorescence friendly' clearing procedure. Cell culture experiments were employed to optimize the sequence of chemical treatments that best preserve fluorescence. Texas red (TxRed), fluorescein isothiocyanate (FITC), RFP and GFP were tested as fluorophores and fluorescent reporter proteins of interest. Fluorescent and control cells were imaged on a microscope using a DSred2 and FITC filter set. The most promising clearing protocols of cell culture experiments were applied to whole xenograft tumour specimens, to test their effectiveness in large unsectioned samples. Fluorescence of TxRed/FITC fluorophores was not found to be significantly affected by any of the test clearing protocols. RFP and GFP fluorescence, however, was found to be significantly greater when cell fixation was in ethanol. Fixation in either PFA or methanol resulted in diminished fluorescence. After ethanol fixation, the RFP and GFP fluorescence proved remarkably robust to subsequent exposure to either methyl salicylate or BABB

  4. Functional imaging in bulk tissue specimens using optical emission tomography: fluorescence preservation during optical clearing

    Energy Technology Data Exchange (ETDEWEB)

    Sakhalkar, H S [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Dewhirst, M [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Oliver, T [Department of Cell Biology, Duke University Medical Center, Durham, NC 27710 (United States); Cao, Y [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Oldham, M [Department of Radiation Oncology Physics, and Biomedical Engineering, Duke University Medical Center, Durham, NC 27710 (United States)

    2007-04-21

    Optical emission computed tomography (optical-ECT) is a technique for imaging the three-dimensional (3D) distribution of fluorescent probes in biological tissue specimens with high contrast and spatial resolution. In optical-ECT, functional information can be imaged by (i) systemic application of functional labels (e.g. fluorophore labelled proteins) and/or (ii) endogenous expression of fluorescent reporter proteins (e.g. red fluorescent protein (RFP), green fluorescent protein (GFP)) in vivo. An essential prerequisite for optical-ECT is optical clearing, a procedure where tissue specimens are made transparent to light by sequential perfusion with fixing, dehydrating and clearing agents. In this study, we investigate clearing protocols involving a selection of common fixing (4% buffered paraformaldehyde (PFA), methanol and ethanol), dehydrating (methanol and ethanol) and clearing agents (methyl salicylate and benzyl-alcohol-benzyl-benzoate (BABB)) in order to determine a 'fluorescence friendly' clearing procedure. Cell culture experiments were employed to optimize the sequence of chemical treatments that best preserve fluorescence. Texas red (TxRed), fluorescein isothiocyanate (FITC), RFP and GFP were tested as fluorophores and fluorescent reporter proteins of interest. Fluorescent and control cells were imaged on a microscope using a DSred2 and FITC filter set. The most promising clearing protocols of cell culture experiments were applied to whole xenograft tumour specimens, to test their effectiveness in large unsectioned samples. Fluorescence of TxRed/FITC fluorophores was not found to be significantly affected by any of the test clearing protocols. RFP and GFP fluorescence, however, was found to be significantly greater when cell fixation was in ethanol. Fixation in either PFA or methanol resulted in diminished fluorescence. After ethanol fixation, the RFP and GFP fluorescence proved remarkably robust to subsequent exposure to either methyl salicylate

  5. Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing.

    Science.gov (United States)

    Zhao, Yingwen; Fu, Guangyuan; Wang, Jun; Guo, Maozu; Yu, Guoxian

    2018-02-23

    Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Extraction of nucleic acids from yeast cells and plant tissues using ethanol as medium for sample preservation and cell disruption.

    Science.gov (United States)

    Linke, Bettina; Schröder, Kersten; Arter, Juliane; Gasperazzo, Tatiana; Woehlecke, Holger; Ehwald, Rudolf

    2010-09-01

    Here we report that dehydrated ethanol is an excellent medium for both in situ preservation of nucleic acids and cell disruption of plant and yeast cells. Cell disruption was strongly facilitated by prior dehydration of the ethanol using dehydrated zeolite. Following removal of ethanol, nucleic acids were extracted from the homogenate pellet using denaturing buffers. The method provided DNA and RNA of high yield and integrity. Whereas cell wall disruption was essential for extraction of DNA and large RNA molecules, smaller molecules such as tRNAs could be selectively extracted from undisrupted, ethanol-treated yeast cells. Our results demonstrate the utility of absolute ethanol for sample fixation, cell membrane and cell wall disruption, as well as preservation of nucleic acids during sample storage.

  7. Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

    2013-01-01

    Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

  8. Functional preservation and quality of life in head and neck radiotherapy

    International Nuclear Information System (INIS)

    Harari, Paul M.; Connor, Nadine P.; Grau, Cai

    2009-01-01

    This book focuses on functional treatment outcomes in head and neck cancer patients from the perspective of experts from around the world in medical and allied health fields. Recent advances in management strategies are presented as they relate to functional preservation and quality of life. Clinical and research knowledge is organized in an approachable manner by means of short chapters, key point tables, and high-quality illustrations and graphics. This method of presentation is very effective for busy clinical practitioners and researchers. Information is provided on site-specific epidemiology and treatment outcome, the impact of different treatment techniques and toxicities on quality of life, and the relationship of toxicity prevention, rehabilitation, and supportive care to quality of life after treatment, Among literature on the treatment of head and neck cancer, this book is unique because of the outstanding list of contributors and the specific focus on functional preservation and quality of life. (orig.)

  9. Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

    Directory of Open Access Journals (Sweden)

    Martin Braun

    Full Text Available Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/- mice and wildtypes (WT. In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24% in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.

  10. A cell transportation solution that preserves live circulating tumor cells in patient blood samples

    International Nuclear Information System (INIS)

    Stefansson, Steingrimur; Adams, Daniel L.; Ershler, William B.; Le, Huyen; Ho, David H.

    2016-01-01

    Circulating tumor cells (CTCs) are typically collected into CellSave fixative tubes, which kills the cells, but preserves their morphology. Currently, the clinical utility of CTCs is mostly limited to their enumeration. More detailed investigation of CTC biology can be performed on live cells, but obtaining live CTCs is technically challenging, requiring blood collection into biocompatible solutions and rapid isolation which limits transportation options. To overcome the instability of CTCs, we formulated a sugar based cell transportation solution (SBTS) that stabilizes cell viability at ambient temperature. In this study we examined the long term viability of human cancer cell lines, primary cells and CTCs in human blood samples in the SBTS for transportation purposes. Four cell lines, 5 primary human cells and purified human PBMCs were tested to determine the viability of cells stored in the transportation solution at ambient temperature for up to 7 days. We then demonstrated viability of MCF-7 cells spiked into normal blood with SBTS and stored for up to 7 days. A pilot study was then run on blood samples from 3 patients with metastatic malignancies stored with or without SBTS for 6 days. CTCs were then purified by Ficoll separation/microfilter isolation and identified using CTC markers. Cell viability was assessed using trypan blue or CellTracker™ live cell stain. Our results suggest that primary/immortalized cell lines stored in SBTS remain ~90 % viable for > 72 h. Further, MCF-7 cells spiked into whole blood remain viable when stored with SBTS for up to 7 days. Finally, live CTCs were isolated from cancer patient blood samples kept in SBTS at ambient temperature for 6 days. No CTCs were isolated from blood samples stored without SBTS. In this proof of principle pilot study we show that viability of cell lines is preserved for days using SBTS. Further, this solution can be used to store patient derived blood samples for eventual isolation of viable CTCs

  11. A cell transportation solution that preserves live circulating tumor cells in patient blood samples.

    Science.gov (United States)

    Stefansson, Steingrimur; Adams, Daniel L; Ershler, William B; Le, Huyen; Ho, David H

    2016-05-06

    Circulating tumor cells (CTCs) are typically collected into CellSave fixative tubes, which kills the cells, but preserves their morphology. Currently, the clinical utility of CTCs is mostly limited to their enumeration. More detailed investigation of CTC biology can be performed on live cells, but obtaining live CTCs is technically challenging, requiring blood collection into biocompatible solutions and rapid isolation which limits transportation options. To overcome the instability of CTCs, we formulated a sugar based cell transportation solution (SBTS) that stabilizes cell viability at ambient temperature. In this study we examined the long term viability of human cancer cell lines, primary cells and CTCs in human blood samples in the SBTS for transportation purposes. Four cell lines, 5 primary human cells and purified human PBMCs were tested to determine the viability of cells stored in the transportation solution at ambient temperature for up to 7 days. We then demonstrated viability of MCF-7 cells spiked into normal blood with SBTS and stored for up to 7 days. A pilot study was then run on blood samples from 3 patients with metastatic malignancies stored with or without SBTS for 6 days. CTCs were then purified by Ficoll separation/microfilter isolation and identified using CTC markers. Cell viability was assessed using trypan blue or CellTracker™ live cell stain. Our results suggest that primary/immortalized cell lines stored in SBTS remain ~90% viable for > 72 h. Further, MCF-7 cells spiked into whole blood remain viable when stored with SBTS for up to 7 days. Finally, live CTCs were isolated from cancer patient blood samples kept in SBTS at ambient temperature for 6 days. No CTCs were isolated from blood samples stored without SBTS. In this proof of principle pilot study we show that viability of cell lines is preserved for days using SBTS. Further, this solution can be used to store patient derived blood samples for eventual isolation of viable CTCs after

  12. A Cell Culture Approach to Optimized Human Corneal Endothelial Cell Function

    Science.gov (United States)

    Bartakova, Alena; Kuzmenko, Olga; Alvarez-Delfin, Karen; Kunzevitzky, Noelia J.; Goldberg, Jeffrey L.

    2018-01-01

    Purpose Cell-based therapies to replace corneal endothelium depend on culture methods to optimize human corneal endothelial cell (HCEC) function and minimize endothelial-mesenchymal transition (EnMT). Here we explore contribution of low-mitogenic media on stabilization of phenotypes in vitro that mimic those of HCECs in vivo. Methods HCECs were isolated from cadaveric donor corneas and expanded in vitro, comparing continuous presence of exogenous growth factors (“proliferative media”) to media without those factors (“stabilizing media”). Identity based on canonical morphology and expression of surface marker CD56, and function based on formation of tight junction barriers measured by trans-endothelial electrical resistance assays (TEER) were assessed. Results Primary HCECs cultured in proliferative media underwent EnMT after three to four passages, becoming increasingly fibroblastic. Stabilizing the cells before each passage by switching them to a media low in mitogenic growth factors and serum preserved canonical morphology and yielded a higher number of cells. HCECs cultured in stabilizing media increased both expression of the identity marker CD56 and also tight junction monolayer integrity compared to cells cultured without stabilization. Conclusions HCECs isolated from donor corneas and expanded in vitro with a low-mitogenic media stabilizing step before each passage demonstrate more canonical structural and functional features and defer EnMT, increasing the number of passages and total canonical cell yield. This approach may facilitate development of HCEC-based cell therapies. PMID:29625488

  13. Investigations on the change of texture of plant cells due to preservative treatments by digital holographic microscopy

    Science.gov (United States)

    Vora, Priyanka; Anand, Arun

    2014-10-01

    Texture change is observed in preserved fruits and vegetables. Responsible factors for texture change during preservative treatments are cell morphology, cell wall structure, cell turger, water content and some biochemical components, and also the environmental conditions. Digital Holographic microscopy (DHM) is a quantitative phase contrast imaging technique, which provides three dimensional optical thickness profiles of transparent specimen. Using DHM the morphology of plant cells preserved by refrigeration or stored in vinegar or in sodium chloride can be obtained. This information about the spatio-temporal evolution of optical volume and thickness can be an important tool in area of food processing. Also from the three dimensional images, the texture of the cell can be retrieved and can be investigated under varying conditions.

  14. Changes in Ocular Surface Characteristics after Switching from Benzalkonium Chloride-Preserved Latanoprost to Preservative-Free Tafluprost or Benzalkonium Chloride-Preserved Tafluprost

    Directory of Open Access Journals (Sweden)

    Naoto Tokuda

    2017-01-01

    Full Text Available Purpose. The aim of the present study was to examine the effects of switching from Latanoprost ophthalmic solution containing a preservative to preservative-free Tafluprost ophthalmic solution or Tafluprost containing a preservative on ocular surfaces. Materials and Methods. Forty patients (40 eyes with glaucoma (mean age: 62.0 ± 10.9 years using Latanoprost with preservative for six months or longer were assigned either to a Tafluprost-containing-preservative group (20 eyes or preservative-free-Tafluprost group (20 eyes. The intraocular pressure, corneal epithelial barrier function (fluorescein uptake concentration with fluorophotometer FL-500, superficial punctate keratopathy (AD classification, and tear film breakup time (TBUT were assessed before switching and at 12 weeks after switching. Results. No significant differences in intraocular pressure were noted after switching in either group. Corneal epithelial barrier function was improved significantly after switching in both the Tafluprost-containing-preservative and the preservative-free-Tafluprost groups. There were no significant differences in AD scores after switching in the Tafluprost-containing-preservative group, but significant improvements were noted in the preservative-free-Tafluprost group. No significant differences in TBUT were noted in the Tafluprost-containing-preservative or preservative-free-Tafluprost groups after switching. Conclusion. After switching from preservative Latanoprost to Tafluprost containing-preservative or preservative-free Tafluprost, corneal epithelial barrier function was improved while the intraocular pressure reduction was retained.

  15. Changes in Ocular Surface Characteristics after Switching from Benzalkonium Chloride-Preserved Latanoprost to Preservative-Free Tafluprost or Benzalkonium Chloride-Preserved Tafluprost.

    Science.gov (United States)

    Tokuda, Naoto; Kitaoka, Yasushi; Matsuzawa, Akiko; Tsukamoto, Ayaka; Sase, Kana; Sakae, Shinsuke; Takagi, Hitoshi

    2017-01-01

    The aim of the present study was to examine the effects of switching from Latanoprost ophthalmic solution containing a preservative to preservative-free Tafluprost ophthalmic solution or Tafluprost containing a preservative on ocular surfaces. Forty patients (40 eyes) with glaucoma (mean age: 62.0 ± 10.9 years) using Latanoprost with preservative for six months or longer were assigned either to a Tafluprost-containing-preservative group (20 eyes) or preservative-free-Tafluprost group (20 eyes). The intraocular pressure, corneal epithelial barrier function (fluorescein uptake concentration with fluorophotometer FL-500), superficial punctate keratopathy (AD classification), and tear film breakup time (TBUT) were assessed before switching and at 12 weeks after switching. No significant differences in intraocular pressure were noted after switching in either group. Corneal epithelial barrier function was improved significantly after switching in both the Tafluprost-containing-preservative and the preservative-free-Tafluprost groups. There were no significant differences in AD scores after switching in the Tafluprost-containing-preservative group, but significant improvements were noted in the preservative-free-Tafluprost group. No significant differences in TBUT were noted in the Tafluprost-containing-preservative or preservative-free-Tafluprost groups after switching. After switching from preservative Latanoprost to Tafluprost containing-preservative or preservative-free Tafluprost, corneal epithelial barrier function was improved while the intraocular pressure reduction was retained.

  16. Atorvastatin helps preserve pancreatic β cell function in obese C57BL/6 J mice and the effect is related to increased pancreas proliferation and amelioration of endoplasmic-reticulum stress

    Science.gov (United States)

    2014-01-01

    Background 3-Hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis. Currently, statins are used as first-line therapy in the treatment of diabetic dyslipidemia. However, effects of statins on β cell function remains unclear. This study aims to examine effects of atorvastatin treatment on pancreatic β cell function in obese C57BL/6 J mice and the possible mechanisms. Methods Diet-induced obesity (DIO) C57BL/6 J mice were treated with atorvastatin (30 mg/kg/day) for 58 days. β cell function was assessed by hyperglycemic clamp and the area of insulin-positive β cells was examined by immunofluorescence. Gene expression was assessed by RT-PCR, and endoplasmic reticulum (ER) stress related proteins were examined by Western blot. Additionally, cell viability and apoptosis of the cholesterol-loaded NIT-1 cells were investigated after atorvastatin treatment. Results Hyperglycemic clamp study revealed that glucose infusion rate (GIR) and insulin stimulation ratio in atorvastatin-treated DIO mice were markedly higher than control mice (P atorvastatin treatment (P atorvastatin-treated mice had significantly larger insulin-positive β cell area (P atorvastatin-treated mice (P atorvastatin protected the pancreatic β cell line of NIT-1 from cholesterol-induced apoptosis. Western blot showed increased expression of anti-apoptotic protein of B-cell lymphoma 2 (Bcl-2). Conclusion Pancreatic β cell function of obese C57BL/6 J mice was preserved after atorvastatin treatment, and this improvement may be attributed to enhanced pancreas proliferation and amelioration of pancreatic ER stress. PMID:24950764

  17. Surgical management of vestibular schwannoma: attempted preservation of hearing and facial function.

    Science.gov (United States)

    Youssef, T F; Matter, A; Ahmed, M R

    2013-05-01

    Vestibular schwannomas are benign tumours which usually originate from the vestibular portion of the VIIIth cranial nerve. Treatment options include observation with serial imaging, stereotactic radiation and microsurgical removal. The goal of surgery was complete eradication of tumour with preservation of hearing and facial nerve function. A retrospective review was undertaken of 24 cases of vestibular schwannoma jointly operated upon by a team of neurosurgeons and otologists at the Suez Canal University Hospital, with assessment of VIIth and VIIIth cranial nerve function, tumour size, and extent of growth. All surgery utilised a retromastoid, suboccipital approach. Complete tumour removal was achieved in 19 patients. Anatomical preservation of the facial nerve was possible in 66.6 per cent of patients. Pre-operative, useful hearing was present in four patients, and preserved in 80 per cent. Cerebrospinal fluid leakage was diagnosed in two (8.3 per cent) patients, who responded to conservative therapy. The retromastoid, suboccipital surgical approach to the skull base can be safely and successfully achieved using a microsurgical technique, with minimal or no damage to neurovascular structures, even for large tumours.

  18. Functional Dehydrated Foods for Health Preservation

    Directory of Open Access Journals (Sweden)

    R. M. S. C. Morais

    2018-01-01

    Full Text Available The market of functional foods has experienced a huge growth in the last decades due to the increased consumers’ awareness in a healthy lifestyle. Dried fruits constitute good snacks, in alternative to salty or sweet ones, and food ingredients due to their taste and nutritional/health benefits. Bioactive molecules are interesting sources to develop functional foods, as they play a major role in improving the health status and minimizing disease risks. The bioactive compounds most widely discussed in literature are presented in this review, for example, polyphenols, phytosterols, and prebiotics. Different technologies to dry bioproducts for producing functional foods or ingredients are presented. New drying techniques for the preservation of bioactive compounds are proposed, focusing more specifically on dielectric drying. A discussion on the techniques that can be used to optimize drying processes is performed. An overview on dehydrated plant based foods with probiotics is provided. The microorganisms used, impregnation procedures, drying methods, and evaluated parameters are presented and discussed. The principal bioactive compounds responsible for nutritional and health benefits of plant derived dried food products—fruits and vegetables, fruits and vegetables by-products, grains, nuts, and algae—are presented. Phytochemical losses occurring during pretreatments and/or drying processes are also discussed.

  19. Clear cell carcinoma of the uterine cervix: clinical characteristics and feasibility of fertility-preserving treatment

    Directory of Open Access Journals (Sweden)

    Jiang X

    2014-01-01

    Full Text Available Xiang Jiang, Ying Jin, Yan Li, Hui-Fang Huang, Ming Wu, Keng Shen, Ling-Ya Pan Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: The objective of this retrospective study was to analyze the clinical characteristics and prognosis of clear cell adenocarcinoma (CCA in the post-diethylstilbestrol (DES era and to evaluate the feasibility of fertility-preserving treatment. The records of 32 patients with CCAs who were treated at Peking Union Medical College Hospital from August 1986 to June 2012 were retrospectively reviewed. Three of the patients had undergone fertility-preserving treatment. The incidence of CCA among cervical adenocarcinomas was 15.2%. The median age was 38 years: 11 patients (34.4% were diagnosed before 30 years of age and two (6.3% after 70 years of age. Ten patients (31.2% were nulliparous. No patient had been exposed to DES. Twenty-nine patients (90.6% presented with obvious symptoms, and the cervix appeared abnormal in 26 patients (81.3%. Cervical Papanicolaou (Pap tests were abnormal in all four patients in whom they were performed (three had high-grade squamous intraepithelial lesions and one had atypical squamous cells of undetermined significance. The distribution by stage was 56.3% stage I, 34.4% stage II, 6.3% stage III, and 3.1% stage IV. Treatments mainly included surgery for patients with stage I to IIA CCA and radiochemotherapy for patients with advanced CCA. The overall 5-year progression-free survival was 72.2%. Patients with stage I to IIA CCA had better 5-year progression-free survival than did patients with stage IIB to IV CCA (81.5% versus 40.0%, P=0.003. The three patients who had undergone fertility-preserving treatment had no recurrences. CCA may also affect adolescents and children without prior DES exposure, who are often misdiagnosed as having functional uterine

  20. Preserving SSC Design Function Using RCM Principles

    International Nuclear Information System (INIS)

    Mohammadi, K.

    2009-01-01

    Reliability-Centered Maintenance (RCM) can be defined as an approach that employs preventive, predictive, proactive, and reactive maintenance practices and strategies in an integrated manner to increase the probability that a Structure, System, or Component (SSC) will function as designed over its life cycle with optimum maintenance. The goal of RCM is to preserve the SSC intended design function at the lowest cost by developing a maintenance strategy that is supported by sound technical and economic justification. RCM has been used extensively by the aircraft, space, defense, power generation, and manufacturing industries where functional failures of SSCs can have the potential to compromise worker or public safety, cause adverse environmental impact, cause loss of production, and/or result in excessive damage to critical SSCs. This paper provides a framework for performing an RCM analysis in support of DOE Order 430.1A (Life Cycle Asset Management) and DOE Order 420.1B (Facility Safety). The influence of RCM on the various aspects of the maintenance program including the work control process is also discussed

  1. Superselective intra-arterial chemoradiotherapy for advanced head and neck cancers. Evaluation of preservation of organ function

    International Nuclear Information System (INIS)

    Akisada, Takeshi; Harada, Tamotsu; Imai, Shigeki; Gyoten, Masayuki; Hiraoka, Takashi

    2008-01-01

    The objective of this study was to evaluate preservation of organ function in the treatment of superselective intra-arterial chemoradiotherapy for advanced head and neck cancers. Among 96 patients receiving concomitant radiation and intra-arterial docetaxel, systemic cisplatin and 5-fluorouracil (FU) chemotherapy, we identified laryngeal preservation rate, studied tracheostomy cases and gastrostomy cases, and evaluated videofluoroscopic examination and videoendoscopy. Laryngeal preservation rate of hypopharyngeal cancer is very high at 96.2%, and that of laryngeal cancer is high at 71.4%. Videofluoroscopic examination revealed improved swallowing function in 2 of 12, no change in 3, slightly worse in 5, and worse in 2 patients. Following treatment, the incidence of aspiration increased to 4 patients. Videoendoscopy revealed residual vallecula in a few cases. Only 7 patients (7.3%) required a tracheostomy and 4 patients (4.2%) required a gastrostomy. Most of the patients are able to swallow after chemoradiation. Our new chemoradiation protocol is as good as other treatment modalities for maintaining organ preservation and function. (author)

  2. Selective preservation of anterior pituitary functions in patients with Sheehan′s syndrome

    Directory of Open Access Journals (Sweden)

    Bashir Ahmad Laway

    2011-01-01

    Full Text Available Background: Sheehan′s syndrome manifests as hypopituitarism following a child birth usually preceded by postpartum hemorrhage. The symptoms range from vague feelings of ill health to symptoms of a full blown panhypopituitarism. A large series of such patients is not described in the literature. Materials and Methods: We present the details of ten women with partial Sheehan′s syndrome. They presented with post-partum hemorrhage and lactation failure. Results: After delivery, seven out of ten patients had regular menstrual cycles indicating preservation of gonadotroph function. Lactotroph, thyrotroph, and somatotroph failure were present in all and corticotrophs preservation was documented in four out of ten patients. The hypophysial magnetic resonance imaging (MRI confirmed empty sella in all. Conclusion: lactotroph, somatotroph and thyrotroph failure are common in patients with Sheehan′s syndrome. In addition to known preservation of gonadotroph axis, corticotroph axis may be preserved in some of these patients arguing against the universal treatment of these patients with glucocorticoids.

  3. Hyperbranched polyglycerol as a colloid in cold organ preservation solutions.

    Directory of Open Access Journals (Sweden)

    Sihai Gao

    Full Text Available Hydroxyethyl starch (HES is a common colloid in organ preservation solutions, such as in University of Wisconsin (UW solution, for preventing graft interstitial edema and cell swelling during cold preservation of donor organs. However, HES has undesirable characteristics, such as high viscosity, causing kidney injury and aggregation of erythrocytes. Hyperbranched polyglycerol (HPG is a branched compact polymer that has low intrinsic viscosity. This study investigated HPG (MW-0.5 to 119 kDa as a potential alternative to HES for cold organ preservation. HPG was synthesized by ring-opening multibranching polymerization of glycidol. Both rat myocardiocytes and human endothelial cells were used as an in vitro model, and heart transplantation in mice as an in vivo model. Tissue damage or cell death was determined by both biochemical and histological analysis. HPG polymers were more compact with relatively low polydispersity index than HES in UW solution. Cold preservation of mouse hearts ex vivo in HPG solutions reduced organ damage in comparison to those in HES-based UW solution. Both size and concentration of HPGs contributed to the protection of the donor organs; 1 kDa HPG at 3 wt% solution was superior to HES-based UW solution and other HPGs. Heart transplants preserved with HPG solution (1 kDa, 3% as compared with those with UW solution had a better functional recovery, less tissue injury and neutrophil infiltration in syngeneic recipients, and survived longer in allogeneic recipients. In cultured myocardiocytes or endothelial cells, significantly more cells survived after cold preservation with the HPG solution than those with the UW solution, which was positively correlated with the maintenance of intracellular adenosine triphosphate and cell membrane fluidity. In conclusion, HPG solution significantly enhanced the protection of hearts or cells during cold storage, suggesting that HPG is a promising colloid for the cold storage of donor organs

  4. [Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].

    Science.gov (United States)

    Castro, A; Dias, P; Pereira, M; Pimenta, J; Friões, F; Rodrigues, R; Ferreira, A; Bettencourt, P

    2001-11-01

    Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. Prospective study. One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.

  5. Preserving the functionality/asset value of the state highway system : technical report.

    Science.gov (United States)

    2010-02-01

    Maintaining, preserving, and enhancing the functionality of state and local roadways of our transportation system : is important because it maintains capacity and efficiency, reduces potential for congestion, maintains safety, reduces : the need for ...

  6. Carboxyl functionalized carbon fibers with preserved tensile strength and electrochemical performance used as anodes of structural lithium-ion batteries

    International Nuclear Information System (INIS)

    Feng, Mengjie; Wang, Shubin; Yu, Yalin; Feng, Qihang; Yang, Jiping; Zhang, Boming

    2017-01-01

    Highlights: • Carboxyl functionalized CF is acquired by simple chemical oxidation method. • These CF have preserved the tensile strength, better electrochemical properties. • The presence of H_3PO_4 prevented the turbostratic carbon from over-oxidization. • There CF can be used as anodes of multifunctional structural battery. • The preservation and improvement is result from the hindered over-oxidization. - Abstract: Carboxyl functionalized carbon fibers with preserved tensile strength and electrochemical properties were acquired through a simple chemical oxidation method, and the proposed underlying mechanism was verified. The surface of carboxyl functionalizing carbon fibers is necessary in acquiring functional groups on the surface of carbon fibers to further improve the thermal, electrical or mechanical properties of the fibers. Functionalization should preserve the tensile strength and electrochemical properties of carbon fibers, because the anodes of structural batteries need to have high strength and electrochemical properties. Functionalized with mixed H_2SO_4/HNO_3 considerably reduced the tensile strength of carbon fibers. By contrast, the appearance of H_3PO_4 preserved the tensile strength of functionalized carbon fibers, reduced the dispersion level of tensile strength values, and effectively increased the concentration of functional acid groups on the surface of carbon fibers. The presence of phosphoric acid hindered the over-oxidation of turbostratic carbon, and consequently preserved the tensile strength of carbon fibers. The increased proportion of turbostratic carbon on the surface of carbon fibers concurrently enhanced the electrochemical properties of carbon fibers.

  7. Immunoregulatory T Cells May Be Involved in Preserving CD4 T Cell Counts in HIV-Infected Long-Term Nonprogressors and Controllers

    DEFF Research Database (Denmark)

    Gaardbo, Julie C; Ronit, Andreas; Hartling, Hans J

    2014-01-01

    BACKGROUND: HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell...... of patients and controls. However, both ECs and LTNPs displayed a large proportion of activated Tregs suggesting immunoregulatory mechanisms to be involved in preserving CD4 T cell counts in HIV-infected nonprogressors....... counts in controllers and in LTNPs. METHODS: Twenty HIV-infected viremic controllers, 5 elite controllers (ECs), and 14 LTNPs were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Regulatory T cells (Tregs), Treg subpopulations, CD161+Th17...

  8. Hsp72 preserves muscle function and slows progression of severe muscular dystrophy.

    Science.gov (United States)

    Gehrig, Stefan M; van der Poel, Chris; Sayer, Timothy A; Schertzer, Jonathan D; Henstridge, Darren C; Church, Jarrod E; Lamon, Severine; Russell, Aaron P; Davies, Kay E; Febbraio, Mark A; Lynch, Gordon S

    2012-04-04

    Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.

  9. Transplantation of rat embryonic stem cell-derived retinal progenitor cells preserves the retinal structure and function in rat retinal degeneration.

    Science.gov (United States)

    Qu, Zepeng; Guan, Yuan; Cui, Lu; Song, Jian; Gu, Junjie; Zhao, Hanzhi; Xu, Lei; Lu, Lixia; Jin, Ying; Xu, Guo-Tong

    2015-11-09

    Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) from rat ESCs (rESCs) and to test their therapeutic effects in rat model. The rESCs (DA8-16) were cultured in N2B27 medium with 2i, and differentiated to two types of RPCs following the SFEBq method with modifications. For rESC-RPC1, the cells were switched to adherent culture at D10, while for rESC-RPC2, the suspension culture was maintained to D14. Both RPCs were harvested at D16. Primary RPCs were obtained from P1 SD rats, and some of them were labeled with EGFP by infection with lentivirus. To generate Rax::EGFP knock-in rESC lines, TALENs were engineered to facilitate homologous recombination in rESCs, which were cotransfected with the targeting vector and TALEN vectors. The differentiated cells were analyzed with live image, immunofluorescence staining, flow cytometric analysis, gene expression microarray, etc. RCS rats were used to mimic the degeneration of retina and test the therapeutic effects of subretinally transplanted donor cells. The structure and function of retina were examined. We established two protocols through which two types of rESC-derived RPCs were obtained and both contained committed retina lineage cells and some neural progenitor cells (NPCs). These rESC-derived RPCs survived in the host retinas of RCS rats and protected the retinal structure and function in early stage following the transplantation. However, the glia enriched rESC-RPC1 obtained through early and longer adherent culture only increased the b-wave amplitude at 4 weeks, while the longer suspension culture gave rise to evidently neuronal differentiation in rESC-RPC2 which significantly improved the visual function of RCS rats. We have successfully differentiated

  10. Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

    Science.gov (United States)

    Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

    2017-05-01

    To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p renal parenchyma volume preservation (89.19 vs 84.27%, p renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

  11. Carboxyl functionalized carbon fibers with preserved tensile strength and electrochemical performance used as anodes of structural lithium-ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mengjie [School of Materials Science and Engineering, Beihang University, Beijing 100191 (China); Wang, Shubin, E-mail: shubinwang@buaa.edu.cn [School of Materials Science and Engineering, Beihang University, Beijing 100191 (China); Key Laboratory of Aerospace Materials and Performance (Ministry of Education), School of Materials Science and Engineering, Beihang University, Beijing 100191 (China); Yu, Yalin; Feng, Qihang; Yang, Jiping; Zhang, Boming [School of Materials Science and Engineering, Beihang University, Beijing 100191 (China)

    2017-01-15

    Highlights: • Carboxyl functionalized CF is acquired by simple chemical oxidation method. • These CF have preserved the tensile strength, better electrochemical properties. • The presence of H{sub 3}PO{sub 4} prevented the turbostratic carbon from over-oxidization. • There CF can be used as anodes of multifunctional structural battery. • The preservation and improvement is result from the hindered over-oxidization. - Abstract: Carboxyl functionalized carbon fibers with preserved tensile strength and electrochemical properties were acquired through a simple chemical oxidation method, and the proposed underlying mechanism was verified. The surface of carboxyl functionalizing carbon fibers is necessary in acquiring functional groups on the surface of carbon fibers to further improve the thermal, electrical or mechanical properties of the fibers. Functionalization should preserve the tensile strength and electrochemical properties of carbon fibers, because the anodes of structural batteries need to have high strength and electrochemical properties. Functionalized with mixed H{sub 2}SO{sub 4}/HNO{sub 3} considerably reduced the tensile strength of carbon fibers. By contrast, the appearance of H{sub 3}PO{sub 4} preserved the tensile strength of functionalized carbon fibers, reduced the dispersion level of tensile strength values, and effectively increased the concentration of functional acid groups on the surface of carbon fibers. The presence of phosphoric acid hindered the over-oxidation of turbostratic carbon, and consequently preserved the tensile strength of carbon fibers. The increased proportion of turbostratic carbon on the surface of carbon fibers concurrently enhanced the electrochemical properties of carbon fibers.

  12. Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium

    NARCIS (Netherlands)

    Smits, Anke M.; van Laake, Linda W.; den Ouden, Krista; Schreurs, Chantal; Szuhai, Karoly; van Echteld, Cees J.; Mummery, Christine L.; Doevendans, Pieter A.; Goumans, Marie-Jose

    2009-01-01

    Recent clinical studies revealed that positive results of cell transplantation on cardiac function are limited to the short- and mid-term restoration phase following myocardial infarction (MI), emphasizing the need for long-term follow-up. These transient effects may depend on the transplanted

  13. Directing functional chemistries on micropatterned conducting polymers for all-polymer cell analysis microsystems

    DEFF Research Database (Denmark)

    Lind, Johan Ulrik; Daugaard, Anders Egede; Andresen, Thomas Lars

    Micrometer scale electrical circuits of PEDOT (poly(3,4-dioxythiophene)) were created by locally oxidizing PEDOT thin films with an agarose stamp containing the oxidizing agent NaOCl. The oxidized PEDOT was removed completely by applying detergents. The process was sufficiently mild that chemical...... groups on the underlying substrate, such as azides or alkynes, were preserved for subsequent specific functionalization. Moreover entire PMOXA (poly(2-methyl-2-oxazoline)) films preventing cell binding could be hidden below the PEDOT and be re-exposed upon stamping, allowing for cell capturing...... microelectrodes on a cell non-adhesive background. Chemically functionalized PEDOT types permitted the introduction of multiple additional types of micropatterned chemistry....

  14. Software preservation

    Directory of Open Access Journals (Sweden)

    Tadej Vodopivec

    2011-01-01

    Full Text Available Comtrade Ltd. covers a wide range of activities related to information and communication technologies; its deliverables include web applications, locally installed programs,system software, drivers, embedded software (used e.g. in medical devices, auto parts,communication switchboards. Also the extensive knowledge and practical experience about digital long-term preservation technologies have been acquired. This wide spectrum of activities puts us in the position to discuss the often overlooked aspect of the digital preservation - preservation of software programs. There are many resources dedicated to digital preservation of digital data, documents and multimedia records,but not so many about how to preserve the functionalities and features of computer programs. Exactly these functionalities - dynamic response to inputs - render the computer programs rich compared to documents or linear multimedia. The article opens the questions on the beginning of the way to the permanent digital preservation. The purpose is to find a way in the right direction, where all relevant aspects will be covered in proper balance. The following questions are asked: why at all to preserve computer programs permanently, who should do this and for whom, when we should think about permanent program preservation, what should be persevered (such as source code, screenshots, documentation, and social context of the program - e.g. media response to it ..., where and how? To illustrate the theoretic concepts given the idea of virtual national museum of electronic banking is also presented.

  15. Prostate Cancer Patient Characteristics Associated With a Strong Preference to Preserve Sexual Function and Receipt of Active Surveillance.

    Science.gov (United States)

    Broughman, James R; Basak, Ramsankar; Nielsen, Matthew E; Reeve, Bryce B; Usinger, Deborah S; Spearman, Kiayni C; Godley, Paul A; Chen, Ronald C

    2018-04-01

    Men with early-stage prostate cancer have multiple options that have similar oncologic efficacy but vary in terms of their impact on quality of life. In low-risk cancer, active surveillance is the option that best preserves patients' sexual function, but it is unknown if patient preference affects treatment selection. Our objectives were to identify patient characteristics associated with a strong preference to preserve sexual function and to determine whether patient preference and baseline sexual function level are associated with receipt of active surveillance in low-risk cancer. In this population-based cohort of men with localized prostate cancer, baseline patient-reported sexual function was assessed using a validated instrument. Patients were also asked whether preservation of sexual function was very, somewhat, or not important. Prostate cancer disease characteristics and treatments received were abstracted from medical records. A modified Poisson regression model with robust standard errors was used to compute adjusted risk ratio (aRR) estimates. All statistical tests were two-sided. Among 1194 men, 52.6% indicated a strong preference for preserving sexual function. Older men were less likely to have a strong preference (aRR = 0.98 per year, 95% confidence interval [CI] = 0.97 to 0.99), while men with normal sexual function were more likely (vs poor function, aRR = 1.59, 95% CI = 1.39 to 1.82). Among 568 men with low-risk cancer, there was no clear association between baseline sexual function or strong preference to preserve function with receipt of active surveillance. However, strong preference may differnetially impact those with intermediate baseline function vs poor function (Pinteraction = .02). Treatment choice may not always align with patients' preferences. These findings demonstrate opportunities to improve delivery of patient-centered care in early prostate cancer.

  16. Effects of glaucoma medications and preservatives on cultured human trabecular meshwork and non-pigmented ciliary epithelial cell lines.

    Science.gov (United States)

    Ammar, David A; Kahook, Malik Y

    2011-10-01

    We investigated the potential cytotoxicity of various topical ophthalmic glaucoma formulations containing different preservatives in cultured human trabecular meshwork (TM) and non-pigmented ciliary epithelial (NPCE) cell lines. We tested 0.004% travoprost preserved with either 0.015% benzalkonium chloride (BAK), sofZia or 0.001% Polyquad (PQ); and 0.005% latanoprost preserved with 0.020% BAK. We also tested a range of BAK concentrations in balanced salt solution (BSS). TM cells were treated for 10 min at 37°C with solutions diluted 1:10 to mimic the reduced penetration of topical preparations to the anterior chamber. Viability was determined by the uptake of the fluorescent vital dye calcein-AM (n = 6). BAK solutions (diluted 1:10) demonstrated a dose-dependent reduction in cell viability in both cell types (TM and NPCE). With a 1:10 dilution of 0.020% BAK, there were significantly more living NPCE cells (89 ± 6%) than TM cells (57 ± 6%; p < 0.001). In TM cells, travoprost + BAK had statistically fewer live cells (83 ± 5%) than both travoprost + sofZia (97 ± 5%) and travoprost + PQ (97 ± 6%; p < 0.05). Compared with BSS-treated NPCE cells, travoprost had statistically fewer live cells (p < 0.05) when preserved with BAK (85 ± 16%), sofZia (91 ± 6%) or PQ (94 ± 2%). These results demonstrate that substitution of BAK from topical ophthalmic drugs results in greater viability of cultured TM cells, the cells involved in the conventional outflow pathway. Cultured NPCE, responsible for aqueous inflow, appear more resilient to BAK.

  17. The preservative polyquaternium-1 increases cytoxicity and NF-kappaB linked inflammation in human corneal epithelial cells

    Science.gov (United States)

    Paimela, Tuomas; Ryhänen, Tuomas; Kauppinen, Anu; Marttila, Liisa; Salminen, Antero

    2012-01-01

    Purpose In numerous clinical and experimental studies, preservatives present in eye drops have had detrimental effects on ocular epithelial cells. The aim of this study was to compare the cytotoxic and inflammatory effects of the preservative polyquaternium-1 (PQ-1) containing Travatan (travoprost 0.004%) and Systane Ultra eye drops with benzalkonium chloride (BAK) alone or BAK-preserved Xalatan (0.005% latanoprost) eye drops in HCE-2 human corneal epithelial cell culture. Methods HCE-2 cells were exposed to the commercial eye drops Travatan, Systane Ultra, Xalatan, and the preservative BAK. Cell viability was determined using colorimetric MTT (3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by release of lactate dehydrogenase (LDH). Induction of apoptosis was measured with a using a colorimetric caspase-3 assay kit. DNA binding of the nuclear factor kappa B (NF-κB) transcription factor, and productions of the proinflammatory cytokines, interleukins IL-6 and IL-8, were determined using an enzyme-linked immunosorbent assay (ELISA) method. Results Cell viability, as measured by the MTT assay, declined by up to 50% after exposure to Travatan or Systane Ultra solutions which contain 0.001% PQ-1. BAK at 0.02% rather than at 0.001% concentration evoked total cell death signs on HCE-2 cells. In addition, cell membrane permeability, as measured by LDH release, was elevated by sixfold with Travatan and by a maximum threefold with Systane Ultra. Interestingly, Travatan and Systane Ultra activated NF-κB and elevated the secretion of inflammation markers IL-6 by 3 to eightfold and IL-8 by 1.5 to 3.5 fold, respectively, as analyzed with ELISA. Conclusions Eye drops containing PQ-1 evoke cytotoxicity and enhance the NF-κB driven inflammation reaction in cultured HCE-2 cells. Our results indicate that these harmful effects of ocular solutions preserved with PQ-1 should be further evaluated in vitro and in vivo. PMID:22605930

  18. Preservation in the Age of Google: Digitization, Digital Preservation, and Dilemmas

    Science.gov (United States)

    Conway, Paul

    2010-01-01

    The cultural heritage preservation community now functions largely within the environment of digital technologies. This article begins by juxtaposing definitions of the terms "digitization for preservation" and "digital preservation" within a sociotechnical environment for which Google serves as a relevant metaphor. It then reviews two reports…

  19. The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.

    Science.gov (United States)

    Isern, Joan; García-García, Andrés; Martín, Ana M; Arranz, Lorena; Martín-Pérez, Daniel; Torroja, Carlos; Sánchez-Cabo, Fátima; Méndez-Ferrer, Simón

    2014-09-25

    Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin(-) MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin(+) cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP(+) Pdgfrα(-) cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.

  20. Preserving the positive functions of the public domain in science

    Directory of Open Access Journals (Sweden)

    Pamela Samuelson

    2003-11-01

    Full Text Available Science has advanced in part because data and scientific methodologies have traditionally not been subject to intellectual property protection. In recent years, intellectual property has played a greater role in scientific work. While intellectual property rights may have a positive role to play in some fields of science, so does the public domain. This paper will discuss some of the positive functions of the public domain and ways in which certain legal developments may negatively impact the public domain. It suggests some steps that scientists can take to preserve the positive functions of the public domain for science.

  1. The parity-preserving massive QED3: Vanishing β-function and no parity anomaly

    Directory of Open Access Journals (Sweden)

    O.M. Del Cima

    2015-11-01

    Full Text Available The parity-preserving massive QED3 exhibits vanishing gauge coupling β-function and is parity and infrared anomaly free at all orders in perturbation theory. Parity is not an anomalous symmetry, even for the parity-preserving massive QED3, in spite of some claims about the possibility of a perturbative parity breakdown, called parity anomaly. The proof is done by using the algebraic renormalization method, which is independent of any regularization scheme, based on general theorems of perturbative quantum field theory.

  2. Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.

    Science.gov (United States)

    Nieuwoudt, Stephan; Fealy, Ciarán E; Foucher, Julie A; Scelsi, Amanda R; Malin, Steven K; Pagadala, Mangesh; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

    2017-09-01

    Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D. Copyright © 2017 the American Physiological Society.

  3. Robot-assisted pancreatoduodenectomy with preservation of the vascular supply for autologous islet cell isolation and transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Giulianotti Piero

    2012-03-01

    Full Text Available Abstract Introduction For patients with chronic pancreatitis presenting with medically intractable abdominal pain, surgical intervention may be the only treatment option. However, extensive pancreatic resections are typically performed open and are associated with a substantial amount of postoperative pain, wound complications and long recovery time. Minimally invasive surgery offers an avenue to improve results; however, current limitations of laparoscopic surgery render its application in the setting of chronic pancreatitis technically demanding. Additionally, pancreatic resections are associated with a high incidence of diabetes. Transplantation of islets isolated from the resected pancreas portion offers a way to prevent post-surgical diabetes; however, preservation of the vascular supply during pancreatic resection, which determines islet cell viability, is technically difficult using current laparoscopic approaches. With recent advances in the surgical field, robotic surgery now provides a means to overcome these obstacles to achieve the end goals of pain relief and preserved endocrine function. We present the first report of a novel, minimally invasive robotic approach for resection of the pancreatic head that preserves vascular supply and enables the isolation of a high yield of viable islets for transplantation. Case presentation A 35-year old Caucasian woman presented with intractable chronic abdominal pain secondary to chronic pancreatitis, with a stricture of her main pancreatic duct at the level of the ampulla of Vater and distal dilatation. She was offered a robotic-assisted pylorus-preserving pancreatoduodenectomy and subsequent islet transplantation, to both provide pain relief and preserve insulin-secretory reserves. Conclusion We present a novel, minimally invasive robotic approach for resection of the pancreatic head with complete preservation of the vascular supply, minimal warm ischemia time (less than three minutes and

  4. Functional Stem Cell Integration into Neural Networks Assessed by Organotypic Slice Cultures.

    Science.gov (United States)

    Forsberg, David; Thonabulsombat, Charoensri; Jäderstad, Johan; Jäderstad, Linda Maria; Olivius, Petri; Herlenius, Eric

    2017-08-14

    Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host. One option for in vitro studies is to examine the integration of exogenous stem cells into an existing active neural network in ex vivo organotypic cultures. Organotypic cultures leave the structural integrity essentially intact while still allowing the microenvironment to be carefully controlled. This allows detailed studies over time of cellular responses and cell-cell interactions, which are not readily performed in vivo. This unit describes procedures for using organotypic slice cultures as ex vivo model systems for studying neural stem cell and embryonic stem cell engraftment and communication with CNS host tissue. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  5. Morphology and function of dog arterial grafts preserved in UW-solution

    NARCIS (Netherlands)

    Vischjager, M.; van Gulik, T. M.; Pfaffendorf, M.; van Zwieten, P. A.; van Marle, J.; Kromhout, J. G.; Klopper, P. J.; Jacobs, M. J.

    1995-01-01

    To assess the function of arterial grafts after prolonged preservation in the University of Wisconsin solution (UW), in vitro and in vivo. Carotid arteries were harvested from dogs and stored for 1-21 days at 4 degrees C in UW (n = 10) or in PBS (0.9% NaCl, pH 7.4), (PBS) (n = 10). Slices were

  6. Growth and Functionality of Cells Cultured on Conducting and Semi-Conducting Surfaces Modified with Self-Assembled Monolayers (SAMs

    Directory of Open Access Journals (Sweden)

    Rajendra K. Aithal

    2016-02-01

    Full Text Available Bioengineering of dermal and epidermal cells on surface modified substrates is an active area of research. The cytotoxicity, maintenance of cell phenotype and long-term functionality of human dermal fibroblast (HDF cells on conducting indium tin oxide (ITO and semi-conducting, silicon (Si and gallium arsenide (GaAs, surfaces modified with self-assembled monolayers (SAMs containing amino (–NH2 and methyl (–CH3 end groups have been investigated. Contact angle measurements and infrared spectroscopic studies show that the monolayers are conformal and preserve their functional end groups. Morphological analyses indicate that HDFs grow well on all substrates except GaAs, exhibiting their normal spindle-shaped morphology and exhibit no visible signs of stress or cytoplasmic vacuolation. Cell viability analyses indicate little cell death after one week in culture on all substrates except GaAs, where cells died within 6 h. Cells on all surfaces proliferate except on GaAs and GaAs-ODT. Cell growth is observed to be greater on SAM modified ITO and Si-substrates. Preservation of cellular phenotype assessed through type I collagen immunostaining and positive staining of HDF cells were observed on all modified surfaces except that on GaAs. These results suggest that conducting and semi-conducting SAM-modified surfaces support HDF growth and functionality and represent a promising area of bioengineering research.

  7. Concurrent chemoradiotherapy for laryngeal preservation in T1/T2 supraglottic squamous cell carcinoma

    International Nuclear Information System (INIS)

    Rikimaru, Fumihide; Matsuo, Mioko; Taura, Masahiko; Higaki, Yuichiro; Tomita, Kichinobu

    2012-01-01

    We treated supraglottic squamous cell carcinoma (T1/2) with chemoradiation for laryngeal preservation and evaluated the effects of the chemoradiation at the dose of 40 Gy as an intermediate evaluation. To investigate the need for this intermediate evaluation, we retrospectively analyzed 46 patients, 43 men and 3 women aged 49 to 86 years, with supraglottic squamous cell carcinoma (T1/2) treated at our institution from January 1997 to May 2008. Overall and cause-specific three-year survival rates were 65% and 77% in all cases, 67% and 75% in T1, and 65% and 77% in T2. The three-year preservation rate of the larynx was 41% in all cases, 51% in T1, and 35% in T2. In the intermediate evaluation, the complete response rate was 58% in all cases, 77% in T1, and 48% in T2. In the cases of larynx preservation, the recurrence rate of the primary site was not significantly different between those cases who did not achieve complete response in the intermediate evaluation and those who did achieve complete response. (author)

  8. Sub-Microscopic Organization and Functional Properties of Cells Stored in a Bank for Frozen Leucocytes and Platelets

    Energy Technology Data Exchange (ETDEWEB)

    Vinograd-Finkel, F. R.; Terentieva, E. I.; Leontovich, V. A.; Skopina, S. B.; Abezgauz, N. N.; Totskaya, A. A. [Central Institute of Haematology and Blood Transfusion, Moscow, USSR (Russian Federation)

    1969-07-15

    Massive transfusions of leucocyte mass containing young and stem cells in addition to adult cells are carried out successfully in the treatment of patients suffering from depressed haemopoiesis. To meet the needs of clinics a leucocyte mass bank-has been established and methods have been developed for the long-term storage of leucocyte mass by keeping it in the frozen state at -196 Degree-Sign C. Various carrier solutions containing cryoprotective substances (dimethylsulphoxide, glycerine, polyvinyl pyrrolidone) have been proposed. These make it possible to conserve from 70 to 90% of live cells for as long as two years or more. The viability of the frozen cells is proved by supravital staining and luminescent microscopy, and also by determining the extent to which their functional properties are preserved, the phagocytic activity of the granulocytes and the ability of the lymphocytes to produce young forms in tissue culture. It has also been observed that their glycolytic activity is preserved (up to 60%). All these data correlate with the data obtained by electron microscopy regarding the extent to which the sub-microscopic organization of frozen leucocytes is preserved. The bank is also used to store a frozen platelet mass, dimethylsulphoxide being used as the cryoprotective agent. The ultrastructure of the platelets and their functional properties (retractile activity) suffer least impairment. (author)

  9. Vildagliptin preserves the mass and function of pancreatic β cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes

    Science.gov (United States)

    Hamamoto, S; Kanda, Y; Shimoda, M; Tatsumi, F; Kohara, K; Tawaramoto, K; Hashiramoto, M; Kaku, K

    2013-01-01

    Aim We investigated the molecular mechanisms by which vildagliptin preserved pancreatic β cell mass and function. Methods Morphological, biochemical and gene expression profiles of the pancreatic islets were investigated in male KK-Ay-TaJcl(KK-Ay) and C57BL/6JJcl (B6) mice aged 8 weeks which received either vildagliptin or a vehicle for 4 weeks. Results Body weight, food intake, fasting blood glucose, plasma insulin and active glucagon-like peptide-1 were unchanged with vildagliptin treatment in both mice. In KK-Ay mice treated with vildagliptin, increased plasma triglyceride (TG) level and islet TG content were decreased, insulin sensitivity significantly improved, and the glucose tolerance ameliorated with increases in plasma insulin levels. Furthermore, vildagliptin increased glucose-stimulated insulin secretion, islet insulin content and pancreatic β cell mass in both strains. By vildagliptin, the expression of genes involved in cell differentiation/proliferation was upregulated in both strains, those related to apoptosis, endoplasmic reticulum stress and lipid synthesis was decreased and those related to anti-apoptosis and anti-oxidative stress was upregulated, in KK-Ay mice. The morphological results were consistent with the gene expression profiles. Conclusion Vildagliptin increases β cell mass by not only directly affecting cell kinetics but also by indirectly reducing cell apoptosis, oxidative stress and endoplasmic reticulum stress in diabetic mice. PMID:22950702

  10. Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway.

    Science.gov (United States)

    Liu, Haiyan; Javaheri, Ali; Godar, Rebecca J; Murphy, John; Ma, Xiucui; Rohatgi, Nidhi; Mahadevan, Jana; Hyrc, Krzysztof; Saftig, Paul; Marshall, Connie; McDaniel, Michael L; Remedi, Maria S; Razani, Babak; Urano, Fumihiko; Diwan, Abhinav

    2017-01-01

    Obesity-induced diabetes is characterized by hyperglycemia, insulin resistance, and progressive beta cell failure. In islets of mice with obesity-induced diabetes, we observe increased beta cell death and impaired autophagic flux. We hypothesized that intermittent fasting, a clinically sustainable therapeutic strategy, stimulates autophagic flux to ameliorate obesity-induced diabetes. Our data show that despite continued high-fat intake, intermittent fasting restores autophagic flux in islets and improves glucose tolerance by enhancing glucose-stimulated insulin secretion, beta cell survival, and nuclear expression of NEUROG3, a marker of pancreatic regeneration. In contrast, intermittent fasting does not rescue beta-cell death or induce NEUROG3 expression in obese mice with lysosomal dysfunction secondary to deficiency of the lysosomal membrane protein, LAMP2 or haplo-insufficiency of BECN1/Beclin 1, a protein critical for autophagosome formation. Moreover, intermittent fasting is sufficient to provoke beta cell death in nonobese lamp2 null mice, attesting to a critical role for lysosome function in beta cell homeostasis under fasting conditions. Beta cells in intermittently-fasted LAMP2- or BECN1-deficient mice exhibit markers of autophagic failure with accumulation of damaged mitochondria and upregulation of oxidative stress. Thus, intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes.

  11. Male fertility preservation before gonadotoxic therapies.

    Science.gov (United States)

    Wyns, C

    2010-01-01

    Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, radiotherapy and preparative regimens for bone marrow transplantation can severely affect male germ cells, including spermatogonial stem cells (SSCs), and lead to permanent loss of fertility. Different options for fertility preservation are dependent on the pubertal state of the patient. Relevant studies were identified by an extensive Medline search of English and French language articles. Sperm cryopreservation prior to gonadotoxic treatment is a well established method after puberty. In case of ejaculation failure by masturbation, assisted ejaculation methods or testicular tissue sampling should be considered. Although no effective gonadoprotective drug is yet available for in vivo spermatogonial stem cell (SSC) protection in humans, current evidence supports the feasibility of immature testicular tissue (ITT) cryopreservation. The different cryopreservation protocols and available fertility restoration options from frozen tissue, i.e. cell suspension transplantation, tissue grafting and in vitro maturation, are presented. RESULTS obtained in humans are discussed in the light of lessons learned from animal studies. Advances in reproductive technology have made fertility preservation a real possibility in young patients whose gonadal function is threatened by gonadotoxic therapies. The putative indications for such techniques, as well as their limitations according to disease, are outlined.

  12. Development of a living membrane comprising of a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane

    NARCIS (Netherlands)

    Schophuizen, C.M.S.; De Napoli, Ilaria; Jansen, J.; Da Silva Teixeira, Sandra; Wilmer, M.; Hoenderop, J.G.; van den Heuvel, L.P.W.; Masereeuw, R.; Stamatialis, Dimitrios

    2015-01-01

    The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a “living membrane”, consisting of a tight kidney cell monolayer with preserved functional organic ion

  13. Blood cell mRNAs and microRNAs: optimized protocols for extraction and preservation.

    Science.gov (United States)

    Eikmans, Michael; Rekers, Niels V; Anholts, Jacqueline D H; Heidt, Sebastiaan; Claas, Frans H J

    2013-03-14

    Assessing messenger RNA (mRNA) and microRNA levels in peripheral blood cells may complement conventional parameters in clinical practice. Working with small, precious samples requires optimal RNA yields and minimal RNA degradation. Several procedures for RNA extraction and complementary DNA (cDNA) synthesis were compared for their efficiency. The effect on RNA quality of freeze-thawing peripheral blood cells and storage in preserving reagents was investigated. In terms of RNA yield and convenience, quality quantitative polymerase chain reaction signals per nanogram of total RNA and using NucleoSpin and mirVana columns is preferable. The SuperScript III protocol results in the highest cDNA yields. During conventional procedures of storing peripheral blood cells at -180°C and thawing them thereafter, RNA integrity is maintained. TRIzol preserves RNA in cells stored at -20°C. Detection of mRNA levels significantly decreases in degraded RNA samples, whereas microRNA molecules remain relatively stable. When standardized to reference targets, mRNA transcripts and microRNAs can be reliably quantified in moderately degraded (quality index 4-7) and severely degraded (quality index <4) RNA samples, respectively. We describe a strategy for obtaining high-quality and quantity RNA from fresh and stored cells from blood. The results serve as a guideline for sensitive mRNA and microRNA expression assessment in clinical material.

  14. [Clinical characteristics and medium-term prognosis of patients with heart failure and preserved systolic function. Do they differ in systolic dysfunction?].

    Science.gov (United States)

    Ojeda, Soledad; Anguita, Manuel; Muñoz, Juan F; Rodríguez, Marcos T; Mesa, Dolores; Franco, Manuel; Ureña, Isabel; Vallés, Federico

    2003-11-01

    To assess the prevalence, clinical profile and medium-term prognosis in patients with heart failure and preserved systolic ventricular function compared to those with systolic dysfunction. 153 patients were included, 62 with preserved systolic ventricular function (left ventricular ejection fraction > or = 45%) and 91 with impaired systolic ventricular function (left ventricular ejection fraction < 45%). The mean follow-up period was 25 10 months. Mean age was similar (66 10 vs. 65 10; p = 0.54). There was a higher proportion of women among patients with preserved systolic function (53% vs. 28%; p < 0.01). Ischemic and idiopathic cardiomyopathy were the most common causes of heart failure in patients with systolic dysfunction, whereas valvular disease and hypertensive cardiopathy were the most common in patients with preserved systolic function. Angiotensin-converting enzyme inhibitors and beta-blockers were more often prescribed in patients with impaired systolic ventricular function (86% vs. 52%; p < 0.01 and 33% vs. 11%; p < 0.01, respectively). There were no differences between the groups in terms of mortality rate (37% vs. 29%), readmission rate for other causes (29% vs. 23%), readmission rate for heart failure (45% vs. 45%), cumulative survival (51% vs. 62%) and the likelihood of not being readmitted for heart failure (50% vs. 52%). In the multivariate analysis, left ventricular ejection fraction was not a predictor of death or readmission because of heart failure. In a large proportion of patients with heart failure, systolic ventricular function is preserved. Despite the clinical differences between patients with preserved and impaired systolic ventricular function, the medium-term prognosis was similar in both groups.

  15. Hormonal, metabolic and cardiovascular responses to hypoglycaemia in Type 1 (insulin-dependent) diabetes with and without residual B cell function

    DEFF Research Database (Denmark)

    Madsbad, S; Hilsted, J; Krarup, T

    1982-01-01

    Hormonal, metabolic and cardiovascular responses to insulin induced hypoglycaemia were investigated in seven Type 1 (insulin-dependent) diabetic patients with residual B cell function, eight Type 1 diabetic patients without B cell function and six healthy subjects. No differences were found between...... the diabetic groups regarding nadir of glucose and rate of recovery to normoglycaemia. The patients with residual B cell function had a glucagon response to hypoglycaemia which was close to that of normal subjects. In patients without B cell function, the glucagon response to hypoglycaemia was present, albeit...... significantly smaller than in the patients with preserved B cell function (0.025 ng/ml, range 0.007-0.042 versus 0.054 ng/ml, range 0.029-0.087). The group without B cell function had signs of an exaggerated rate of lipolysis and ketogenesis compared with the patients with B cell function and the normal...

  16. Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice is Critical for Development and Function of Human T and B Cells

    Science.gov (United States)

    2011-05-17

    class switch was preserved in DRAG mice. The human identity of Ig heavy and Figure 4. Human T cells developed by DRAG mice are functional. At 6 months...HSC-infused DRAG and control mice were immunized with 1 flocculation unit of TT vaccine (Sanofi Pasteur ) by the intramuscular route, and the titers...and CD8 T cells with preserved integrity of both TCR and non-TCR signaling pathways. It has been suggested that low frequency and functional

  17. Emergency Pancreatoduodenectomy with Preservation of Gastroduodenal Artery for Massive Gastrointestinal Bleeding due to Duodenal Metastasis by Clear Cell Renal Cell Carcinoma in a Patient with Celiac Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Kyriakos Neofytou

    2014-01-01

    Full Text Available Duodenal metastasis from renal cell carcinoma is rare, and even rarer is a massive gastrointestinal bleeding from such tumours. Coeliac occlusive disease, although rarely symptomatic, can lead to ischaemic changes with anastomotic dehiscence and leaks when a patient undergoes pancreatoduodenectomy. A 41-year-old man with known metastasis to the adrenal glands and the second part of the duodenum close to the ampulla of Vater from clear cell renal cell carcinoma was admitted to our department due to massive gastrointestinal bleeding from the duodenal metastasis. Endoscopic control of the bleed was not possible, while the bleeding vessel embolization was able to control the haemorrhage only temporarily. An angiography during the embolization demonstrated the presence of stenosis of the coeliac artery and also hypertrophic inferior pancreaticoduodenal arteries supplying the proper hepatic artery via the gastroduodenal artery (GDA. The patient underwent emergency pancreatoduodenectomy with preservation of the gastroduodenal artery. The patient had an uneventful recovery and did not experience further bleeding. Also the blood flow to the liver was compromised as shown by the normal liver function tests (LFTs postoperatively. To the best of our knowledge, this is the first report of a preservation of the GDA during an emergency pancreatoduodenectomy.

  18. Strain preservation of experimental animals: vitrification of two-cell stage embryos for multiple mouse strains.

    Science.gov (United States)

    Eto, Tomoo; Takahashi, Riichi; Kamisako, Tsutomu

    2015-04-01

    Strain preservation of experimental animals is crucial for experimental reproducibility. Maintaining complete animal strains, however, is costly and there is a risk for genetic mutations as well as complete loss due to disasters or illness. Therefore, the development of effective vitrification techniques for cryopreservation of multiple experimental animal strains is important. We examined whether a vitrification method using cryoprotectant solutions, P10 and PEPeS, is suitable for preservation of multiple inbred and outbred mouse strains. First, we investigated whether our vitrification method using cryoprotectant solutions was suitable for two-cell stage mouse embryos. In vitro development of embryos exposed to the cryoprotectant solutions was similar to that of fresh controls. Further, the survival rate of the vitrified embryos was extremely high (98.1%). Next, we collected and vitrified two-cell stage embryos of 14 mouse strains. The average number of embryos obtained from one female was 7.3-33.3. The survival rate of vitrified embryos ranged from 92.8% to 99.1%, with no significant differences among mouse strains. In vivo development did not differ significantly between fresh controls and vitrified embryos of each strain. For strain preservation using cryopreserved embryos, two offspring for inbred lines and one offspring for outbred lines must be produced from two-cell stage embryos collected from one female. The expected number of surviving fetuses obtained from embryos collected from one female of either the inbred or outbred strains ranged from 2.9 to 19.5. The findings of the present study indicated that this vitrification method is suitable for strain preservation of multiple mouse strains. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. The importance of phrenic nerve preservation and its effect on long-term postoperative lung function after pneumonectomy.

    Science.gov (United States)

    Kocher, Gregor J; Poulson, Jannie Lysgaard; Blichfeldt-Eckhardt, Morten Rune; Elle, Bo; Schmid, Ralph A; Licht, Peter B

    2016-04-01

    The importance of phrenic nerve preservation during pneumonectomy remains controversial. We previously demonstrated that preservation of the phrenic nerve in the immediate postoperative period preserved lung function by 3-5% but little is known about its long-term effects. We, therefore, decided to investigate the effect of temporary ipsilateral cervical phrenic nerve block on dynamic lung volumes in mid- to long-term pneumonectomy patients. We investigated 14 patients after a median of 9 years post pneumonectomy (range: 1-15 years). Lung function testing (spirometry) and fluoroscopic and/or sonographic assessment of diaphragmatic motion on the pneumonectomy side were performed before and after ultrasonographic-guided ipsilateral cervical phrenic nerve block by infiltration with lidocaine. Ipsilateral phrenic nerve block was successfully achieved in 12 patients (86%). In the remaining 2 patients, diaphragmatic motion was already paradoxical before the nerve block. We found no significant difference on dynamic lung function values (FEV1 'before' 1.39 ± 0.44 vs FEV1 'after' 1.38 ± 0.40; P = 0.81). Induction of a temporary diaphragmatic palsy did not significantly influence dynamic lung volumes in mid- to long-term pneumonectomy patients, suggesting that preservation of the phrenic nerve is of greater importance in the immediate postoperative period after pneumonectomy. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  20. Ureterocystoplasty using the lower pole ureter of a duplex kidney with preservation of ipsilateral renal function

    OpenAIRE

    John Lazarus

    2012-01-01

    We describe the case of a 9 year old boy with neurogenic bladder dysfunction who co-incidentally had a unilateral duplex kidney with Grade 5 vesico-ureteric reflux into a poorly functioning lower moiety allowing heminephrectomy and ureterocystoplasty with preservation of ipsilateral renal function.

  1. How preservation time changes the linear viscoelastic properties of porcine liver.

    Science.gov (United States)

    Wex, C; Stoll, A; Fröhlich, M; Arndt, S; Lippert, H

    2013-01-01

    The preservation time of a liver graft is one of the crucial factors for the success of a liver transplantation. Grafts are kept in a preservation solution to delay cell destruction and cellular edema and to maximize organ function after transplantation. However, longer preservation times are not always avoidable. In this paper we focus on the mechanical changes of porcine liver with increasing preservation time, in order to establish an indicator for the quality of a liver graft dependent on preservation time. A time interval of 26 h was covered and the rheological properties of liver tissue studied using a stress-controlled rheometer. For samples of 1 h preservation time 0.8% strain was found as the limit of linear viscoelasticity. With increasing preservation time a decrease in the complex shear modulus as an indicator for stiffness was observed for the frequency range from 0.1 to 10 Hz. A simple fractional derivative representation of the Kelvin Voigt model was applied to gain further information about the changes of the mechanical properties of liver with increasing preservation time. Within the small shear rate interval of 0.0001-0.01 s⁻¹ the liver showed Newtonian-like flow behavior.

  2. Subretinal electrical stimulation preserves inner retinal function in RCS rat retina.

    Science.gov (United States)

    Ciavatta, Vincent T; Mocko, Julie A; Kim, Moon K; Pardue, Machelle T

    2013-01-01

    did not increase with IR light. The larger post-receptoral responses (Vmax), greater post-receptoral sensitivity (logσ), and larger oscillatory potentials suggest SES-treated eyes maintained better inner retinal function than the opposite, untreated eyes. This suggests that in addition to preserving photoreceptors in RCS rats, SES may also promote more robust signal transmission through the retinal network compared to the control eyes. These studies suggest that the protective effects of SES on RCS retinal function cannot be improved with additional subretinal current induction from the MPA, or the charge injection provided by ERG Ganzfeld flashes was not adequately mimicked by the flashing IR light used in this study.

  3. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    Science.gov (United States)

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge. © 2014 The Authors. The Journal of Physiology © 2014

  4. Preserving and using germplasm and dissociated embryonic cells for conserving Caribbean and Pacific coral.

    Science.gov (United States)

    Hagedorn, Mary; Carter, Virginia; Martorana, Kelly; Paresa, Malia K; Acker, Jason; Baums, Iliana B; Borneman, Eric; Brittsan, Michael; Byers, Michael; Henley, Michael; Laterveer, Michael; Leong, Jo-Ann; McCarthy, Megan; Meyers, Stuart; Nelson, Brian D; Petersen, Dirk; Tiersch, Terrence; Uribe, Rafael Cuevas; Woods, Erik; Wildt, David

    2012-01-01

    Coral reefs are experiencing unprecedented degradation due to human activities, and protecting specific reef habitats may not stop this decline, because the most serious threats are global (i.e., climate change), not local. However, ex situ preservation practices can provide safeguards for coral reef conservation. Specifically, modern advances in cryobiology and genome banking could secure existing species and genetic diversity until genotypes can be introduced into rehabilitated habitats. We assessed the feasibility of recovering viable sperm and embryonic cells post-thaw from two coral species, Acropora palmata and Fungia scutaria that have diffferent evolutionary histories, ecological niches and reproductive strategies. In vitro fertilization (IVF) of conspecific eggs using fresh (control) spermatozoa revealed high levels of fertilization (>90% in A. palmata; >84% in F. scutaria; P>0.05) that were unaffected by tested sperm concentrations. A solution of 10% dimethyl sulfoxide (DMSO) at cooling rates of 20 to 30°C/min most successfully cryopreserved both A. palmata and F. scutaria spermatozoa and allowed producing developing larvae in vitro. IVF success under these conditions was 65% in A. palmata and 53% in F. scutaria on particular nights; however, on subsequent nights, the same process resulted in little or no IVF success. Thus, the window for optimal freezing of high quality spermatozoa was short (∼5 h for one night each spawning cycle). Additionally, cryopreserved F. scutaria embryonic cells had∼50% post-thaw viability as measured by intact membranes. Thus, despite some differences between species, coral spermatozoa and embryonic cells are viable after low temperature (-196°C) storage, preservation and thawing. Based on these results, we have begun systematically banking coral spermatozoa and embryonic cells on a large-scale as a support approach for preserving existing bio- and genetic diversity found in reef systems.

  5. Preserving and using germplasm and dissociated embryonic cells for conserving Caribbean and Pacific coral.

    Directory of Open Access Journals (Sweden)

    Mary Hagedorn

    Full Text Available Coral reefs are experiencing unprecedented degradation due to human activities, and protecting specific reef habitats may not stop this decline, because the most serious threats are global (i.e., climate change, not local. However, ex situ preservation practices can provide safeguards for coral reef conservation. Specifically, modern advances in cryobiology and genome banking could secure existing species and genetic diversity until genotypes can be introduced into rehabilitated habitats. We assessed the feasibility of recovering viable sperm and embryonic cells post-thaw from two coral species, Acropora palmata and Fungia scutaria that have diffferent evolutionary histories, ecological niches and reproductive strategies. In vitro fertilization (IVF of conspecific eggs using fresh (control spermatozoa revealed high levels of fertilization (>90% in A. palmata; >84% in F. scutaria; P>0.05 that were unaffected by tested sperm concentrations. A solution of 10% dimethyl sulfoxide (DMSO at cooling rates of 20 to 30°C/min most successfully cryopreserved both A. palmata and F. scutaria spermatozoa and allowed producing developing larvae in vitro. IVF success under these conditions was 65% in A. palmata and 53% in F. scutaria on particular nights; however, on subsequent nights, the same process resulted in little or no IVF success. Thus, the window for optimal freezing of high quality spermatozoa was short (∼5 h for one night each spawning cycle. Additionally, cryopreserved F. scutaria embryonic cells had∼50% post-thaw viability as measured by intact membranes. Thus, despite some differences between species, coral spermatozoa and embryonic cells are viable after low temperature (-196°C storage, preservation and thawing. Based on these results, we have begun systematically banking coral spermatozoa and embryonic cells on a large-scale as a support approach for preserving existing bio- and genetic diversity found in reef systems.

  6. Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice.

    Science.gov (United States)

    Sapieha, P; Chen, J; Stahl, A; Seaward, M R; Favazza, T L; Juan, A M; Hatton, C J; Joyal, J-S; Krah, N M; Dennison, R J; Tang, J; Kern, T S; Akula, J D; Smith, L E H

    2012-07-23

    Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ω-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks-26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ω-3 or ω-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. The ω-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ω-6PUFA-rich diet. There was also an enhanced ability of ω-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ω-3PUFAs. This study identifies beneficial effects of dietary ω-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ω-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ω-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM.

  7. Ant brood function as life preservers during floods.

    Directory of Open Access Journals (Sweden)

    Jessica Purcell

    Full Text Available Social organisms can surmount many ecological challenges by working collectively. An impressive example of such collective behavior occurs when ants physically link together into floating 'rafts' to escape from flooded habitat. However, raft formation may represent a social dilemma, with some positions posing greater individual risks than others. Here, we investigate the position and function of different colony members, and the costs and benefits of this functional geometry in rafts of the floodplain-dwelling ant Formica selysi. By causing groups of ants to raft in the laboratory, we observe that workers are distributed throughout the raft, queens are always in the center, and 100% of brood items are placed on the base. Through a series of experiments, we show that workers and brood are extremely resistant to submersion. Both workers and brood exhibit high survival rates after they have rafted, suggesting that occupying the base of the raft is not as costly as expected. The placement of all brood on the base of one cohesive raft confers several benefits: it preserves colony integrity, takes advantage of brood buoyancy, and increases the proportion of workers that immediately recover after rafting.

  8. P7C3 Neuroprotective Chemicals Block Axonal Degeneration and Preserve Function after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Terry C. Yin

    2014-09-01

    Full Text Available The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in a rodent model of blast-mediated traumatic brain injury (TBI. This protective quality may be linked to the ability of P7C3 molecules to activate nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in nicotinamide adenine dinucleotide salvage. Initiation of daily treatment with our recently reported lead agent, P7C3-S243, 1 day after blast-mediated TBI blocks axonal degeneration and preserves normal synaptic activity, learning and memory, and motor coordination in mice. We additionally report persistent neurologic deficits and acquisition of an anxiety-like phenotype in untreated animals 8 months after blast exposure. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both, such as occurs in TBI.

  9. A comparison of methods of determining the 100 percent survival of preserved red cells

    International Nuclear Information System (INIS)

    Valeri, C.R.; Pivacek, L.E.; Ouellet, R.; Gray, A.

    1984-01-01

    Studies were done to compare three methods to determine the 100 percent survival value from which to estimate the 24-hour posttransfusion survival of preserved red cells. The following methods using small aliquots of 51 Cr-labeled autologous preserved red cells were evaluated: First, the 125 I-albumin method, which is an indirect measurement of the recipient's red cell volume derived from the plasma volume measured using 125 I-labeled albumin and the total body hematocrit. Second, the body surface area method (BSA) in which the recipient's red cell volume is derived from a body surface area nomogram. Third, an extrapolation method, which extrapolates to zero time the radioactivity associated with the red cells in the recipient's circulation from 10 to 20 or 15 to 30 minutes after transfusion. The three methods gave similar results in all studies in which less than 20 percent of the transfused red cells were nonviable (24-hour posttransfusion survival values of between 80-100%), but not when more than 20 percent of the red cells were nonviable. When 21 to 35 percent of the transfused red cells were nonviable (24-hour posttransfusion survivals of 65 to 79%), values with the 125 I-albumin method and the body surface area method were about 5 percent lower (p less than 0.001) than values with the extrapolation method. When greater than 35 percent of the red cells were nonviable (24-hour posttransfusion survival values of less than 65%), values with the 125 I-albumin method and the body surface area method were about 10 percent lower (p less than 0.001) than those obtained by the extrapolation method

  10. Stabilization Of Apoptotic Cells: Generation Of Zombie Cells

    Directory of Open Access Journals (Sweden)

    José A. Sánchez Alcázar

    2015-08-01

    Stabilization of apoptotic cells can be used for reliable detection and quantification of apoptosis in cultured cells and may allow a safer administration of apoptotic cells in clinical applications. Furthermore, it opens new avenues in the functional reconstruction of apoptotic cells for longer preservation.

  11. Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease

    DEFF Research Database (Denmark)

    Hoffmann, Kristine; Frederiksen, Kristian S; Sobol, Nanna Aue

    2013-01-01

    ('Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: the Effect of Physical Exercise') trial is to establish whether aerobic exercise is effective in improving cognition as well as in reducing the prevalence of psychiatric symptoms among patients......Exercise is hypothesized to improve cognition, physical performance, functional ability and quality of life, but evidence is scarce. Previous studies were of short duration, often underpowered and involving home-based light exercise programs in patients with undefined dementia. The aim of the ADEX...

  12. Pulmonary preservation studies: effects on endothelial function and pulmonary adenine nucleotides.

    Science.gov (United States)

    Paik, Hyo Chae; Hoffmann, Steven C; Egan, Thomas M

    2003-02-27

    Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-flushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular.

  13. Late follow-up of patients submitted to subtotal splenectomy: late clinical, laboratory, imaging and functional with preservation of the upper splenic pole

    Directory of Open Access Journals (Sweden)

    Andy Petroianu

    2008-09-01

    Full Text Available objective: To evaluate the follow-up of patients submitted to splenectomy with preservation of the upper splenic pole. Methods: All patients undergoing subtotal splenectomy were invited to be reviewed. A total of 86 patients submitted to this surgery were studied. The procedure was performed due to one of the following conditions: portal hypertension due to schistosomiasis (n = 43, trauma (n = 31, Gaucher’s disease (n = 4, myeloid hepatosplenomegaly due to myelofibrosis (n = 3, splenomegalic retarded growth and sexual development (n = 2, severe pain due to splenic ischemia (n = 2 and pancreatic cystadenoma (n = 1. All patients underwent hematologic tests, immunological assessment, abdominal ultrasonography, computed tomography (CT, scintigraphy and endoscopy. Rresults: Increased white blood cell and platelet counts were the only hematological abnormalities. No immune deficit was found. Esophageal varices were still present in patients who underwent surgery because of portal hypertension, but none had a re-bleeding event. The ultrasonography, tomography and scintigraphy confirmed the presence of functional splenic remnants without significant size alteration. Conclusions: Subtotal splenectomy seems to be a safe procedure that can be useful to treat conditions involving the spleen. The functions of the splenic remnants are preserved during long periods of time.

  14. Good Preservation of Stromal Cells and No Apoptosis in Human Ovarian Tissue after Vitrification

    Directory of Open Access Journals (Sweden)

    Raffaella Fabbri

    2014-01-01

    Full Text Available The aim of this study was to develop a vitrification procedure for human ovarian tissue cryopreservation in order to better preserve the ovarian tissue. Large size samples of ovarian tissue retrieved from 15 female-to-male transgender subjects (18–38 years were vitrified using two solutions (containing propylene glycol, ethylene glycol, and sucrose at different concentrations in an open system. Light microscopy, transmission electron microscopy, and TUNEL assay were applied to evaluate the efficiency of the vitrification protocol. After vitrification/warming, light microscopy showed oocyte nucleus with slightly thickened chromatin and irregular shape, while granulosa and stromal cells appeared well preserved. Transmission electron microscopy showed oocytes with slightly irregular nuclear shape and finely dispersed chromatin. Clear vacuoles and alterations in cellular organelles were seen in the oocyte cytoplasm. Stromal cells had a moderately dispersed chromatin and homogeneous cytoplasm with slight vacuolization. TUNEL assay revealed the lack of apoptosis induction by vitrification in all ovarian cell types. In conclusion after vitrification/warming the stromal compartment maintained morphological and ultrastructural features similar to fresh tissue, while the oocyte cytoplasm was slightly damaged. Although these data are encouraging, further studies are necessary and essential to optimize vitrification procedure.

  15. Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration

    Energy Technology Data Exchange (ETDEWEB)

    Sheard, Michael A., E-mail: msheard@chla.usc.edu [Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology-Oncology, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Ghent, Matthew V., E-mail: mattghent@gmail.com [Department of Pathology, Keck School of Medicine, University of Southern California, Health Sciences Campus, Los Angeles, CA 90089 (United States); Cabral, Daniel J., E-mail: dcabral14@gmail.com [Cancer Center and Departments of Cell Biology & Biochemistry, Pharmacology & Neuroscience, Internal Medicine and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 (United States); Lee, Joanne C., E-mail: joannebarnhart@gmail.com [Cancer Center and Departments of Cell Biology & Biochemistry, Pharmacology & Neuroscience, Internal Medicine and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 (United States); Khankaldyyan, Vazgen, E-mail: khangaldian@yahoo.com [Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology-Oncology, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Ji, Lingyun, E-mail: lingyun.ji@med.usc.edu [Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology-Oncology, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Wu, Samuel Q., E-mail: swu@chla.usc.edu [Medical Genetics, Children' s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States); Kang, Min H., E-mail: min.kang@ttuhsc.edu [Cancer Center and Departments of Cell Biology & Biochemistry, Pharmacology & Neuroscience, Internal Medicine and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 (United States); and others

    2015-05-15

    Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival, expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. - Highlights: • Establishing new ALL cell lines in 5% oxygen resulted in higher glycolytic expression and function. • Establishing new ALL cell lines in 5% oxygen resulted in higher proliferation and lower cell death. • The divergent metabolic phenotypes selected in 5% and 20% oxygen are semi-permanent.

  16. Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration

    International Nuclear Information System (INIS)

    Sheard, Michael A.; Ghent, Matthew V.; Cabral, Daniel J.; Lee, Joanne C.; Khankaldyyan, Vazgen; Ji, Lingyun; Wu, Samuel Q.; Kang, Min H.

    2015-01-01

    Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival, expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. - Highlights: • Establishing new ALL cell lines in 5% oxygen resulted in higher glycolytic expression and function. • Establishing new ALL cell lines in 5% oxygen resulted in higher proliferation and lower cell death. • The divergent metabolic phenotypes selected in 5% and 20% oxygen are semi-permanent

  17. Prediction of preservative sensitization potential using surface marker CD86 and/or CD54 expression on human cell line, THP-1.

    Science.gov (United States)

    Sakaguchi, Hitoshi; Miyazawa, Masaaki; Yoshida, Yukiko; Ito, Yuichi; Suzuki, Hiroyuki

    2007-02-01

    Preservatives are important components in many products, but have a history of purported allergy. Several assays [e.g., guinea pig maximization test (GPMT), local lymph node assay (LLNA)] are used to evaluate allergy potential of preservatives. We recently developed the human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test using human THP-1 cells. This test evaluates the augmentation of CD86 and CD54 expression, which are key events in the sensitization process, as an indicator of allergy following treatment with test chemical. Earlier, we found that a sub-toxic concentration was needed for the up-regulation of surface marker expression. In this study, we further evaluate the capability of h-CLAT to predict allergy potential using eight preservatives. Cytotoxicity was determined using propidium iodide with flow cytometry analysis and five doses that produce a 95, 85, 75, 65, and 50% cell viability were selected. If a material did not have any cytotoxicity at the highest technical dose (HTD), five doses are set using serial 1.3 dilutions of the HTD. The test materials used were six known allergic preservatives (e.g., methylchloroisothiazolinone/methylisothiazolinone, formaldehyde), and two non-allergic preservatives (methylparaben and 4-hydroxybenzoic acid). All allergic preservatives augmented CD86 and/or CD54 expression, indicating h-CLAT correctly identified the allergens. No augmentation was observed with the non-allergic preservatives; also correctly identified by h-CLAT. In addition, we report two threshold concentrations that may be used to categorize skin sensitization potency like the LLNA estimated concentration that yield a three-fold stimulation (EC3) value. These corresponding values are the estimated concentration which gives a relative fluorescence intensity (RFI) = 150 for CD86 and an RFI = 200 for CD54. These data suggest that h-CLAT, using THP-1 cells, may be able to predict the allergy potential of preservatives and

  18. Blockade of Inflammation and Apoptosis Pathways by siRNA Prolongs Cold Preservation Time and Protects Donor Hearts in a Porcine Model

    Directory of Open Access Journals (Sweden)

    Jia Wei

    2017-12-01

    Full Text Available In donor hearts from mini pigs, overtime cold preservation and ischemia-reperfusion injury cause poor graft quality and impaired heart function. Blockage of complement, apoptosis, and inflammation is considered a strategy for attenuating ischemia-reperfusion injury and protecting cardiac function. Minipig donor hearts were perfused and preserved in Celsior solution or transfection reagent containing Celsior solution with scramble siRNA or siRNAs targeting complement 3, caspase-8, caspase-3, and nuclear factor κB-p65 genes at 4°C and subsequently hemo-reperfused ex vivo (38°C or transplanted into recipients. The protective effect of the siRNA solution was evaluated by measuring cell apoptosis, structural alteration, protein markers for tissue damage and oxidative stress, and cardiac function. We found a reduction in cell apoptosis, myocardial damage, and tissue inflammation by reduced biochemistry and markers and protein expression of proinflammatory cytokines and improvement in cardiac function, as shown by the improved hemodynamic indices in 12-hr-preserved siRNA-treated hearts of both ex vivo and orthotopic transplantation models. These findings demonstrate that blockade of inflammation and apoptosis pathways using siRNA can prolong cold preservation time and better protect donor heart function in cardiac transplantation of large animals, which may be beneficial for human heart preservation.

  19. Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries.

    Directory of Open Access Journals (Sweden)

    Jiaqiang Xiong

    Full Text Available Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx. For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now. In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes. Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs. Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs, and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.

  20. Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries.

    Science.gov (United States)

    Xiong, Jiaqiang; Lu, Zhiyong; Wu, Meng; Zhang, Jinjin; Cheng, Jing; Luo, Aiyue; Shen, Wei; Fang, Li; Zhou, Su; Wang, Shixuan

    2015-01-01

    Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above methods are subject to their scope (females with no husband or prepubertal females with no mature oocytes). Thus, many females who suffer from cancers would not adopt the above methods pre- and post-CTx due to their uncertainty, safety and cost-effectiveness. Therefore, millions of women have achieved long-term survival after thorough CTx treatment and have desired to rescue their ovarian function and fertility with economic, durable and reliable methods. Recently, some studies showed that mice with infertility caused by CTx can produce normal offspring through intraovarian injection of exogenous female germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice without immune rejection in the same strain, it is difficult to obtain human female germline stem cells (hFGSCs), and immune rejection could occur between different individuals. In this study, infertility in mice was caused by CTx, and the ability of FGSCs to restore ovarian function or even produce offspring was assessed. We had successfully isolated and purified the FGSCs from adult female mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were transplanted into ovaries of mice with infertility caused by CTx. Finally, ovarian function was restored and the recipients produced offspring long-term. These findings showed that mice with CTx possessed FGSCs, restoring ovarian function and avoiding immune rejection from exogenous germline stem cells.

  1. Preservation of parotid function with uncomplicated conformal radiotherapy

    International Nuclear Information System (INIS)

    Maes, Annelies; Weltens, Caroline; Flamen, Patrick; Lambin, Philippe; Bogaerts, Ria; Liu, Xuan; Baetens, Jan; Hermans, Robert; Van den Bogaert, Walter

    2002-01-01

    Background and purpose: To evaluate (1) parotid function, (2) subjective xerostomia and (3) pattern of relapses after conformal parotid-sparing radiotherapy (RT) for head and neck cancer. (4) To study dose-response curves of parotid glands. Material and methods: From September 1999 to November 2000, 39 head and neck cancer patients requiring bilateral neck RT were treated with a fairly simple conformal RT technique (three-field set-up+anterior lower neck field; two opposed oblique boost fields). The contralateral parotid was spared. Parotid function was assessed by salivary gland scintigraphies performed before, early (median 4 weeks) and late (median 28 weeks) after RT. Xerostomia was monitored by visual analogue scales (VAS) and LENT SOMA scores. Location of locoregional recurrences was studied in relation to the radiation fields. A dose-response curve of parotids was created using logistic regression. Results: (1) Early after RT, on salivary gland scintigraphy, the mean loss of secretion function in the spared parotid was 67% and total in the non-spared. Late after RT, the mean loss remained 19% in the spared and total in the non-spared parotid. Normal excretion function was regained in 75% of the spared parotids. (2) Late after RT, 78% of patients had no, minimal or acceptable subjective xerostomia. (3) No recurrence was seen near the spared parotid (11/39 locoregional recurrences). (4) The dose-response curve of parotids showed that the mean parotid dose should preferentially be ≤20 Gy, to obtain a good chance (≥70%) for preservation of its function on scintigraphy. Conclusions: An easy conformal parotid-sparing RT technique prevents moderate or severe subjective xerostomia in 78% of patients. In the spared parotids, nearly complete to complete recovery is obtained after 6-12 months

  2. PRMT7 Preserves Satellite Cell Regenerative Capacity

    Directory of Open Access Journals (Sweden)

    Roméo Sébastien Blanc

    2016-02-01

    Full Text Available Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells, which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.

  3. Nonperturbative renormalization-group approach preserving the momentum dependence of correlation functions

    Science.gov (United States)

    Rose, F.; Dupuis, N.

    2018-05-01

    We present an approximation scheme of the nonperturbative renormalization group that preserves the momentum dependence of correlation functions. This approximation scheme can be seen as a simple improvement of the local potential approximation (LPA) where the derivative terms in the effective action are promoted to arbitrary momentum-dependent functions. As in the LPA, the only field dependence comes from the effective potential, which allows us to solve the renormalization-group equations at a relatively modest numerical cost (as compared, e.g., to the Blaizot-Mendéz-Galain-Wschebor approximation scheme). As an application we consider the two-dimensional quantum O(N ) model at zero temperature. We discuss not only the two-point correlation function but also higher-order correlation functions such as the scalar susceptibility (which allows for an investigation of the "Higgs" amplitude mode) and the conductivity. In particular, we show how, using Padé approximants to perform the analytic continuation i ωn→ω +i 0+ of imaginary frequency correlation functions χ (i ωn) computed numerically from the renormalization-group equations, one can obtain spectral functions in the real-frequency domain.

  4. Observation on the changes of serum erythropoietin (EPO) and ferritin (SF) levels after preserved red cells (PRC) transfusion in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Li Keqin; Lv Haijun; Li Xinghua

    2008-01-01

    Objective: To study the changes of serum EPO and SF levels after preserved red cells transfusion in patients with IDA. Methods: Serum EPO and SF levels were detected with RIA both before and after transfusing preserved red cells in 35 patients with IDA as well as in 30 controls. Results: Before transfusion serum EPO levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Transfusing preserved red cells is an effective treatment and has important role in clinical application. (authors)

  5. ACHP | Tribal Historic Preservation Officers

    Science.gov (United States)

    preservation of significant historic properties. Those functions include identifying and maintaining Working with Section 106 Federal, State, & Tribal Programs Training & Education Publications Search skip specific nav links Home arrow Historic Preservation Programs & Officers arrow THPOs

  6. Effect of cold nerve allograft preservation on antigen presentation and rejection

    Science.gov (United States)

    Ray, Wilson Z.; Kale, Santosh S.; Kasukurthi, Rahul; Papp, Esther M.; Johnson, Philip J.; Santosa, Katherine B.; Yan, Ying; Hunter, Daniel A.; Mackinnon, Susan E.; Tung, Thomas H.

    2010-01-01

    Object Nerve allotransplantation provides a temporary scaffold for host nerve regeneration and allows for the reconstruction of significant segmental nerve injuries. The need for systemic the current clinical utilization of nerve allografts, although this need is reduced by the practice of cold nerve allograft preservation. Activation of T cells in response to alloantigen presentation occurs in the context of donor antigen presenting cells (direct pathway) or host antigen-presenting cells (indirect pathway). The relative role of each pathway in eliciting an alloimmune response and its potential for rejection of the nerve allograft model has not previously been investigated. The objective of this investigation was to study the effect of progressive periods of cold nerve allograft preservation on antigen presentation and the alloimmune response. Methods The authors used wild type C57Bl/6 (B6), BALB/c, and major histocompatibility Class II–deficient (MHC−/−) C57Bl/6 mice as both nerve allograft recipients and donors. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap. Progressive cold preservation of donor nerve allografts was used. Quantitative assessment was made after 3 weeks using nerve histomorphometry. Results The donor-recipient combination lacking a functional direct pathway (BALB/c host with MHC−/− graft) rejected nerve allografts as vigorously as wild-type animals. Without an intact indirect pathway (MHC−/− host with BALB/c graft), axonal regeneration was improved (p < 0.052). One week of cold allograft preservation did not improve regeneration to any significant degree in any of the donor-recipient preservation did improve regeneration significantly (p < 0.05) for all combinations compared with wild-type animals without pretreatment. However, only in the presence of an intact indirect pathway (no direct pathway) did 4 weeks of cold preservation improve regeneration significantly compared with 1 week and no

  7. Functional adrenal cortex preservation: A good reason for posterior retroperitoneal endoscopic approach.

    Science.gov (United States)

    Vidal, Óscar; Delgado-Oliver, Eduardo; Díaz Del Gobbo, Rafael; Hanzu, Felicia; Squarcia, Mattia; Martínez, Daniel; Fuster, David; Fondevila, Constantino

    2018-05-24

    Cortical-sparing adrenalectomy is a suitable treatment for hereditary and sporadic bilateral pheochromocytoma, in cases of low risk of malignancy, to reduce the possibility of adrenal insufficiency assuming the chance of local recurrence. The aim of the study is to analyze the functional results of partial adrenalectomy by retroperitoneal endoscopic approach in single-adrenal patients or patients requiring bilateral adrenalectomy. Prospective study between January 2015 and February 2016 including pheochromocytoma patients diagnosed with low risk of malignant mutations. All patients agreed to be included in the study. Experienced endocrine surgeons who have been trained in minimally invasive endocrine surgery performed the procedure using the same surgical technique. Demographic variables and clinical characteristics were collected, subsequently carrying out the descriptive analysis of the data. A total of 6 patients were registered, four associated with MEN type 2 syndrome and two in the context of VHL syndrome. Retroperitoneoscopic resection was performed without laparoscopic or open conversion and no postoperative complications; the average hospital stay was 2.5 days. Preservation of the functional cortex without corticosteroids was achieved in 5 (83%) of out 6 cases with a follow-up of 26.2 ± 6 months. Today, these 5 patients have a preserved adrenal function without hormone replacement. Cortical-sparing adrenalectomy by the retroperitoneal endoscopic approach, in expert hands, is safe and feasible for the treatment of hereditary and sporadic pheochromocytoma in a context of low malignancy, making it possible to avoid the need for corticoid replacement in most cases. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Yeasts preservation: alternatives for lyophilisation

    OpenAIRE

    Nyanga, Loveness K.; Nout, Martinus J. R.; Smid, Eddy J.; Boekhout, Teun; Zwietering, Marcel H.

    2012-01-01

    The aim of the study was to compare the effect of two low-cost, low technology traditional methods for drying starter cultures with standard lyophilisation. Lyophilised yeast cultures and yeast cultures preserved in dry rice cakes and dry plant fibre strands were examined for viable cell counts during 6 months storage at 4 and 25 °C. None of the yeast cultures showed a significant loss in viable cell count during 6 months of storage at 4 °C upon lyophilisation and preservation in dry rice cak...

  9. Design of Connectivity Preserving Flocking Using Control Lyapunov Function

    OpenAIRE

    Erfianto, Bayu; Bambang, Riyanto T.; Hindersah, Hilwadi; Muchtadi-Alamsyah, Intan

    2016-01-01

    This paper investigates cooperative flocking control design with connectivity preserving mechanism. During flocking, interagent distance is measured to determine communication topology of the flocks. Then, cooperative flocking motion is built based on cooperative artificial potential field with connectivity preserving mechanism to achieve the common flocking objective. The flocking control input is then obtained by deriving cooperative artificial potential field using control Lyapunov functio...

  10. Emittance preservation

    Energy Technology Data Exchange (ETDEWEB)

    Kain, V; Arduini, G; Goddard, B; Holzer, B J; Jowett, J M; Meddahi, M; Mertens, T; Roncarolo, F; Schaumann, M; Versteegen, R; Wenninger, J [European Organization for Nuclear Research, Geneva (Switzerland)

    2012-07-01

    Emittance measurements during the LHC proton run 2011 indicated a blow-up of 20 % to 30 % from LHC injection to collisions. This presentation will show the emittance preservation throughout the different parts of the LHC cycle and discuss the current limitations on emittance determination. An overview of emittance preservation through the injector complex as function of bunch intensity will also be given. Possible sources for the observed blow-up and required tests in 2012 will be presented. Possible improvements of emittance diagnostics and analysis tools for 2012 will be shown.

  11. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.

    Science.gov (United States)

    Egawa, Junji; Schilling, Jan M; Cui, Weihua; Posadas, Edmund; Sawada, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E; Fannon-Pavlich, McKenzie J; Mandyam, Chitra D; Roth, David M; Patel, Hemal H; Patel, Piyush M; Head, Brian P

    2017-08-01

    Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav-1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav-1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron-targeted Cav-1-overexpressing transgenic (Tg) mouse [synapsin-driven Cav-1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus-dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild-type controls. Neuron-targeted overexpression of Cav-1 in the adult brain prevents hippocampus-dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron-targeted Cav-1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma-associated maladaptive plasticity.-Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic-Harpf, A. E., Fannon-Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. © FASEB.

  12. Environmental education on wood preservatives and preservative ...

    African Journals Online (AJOL)

    The development and use of wood preservatives in Nigeria should address not only the cost and demand functions but also the potential hazards in environmental equations. Forest products specialists are often asked about the perceived risks and environmental costs of treated wood products. Evidently, the civil society is ...

  13. Normal central retinal function and structure preserved in retinitis pigmentosa.

    Science.gov (United States)

    Jacobson, Samuel G; Roman, Alejandro J; Aleman, Tomas S; Sumaroka, Alexander; Herrera, Waldo; Windsor, Elizabeth A M; Atkinson, Lori A; Schwartz, Sharon B; Steinberg, Janet D; Cideciyan, Artur V

    2010-02-01

    To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP). Patients with simplex, multiplex, or autosomal recessive RP (n = 238; ages 9-82 years) were studied with static chromatic perimetry. A subset was evaluated with optical coherence tomography (OCT). Co-localized visual sensitivity and photoreceptor nuclear layer thickness were measured across the central retina to establish the relationship of function and structure. Comparisons were made to patients with Usher syndrome (n = 83, ages 10-69 years). Cross-sectional psychophysical data identified patients with RP who had normal rod- and cone-mediated function in the central retina. There were two other patterns with greater dysfunction, and longitudinal data confirmed that progression can occur from normal rod and cone function to cone-only central islands. The retinal extent of normal laminar architecture by OCT corresponded to the extent of normal visual function in patients with RP. Central retinal preservation of normal function and structure did not show a relationship with age or retained peripheral function. Usher syndrome results were like those in nonsyndromic RP. Regional disease variation is a well-known finding in RP. Unexpected was the observation that patients with presumed recessive RP can have regions with functionally and structurally normal retina. Such patients will require special consideration in future clinical trials of either focal or systemic treatment. Whether there is a common molecular mechanism shared by forms of RP with normal regions of retina warrants further study.

  14. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

    Science.gov (United States)

    Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

    2016-05-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  15. Preservation of Bacillus firmus Strain 37 and Optimization of Cyclodextrin Biosynthesis by Cells Immobilized on Loofa Sponge

    Directory of Open Access Journals (Sweden)

    Cristiane Moriwaki

    2012-08-01

    Full Text Available The preservation of Bacillus firmus strain 37 cells by lyophilization was evaluated and response surface methodology (RSM was used to optimize the β-cyclodextrin (β-CD production by cells immobilized on loofa sponge. Interactions were studied with the variables temperature, pH and dextrin concentration using a central composite design (CCD. Immobilization time influence on β-CD production was also investigated. B. firmus strain 37 cells remained viable after one year of storage, showing that the lyophilization is a suitable method for preservation of the microorganism. From the three-dimensional diagrams and contour plots, the best conditions for β-CD production were determined: temperature 60 °C, pH 8, and 18% dextrin. Considering that the amount of dextrin was high, a new assay was carried out, in which dextrin concentrations of 10, 15, and 18% were tested and the temperature of 60 °C and pH 8 were maintained. The results achieved showed very small differences and therefore, for economic reasons, the use of 10% dextrin is suggested. Increasing the immobilization time of cells immobilized on synthetic sponge the β-CD production decreased and did not change for cells immobilized on loofa sponge. The results of this research are important for microorganism preservation and essential in the optimization of the biosynthesis of CD.

  16. Retinal Pigmented Epithelial Cells Obtained from Human Induced Pluripotent Stem Cells Possess Functional Visual Cycle Enzymes in Vitro and in Vivo*

    Science.gov (United States)

    Maeda, Tadao; Lee, Mee Jee; Palczewska, Grazyna; Marsili, Stefania; Tesar, Paul J.; Palczewski, Krzysztof; Takahashi, Masayo; Maeda, Akiko

    2013-01-01

    Differentiated retinal pigmented epithelial (RPE) cells have been obtained from human induced pluripotent stem (hiPS) cells. However, the visual (retinoid) cycle in hiPS-RPE cells has not been adequately examined. Here we determined the expression of functional visual cycle enzymes in hiPS-RPE cells compared with that of isolated wild-type mouse primary RPE (mpRPE) cells in vitro and in vivo. hiPS-RPE cells appeared morphologically similar to mpRPE cells. Notably, expression of certain visual cycle proteins was maintained during cell culture of hiPS-RPE cells, whereas expression of these same molecules rapidly decreased in mpRPE cells. Production of the visual chromophore, 11-cis-retinal, and retinosome formation also were documented in hiPS-RPE cells in vitro. When mpRPE cells with luciferase activity were transplanted into the subretinal space of mice, bioluminance intensity was preserved for >3 months. Additionally, transplantation of mpRPE into blind Lrat−/− and Rpe65−/− mice resulted in the recovery of visual function, including increased electrographic signaling and endogenous 11-cis-retinal production. Finally, when hiPS-RPE cells were transplanted into the subretinal space of Lrat−/− and Rpe65−/− mice, their vision improved as well. Moreover, histological analyses of these eyes displayed replacement of dysfunctional RPE cells by hiPS-RPE cells. Together, our results show that hiPS-RPE cells can exhibit a functional visual cycle in vitro and in vivo. These cells could provide potential treatment options for certain blinding retinal degenerative diseases. PMID:24129572

  17. Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual β cell function

    Directory of Open Access Journals (Sweden)

    Dib Sergio A

    2009-12-01

    Full Text Available Abstract Type 1A diabetes mellitus (T1ADM is a progressive autoimmune disease mediated by T lymphocytes with destruction of beta cells. Up to now, we do not have precise methods to assess the beta cell mass, "in vivo" or "ex-vivo". The studies about its genetic susceptibility show strong association with class II antigens of the HLA system (particularly DQ. Others genetics associations are weaker and depend on the population studied. A combination of precipitating events may occur at the beginning of the disease. There is a silent loss of immune-mediated beta cells mass which velocity has an inverse relation with the age, but it is influenced by genetic and metabolic factors. We can predict the development of the disease primarily through the determination of four biochemically islet auto antibodies against antigens like insulin, GAD65, IA2 and Znt8. Beta cell destruction is chronically progressive but at clinical diagnosis of the disease a reserve of these cells still functioning. The goal of secondary disease prevention is halt the autoimmune attack on beta cells by redirecting or dampening the immune system. It is remains one of the foremost therapeutic goals in the T1ADM. Glycemic intensive control and immunotherapeutic agents may preserve beta-cell function in newly diagnosed patients with T1ADM. It may be assessed through C-peptide values, which are important for glycemic stability and for the prevention of chronic complications of this disease. This article will summarize the etiopathogenesis mechanisms of this disease and the factors can influence on residual C-peptide and the strategies to it preservation.

  18. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  19. Preservation of visual cortical function following retinal pigment epithelium transplantation in the RCS rat using optical imaging techniques.

    Science.gov (United States)

    Gias, Carlos; Jones, Myles; Keegan, David; Adamson, Peter; Greenwood, John; Lund, Ray; Martindale, John; Johnston, David; Berwick, Jason; Mayhew, John; Coffey, Peter

    2007-04-01

    The aim of this study was to determine the extent of cortical functional preservation following retinal pigment epithelium (RPE) transplantation in the Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and spectroscopy. The cortical responses to visual stimulation in transplanted rats at 6 months post-transplantation were compared with those from age-matched untreated dystrophic and non-dystrophic rats. Our results show that cortical responses were evoked in non-dystrophic rats to both luminance changes and pattern stimulation, whereas no response was found in untreated dystrophic animals to any of the visual stimuli tested. In contrast, a cortical response was elicited in most of the transplanted rats to luminance changes and in many of those a response was also evoked to pattern stimulation. Although the transplanted rats did not respond to high spatial frequency information we found evidence of preservation in the cortical processing of luminance changes and low spatial frequency stimulation. Anatomical sections of transplanted rat retinas confirmed the capacity of RPE transplantation to rescue photoreceptors. Good correlation was found between photoreceptor survival and the extent of cortical function preservation determined with optical imaging techniques. This study determined the efficacy of RPE transplantation to preserve visual cortical processing and established optical imaging as a powerful technique for its assessment.

  20. Reduced in vivo ocular surface toxicity with polyquad-preserved travoprost versus benzalkonium-preserved travoprost or latanoprost ophthalmic solutions.

    Science.gov (United States)

    Liang, Hong; Brignole-Baudouin, Françoise; Riancho, Luisa; Baudouin, Christophe

    2012-01-01

    The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution(travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride(BAK)-preserved travoprost 0.004% ophthalmic solution(travoprost BAK) and BAK-preserved latanoprost 0.005%ophthalmic solution (latanoprost BAK). Adult male New Zealand albino rabbits (n = 36) were randomly divided into 6 groups. Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5-min intervals.The ocular surface reactions were investigated at hour 4 and day 1 using slitlamp examination; in vivo confocal microscopy (IVCM) for cornea, limbus and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression cytology and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not induce obvious irritation by clinical observation, changes in microstructures of the whole ocular surface as measured by IVCM analysis,inflammatory infiltration or cell damage as measured by impression cytology, altered levels of goblet cell counts or numerous CD45+ cells in the cornea. In contrast, all BAK-containing products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in the ocular surface microstructure,significant total ocular surface toxicity scores,damaged epithelial cells, inflammatory cell infiltration and decreased goblet cell density. Travoprost PQ did not elicitocular surface toxicity when administered to rabbit eyes.These results suggest a greater safety advantage for the ocular surface of patients receiving chronic glaucoma treatment with PQ-preserved drugs.

  1. Left atrial function in heart failure with impaired and preserved ejection fraction.

    Science.gov (United States)

    Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

    2014-09-01

    Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

  2. Risk factors for bowel dysfunction after sphincter-preserving rectal cancer surgery: a prospective study using the Memorial Sloan Kettering Cancer Center bowel function instrument.

    Science.gov (United States)

    Ihn, Myong Hoon; Kang, Sung-Bum; Kim, Duck-Woo; Oh, Heung-Kwon; Lee, Soo Young; Hong, Sa Min

    2014-08-01

    Until recently, no studies have prospectively evaluated bowel function after sphincter-preserving surgery for rectal cancer with the use of a validated bowel function scoring system. The aim of this study was to investigate possible risk factors for altered bowel function after sphincter-preserving surgery. This was a prospective study. The study was conducted between January 2006 and May 2012 at the authors' institution. Patients who underwent sphincter-preserving rectal cancer surgery were recruited. Bowel function was assessed 1 day before (baseline) and at 1 year after sphincter-preserving surgery or temporary ileostomy takedown with the use of the Memorial Sloan Kettering Cancer Center questionnaire. Multivariable analysis was performed to identify the factors associated with altered bowel function after surgery. Overall, 266 patients were eligible for the analysis. The tumor was located in the upper, middle, and lower rectum in 68 (25.5%), 113 (42.5%), and 85 (32.0%) patients. Intersphincteric resection and temporary ileostomy were performed in 18 (6.8%) and 129 (48.5%) patients. The mean Memorial Sloan Kettering Cancer Center score was 64.5 ± 7.6 at 1 year after sphincter-preserving surgery or temporary ileostomy takedown. The Memorial Sloan Kettering Cancer Center score decreased in 163/266 patients (61.3%) between baseline and 1 year after surgery. Tumor location (p = 0.01), operative method (p = 0.03), anastomotic type (p = 0.01), and temporary ileostomy (p = 0.01) were associated with altered bowel function after sphincter-preserving surgery in univariate analyses. In multivariable analysis, only tumor location was independently associated with impaired bowel function after sphincter-preserving rectal cancer surgery. This study was limited by its nonrandomized design and the lack of measurement before preoperative chemoradiotherapy. We suggest that preoperative counseling should be implemented to inform patients of the risk of bowel dysfunction

  3. Study on changes of serum ferritin (SF), folic acid (FA) and vitamin B12 levels after transfusion of preserved red cells (PRC) in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Liu Hongsu; Li Xinhua; Li Keqin

    2008-01-01

    Objective: To explore the changes of serum SF, FA and VitB 12 levels after transfusion of preserved red cells in patients with IDA. Methods: Serum SF, FA and VitB 12 levels (with RIA) were detected both before and after transfusion of preserved red cells in 32 patients with IDA as well as in 35 controls. Results: Before transfusion of preserved red cells, the serum SF levels were significantly lower than those in controls (P 12 levels were significantly higher (P 12 were not much different from those in the controls. Conclusion: Transfusion of preserved red cells proves to be very useful. (authors)

  4. Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells.

    Science.gov (United States)

    Müller, Lars U W; Milsom, Michael D; Kim, Mi-Ok; Schambach, Axel; Schuesler, Todd; Williams, David A

    2008-06-01

    Fanconi anemia (FA) is a rare recessive syndrome, characterized by congenital anomalies, bone marrow failure, and predisposition to cancer. Two earlier clinical trials utilizing gamma-retroviral vectors for the transduction of autologous FA hematopoietic stem cells (HSCs) required extensive in vitro manipulation and failed to achieve detectable long-term engraftment of transduced HSCs. As a strategy for minimizing ex vivo manipulation, we investigated the use of a "rapid" lentiviral transduction protocol in a murine Fanca(-/-) model. Importantly, while this and most murine models of FA fail to completely mimic the human hematopoietic phenotype, we observed a high incidence of HSC transplant engraftment failure and low donor chimerism after conventional transduction (CT) of Fanca(-/-) donor cells. In contrast, rapid transduction (RT) of Fanca(-/-) HSCs preserved engraftment to the level achieved in wild-type cells, resulting in long-term multilineage engraftment of gene-modified cells. We also demonstrate the correction of the characteristic hypersensitivity of FA cells against the cross-linking agent mitomycin C (MMC), and provide evidence for the advantage of using pharmacoselection as a means of further increasing gene-modified cells after RT. Collectively, these data support the use of rapid lentiviral transduction for gene therapy in FA.

  5. Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy.

    Science.gov (United States)

    Tschernutter, M; Schlichtenbrede, F C; Howe, S; Balaggan, K S; Munro, P M; Bainbridge, J W B; Thrasher, A J; Smith, A J; Ali, R R

    2005-04-01

    The Royal College of Surgeons (RCS) rat is a well-characterized model of autosomal recessive retinitis pigmentosa (RP) due to a defect in the retinal pigment epithelium (RPE). It is homozygous for a null mutation in the gene encoding , a receptor tyrosine kinase found in RPE cells, that is required for phagocytosis of shed photoreceptor outer segments. The absence of Mertk results in accumulation of outer segment debris. This subsequently leads to progressive loss of photoreceptor cells. In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA driven by a spleen focus forming virus (SFFV) promoter. The vector was subretinally injected into the right eye of 10-day-old RCS rats; the left eye was left untreated as an internal control. Here, we present a detailed assessment of the duration and extent of the morphological rescue and the resulting functional benefits. We examined animals at various time points over a period of 7 months by light and electron microscopy, and electroretinography. We observed correction of the phagocytic defect, slowing of photoreceptor cell loss and preservation of retinal function for up to 7 months. This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders.

  6. The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells.

    Science.gov (United States)

    Datta, Sandipan; Baudouin, Christophe; Brignole-Baudouin, Francoise; Denoyer, Alexandre; Cortopassi, Gino A

    2017-04-01

    Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 μM) and O2 consumption (IC50, 10.9 μM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107-667 μM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 μM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 μM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients.

  7. A non-canonical function of Ezh2 preserves immune homeostasis.

    Science.gov (United States)

    Vasanthakumar, Ajithkumar; Xu, Dakang; Lun, Aaron Tl; Kueh, Andrew J; van Gisbergen, Klaas Pjm; Iannarella, Nadia; Li, Xiaofang; Yu, Liang; Wang, Die; Williams, Bryan Rg; Lee, Stanley Cw; Majewski, Ian J; Godfrey, Dale I; Smyth, Gordon K; Alexander, Warren S; Herold, Marco J; Kallies, Axel; Nutt, Stephen L; Allan, Rhys S

    2017-04-01

    Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We further show that Ezh2 directly methylates the NKT cell lineage defining transcription factor PLZF, leading to its ubiquitination and subsequent degradation. Sustained PLZF expression in Ezh2-deficient mice is associated with the expansion of a subset of NKT cells that cause immune perturbation. Taken together, we have identified a chromatin-independent function of Ezh2 that impacts on the development of the immune system. © 2017 The Authors.

  8. The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study

    Directory of Open Access Journals (Sweden)

    Sebastien Giraud

    2018-02-01

    Full Text Available University of Wisconsin (UW solution is not optimal for preservation of marginal organs. Polyethylene glycol (PEG could improve protection. Similarly formulated solutions containing either 15 or 20 g/L PEG 20 kDa or 5, 15 and 30 g/L PEG 35 kDa were tested in vitro on kidney endothelial cells, ex vivo on preserved kidneys, and in vivo in a pig kidney autograft model. In vitro, all PEGs provided superior preservation than UW in terms of cell survival, adenosine triphosphate (ATP production, and activation of survival pathways. Ex vivo, tissue injury was lower with PEG 20 kDa compared to UW or PEG 35 kDa. In vivo, function recovery was identical between UW and PEG 35 kDa groups, while PEG 20 kDa displayed swifter recovery. At three months, PEG 35 kDa 15 and 30 g/L animals had worse outcomes than UW, while 5 g/L PEG 35 kDa was similar. PEG 20 kDa was superior to both UW and PEG 35 kDa in terms of function and fibrosis development, with low activation of damage pathways. PEG 20 kDa at 15 g/L was superior to 20 g/L. While in vitro models did not discriminate between PEGs, in large animal models of transplantation we showed that PEG 20 kDa offers a higher level of protection than UW and that longer chains such as PEG 35 kDa must be used at low doses, such as found in Institut George Lopez (IGL1, 1g/L.

  9. Middle-preserving pancreatectomy for advanced transverse colon cancer invading the duodenun and non-functioning endocrine tumor in the pancreatic tail.

    Science.gov (United States)

    Noda, Hiroshi; Kato, Takaharu; Kamiyama, Hidenori; Toyama, Nobuyuki; Konishi, Fumio

    2011-02-01

    A 73-year-old female was referred to our hospital with a diagnosis of advanced transverse colon cancer with severe anemia and body weight loss. Preoperative evaluations, including colonoscopy, gastroduodenoscopy, and computed tomography, revealed not only a transverse colon cancer massively invading the duodenum, but also a non-functioning endocrine tumor in the pancreatic tail. We performed middle-preserving pancreatectomy (MPP) with right hemicolectomy for these tumors with a curative intent. After the resection, about 6 cm of the body of the pancreas was preserved, and signs of diabetes mellitus have not appeared. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. After a 33-day hospital stay, the patient returned to daily life without signs of pancreatic exocrine insufficiency. Although the long-term follow-up of the patient is indispensable, in this case, MPP might be able to lead to the curative resection of transverse colon cancer massively invading the duodenum and non-functioning endocrine tumor in the pancreatic tail with preservation of pancreatic function.

  10. Complement Receptor 3 Has Negative Impact on Tumor Surveillance through Suppression of Natural Killer Cell Function

    Directory of Open Access Journals (Sweden)

    Cheng-Fei Liu

    2017-11-01

    Full Text Available Complement receptor 3 (CR3 is expressed abundantly on natural killer (NK cells; however, whether it plays roles in NK cell-dependent tumor surveillance is largely unknown. Here, we show that CR3 is an important negative regulator of NK cell function, which has negative impact on tumor surveillance. Mice deficient in CR3 (CD11b−/− mice exhibited a more activated NK phenotype and had enhanced NK-dependent tumor killing. In a B16-luc melanoma-induced lung tumor growth and metastasis model, mice deficient in CR3 had reduced tumor growth and metastases, compared with WT mice. In addition, adaptive transfer of NK cells lacking CR3 (into NK-deficient mice mediated more efficient suppression of tumor growth and metastases, compared with the transfer of CR3 sufficient NK cells, suggesting that CR3 can impair tumor surveillance through suppression of NK cell function. In vitro analyses showed that engagement of CR3 with iC3b (classical CR3 ligand on NK cells negatively regulated NK cell activity and effector functions (i.e. direct tumor cell killing, antibody-dependent NK-mediated tumor killing. Cell signaling analyses showed that iC3b stimulation caused activation of Src homology 2 domain-containing inositol-5-phosphatase-1 (SHIP-1 and JNK, and suppression of ERK in NK cells, supporting that iC3b mediates negative regulation of NK cell function through its effects on SHIP-1, JNK, and ERK signal transduction pathways. Thus, our findings demonstrate a previously unknown role for CR3 in dysregulation of NK-dependent tumor surveillance and suggest that the iC3b/CR3 signaling is a critical negative regulator of NK cell function and may represent a new target for preserving NK cell function in cancer patients and improving NK cell-based therapy.

  11. Early beneficial effect of preservation of papillo-annular continuity in mitral valve replacement on left ventricular function.

    Science.gov (United States)

    Dilip, D; Chandra, A; Rajashekhar, D; Padmanabhan, M

    2001-05-01

    Impairment of left ventricular (LV) function after mitral valve replacement (MVR) has been the most important factor to determine morbidity and mortality. With this in mind, LV performance in the postoperative period was assessed with and without preservation of papillo-annular continuity in MVR. Between March 1994 and August 1998, a total of 383 valve prostheses (202 MVR, 65 AVR, 58 MVR+AVR) were implanted in 325 patients, 177 of whom underwent MVR with Starr Edwards ball cage prostheses (the study group). Of these 177 patients, 105 had MVR with preservation of the posterior mitral leaflet (group I), and 72 had conventional MVR (group II). Predominant lesions were mitral stenosis in 81, mitral regurgitation in 42, and mixed mitral lesion (MS/MR) in 54. Concomitant tricuspid valve annuloplasty was performed in 13, and atrial septal defect repair in five. Sixteen patients underwent MVR for mitral restenosis. In-vivo performance of the prostheses and LV function was evaluated by M-mode and Doppler echocardiography. At 3-6 months clinical improvement was seen in NYHA class, with reduction in cardiothoracic ratio among patients with preserved papillo-annular continuity, irrespective of lesion type. Significant reductions (p versus 44.64 +/- 8.54 postop.; p versus 41.21 +/- 7.16 postop.; p versus 28.81 +/- 5.79 postop.; p versus 64.47 +/- 7.93; p <0.05). Further analysis of data in group I patients showed significant reductions in left atrial dimensions, LVESD and peak gradient, along with improved ejection fraction compared with conventional (group II) patients. Deterioration in LV function in patients undergoing conventional MVR indicates chordal resection as a putative mechanism. This study supports the concept that maintenance of continuity between the mitral annulus and papillary muscles has a beneficial effect on postoperative LV function, and is particularly important in patients with mitral stenosis with depressed preoperative LV systolic function.

  12. Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

    Science.gov (United States)

    Berg, Ulla B; Németh, Antal

    2018-04-01

    On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

  13. A High Frequency of HIV-Specific Circulating Follicular Helper T Cells Is Associated with Preserved Memory B Cell Responses in HIV Controllers.

    Science.gov (United States)

    Claireaux, M; Galperin, M; Benati, D; Nouël, A; Mukhopadhyay, M; Klingler, J; de Truchis, P; Zucman, D; Hendou, S; Boufassa, F; Moog, C; Lambotte, O; Chakrabarti, L A

    2018-05-08

    Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4 + T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet + ), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA - CXCR5 + CD4 + T cell population, proved more frequent in the controller group ( P = 0.002). The frequency of PD-1 expression in Tet + cTfh was increased in both groups (median, >75%) compared to total cTfh (<30%), but the intensity of PD-1 expression per cell remained higher in the treated patient group ( P = 0.02), pointing to the persistence of abnormal immune activation in treated patients. The function of cTfh, analyzed by the capacity to promote IgG secretion in cocultures with autologous memory B cells, did not show major differences between groups in terms of total IgG production but proved significantly more efficient in the controller group when measuring HIV-specific IgG production. The frequency of Tet + cTfh correlated with HIV-specific IgG production ( R = 0.71 for Gag-specific and R = 0.79 for Env-specific IgG, respectively). Taken together, our findings indicate that key cTfh-B cell interactions are preserved in controlled HIV infection, resulting in potent memory B cell responses that may play an underappreciated role in HIV control. IMPORTANCE The rare patients who spontaneously control HIV replication in the absence of therapy provide a unique model to identify determinants of an effective anti-HIV immune response. HIV controllers show signs of particularly efficient antiviral T cell responses, while their humoral response was until recently

  14. Morphological and functional rescue in RCS rats after RPE cell line transplantation at a later stage of degeneration.

    Science.gov (United States)

    Wang, Shaomei; Lu, Bin; Girman, Sergej; Holmes, Toby; Bischoff, Nicolas; Lund, Raymond D

    2008-01-01

    It is well documented that grafting of cells in the subretinal space of Royal College of Surgeons (RCS) rats limits deterioration of vision and loss of photoreceptors if performed early in postnatal life. What is unclear is whether cells introduced later, when photoreceptor degeneration is already advanced, can still be effective. This possibility was examined in the present study, using the human retinal pigment epithelial cell line, ARPE-19. Dystrophic RCS rats (postnatal day [P] 60) received subretinal injection of ARPE-19 cells (2 x 10(5)/3 microL/eye). Spatial frequency was measured by recording optomotor responses at P100 and P150, and luminance threshold responses were recorded from the superior colliculus at P150. Retinas were stained with cresyl violet, retinal cell-specific markers, and a human nuclear marker. Control animals were injected with medium alone. Animals comparably treated with grafts at P21 were available for comparison. All animals were treated with immunosuppression. Later grafts preserved both spatial frequency and threshold responses over the control and delayed photoreceptor degeneration. There were two to three layers of rescued photoreceptors even at P150, compared with a scattered single layer in sham and untreated control retinas. Retinal cell marker staining showed an orderly array of the inner retinal lamination. The morphology of the second-order neurons was better preserved around the grafted area than in regions distant from graft. Sham injection had little effect in rescuing the photoreceptors. RPE cell line transplants delivered later in the course of degeneration can preserve not only the photoreceptors and inner retinal lamination but also visual function in RCS rats. However, early intervention can achieve better rescue.

  15. Different Immunological Phenotypes Associated with Preserved CD4+ T Cell Counts in HIV-Infected Controllers and Viremic Long Term Non-Progressors

    DEFF Research Database (Denmark)

    Gaardbo, Julie Christine; Hartling, Hans J; Ronit, Andreas

    2013-01-01

    HIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell...

  16. Preserved speech abilities and compensation following prefrontal damage.

    Science.gov (United States)

    Buckner, R L; Corbetta, M; Schatz, J; Raichle, M E; Petersen, S E

    1996-02-06

    Lesions to left frontal cortex in humans produce speech production impairments (nonfluent aphasia). These impairments vary from subject to subject and performance on certain speech production tasks can be relatively preserved in some patients. A possible explanation for preservation of function under these circumstances is that areas outside left prefrontal cortex are used to compensate for the injured brain area. We report here a direct demonstration of preserved language function in a stroke patient (LF1) apparently due to the activation of a compensatory brain pathway. We used functional brain imaging with positron emission tomography (PET) as a basis for this study.

  17. Parenteral Lipid Dose Restriction With Soy Oil, Not Fish Oil, Preserves Retinal Function in Neonatal Piglets.

    Science.gov (United States)

    Lansing, Marihan; Sauvé, Yves; Dimopoulos, Ioannis; Field, Catherine J; Suh, Miyoung; Wizzard, Pamela; Goruk, Susan; Lim, David; Muto, Mitsuru; Wales, Paul; Turner, Justine

    2018-03-13

    A dietary supply of docosahexaenoic acid (DHA) and arachidonic acid (AA) is critical for neonatal retinal development. Both are absent/minimal in parenteral nutrition (PN) using soy-oil emulsions ([SO] Intralipid®) traditionally used for neonatal intestinal failure. In contrast, fish-oil emulsions ([FO] Omegaven®) are enriched in DHA/AA. The aim of this study was to compare retinal function and fatty acid content in neonatal piglets fed PN with SO or FO. Two-5-day-old piglets were randomly allocated to SO (n = 4) or FO (n = 4), provided at equivalent doses (5g/kg/d). After 14 days of PN, retinal function was assessed by electroretinography and retinas were harvested for fatty acid content analysis. Sow-fed piglets served as a reference (REF). Light flash-elicited stoppage of cone and rod dark-currents (a-waves) and the ensuing postsynaptic activation of cone and rod ON bipolar cells (b-waves) were comparable between SO and REF. Responses recorded from FO were subnormal (P DHA content was similar in both groups (FO, 14.59% vs SO, 12.22%; P = 0.32); while AA was lower in FO (FO, 6.01% vs SO, 8.21%; P = .001). Paradoxically, FO containing more DHA and AA did not preserve retinal function when compared with the same low dose of SO. This may be due to the reduced AA enrichment in the retina with FO treatment. Further investigation into the ideal amounts of DHA and AA for optimal neonatal retinal function is required. © 2018 American Society for Parenteral and Enteral Nutrition.

  18. Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway

    International Nuclear Information System (INIS)

    Campos, Dijon Henrique Salomé de; Leopoldo, André Soares; Lima-Leopoldo, Ana Paula; Nascimento, André Ferreira do; Oliveira-Junior, Silvio Assis de; Silva, Danielle Cristina Tomaz da; Sugizaki, Mario Mateus; Padovani, Carlos Roberto; Cicogna, Antonio Carlos

    2014-01-01

    Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle

  19. Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Dijon Henrique Salomé de, E-mail: dijoncampos@gmail.com [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Leopoldo, André Soares; Lima-Leopoldo, Ana Paula [Departamento de Esportes - Centro de Educação Física e Desportos da Universidade Federal do Espírito Santo (UFES), Vitória, ES (Brazil); Nascimento, André Ferreira do [Instituto de Ciências da Saúde da Universidade Federal do Mato Grosso (UFMT), Sinop, MT (Brazil); Oliveira-Junior, Silvio Assis de [Escola de Fisioterapia da Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil); Silva, Danielle Cristina Tomaz da [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Sugizaki, Mario Mateus [Instituto de Ciências da Saúde da Universidade Federal do Mato Grosso (UFMT), Sinop, MT (Brazil); Padovani, Carlos Roberto [Departamento de Bioestatística, Instituto de Ciências Biológicas da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Cicogna, Antonio Carlos, E-mail: dijoncampos@gmail.com [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil)

    2014-10-15

    Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle.

  20. Comparison of the effects of ophthalmic solutions on human corneal epithelial cells using fluorescent dyes.

    Science.gov (United States)

    Xu, Manlong; Sivak, Jacob G; McCanna, David J

    2013-11-01

    To investigate the effect of differently preserved ophthalmic solutions on the viability and barrier function of human corneal epithelial cells (HCEC) using fluorescent dyes. HCEC monolayers were exposed to the ophthalmic solutions containing benzalkonium chloride (BAK), edetate disodium, polyquad, stabilized oxychloro complex (Purite), sodium perborate, or sorbic acid for 5 min, 15 min, and 1 h. At 24 h after exposure, the cultures were assessed for metabolic activity using alamarBlue. The enzyme activity, membrane integrity, and apoptosis were evaluated using confocal microscopy. Barrier function was assessed using sodium fluorescein. The metabolic assay showed that the BAK-preserved ophthalmic solutions significantly reduced cell viability after a 5-min exposure compared to the phosphate buffered saline treated control (POphthalmic solutions with new preservatives had varying time-dependent adverse effects on cell viability, and the preservative-free solution had the least effect on HCEC. Sodium fluorescein permeability showed that HCEC monolayers treated with BAK-preserved solutions were more permeable to sodium fluorescein than those treated by the other ophthalmic solutions (Psolutions had greater adverse effects on metabolic activity, enzyme activity, membrane integrity, cell viability, and barrier function than the solutions that were not preserved with BAK. Our study suggests that BAK-free especially, preservative-free ophthalmic solutions are safer alternatives to BAK-preserved ones.

  1. Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life® in pig lung transplantation model.

    Science.gov (United States)

    Glorion, M; Polard, V; Favereau, F; Hauet, T; Zal, F; Fadel, E; Sage, E

    2017-10-25

    We describe the results of adding a new biological agent HEMO 2 life ® to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMO 2 life ® is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex ® ) was compared with Perfadex ® associated with HEMO 2 life ® and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMO 2 life ® group led to significant improvement in functional parameters: reduction of graft vascular resistance (p preservation improves early graft function after prolonged cold ischemia in lung transplantation.

  2. In Vivo Effects of Preservative-free and Preserved Prostaglandin Analogs: Mouse Ocular Surface Study.

    Science.gov (United States)

    Kim, Jee Hyun; Kim, Eun Joo; Kim, Yeoun-Hee; Kim, Yong Il; Lee, Se-Hyung; Jung, Jae-Chang; Lee, Kyoo Won; Park, Young Jeung

    2015-08-01

    Chronic use of topical hypotensive agents induces several side effects caused by preservatives. The purpose of this study was to evaluate the effects of prostaglandin analogs with varying concentrations of benzalkonium chloride (BAC), preservative-free (PF), and alternative preservatives on mouse corneal tissue. Thirty-five, 8- to 10-week-old female C57BL/6 mice (five mice for each group) were used for this study. To the control group, we applied normal saline, and to each drug-treated group we applied 0.02% BAC, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), travoprost 0.004% (with 0.001% polyquad) or tafluprost 0.0015% with/without 0.001% BAC, once a day (9 p.m.) for 4 weeks. Corneal fluorescein staining was evaluated in all groups. After harvest, the corneal tissues were embedded in paraffin and then Hematoxylin-Eosin stain was performed for histopathological examination. Immunofluorescence staining was done against TNF-α, IL-6, HLA DR, pJNK, and pAkt. In corneal fluorescein staining, severe punctate epithelial keratitis was seen in the groups of 0.02% BAC, 0.02% BAC containing bimatoprost 0.01% and latanoprost 0.005%. The surface desquamation, irregular surface, loss of cell borders, anisocytosis and stromal shrinkage were observed in the groups of BAC-containing eye drops. Moreover, the groups treated with BAC-containing eye drops have high inflammatory markers, significantly decreased cell viability-related signal, pAkt, and higher apoptosis-inducing signal, pJNK, than the control group. On the other hand, travoprost 0.004% and PF tafluprost 0.0015% have less cellular morphologic changes, lower inflammation, and higher cellular viability than BAC-containing formulations. Corneal damage, increased inflammation and apoptosis and low cell viability were observed in BAC-containing groups. PF or alternatively preserved glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.

  3. Evaluation of freeze fixation as a phytoplankton preservation method for microautoradiography

    International Nuclear Information System (INIS)

    Paerl, H.W.

    1984-01-01

    Quantitative microautoradiography of marine and freshwater phytoplankton has been hampered by the fact that chemical techniques used to maintain structural integrity cause leakage of isotopically labeled cell constituents. Chemography, poor preservation of structural integrity, and leakage of cell constituents can all be avoided by quick-freezing filtered samples in liquid N 2 and then freeze-drying them before autoradiographic preparation. Leakage of fixed 14 C and 33 P and preservation of cell shapes and sizes by these preservation techniques are evaluated in diverse marine and freshwater phytoplankton communities

  4. Ranking of critical species to preserve the functionality of mutualistic networks using the k-core decomposition.

    Science.gov (United States)

    García-Algarra, Javier; Pastor, Juan Manuel; Iriondo, José María; Galeano, Javier

    2017-01-01

    Network analysis has become a relevant approach to analyze cascading species extinctions resulting from perturbations on mutualistic interactions as a result of environmental change. In this context, it is essential to be able to point out key species, whose stability would prevent cascading extinctions, and the consequent loss of ecosystem function. In this study, we aim to explain how the k -core decomposition sheds light on the understanding the robustness of bipartite mutualistic networks. We defined three k -magnitudes based on the k -core decomposition: k -radius, k -degree, and k -risk. The first one, k -radius, quantifies the distance from a node to the innermost shell of the partner guild, while k -degree provides a measure of centrality in the k -shell based decomposition. k -risk is a way to measure the vulnerability of a network to the loss of a particular species. Using these magnitudes we analyzed 89 mutualistic networks involving plant pollinators or seed dispersers. Two static extinction procedures were implemented in which k -degree and k -risk were compared against other commonly used ranking indexes, as for example MusRank, explained in detail in Material and Methods. When extinctions take place in both guilds, k -risk is the best ranking index if the goal is to identify the key species to preserve the giant component. When species are removed only in the primary class and cascading extinctions are measured in the secondary class, the most effective ranking index to identify the key species to preserve the giant component is k -degree. However, MusRank index was more effective when the goal is to identify the key species to preserve the greatest species richness in the second class. The k -core decomposition offers a new topological view of the structure of mutualistic networks. The new k -radius, k -degree and k -risk magnitudes take advantage of its properties and provide new insight into the structure of mutualistic networks. The k -risk and k

  5. Ranking of critical species to preserve the functionality of mutualistic networks using the k-core decomposition

    Directory of Open Access Journals (Sweden)

    Javier García-Algarra

    2017-05-01

    Full Text Available Background Network analysis has become a relevant approach to analyze cascading species extinctions resulting from perturbations on mutualistic interactions as a result of environmental change. In this context, it is essential to be able to point out key species, whose stability would prevent cascading extinctions, and the consequent loss of ecosystem function. In this study, we aim to explain how the k-core decomposition sheds light on the understanding the robustness of bipartite mutualistic networks. Methods We defined three k-magnitudes based on the k-core decomposition: k-radius, k-degree, and k-risk. The first one, k-radius, quantifies the distance from a node to the innermost shell of the partner guild, while k-degree provides a measure of centrality in the k-shell based decomposition. k-risk is a way to measure the vulnerability of a network to the loss of a particular species. Using these magnitudes we analyzed 89 mutualistic networks involving plant pollinators or seed dispersers. Two static extinction procedures were implemented in which k-degree and k-risk were compared against other commonly used ranking indexes, as for example MusRank, explained in detail in Material and Methods. Results When extinctions take place in both guilds, k-risk is the best ranking index if the goal is to identify the key species to preserve the giant component. When species are removed only in the primary class and cascading extinctions are measured in the secondary class, the most effective ranking index to identify the key species to preserve the giant component is k-degree. However, MusRank index was more effective when the goal is to identify the key species to preserve the greatest species richness in the second class. Discussion The k-core decomposition offers a new topological view of the structure of mutualistic networks. The new k-radius, k-degree and k-risk magnitudes take advantage of its properties and provide new insight into the structure of

  6. Preserved cardiac function despite marked impairment of cAMP generation.

    Directory of Open Access Journals (Sweden)

    Mei Hua Gao

    Full Text Available So many clinical trials of positive inotropes have failed, that it is now axiomatic that agents that increase cAMP are deleterious to the failing heart. An alternative strategy is to alter myocardial Ca(2+ handling or myofilament response to Ca(2+ using agents that do not affect cAMP. Although left ventricular (LV function is tightly linked to adenylyl cyclase (AC activity, the beneficial effects of AC may be independent of cAMP and instead stem from effects on Ca(2+ handling. Here we ask whether an AC mutant molecule that reduces LV cAMP production would have favorable effects on LV function through its effects on Ca(2+ handling alone.We generated transgenic mice with cardiac-directed expression of an AC6 mutant (AC6mut. Cardiac myocytes showed impaired cAMP production in response to isoproterenol (74% reduction; p<0.001, but LV size and function were normal. Isolated hearts showed preserved LV function in response to isoproterenol stimulation. AC6mut expression was associated with increased sarcoplasmic reticulum Ca(2+ uptake and the EC50 for SERCA2a activation was reduced. Cardiac myocytes isolated from AC6mut mice showed increased amplitude of Ca(2+ transients in response to isoproterenol (p = 0.0001. AC6mut expression also was associated with increased expression of LV S100A1 (p = 0.03 and reduced expression of phospholamban protein (p = 0.01.LV AC mutant expression is associated with normal cardiac function despite impaired cAMP generation. The mechanism appears to be through effects on Ca(2+ handling - effects that occur despite diminished cAMP.

  7. Proline-rich tyrosine kinase 2 (Pyk2) mediates vascular endothelial-cadherin-based cell-cell adhesion by regulating beta-catenin tyrosine phosphorylation

    NARCIS (Netherlands)

    van Buul, Jaap D.; Anthony, Eloise C.; Fernandez-Borja, Mar; Burridge, Keith; Hordijk, Peter L.

    2005-01-01

    Vascular endothelial-cadherin (VE-cadherin) controls endothelial cell-cell adhesion and preserves endothelial integrity. In order to maintain endothelial barrier function, VE-cadherin function is tightly regulated through mechanisms that involve protein phosphorylation and cytoskeletal dynamics.

  8. Evidence of In Vitro Preservation of Human Nephrogenesis at the Single-Cell Level

    Directory of Open Access Journals (Sweden)

    Naomi Pode-Shakked

    2017-07-01

    Full Text Available During nephrogenesis, stem/progenitor cells differentiate and give rise to early nephron structures that segment to proximal and distal nephron cell types. Previously, we prospectively isolated progenitors from human fetal kidney (hFK utilizing a combination of surface markers. However, upon culture nephron progenitors differentiated and could not be robustly maintained in vitro. Here, by culturing hFK in a modified medium used for in vitro growth of mouse nephron progenitors, and by dissection of NCAM+/CD133− progenitor cells according to EpCAM expression (NCAM+/CD133−/EpCAM−, NCAM+/CD133−/EpCAMdim, NCAM+/CD133−/EpCAMbright, we show at single-cell resolution a preservation of uninduced and induced cap mesenchyme as well as a transitioning mesenchymal-epithelial state. Concomitantly, differentiating and differentiated epithelial lineages are also maintained. In vitro expansion of discrete stages of early human nephrogenesis in nephron stem cell cultures may be used for drug screening on a full repertoire of developing kidney cells and for prospective isolation of mesenchymal or epithelial renal lineages for regenerative medicine.

  9. A simple and fast method for fixation of cultured cell lines that preserves cellular structures containing gamma-tubulin.

    Science.gov (United States)

    Alvarado-Kristensson, Maria

    2018-01-01

    When using fluorescence microscope techniques to study cells, it is essential that the cell structure and contents are preserved after preparation of the samples, and that the preparation method employed does not create artefacts that can be perceived as cellular structure/components. γ-Tubulin forms filaments that in some cases are immunostained with an anti-γ-tubulin antibody, but this immunostaining is not reproducible [[1], [2

  10. Hölder seminorm preserving linear bijections and isometries

    Indian Academy of Sciences (India)

    onto lipα(Y ) that preserve the Hölder seminorm. Keywords. Lipschitz function; isometry; linear preserver problem; Banach–Stone theorem. 1. Introduction. The main ... In the context of Lipschitz functions, it seems more natural to raise this type of linear .... being the adjoint map of , is nonempty by the Hahn–Banach theorem.

  11. Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway

    Directory of Open Access Journals (Sweden)

    Dijon Henrique Salomé de Campos

    2014-10-01

    Full Text Available Background: Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Objective: Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. Methods: 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV. Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Results: Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. Conclusion: The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle.

  12. ACS6, a Hydrogen sulfide-donating derivative of sildenafil, inhibits homocysteine-induced apoptosis by preservation of mitochondrial function

    Directory of Open Access Journals (Sweden)

    Tang Xiao-Qing

    2011-08-01

    Full Text Available Abstract Background The hydrogen sulfide-releasing sildenafil, ACS6, has been demonstrated to inhibit superoxide formation through donating hydrogen sulfide (H2S. We have found that H2S antagonizes homocysteine-induced oxidative stress and neurotoxicity. The aim of the present study is to explore the protection of ACS6 against homocysteine-triggered cytotoxicity and apoptosis and the molecular mechanisms underlying in PC12 cells. Methods Cell viability was determined by Cell Counting Kit-8 assay. Cell apoptosis was observed using the chromatin dye Hoechst 33258 and analyzed by Flow Cytometry after propidium iodide staining. Mitochondrial membrane potential was monitored using the fluorescent dye Rh123. Intracellular reactive oxygen species were determined by oxidative conversion of cell permeable 2',7'-dichlorfluorescein-diacetate to fluorescent 2',7'-dichlorfluorescein. The expression of cleaved caspase-3 and bcl-2 and the accumulation of cytosolic cytochrome c were analyzed by Western blot. Results We show that ACS6 protects PC12 cells against cytotoxicity and apoptosis induced by homocysteine and blocks homocysteine-triggered cytochrome c release and caspase-3 activation. ACS6 treatment results in not only prevention of homocysteine-caused mitochondrial membrane potential (Δψ loss and reactive oxygen species (ROS overproduction but also reversal of Bcl-2 down-expression. Conclusions These results indicate that ACS6 protects PC12 cells against homocysteine-induced cytotoxicity and apoptosis by preservation of mitochondrial function though inhibiting both loss of Δψ and accumulation of ROS as well as modulating the expression of Bcl-2. Our study provides evidence both for a neuroprotective effect of ACS6 and for further evaluation of ACS6 as novel neuroprotectants for Alzheimer's disease associated with homocysteine.

  13. Assessment of laryngeal functions in patients with squamous cell carcinoma of the larynx or hypopharynx treated with concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    Taguchi, Takahide; Tsukuda, Mamoru; Nagao, Jun-ichi

    2010-01-01

    The laryngeal functions in patients with laryngeal or hypopharyngeal cancer treated with concurrent chemoradiotherapy (CCRT) were evaluated. We reviewed the records of 32 patients with resectable stage II to IV squamous cell carcinoma of the larynx or hypopharynx treated with CCRT as a initial treatment between October 1998 and September 2003. A questionnaire survey and measurements of maximum phonation time, GRBAS and range of voice/speaking fundamental frequency were performed, and the method of food intake in the swallowing ability scale and the presence of tracheostoma were assessed for evaluating laryngeal functions after CCRT. After CCRT for laryngeal or hypopharyngeal cancer, the phonatory functions appeared to be preserved in 75% of the patients in terms of sustainability; however, there were some cases presenting hoarseness and narrowed range of voice. Oral intake was possible in most cases (97%) without a history of aspiration pneumonia. In 2 cases, permanent tracheostoma had to be retained. It was concluded that laryngeal functions could be preserved in most cases after CCRT, though the tracheostoma might not be closed in some patients with laryngeal cancer. (author)

  14. Prolonged platelet preservation by transient metabolic suppression

    NARCIS (Netherlands)

    Badlou, Bahram Alamdary

    2006-01-01

    Introduction: Different clinical studies have shown that transfusion of stored platelets results in better haemostasis in patients with thrombocytopenia with and without a platelet function defect. Objectives: Current preservation procedures aim to optimally preserve the metabolic status of

  15. Cost Model for Digital Preservation: Cost of Digital Migration

    DEFF Research Database (Denmark)

    Kejser, Ulla Bøgvad; Nielsen, Anders Bo; Thirifays, Alex

    2011-01-01

    The Danish Ministry of Culture has funded a project to set up a model for costing preservation of digital materials held by national cultural heritage institutions. The overall objective of the project was to increase cost effectiveness of digital preservation activities and to provide a basis...... for comparing and estimating future cost requirements for digital preservation. In this study we describe an activity-based costing methodology for digital preservation based on the Open Archice Information System (OAIS) Reference Model. Within this framework, which we denote the Cost Model for Digital...... Preservation (CMDP), the focus is on costing the functional entity Preservation Planning from the OAIS and digital migration activities. In order to estimate these costs we have identified cost-critical activities by analysing the functions in the OAIS model and the flows between them. The analysis has been...

  16. Alternative food-preservation technologies: efficacy and mechanisms.

    Science.gov (United States)

    Lado, Beatrice H; Yousef, Ahmed E

    2002-04-01

    High-pressure processing, ionizing radiation, pulsed electric field and ultraviolet radiation are emerging preservation technologies designed to produce safe food, while maintaining its nutritional and sensory qualities. A sigmoid inactivation pattern is observed in most kinetic studies. Damage to cell membranes, enzymes or DNA is the most commonly cited cause of death of microorganisms by alternative preservation technologies.

  17. Ex-vivo machine perfusion for kidney preservation.

    Science.gov (United States)

    Hamar, Matyas; Selzner, Markus

    2018-06-01

    Machine perfusion is a novel strategy to decrease preservation injury, improve graft assessment, and increase organ acceptance for transplantation. This review summarizes the current advances in ex-vivo machine-based kidney preservation technologies over the last year. Ex-vivo perfusion technologies, such as hypothermic and normothermic machine perfusion and controlled oxygenated rewarming, have gained high interest in the field of organ preservation. Keeping kidney grafts functionally and metabolically active during the preservation period offers a unique chance for viability assessment, reconditioning, and organ repair. Normothermic ex-vivo kidney perfusion has been recently translated into clinical practice. Preclinical results suggest that prolonged warm perfusion appears superior than a brief end-ischemic reconditioning in terms of renal function and injury. An established standardized protocol for continuous warm perfusion is still not available for human grafts. Ex-vivo machine perfusion represents a superior organ preservation method over static cold storage. There is still an urgent need for the optimization of the perfusion fluid and machine technology and to identify the optimal indication in kidney transplantation. Recent research is focusing on graft assessment and therapeutic strategies.

  18. Fecoflowmetric Analysis of Anorectal Motor Function in Postoperative Anal-Preserving Surgery Patients With Low Rectal Cancer Comparison With the Wexner Score and Anorectal Manometry

    Science.gov (United States)

    Ryu, Yasuhiko; Akagi, Yoshito; Yagi, Minoru; Sasatomi, Teruo; Kinugasa, Tetsushi; Yamaguchi, Keizo; Oka, Yousuke; Fukahori, Suguru; Shiratsuchi, Ichitaro; Yoshida, Takefumi; Gotanda, Yukito; Tanaka, Natsuki; Ohchi, Takafumi; Romeo, Kansakar; Shirouzu, Kazuo

    2015-01-01

    The aim of this study was to elucidate whether fecoflowmetry (FFM) could evaluate more detailed evacuative function than anorectal manometry by comparing between FFM or anorectal manometric findings and the clinical questionnaires and the types of surgical procedure in the patients who received anal-preserving surgery. Fifty-three patients who underwent anal-preserving surgery for low rectal cancer were enrolled. The relationships between FFM or the manometric findings and the clinical questionnaires and the types of procedure of anal-preserving surgery were evaluated. There were significant differences between FFM markers and the clinical questionnaire and the types of the surgical procedure, whereas no significant relationship was observed between the manometric findings and the clinical questionnaire and the types of the surgical procedure. FFM might be feasible and useful for the objective assessment of evacuative function and may be superior to manometry for patients undergoing anal-preserving surgery. PMID:25594637

  19. A case of Lamin C gene-mutation with preserved systolic function and ventricular dysrrhythmia

    Directory of Open Access Journals (Sweden)

    Kevin Kit Ng

    2013-02-01

    Full Text Available Lamin A/C gene-related cardiomyopathy is associated with progressive heart failure and malignant arrhythmias. Current guidelines advise the use of implantable defibrillators to prevent arrhythmogenic sudden cardiac death only in situations where there is evidence of severe left ventricular dysfunction. We describe a case of a woman with genetically confirmed Lamin C deficiency with preserved left ventricular function in whom an implantable defibrillator was inserted and within a month of implantation was used to terminate symptomatic ventricular tachycardia.

  20. Using computer graphics to preserve function in resection of malignant melanoma of the foot.

    Science.gov (United States)

    Kaufman, M; Vantuyl, A; Japour, C; Ghosh, B C

    2001-08-01

    The increasing incidence of malignant melanoma challenges physicians to find innovative ways to preserve function and appearance in affected areas that require partial resection. We carefully planned the resection of a malignant lesion between the third and fourth toes of a 77-year-old man with the aid of computer technology. The subsequent excision of the third, fourth, and fifth digits was executed such that the new metatarsal arc formed would approximate the dimensions of the optimal hyperbola, thereby minimizing gait disturbance.

  1. Recovery from diabetes insipidus and preservation of thyroid function after craniopharyngioma removal and pituitary stalk sectioning.

    Science.gov (United States)

    Ogawa, Yoshikazu; Niizuma, Kuniyasu; Tominaga, Teiji

    2017-11-01

    Craniopharyngioma is a slow-growing tumor, but long-term tumor control with maintenance of quality of life is sometimes very difficult to achieve, and hypothalamic disturbance should be strictly avoided in the treatment. However, management of the pituitary gland and/or pituitary stalk varies among surgeons and institutions. This retrospective review identified 44 patients, 24 males and 20 females with craniopharyngiomas who were initially treated by surgery through the extended transsphenoidal approach with pituitary stalk sectioning at a single institute. If the tumor bed involved the posterior lobe of the pituitary gland, pituitary stalk, anterior and/or mid portion of the third ventricle floor, these structures were removed en-bloc together with the tumor. The closest attention was paid to preserve fine arteries running along the surface of optic chiasm and the lateral walls of the third ventricle. Surgical outcome and changes in postoperative endocrinological status were investigated. Gross total removal was achieved in 40 of 44 patients (91%), and all patients could discharge without autonomic and/or thermal disturbances. Tumor remnants were identified with tight adhesion to the perforating arteries in 2 cases, tight adhesion to mammillary bodies in 1, and optic chiasm in 1. Administration of anti-diuretic hormone could be discontinued in 23 of 44 patients (52.3%) with improved diabetes insipidus (DI), although no patient could discontinue glucocorticoid administration. Preservation of thyroid function was achieved in another 23 of 44 patients (52.3%), and recovery from DI was correlated with preservation of thyroid function (p=0.016). Pituitary dysfunction is partially reversible even with pituitary stalk sectioning. Regrowth of tumor in the anterior and/or mid portion of the third ventricle floor including pituitary stalk can possibly be prevented by aggressive tumor removal, and co-achievement of long-term tumor control with maintenance of quality of life

  2. Mast Cell Function

    Science.gov (United States)

    da Silva, Elaine Zayas Marcelino; Jamur, Maria Célia

    2014-01-01

    Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role. PMID:25062998

  3. Development of a living membrane comprising a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane.

    Science.gov (United States)

    Schophuizen, Carolien M S; De Napoli, Ilaria E; Jansen, Jitske; Teixeira, Sandra; Wilmer, Martijn J; Hoenderop, Joost G J; Van den Heuvel, Lambert P W; Masereeuw, Rosalinde; Stamatialis, Dimitrios

    2015-03-01

    The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a "living membrane", consisting of a tight kidney cell monolayer with preserved functional organic ion transporters on a suitable artificial membrane surface. In this work, we applied a unique conditionally immortalized proximal tubule epithelial cell (ciPTEC) line with an optimized coating strategy on polyethersulfone (PES) membranes to develop a living membrane with a functional proximal tubule epithelial cell layer. PES membranes were coated with combinations of 3,4-dihydroxy-l-phenylalanine and human collagen IV (Coll IV). The optimal coating time and concentrations were determined to achieve retention of vital blood components while preserving high water transport and optimal ciPTEC adhesion. The ciPTEC monolayers obtained were examined through immunocytochemistry to detect zona occludens 1 tight junction proteins. Reproducible monolayers were formed when using a combination of 2 mg ml(-1) 3,4-dihydroxy-l-phenylalanine (4 min coating, 1h dissolution) and 25 μg ml(-1) Coll IV (4 min coating). The successful transport of (14)C-creatinine through the developed living membrane system was used as an indication for organic cation transporter functionality. The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2). In conclusion, this study shows the successful development of a living membrane consisting of a reproducible ciPTEC monolayer on PES membranes, an important step towards the development of a bioartificial kidney. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. The Late Devonian Gogo Formation Lägerstatte of Western Australia: Exceptional Early Vertebrate Preservation and Diversity

    Science.gov (United States)

    Long, John A.; Trinajstic, Kate

    2010-05-01

    The Gogo Formation of Western Australia preserves a unique Late Devonian (Frasnian) reef fauna. The exceptional three-dimensional preservation of macrofossils combined with unprecedented soft-tissue preservation (including muscle bundles, nerve cells, and umbilical structures) has yielded a particularly rich assemblage with almost 50 species of fishes described. The most significant discoveries have contributed to resolving placoderm phylogeny and elucidating their reproductive physiology. Specifically, these discoveries have produced data on the oldest known vertebrate embryos; the anatomy of the primitive actinopterygian neurocranium and phylogeny of the earliest actinopterygians; the histology, radiation, and plasticity of dipnoan (lungfish) dental and cranial structures; the anatomy and functional morphology of the extinct onychodonts; and the anatomy of the primitive tetrapodomorph head and pectoral fin.

  5. Recommendations for the definition of clinical responder in insulin preservation studies.

    Science.gov (United States)

    Beam, Craig A; Gitelman, Stephen E; Palmer, Jerry P

    2014-09-01

    Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials prespecify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In this article, we propose a clinical responder definition to specifically assist researchers and regulatory agencies in interpreting the clinical importance of statistically significant findings for studies of interventions intended to preserve β-cell function in newly diagnosed type 1 diabetes. We focus on studies of 6-month β-cell preservation in type 1 diabetes as measured by 2-h-stimulated C-peptide. We introduce criteria (bias, reliability, and external validity) for the assessment of responder definitions to ensure they meet U.S. Food and Drug Administration and European Medicines Agency guidelines. Using data from several published TrialNet studies, we evaluate our definition (no decrease in C-peptide) against published alternatives and determine that our definition has minimum bias with external validity. We observe that reliability could be improved by using changes in C-peptide later than 6 months beyond baseline. In sum, to support efficacy claims of β-cell preservation therapies in type 1 diabetes submitted to U.S. and European regulatory agencies, we recommend use of our definition. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Acid-base buffering in organ preservation solutions as a function of temperature: new parameters for comparing buffer capacity and efficiency.

    Science.gov (United States)

    Baicu, Simona C; Taylor, Michael J

    2002-08-01

    Control of acidity and preventing intracellular acidosis are recognized as critical properties of an effective organ preservation solution. Buffer capacity and efficiency are therefore important for comparing the relative merits of preservation fluids for optimum hypothermic storage, but these parameters are not available for the variety of organ preservation solutions of interest in transplantation today. Moreover, buffer capacity is dependent upon both concentration and pH such that buffer capacity is not easily predicted for a complex solution containing multiple buffer species. Using standard electrometric methods to measure acid dissociation constants, this study was undertaken to determine the maximum and relative buffer capacities of a variety of new and commonly used hypothermic preservation solutions as a function of temperature. The reference data provided by these measurements show that comparative buffer capacity and efficiency vary widely between the commonly used solutions. Moreover, the fluids containing zwitterionic sulfonic acid buffers such as Hepes possess superior buffering for alpha-stat pH regulation in the region of physiological importance.

  7. Hearing preservation and facial nerve function after microsurgery for intracanalicular vestibular schwannomas: comparison of middle fossa and retrosigmoid approaches.

    Science.gov (United States)

    Noudel, R; Gomis, P; Duntze, J; Marnet, D; Bazin, A; Roche, P H

    2009-08-01

    Therapeutic options for vestibular schwannomas (VS) include microsurgery, stereotactic radiosurgery and conservative management. Early treatment of intracanalicular vestibular schwannomas (IVS) may be advisable because their spontaneous course will show hearing loss in most cases. Advanced microsurgical techniques and continuous intraoperative monitoring of cranial nerves may allow hearing preservation (HP) without facial nerve damage. However, there are still controversies about the definition of hearing preservation, and the best surgical approach that should be used. In this study, we reviewed the main data from the recent literature on IVS surgery and compared hearing, facial function and complication rates after the retrosigmoid (RS) and middle fossa (MF) approaches, respectively. The results showed that the average HP rate after IVS surgery ranged from 58% (RS) to 62% (MF). HP varied widely depending on the audiometric criteria that were used for definition of serviceable hearing. There was a trend to show that the MF approach offered a better quality of postoperative hearing (not statistically significant), whereas the RS approach offered a better facial nerve preservation and fewer complications (not statistically significant). We believe that the timing of treatment in the course of the disease and selection between radiosurgical versus microsurgical procedure are key issues in the management of IVS. Preservation of hearing and good facial nerve function in surgery for VS is a reasonable goal for many patients with intracanalicular tumors and serviceable hearing. Once open surgery has been decided, selection of the approach mainly depends on individual anatomical considerations and experience of the surgeon.

  8. Is verbal episodic memory in elderly with amyloid deposits preserved through altered neuronal function?

    Science.gov (United States)

    Ossenkoppele, Rik; Madison, Cindee; Oh, Hwamee; Wirth, Miranka; van Berckel, Bart N M; Jagust, William J

    2014-08-01

    A potential mechanism that enables intellectual preservation in cognitively normal elderly that harbor beta-amyloid (Aβ) pathology is heightened cerebral glucose metabolism. To investigate cross-sectional inter-relationships between Aβ, glucose metabolism, and cognition, 81 subjects (mean age: 75 ± 7 years) underwent [(11)C]Pittsburgh Compound-B and [(18)F]fluorodeoxyglucose positron emission tomography scans and neuropsychological testing. They were divided into low-Aβ (n = 53), intermediate-Aβ (n = 13) and high-Aβ (n = 15) groups as defined by their global cortical [(11)C]PIB retention. Glucose metabolism was assessed using a MetaROI mask that covers metabolically critical regions in Alzheimer's disease (AD) (i.e., posterior cingulate and bilateral angular and inferior temporal gyri). Previously validated factor scores for verbal and visual episodic memory, semantic memory, working memory, and executive functioning were used to evaluate cognitive performances. Greater Aβ deposition in the precuneus was associated with higher metabolic activity (at trend level) and lower visual episodic memory scores. Glucose metabolism did not correlate with cognition across all subjects. However, heightened metabolic activity was associated with better verbal episodic memory performance in subjects with elevated amyloid levels. This preliminary study suggests that neural compensation, as a manifestation of brain reserve, enables elderly supposedly on the path to AD, at least temporarily, to preserve cognitive function. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Removal of vestibular schwannoma and facial nerve preservation using small suboccipital retrosigmoid craniotomy

    Institute of Scientific and Technical Information of China (English)

    CHEN Ling; CHEN Li-hua; LING Feng; LIU Yun-sheng; Madjid Samii; Amir Samii

    2010-01-01

    Background Vestibular schwannoma, the commonest form of intracranial schwannoma, arises from the Schwann cells investing the vestibular nerve. At present, the surgery for vestibular schwannoma remains one of the most complicated operations demanding for surgical skills in neurosurgery. And the trend of minimal invasion should also be the major influence on the management of patients with vestibular schwannomas. We summarized the microsurgical removal experience in a recent series of vestibular schwannomas and presented the operative technique and cranial nerve preservation in order to improve the rates of total tumor removal and facial nerve preservation.Methods A retrospective analysis was performed in 145 patients over a 7-year period who suffered from vestibular schwannomas that had been microsurgicaily removed by suboccipital retrosigmoid transmeatus approach with small craniotomy. CT thinner scans revealed the tumor size in the internal auditory meatus and the relationship of the posterior wall of the internal acoustic meatus to the bone labyrinths preoperatively. Brain stem evoked potential was monitored intraoperatively. The posterior wall of the internal acoustic meatus was designedly drilled off. Patient records and operative reports, including data from the electrophysiological monitoring, follow-up audiometric examinations, and neuroradiological findings were analyzed.Results Total tumor resection was achieved in 140 cases (96.6%) and subtotal resection in 5 cases. The anatomical integrity of the facial nerve was preserved in 91.0% (132/145) of the cases. Intracranial end-to-end anastomosis of the facial nerve was performed in 7 cases. Functional preservation of the facial nerve was achieved in 115 patients (Grade Ⅰ and Grade Ⅱ, 79.3%). No patient died in this series. Preservation of nerves and vessels were as important as tumor removal dudng the operation. CT thinner scan could show the relationship between the posterior wall of the internal

  10. Optimization of preservation activities and preservation engineering (1)

    International Nuclear Information System (INIS)

    Aoki, Takayuki; Mimaki, Hidehito; Oda, Mitsuyuki

    2004-01-01

    In order to deal with the optimization of preservation activities and 'preservation engineering' which makes it possible, the relation between general society and preservation, the content and the structure of preservation activities, and the viewpoint and the approach of the optimization of the preventive preservation are described. The optimization of the preventive preservation is shown respectively in the four stages of planning, implementation, result evaluation and countermeasure. (K. Kato)

  11. Normothermic perfusion: a new paradigm for organ preservation.

    Science.gov (United States)

    Brockmann, Jens; Reddy, Srikanth; Coussios, Constantin; Pigott, David; Guirriero, Dino; Hughes, David; Morovat, Alireza; Roy, Debabrata; Winter, Lucy; Friend, Peter J

    2009-07-01

    Transplantation of organs retrieved after cardiac arrest could increase the donor organ supply. However, the combination of warm ischemia and cold preservation is highly detrimental to the reperfused organ. Our objective was to maintain physiological temperature and organ function during preservation and thereby alleviate this injury and allow successful transplantation. We have developed a liver perfusion device that maintains physiological temperature with provision of oxygen and nutrition. Reperfusion experiments suggested that this allows recovery of ischemic damage. In a pig liver transplant model, we compared the outcome following either conventional cold preservation or warm preservation. Preservation periods of 5 and 20 hours and durations of warm ischemia of 40 and 60 minutes were tested. After 20 hours preservation without warm ischemia, post-transplant survival was improved (27%-86%, P = 0.026), with corresponding differences in transaminase levels and histological analysis. With the addition of 40 minutes warm ischemia, the differences were even more marked (cold vs. warm groups 0% vs. 83%, P = 0.001). However, with 60 minutes warm ischemia and 20 hours preservation, there were no survivors. Analysis of hemodynamic and liver function data during perfusion showed several factors to be predictive of posttransplant survival, including bile production, base excess, portal vein flow, and hepatocellular enzymes. Organ preservation by warm perfusion, maintaining physiological pressure and flow parameters, has enabled prolonged preservation and successful transplantation of both normal livers and those with substantial ischemic damage. This technique has the potential to address the shortage of organs for transplantation.

  12. Initial Results of Bladder Preserving Approach by Chemo-Radiotherapy in Patients with Muscle Invading Transitional Cell Carcinoma

    International Nuclear Information System (INIS)

    Aboziada, M.A.; Hamza, H.; Abdlrahem, A.M.

    2009-01-01

    This study was conducted to test the efficacy and tolerability of trimodality treatment for invasive bladder cancer and to test the possibility of bladder sparing. Methods: This study had been carried out on 50 patients with transitional cell carcinoma (TCC) stage T2- T3 tumors with adequate performance status and renal function. All patients were subjected to maximum transurethral resection of bladder tumors (TURBT). Patients were then subjected to chemo-radiation that was executed in two treatment phases. Phase I was external radiotherapy in the form of 46 Gy /23 fractions /5 weeks to whole pelvis with concurrent cisplatin 40 mg/m 2 weekly. Phase II was 20 Gy /10 fractions /2 weeks to the bladder tumor with concurrent cisplatin 40 mg/m2 weekly. After phase I, patients who had complete response (CR) or partial response (PR) were subjected to phase II and patients who had stationary disease (SD) were subjected to salvage cystectomy. After the end of treatment, patients who had CR were subjected to bladder preservation. Radiological and cystoscopic reevaluation was done to assess the tumor response after phase I and phase II. After completion of the scheduled treatment, patients were under follow up for clinical examination, radiological, and cystoscopic assessment. Results: The treatment schedule was tolerable and was associated with infrequent incidence of moderate toxicity that was easily controlled without interruption of treatment. Bladder preservation was achieved in 72% of patients. The actuarial relapse free survival and overall survival at a median follow up 18 months for patients who were candidate for bladder preservation were 81% and 100%; respectively. Invasive recurrence (16%) sal-Jvaged with cystectomy and superficial recurrence (6%) successfully treated with Bacilles bilie de Calmette- Guerin. Conclusions: This study indicates that in spite of a relatively small number of patients and short follow-up period; the trimodality treatment could be an

  13. Random heteropolymers preserve protein function in foreign environments

    Science.gov (United States)

    Panganiban, Brian; Qiao, Baofu; Jiang, Tao; DelRe, Christopher; Obadia, Mona M.; Nguyen, Trung Dac; Smith, Anton A. A.; Hall, Aaron; Sit, Izaac; Crosby, Marquise G.; Dennis, Patrick B.; Drockenmuller, Eric; Olvera de la Cruz, Monica; Xu, Ting

    2018-03-01

    The successful incorporation of active proteins into synthetic polymers could lead to a new class of materials with functions found only in living systems. However, proteins rarely function under the conditions suitable for polymer processing. On the basis of an analysis of trends in protein sequences and characteristic chemical patterns on protein surfaces, we designed four-monomer random heteropolymers to mimic intrinsically disordered proteins for protein solubilization and stabilization in non-native environments. The heteropolymers, with optimized composition and statistical monomer distribution, enable cell-free synthesis of membrane proteins with proper protein folding for transport and enzyme-containing plastics for toxin bioremediation. Controlling the statistical monomer distribution in a heteropolymer, rather than the specific monomer sequence, affords a new strategy to interface with biological systems for protein-based biomaterials.

  14. Intradialytic Cognitive and Exercise Training May Preserve Cognitive Function.

    Science.gov (United States)

    McAdams-DeMarco, Mara A; Konel, Jonathan; Warsame, Fatima; Ying, Hao; Fernández, Marlís González; Carlson, Michelle C; Fine, Derek M; Appel, Lawrence J; Segev, Dorry L

    2018-01-01

    Cognitive decline is common and increases mortality risk in hemodialysis patients. Intradialytic interventions like cognitive training (CT) and exercise training (ET) may preserve cognitive function. We conducted a pilot randomized controlled trial of 20 hemodialysis patients to study the impact of 3 months of intradialytic CT (tablet-based brain games) (n = 7), ET (foot peddlers) (n = 6), or standard of care (SC) (n = 7) on cognitive function. Global cognitive function was measured by the Modified Mini Mental Status Exam (3MS), psychomotor speed was measured by Trail Making Tests A and B (TMTA and TMTB), and executive function was assessed by subtracting (TMTB - TMTA). Lower 3MS scores and slower TMTA and TMTB times reflected worse cognitive function. P values for differences were generated using analysis of variance, and 95% confidence intervals (CIs) and P values were generated from linear regression. Patients with SC experienced a decrease in psychomotor speed and executive function by 3 months (TMTA: 15 seconds; P  = 0.055; TMTB: 47.4 seconds; P  = 0.006; TMTB - TMTA; 31.7 seconds; P  = 0.052); this decline was not seen among those with CT or ET (all P > 0.05). Compared with SC, the difference in the mean change in 3MS score was -3.29 points (95% CI: -11.70 to 5.12; P  = 0.42) for CT and 4.48 points (95% CI: -4.27 to 13.22; P  = 0.30) for ET. Compared with SC, the difference in mean change for TMTA was -15.13 seconds (95% CI: -37.64 to 7.39; P  = 0.17) for CT and -17.48 seconds (95% CI: -41.18 to 6.22; P  = 0.14) for ET, for TMTB, the difference was -46.72 seconds (95% CI: -91.12 to -2.31; P  = 0.04) for CT and -56.21 seconds (95% CI: -105.86 to -6.56; P  = 0.03) for ET, and for TMTB - TMTA, the difference was -30.88 seconds (95% CI: -76.05 to 14.28; P  = 0.16) for CT and -34.93 seconds (95% CI: -85.43 to 15.56; P  = 0.16) for ET. Preliminary findings of our pilot study suggested that cognitive decline in psychomotor speed

  15. Effects of the ionising radiations on the structure and the function of the intestinal epithelial cell

    International Nuclear Information System (INIS)

    Haton, C.

    2005-06-01

    The intestinal mucosa is a particularly radio-sensitive tissue and damage may occur following either accidental or therapeutic exposure. the deleterious actions of ionizing radiation are linked to the formation of sometimes overwhelming quantities of reactive oxygen species (R.O.S.). Production of R.O.S. is both direct and indirect from the secondary effects of irradiation. A better comprehension of the underlying mechanisms of injury will lead to more adapted therapeutic approaches to limit the harmful effects of irradiation. The homeostasis of the intestinal epithelium is regulated by three factors: proliferation, apoptosis and differentiation. these three factors were studied using the cell model, HT29, in order to analyze modulations of this balance after irradiation. our results, in agreement with other data, showed the establishment of mitotic delay. This arrest of proliferation was followed by apoptosis to be the major mechanism leading to cell death in this model. thus, for the first time, we have shown that irradiated intestinal epithelial cells preserve their capacity to differentiate. This indicates, although indirectly, that intestinal cells have and preserve an intrinsic capacity restore a functional epithelium. R.O.S. are considered as intermediates between the physical nature of radiations and biological responses. It seems essential to understand anti-oxidant mechanisms used by the cell for defence against the deleterious effects of R.O.S post exposure. This study of several anti-oxidant defence mechanisms of intestinal mucosa, was carried out in vivo in the mouse at different times following abdominal irradiation. We observed an early mitochondrial response in the hours following irradiation revealing this organelle as a particular target. We demonstrated a strong alteration of anti-oxidant capacity as revealed by a decrease in S.O.D.s, catalase and an increase of the G.P.X.s and M.T.s. A part of these modifications appeared to depend on an

  16. X-ray photoelectron emission spectromicroscopic analysis of arborescent lycopsid cell wall composition and Carboniferous coal ball preservation

    Energy Technology Data Exchange (ETDEWEB)

    Boyce, C. Kevin [Department of the Geophysical Sciences, University of Chicago, Chicago, IL 60637 (United States); Abrecht, Mike; Zhou, Dong; Gilbert, P.U.P.A. [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States)

    2010-08-01

    Two alternative processes complicate understanding of the biochemical origins and geochemical alteration of organic matter over geologic time: selective preservation of original biopolymers and in situ generation of new geopolymers. One of the best constrained potential sources of bio- and geochemical information about extinct fossil plants is frequently overlooked. Permineralized anatomically preserved plant fossils allow analysis of individual cell and tissue types that have an original biochemical composition already known from living plants. The original composition of more enigmatic fossils can be constrained by geochemical comparisons to tissues of better understood fossils from the same locality. This strategy is possible using synchrotron-based techniques for submicron-scale imaging with X-rays over a range of frequencies in order to provide information concerning the relative abundance of different organic bonds with X-ray Absorption Near Edge Spectroscopy. In this study, X-ray PhotoElectron Emission spectroMicroscopy (X-PEEM) was used to analyze the tissues of Lepidodendron, one of the lycopsid trees that were canopy dominants of many Pennsylvanian coal swamp forests. Its periderm or bark - the single greatest biomass contributor to many Late Paleozoic coals - is found to have a greater aliphatic content and an overall greater density of organic matter than lignified wood. Because X-PEEM allows simultaneous analysis of organic matter and matrix calcite in fully mineralized fossils, this technique also has great potential for analysis of fossil preservation, including documentation of significant traces of organic matter entrained in the calcite crystal fabric that fills the cell lumens. (author)

  17. Effects of blood transportation on human peripheral mononuclear cell yield, phenotype and function: implications for immune cell biobanking.

    Directory of Open Access Journals (Sweden)

    Anita Posevitz-Fejfár

    Full Text Available Human biospecimen collection, processing and preservation are rapidly emerging subjects providing essential support to clinical as well as basic researchers. Unlike collection of other biospecimens (e.g. DNA and serum, biobanking of viable immune cells, such as peripheral blood mononuclear cells (PBMC and/or isolated immune cell subsets is still in its infancy. While certain aspects of processing and freezing conditions have been studied in the past years, little is known about the effect of blood transportation on immune cell survival, phenotype and specific functions. However, especially for multicentric and cooperative projects it is vital to precisely know those effects. In this study we investigated the effect of blood shipping and pre-processing delay on immune cell phenotype and function both on cellular and subcellular levels. Peripheral blood was collected from healthy volunteers (n = 9: at a distal location (shipped overnight and in the central laboratory (processed immediately. PBMC were processed in the central laboratory and analyzed post-cryopreservation. We analyzed yield, major immune subset distribution, proliferative capacity of T cells, cytokine pattern and T-cell receptor signal transduction. Results show that overnight transportation of blood samples does not globally compromise T- cell subsets as they largely retain their phenotype and proliferative capacity. However, NK and B cell frequencies, the production of certain PBMC-derived cytokines and IL-6 mediated cytokine signaling pathway are altered due to transportation. Various control experiments have been carried out to compare issues related to shipping versus pre-processing delay on site. Our results suggest the implementation of appropriate controls when using multicenter logistics for blood transportation aiming at subsequent isolation of viable immune cells, e.g. in multicenter clinical trials or studies analyzing immune cells/subsets. One important conclusion might

  18. Development of a Proactive Care Program (U-CARE) to Preserve Physical Functioning of Frail Older People in Primary Care

    NARCIS (Netherlands)

    Bleijenberg, N.; Ten Dam, V.H.; Drubbel, I.; Numans, M.E.; De Wit, N.J.; Schuurmans, M.J.

    2013-01-01

    Purpose: Care for older patients in primary care is currently reactive, fragmented, and time consuming. An innovative structured and proactive primary care program (U-CARE) has been developed to preserve physical functioning and enhance quality of life of frail older people. This study describes in

  19. Preservation Method and Phosphate Buffered Saline Washing Affect the Acute Myeloid Leukemia Proteome

    Directory of Open Access Journals (Sweden)

    Rebecca Wangen

    2018-01-01

    Full Text Available Acute myeloid leukemia (AML primary cells can be isolated from peripheral blood, suspended with media containing bovine serum and cryoprotectant, and stored in liquid nitrogen before being processed for proteomic analysis by mass spectrometry (MS. The presence of bovine serum and human blood proteins in AML samples can hamper the identifications of proteins, and thereby reduce the proteome coverage of the study. Herein, we have established the effect of phosphate buffered saline (PBS washing on AML patient samples stored in media. Although PBS washes effectively removed serum and blood contaminants, the saline wash resulted in cell burst and remarkable protein material loss. We also compared different methods to preserve the AML proteome from THP-1 and Molm-13 cell lines before MS analysis: (1 stored in media containing bovine serum and dimethyl sulfoxide (DMSO; (2 stored as dried cell pellets; and (3 stored as cell lysates in 4% sodium dodecyl sulfate (SDS. MS analysis of differently preserved AML cell samples shows that preservation with DMSO produce a high number of fragile cells that will burst during freezing and thawing. Our studies encourage the use of alternative preservation methods for future MS analysis of the AML proteome.

  20. Optimization of preservation activities and preservation engineering (2)

    International Nuclear Information System (INIS)

    Aoki, Takayuki; Mimaki, Hidehito; Oda, Mitsuyuki

    2004-01-01

    In order to deal with the optimization of preservation activities and 'preservation engineering' which makes it possible, the viewpoint and the approach of the optimization of the ex post facto preservation and the content to be possessed in 'preservation engineering' are described. The optimization of the ex post facto preservation is shown respectively in the four stages of planning, implementation, result evaluation and countermeasure. (K. Kato)

  1. Randomised trial of mitral valve repair with leaflet resection versus leaflet preservation on functional mitral stenosis (The CAMRA CardioLink-2 Trial).

    Science.gov (United States)

    Chan, Vincent; Chu, Michael W A; Leong-Poi, Howard; Latter, David A; Hall, Judith; Thorpe, Kevin E; de Varennes, Benoit E; Quan, Adrian; Tsang, Wendy; Dhingra, Natasha; Yared, Kibar; Teoh, Hwee; Chu, F Victor; Chan, Kwan-Leung; Mesana, Thierry G; Connelly, Kim A; Ruel, Marc; Jüni, Peter; Mazer, C David; Verma, Subodh

    2017-05-30

    The gold-standard treatment of severe mitral regurgitation (MR) due to degenerative disease is valve repair, which is surgically performed with either a leaflet resection or leaflet preservation approach. Recent data suggest that functional mitral stenosis (MS) may occur following valve repair using a leaflet resection strategy, which adversely affects patient prognosis. A randomised comparison of these two approaches to mitral repair on functional MS has not been conducted. This is a prospective, multicentre randomised controlled trial designed to test the hypothesis that leaflet preservation leads to better preservation of mitral valve geometry, and therefore, will be superior to leaflet resection for the primary outcome of functional MS as assessed by 12-month mean mitral valve gradient at peak exercise. Eighty-eight patients with posterior leaflet prolapse will be randomised intraoperatively once deemed by the operating surgeon to feasibly undergo mitral repair using either a leaflet resection or leaflet preservation approach. Secondary end points include comparison of repair strategies with regard to mitral valve orifice area, leaflet coaptation height, 6 min walk test and a composite major adverse event end point consisting of recurrent MR ≥2+, death or hospital readmission for congestive heart failure within 12 months of surgery. Institutional ethics approval has been obtained from all enrolling sites. Overall, there remains clinical equipoise regarding the mitral valve repair strategy that is associated with the least likelihood of functional MS. This trial hopes to introduce high-quality evidence to help surgical decision making in this context. NCT02552771. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Preservation of autophagy should not direct nutritional therapy

    NARCIS (Netherlands)

    McClave, S.A.; Weijs, P.J.M.

    2015-01-01

    PURPOSE OF REVIEW: Recent reports in the literature have proposed that forced mandatory feeding should be avoided in the first week of critical illness to preserve autophagy, in order to maximize responses to oxidative stress, preserve organ function, and improve outcomes. RECENT FINDINGS: Autophagy

  3. Cost Model for Digital Preservation: Cost of Digital Migration

    Directory of Open Access Journals (Sweden)

    Ulla Bøgvad Kejser

    2011-03-01

    Full Text Available The Danish Ministry of Culture has funded a project to set up a model for costing preservation of digital materials held by national cultural heritage institutions. The overall objective of the project was to increase cost effectiveness of digital preservation activities and to provide a basis for comparing and estimating future cost requirements for digital preservation. In this study we describe an activity-based costing methodology for digital preservation based on the Open Archice Information System (OAIS Reference Model. Within this framework, which we denote the Cost Model for Digital Preservation (CMDP, the focus is on costing the functional entity Preservation Planning from the OAIS and digital migration activities. In order to estimate these costs we have identified cost-critical activities by analysing the functions in the OAIS model and the flows between them. The analysis has been supplemented with findings from the literature, and our own knowledge and experience. The identified cost-critical activities have subsequently been deconstructed into measurable components, cost dependencies have been examined, and the resulting equations expressed in a spreadsheet. Currently the model can calculate the cost of different migration scenarios for a series of preservation formats for text, images, sound, video, geodata, and spreadsheets. In order to verify the model it has been tested on cost data from two different migration projects at the Danish National Archives (DNA. The study found that the OAIS model provides a sound overall framework for the cost breakdown, but that some functions need additional detailing in order to cost activities accurately. Running the two sets of empirical data showed among other things that the model underestimates the cost of manpower-intensive migration projects, while it reinstates an often underestimated cost, which is the cost of developing migration software. The model has proven useful for estimating the

  4. Preserved ex vivo inflammatory status in decidual cells from women with preterm labor and subclinical intrauterine infection.

    Directory of Open Access Journals (Sweden)

    Violeta Castro-Leyva

    Full Text Available OBJECTIVE: To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection. METHODS: Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10, pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α, and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9 were measured in the supernatants using Bio-Plex, and prostaglandin E(2 (PGE(2 was measured by enzyme immunoassay. RESULTS: Subclinical infection was confirmed in 10 women (28.5%. Microorganisms isolated were Ureaplasma urealyticum (4, group B streptococci (3, Gardnerella vaginalis (1, and Escherichia coli (2. We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE(2 was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages. CONCLUSIONS: Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.

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

    Directory of Open Access Journals (Sweden)

    Tatsuki Ueda

    2016-01-01

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

  6. Beneficial effects of young coconut juice on preserving neuronal cell density, lipid, renal and liver profiles in ovariectomized rats. A preliminary study.

    Directory of Open Access Journals (Sweden)

    Kolip Payanglee

    2017-04-01

    Full Text Available Our previous study showed that young coconut juice (YCJ at a high dose of 100 mL/kgBW had many health benefits e.g. it delayed Alzheimer’s pathologies, preserved neuronal cells, accelerated wound healing and prevented osteoporosis. However, such a large dose of YCJ over a period of time started to have unfavourable side effects e.g. the deposition of glycogen in the liver. Therefore, our aim in the present study was to investigate the lowest neuroprotective dose of YCJ that would cause the least side effects for long-term consumption by postmenopausal women, using ovariectomized (ovx rats as a model for postmenopausal women. Three lower doses of YCJ (10, 20 and 40 mL/kg body weight were applied. The results clearly showed that the OY10 group was the best dose to help to preserve neuronal cells in both the hippocampus and the prefrontal cortex with cell numbers being higher than for the ovx group at various degrees of significance in each brain region. After 10 weeks of treatment, the circulating levels of BUN, creatinine, cholesterol, triglyceride, HDL, LDL, AST, ALT, ALP, total protein, albumin, calcium and phosphorus of the OY10 group were not significantly different from those of the sham and ovx groups. This study has confirmed that feeding YCJ had beneficial effects on the serum lipid profile, and maintained liver and renal functions for up to 10 weeks after administration. YCJ consumption at 10 mL/kgBW/day for 10 weeks, however, did increase body weight and serum glucose when compared with the control groups. Therefore, supplementation with YCJ in postmenopausal women with a diabetic condition should only be allowed under supervision by a physician.

  7. Development of a Cytocompatible Scaffold from Pig Immature Testicular Tissue Allowing Human Sertoli Cell Attachment, Proliferation and Functionality

    Directory of Open Access Journals (Sweden)

    Maxime Vermeulen

    2018-01-01

    Full Text Available Cryopreservation of immature testicular tissue before chemo/radiotherapy is the only option to preserve fertility of cancer-affected prepubertal boys. To avoid reintroduction of malignant cells, development of a transplantable scaffold by decellularization of pig immature testicular tissue (ITT able to support decontaminated testicular cells could be an option for fertility restoration in these patients. We, therefore, compared decellularization protocols to produce a cytocompatible scaffold. Fragments of ITT from 15 piglets were decellularized using three protocols: sodium dodecyl sulfate (SDS-Triton (ST, Triton-SDS-Triton (TST and trypsin 0.05%/ethylenediaminetetraacetic acid (EDTA 0.02%-Triton (TET with varying detergent concentrations. All protocols were able to lower DNA levels. Collagen retention was demonstrated in all groups except ST 1%, and a significant decrease in glycosaminoglycans was observed in the TST 1% and TET 1% groups. When Sertoli cells (SCs were cultured with decellularized tissue, no signs of cytotoxicity were detected. A higher SC proliferation rate and greater stem cell factor secretion were observed than with SCs cultured without scaffold. ST 0.01% and TET 3% conditions offered the best compromise in terms of DNA elimination and extracellular matrix (ECM preservation, while ensuring good attachment, proliferation and functionality of human SCs. This study demonstrates the potential of using decellularized pig ITT for human testicular tissue engineering purposes.

  8. Apoptosis-Inducing-Factor-Dependent Mitochondrial Function Is Required for T Cell but Not B Cell Function.

    Science.gov (United States)

    Milasta, Sandra; Dillon, Christopher P; Sturm, Oliver E; Verbist, Katherine C; Brewer, Taylor L; Quarato, Giovanni; Brown, Scott A; Frase, Sharon; Janke, Laura J; Perry, S Scott; Thomas, Paul G; Green, Douglas R

    2016-01-19

    The role of apoptosis inducing factor (AIF) in promoting cell death versus survival remains controversial. We report that the loss of AIF in fibroblasts led to mitochondrial electron transport chain defects and loss of proliferation that could be restored by ectopic expression of the yeast NADH dehydrogenase Ndi1. Aif-deficiency in T cells led to decreased peripheral T cell numbers and defective homeostatic proliferation, but thymic T cell development was unaffected. In contrast, Aif-deficient B cells developed and functioned normally. The difference in the dependency of T cells versus B cells on AIF for function and survival correlated with their metabolic requirements. Ectopic Ndi1 expression rescued homeostatic proliferation of Aif-deficient T cells. Despite its reported roles in cell death, fibroblasts, thymocytes and B cells lacking AIF underwent normal death. These studies suggest that the primary role of AIF relates to complex I function, with differential effects on T and B cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Yeasts preservation: alternatives for lyophilisation

    NARCIS (Netherlands)

    Nyanga, L.K.; Nout, M.J.R.; Smid, E.J.; Boekhout, T.; Zwietering, M.H.

    2012-01-01

    The aim of the study was to compare the effect of two low-cost, low technology traditional methods for drying starter cultures with standard lyophilisation. Lyophilised yeast cultures and yeast cultures preserved in dry rice cakes and dry plant fibre strands were examined for viable cell counts

  10. A comparison of preservative-free diclofenac and preserved diclofenac eye drops after cataract surgery in patients with diabetic retinopathy.

    Science.gov (United States)

    Yasuda, Kanako; Miyazawa, Akiko; Shimura, Masahiko

    2012-06-01

    The aim of this study was to compare the anti-inflammatory efficacy of preservative-free and preserved 0.1% diclofenac eye drops for the management of postoperative inflammation after cataract surgery in patients with nonproliferative diabetic retinopathy and in normal controls. Forty-two diabetic patients and 50 normal control patients who underwent small-incision phacoemulsification cataract surgery bilaterally received topical preservative-free diclofenac in 1 eye and preserved diclofenac in the other eye. The corrected distance visual acuity (CDVA) as determined by a logarithm of the minimum angle of resolution (logMAR) chart, intraocular pressure (IOP), foveal thickness (FT) using optical coherence tomography (OCT), and the anterior chamber flare (ACF) score measured with a laser flare cell meter were monitored for 12 weeks after surgery. In the eyes with diabetic retinopathy, there were no significant differences in CDVA, IOP, FT, and ACF score between the right and left eyes at the initial exam. After cataract surgery, changes in CDVA, IOP, and FT were not influenced by the preservative in the diclofenac eye drops. In contrast, the ACF score in the eyes treated with preserved diclofenac showed slower recovery from postoperative inflammation than the eyes treated with preservative-free diclofenac. In the normal control eyes, similar but milder changes were observed in each of the clinical parameters. Because preservative suppressed the anti-inflammatory efficacy of topical diclofenac after cataract surgery, preservative-free diclofenac may have an improved safety profile during postoperative treatment, especially in patients with diabetic retinopathy.

  11. Stereotactic radiotherapy of vestibular schwannoma. Hearing preservation, vestibular function, and local control following primary and salvage radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Putz, Florian; Mueller, Jan; Wimmer, Caterina; Goerig, Nicole; Knippen, Stefan; Semrau, Sabine; Fietkau, Rainer; Lettmaier, Sebastian [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Radiation Oncology, Erlangen (Germany); Iro, Heinrich; Grundtner, Philipp [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Otorhinolaryngology - Head and Neck Surgery, Erlangen (Germany); Eyuepoglu, Ilker; Roessler, Karl [Friedrich-Alexander-University Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany)

    2017-03-15

    The aim of this publication is to present long-term data on functional outcomes and tumor control in a cohort of 107 patients treated with stereotactic radiotherapy (RT) for vestibular schwannoma. Included were 107 patients with vestibular schwannoma (primary or recurrent following resection) treated with stereotactic RT (either fractioned or single-dose radiosurgery) between October 2002 and December 2013. Local control and functional outcomes were determined. Analysis of hearing preservation was limited to a subgroup of patients with complete audiometric data collected before treatment and during follow-up. Vestibular function test (FVT) results could be analyzed in a subset of patients and were compared to patient-reported dizziness. After a mean follow-up of 46.3 months, actuarial local control for the whole cohort was 100% after 2, 97.6% after 5, and 94.1% after 10 years. In patients with primary RT, serviceable hearing was preserved in 72%. Predictors for preservation of serviceable hearing in multivariate analysis were time of follow-up (odds ratio, OR = 0.93 per month; p = 0.021) and pre-RT tumor size (Koos stage I-IIa vs. IIb-IV; OR = 0.15; p = 0.031). Worsening of FVT results was recorded in 17.6% (N = 3). Profound discrepancy of patient-reported dizziness and FVT results was observed after RT. In patients with primary RT, worsening of facial nerve function occurred in 1.7% (N = 1). Stereotactic RT of vestibular schwannoma provides good functional outcomes and high control rates. Dependence of hearing preservation on time of follow-up and initial tumor stage has to be considered. (orig.) [German] Praesentation von Langzeitdaten zu funktionellen Ergebnissen und Tumorkontrolle nach stereotaktischer Radiotherapie (RT) in einer Kohorte von 107 Patienten mit Akustikusneurinom. Zwischen Oktober 2002 und Dezember 2013 wurden 107 Patienten mit Akustikusneurinom (primaer oder rezidiviert nach vorangegangener Resektion) mittels stereotaktischer RT behandelt

  12. Dopamine improves hypothermic machine preservation of the liver.

    Science.gov (United States)

    Minor, Thomas; Lüer, Bastian; Efferz, Patrik

    2011-10-01

    Hypothermic machine preservation (HMP) is currently reconsidered as alternative to standard cold storage of organs from non-heart-beating donors. The present study was aimed at investigating the possible synergistic effect of HMP and the addition of dopamine to the circulating perfusate during preservation. Cardiac arrest was induced in male Wistar rats (250-300 g) by phrenotomy. Thirty minutes later livers were flushed via the portal vein and subjected to 20 h of HMP at 5ml/min at 4°C. During HMP the preservation solution was equilibrated with 100% oxygen and dopamine was added at 0, 10, 50 or 100 μM (D0, D10, D50, D100; n=6 resp.). Graft viability was assessed thereafter upon warm reperfusion in vitro for 2h. During HMP, D50 and D100 significantly reduced hepatic release of ALT to about 50%. No influence of dopamine was found on vascular resistance, oxygen uptake or lactate production at any concentration. D50 significantly reduced enzyme release during reperfusion (∼50%), enhanced bile flow and oxygen consumption. D10 was less effective while D100 even rose enzyme release compared with D0. Enhanced oxygen free radical mediated lipid peroxidation (LPO), found in the tissue of D0 livers was significantly reduced by D50; D50 significantly abrogated molecular upregulation of vWillebrand factor upon reperfusion suggesting vascular protection of the endothelial cell. Efficiency of HMP might be increased by stimulating livers with dopamine during ex vivo preservation, limiting vascular side effects and improving functional recovery upon early reperfusion. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging

    Directory of Open Access Journals (Sweden)

    Vivian eCapilla-Gonzalez

    2013-09-01

    Full Text Available The subventricular zone (SVZ is the largest source of newly generated cells in the adult mammalian brain. SVZ-derived neuroblasts migrate via the rostral migratory stream (RMS to the olfactory bulb (OB, where they differentiate into mature neurons. Additionally, a small proportion of SVZ-derived cells contribute to the generation of myelinating oligodendrocytes. The production of new cells in the SVZ decreases during aging, affecting the incorporation of new neurons into the OB. However, the age-related changes that occur across the RMS are not fully understood. In this study we evaluate how aging affects the cellular organization of migrating neuroblast chains, the proliferation, and the fate of the newly generated cells in the SVZ-OB system. By using electron microscopy and immunostaining, we found that the RMS path becomes discontinuous and its cytoarchitecture is disorganized in aged mice (24-month-old mice. Subsequently, OB neurogenesis was impaired in the aged brain while the production of oligodendrocytes was not compromised. These findings provide new insight into oligodendrocyte preservation throughout life. Further exploration of this matter could help the development of new strategies to prevent neurological disorders associated with senescence.

  14. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

    Science.gov (United States)

    Tinkum, Kelsey L; Stemler, Kristina M; White, Lynn S; Loza, Andrew J; Jeter-Jones, Sabrina; Michalski, Basia M; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S; Piwnica-Worms, David; Piwnica-Worms, Helen

    2015-12-22

    Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

  15. Hardwiring stem cell communication through tissue structure

    Science.gov (United States)

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-01-01

    Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. PMID:26967287

  16. Kinetics of cellular viability in warm versus cold ischemia conditions of kidney preservation. A biometric study.

    Science.gov (United States)

    Savioz, D; Bolle, J F; Graf, J D; Jeanjacquot, A; Savioz, M; Dietler, G; Favre, H; Leski, M; Morel, D; Morel, P

    1996-08-15

    We have determined the kinetics of the cellular viability ratio (CVR), defined as the number of living cells over the total cell count, in pig kidneys using propidium iodide and fluorescein diacetate staining, as a function of time and preservation conditions. The kidneys were preserved in warm or cold ischemia in order to mimic the conditions of transplantation from non-heart-beating donors or multiple removal with optimal preservation of the graft, respectively. To determine the CVR, the cells were obtained by a fine-needle aspiration biopsy, which minimizes the damage to the graft. A biometric analysis by regression enabled the determination of the time dependence for warm ischemia (CVR(t) = 80.0 x e(-0.733-t)(+2.7/-0.36)) and for cold ischemia (CVR(t) = 80.0 x e(-0.022-t)(+1.57/-0.64)) with a confidence interval of 95%. These master curves allow us to predict, under the described conditions, the CVR after a given ischemia time. The half-life of the cells can be deduced from the time-dependent CVR(t), and is 0.64 hr (38 min) for warm ischemia and 21.4 hr for cold ischemia. Further, the CVR for a given kidney can be used to assess its condition at removal: if the CVR is below 48% at 2 hr after removal, one can conclude that the organ has suffered a period of warm ischemia.

  17. Knowledge preservation in scope of International Nuclear Information System (INIS)

    International Nuclear Information System (INIS)

    Mohd Hafizal Yusof; Habibah Adnan; Iberahim Ali

    2012-01-01

    Knowledge preservation is one of the important aspects in knowledge management. Developing organization must look back how they preserve their knowledge from loss because of retirement and so on. One approach suggested by International Atomic Energy Agency (IAEA) through establishment of International Nuclear Information System (INIS) that can functioned as database and research centres where its operation based on cooperation between the member states. This system also can function as main contributor to knowledge preservation centres based on research in nuclear science and technology related. The main objectives of this paper is to see how far this system relevant to meet this agency to preserve their knowledge. Besides that, the process of increasing individual competency also is discussed in context of INIS scope. (author)

  18. Successful transportation of human corneal endothelial tissues without cool preservation in varying Indian tropical climatic conditions and in vitro cell expansion using a novel polymer.

    Science.gov (United States)

    Rao, Srinivas K; Sudhakar, John; Parikumar, Periyasamy; Natarajan, Sundaram; Insaan, Aditya; Yoshioka, Hiroshi; Mori, Yuichi; Tsukahara, Shigeo; Baskar, Subramani; Manjunath, Sadananda Rao; Senthilkumar, Rajappa; Thamaraikannan, Paramasivam; Srinivasan, Thangavelu; Preethy, Senthilkumar; Abraham, Samuel J K

    2014-02-01

    Though the transplantation of human corneal endothelial tissue (CET) separated from cadaver cornea is in practice, its transportation has not been reported. We report the successful transportation of CET in varying Indian climatic conditions without cool preservation and the in vitro expansion of Human Corneal Endothelial Precursor Cells (HCEPCs) using a novel Thermo-reversible gelation polymer (TGP). CET from cadaver corneas (n = 67), unsuitable for transplantation, were used. In phase I, CET was transported in Basal Culture Medium (Group I) and TGP (Group II) and in Phase II, in TGP cocktail alone, from three hospitals 250-2500 km away, to a central laboratory. The transportation time ranged from 6 h to 72 h and the outdoor temperature between 20°C and 41°C. On arrival, CET were processed, cells were expanded upto 30 days in basal culture medium (Group A) and TGP scaffold (Group B). Cell viability and morphology were documented and Reverse transcription polymerase chain reaction (RT-PCR) characterization undertaken. In Phase I, TGP yielded more viable cells (0.11 × 10(6) cells) than Group I (0.04 × 10(6) cells). In Phase II, the average cell count was 5.44 × 10(4) cells. During expansion, viability of HCEPCs spheres in TGP was maintained for a longer duration. The cells from both the groups tested positive for B-3 tubulin and negative for cytokeratins K3 and K12, thereby proving them to be HCEPCs. TGP preserves the CET during transportation without cool preservation and supports in vitro expansion, with a higher yield of HCEPCs, similar to that reported in clinical studies.

  19. Successful transportation of human corneal endothelial tissues without cool preservation in varying Indian tropical climatic conditions and in vitro cell expansion using a novel polymer

    Directory of Open Access Journals (Sweden)

    Srinivas K Rao

    2014-01-01

    Full Text Available Background: Though the transplantation of human corneal endothelial tissue (CET separated from cadaver cornea is in practice, its transportation has not been reported. We report the successful transportation of CET in varying Indian climatic conditions without cool preservation and the in vitro expansion of Human Corneal Endothelial Precursor Cells (HCEPCs using a novel Thermo-reversible gelation polymer (TGP. Materials and Methods: CET from cadaver corneas (n = 67, unsuitable for transplantation, were used. In phase I, CET was transported in Basal Culture Medium (Group I and TGP (Group II and in Phase II, in TGP cocktail alone, from three hospitals 250-2500 km away, to a central laboratory. The transportation time ranged from 6 h to 72 h and the outdoor temperature between 20°C and 41°C. On arrival, CET were processed, cells were expanded upto 30 days in basal culture medium (Group A and TGP scaffold (Group B. Cell viability and morphology were documented and Reverse transcription polymerase chain reaction (RT-PCR characterization undertaken. Results: In Phase I, TGP yielded more viable cells (0.11 × 10 6 cells than Group I (0.04 × 10 6 cells. In Phase II, the average cell count was 5.44 × 10 4 cells. During expansion, viability of HCEPCs spheres in TGP was maintained for a longer duration. The cells from both the groups tested positive for B-3 tubulin and negative for cytokeratins K3 and K12, thereby proving them to be HCEPCs. Conclusion: TGP preserves the CET during transportation without cool preservation and supports in vitro expansion, with a higher yield of HCEPCs, similar to that reported in clinical studies.

  20. Essential Function of Dicer in Resolving DNA Damage in the Rapidly Dividing Cells of the Developing and Malignant Cerebellum

    Directory of Open Access Journals (Sweden)

    Vijay Swahari

    2016-01-01

    Full Text Available Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function in the DNA damage response, we examined whether Dicer was important for preserving genomic integrity in the developing brain. We report that deletion of Dicer in the developing mouse cerebellum resulted in the accumulation of DNA damage leading to cerebellar progenitor degeneration, which was rescued with p53 deficiency; deletion of DGCR8 also resulted in similar DNA damage and cerebellar degeneration. Dicer deficiency also resulted in DNA damage and death in other rapidly dividing cells including embryonic stem cells and the malignant cerebellar progenitors in a mouse model of medulloblastoma. Together, these results identify an essential function of Dicer in resolving the spontaneous DNA damage that occurs during the rapid proliferation of developmental progenitors and malignant cells.

  1. Mechanism to preserve phrenic nerve function during photosensitization reaction: drug uptake and photosensitization reaction effect on electric propagation

    Science.gov (United States)

    Takahashi, Haruka; Hamada, Risa; Ogawa, Emiyu; Arai, Tsunenori

    2018-02-01

    To study a mechanism of phrenic nerve preservation phenomena during a photosensitization reaction, we investigated an uptake of talaporfin sodium and photosensitization reaction effect on an electric propagation. Right phrenic nerve was completely preserved after superior vena cava isolations using the photosensitization reaction in canine animal experiments, in spite of adjacent myocardium was electrically blocked. We predicted that low drug uptake and/or low photosensitization reaction effect on the nerve might be a mechanism of that phenomena. To investigate uptake to various nerve tissue, a healthy extracted crayfish ventral nerve cord and an extracted porcine phrenic nerve were immersed in 20 μg/ml talaporfin sodium solution for 0-240 min. The mean talaporfin sodium fluorescence brightness increased depending on the immersion time. This brightness saturated around the immersion time of 120 min. We found that talaporfin sodium uptake inside the perineurium which directly related to the electric propagation function was lower than that of outside in the porcine phrenic nerve. To investigate photosensitization reaction effect on electric propagation, the crayfish nerve was immersed into the same solution for 15 min and irradiated by a 663 nm laser light with 120 mW/cm2. Since we found the action potential disappeared when the irradiation time was 25-65 s, we consider that the crayfish nerve does not tolerant to the photosensitization reaction on electric propagation function at atmospheric pressure. From these results, we think that the low uptake of talaporfin sodium inside the perineurium and low oxygen partial pressure of nerve might be the possible mechanism to preserve phrenic nerve in vivo.

  2. Sodium benzoate, a food preservative, affects the functional and activation status of splenocytes at non cytotoxic dose.

    Science.gov (United States)

    Yadav, Ashish; Kumar, Arvind; Das, Mukul; Tripathi, Anurag

    2016-02-01

    Sodium benzoate (SB) is a widely used food preservative due to its bacteriostatic and fungistatic properties. The acceptable daily intake of SB is 5 mg/kg-bw, however, it has been found to be used in the food commodities at relatively high levels (2119 mg/kg). Earlier studies on SB have shown its immunosuppressive properties, but comprehensive immunotoxicity data is lacking. Our studies have shown that SB was non cytotoxic in splenocytes up to 1000 μg/ml for 72 h, however at 2500 μg/ml it was found to be cytotoxic. Thus, 1000 μg/ml dose of SB was chosen for the subsequent experiments. SB significantly suppresses the proliferation of Con A and LPS stimulated splenocytes at 72 h, while allogenic response of T cells was significantly decreased after 96 h. SB did not affect the relative expression of CD3e or CD4 molecules following 72 h exposure, however, it downregulated the relative expression of CD8 co-receptor. Further, exposure of splenocytes to SB for 72 h led to reduced expression of CD28 and CD95, which play a vital role in T cell activation. SB also suppresses the relative expression of CD19, CD40 and CD95 receptors on B cells after 72 h. In addition to the functional responses, SB lowered the expression of IL4, IL6, IFNγ and IL17 cytokines in Con A stimulated splenocytes; and IL6, IFNγ and TNFα in LPS stimulated splenocytes following 48 h of exposure. Taken together, the present study is suggestive of the immunomodulatory potential of SB. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Genomic and post-genomic effects of anti-glaucoma drugs preservatives in trabecular meshwork

    Energy Technology Data Exchange (ETDEWEB)

    Izzotti, Alberto, E-mail: izzotti@unige.it [Mutagenesis Unit, IRCCS AOU San Martino – IST, Genova (Italy); Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); La Maestra, Sebastiano; Micale, Rosanna Tindara; Longobardi, Maria Grazia [Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); Saccà, Sergio Claudio [Ophthalmology Unit, IRCCS AOU San Martino-IST, Genova (Italy)

    2015-02-15

    Highlights: • Glaucoma drug preservatives induce DNA damage in trabecular meshwork cells. • Cellular alteration is related with the occurrence of activation of apoptosis through the intrinsic pathway. • Drug preservatives unable to induce cell damage are ineffective in killing bacteria. • Anti glaucoma drugs should be formulated as single-dose usage devoid of genotoxic preservatives. - Abstract: Oxidative stress plays an important role in glaucoma. Some preservatives of anti-glaucoma drugs, commonly used in glaucoma therapy, can prevent or induce oxidative stress in the trabecular meshwork. The aim of this study is to evaluate cellular and molecular damage induced in trabecular meshwork by preservatives contained in anti-glaucoma drugs. Cell viability (MTT test), DNA fragmentation (Comet test), oxidative DNA damage (8-oxo-dG), and gene expression (cDNA microarray) have been evaluated in trabecular meshwork specimens and in human trabecular meshwork cells treated with benzalkonium chloride, polyQuad, purite, and sofzia-like mixture. Moreover, antimicrobial effectiveness and safety of preservative contents in drugs was tested. In ex vivo experiments, benzalkonium chloride and polyQuad induced high level of DNA damage in trabecular meshwork specimens, while the effect of purite and sofzia were more attenuated. The level of DNA fragmentation induced by benzalkonium chloride was 2.4-fold higher in subjects older than 50 years than in younger subjects. Benzalkonium chloride, and polyQuad significantly increased oxidative DNA damage as compared to sham-treated specimens. Gene expression was altered by benzalkonium chloride, polyQuad, and purite but not by sofzia. In in vitro experiments, benzalkonium chloride and polyQuad dramatically decreased trabecular meshwork cell viability, increased DNA fragmentation, and altered gene expression. A lesser effect was also exerted by purite and sofzia. Genes targeted by these alterations included Fas and effector caspase-3

  4. Preserved consciousness in vegetative and minimal conscious states

    DEFF Research Database (Denmark)

    Kondziella, Daniel; Nielsen, Christian Thomas Friberg; Frokjaer, Vibe G

    2016-01-01

    Active, passive and resting state paradigms using functional MRI (fMRI) or EEG may reveal consciousness in the vegetative (VS) and the minimal conscious state (MCS). A meta-analysis was performed to assess the prevalence of preserved consciousness in VS and MCS as revealed by fMRI and EEG.......0001)) and to show preserved functional cortical connectivity during passive paradigms (55% vs 26%; OR 3.53 (95% CI 2.49 to 4.99; ppreserved consciousness more often than active paradigms (38% vs 24%; OR 1.98 (95% CI 1.54 to 2.54; p... were insufficient for statistical evaluation. In conclusion, active paradigms may underestimate the degree of consciousness as compared to passive paradigms. While MCS patients show signs of preserved consciousness more frequently in both paradigms, roughly 15% of patients with a clinical diagnosis...

  5. Regulation of satellite cell function in sarcopenia

    Directory of Open Access Journals (Sweden)

    Stephen E Alway

    2014-09-01

    Full Text Available The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell function that is impacted by the environment (niche of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia, and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration. While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function.

  6. Regulation of Satellite Cell Function in Sarcopenia

    Science.gov (United States)

    Alway, Stephen E.; Myers, Matthew J.; Mohamed, Junaith S.

    2014-01-01

    The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell) function that is impacted by the environment (niche) of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse, or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins, and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration). While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function. PMID:25295003

  7. Novel approaches in food-processing technology: new technologies for preserving foods and modifying function.

    Science.gov (United States)

    Knorr, D

    1999-10-01

    Recent advances in emerging food-processing technologies, such as high hydrostatic pressure or high-intensity electric field pulses, allow targeted and sophisticated modification and preservation of foods. We are beginning to understand the mechanisms involved in pressure inactivation of bacterial spores and have been collecting considerable amounts of kinetic data regarding inactivation mechanisms of enzymes and vegetative microorganisms. We are also gaining more insight into the permeabilization of plant membranes and related biosynthetic responses, making progress in food structure engineering and food modification for function, and have been initiating process developments for gentle processing of delicate biomaterials based on pressure-assisted phase transitions of water.

  8. Beneficial bread without preservatives

    OpenAIRE

    Denkova, Zapryana; Denkova, Rositsa

    2014-01-01

    Besides their inherent nutritional value functional foods contain substances that have beneficial impact on the functioning of organs and systems in the human body and reduce the risk of disease. Bread and bakery goods are basic foods in the diet of contemporary people. Preservatives are added to the composition of foods in order to ensure their microbiological safety, but these substances affect directly the balance of microflora in the tract. A great problem is mold and bacterial spoilage (...

  9. Induction of Functional Hair-Cell-Like Cells from Mouse Cochlear Multipotent Cells

    Directory of Open Access Journals (Sweden)

    Quanwen Liu

    2016-01-01

    Full Text Available In this paper, we developed a two-step-induction method of generating functional hair cells from inner ear multipotent cells. Multipotent cells from the inner ear were established and induced initially into progenitor cells committed to the inner ear cell lineage on the poly-L-lysine substratum. Subsequently, the committed progenitor cells were cultured on the mitotically inactivated chicken utricle stromal cells and induced into hair-cell-like cells containing characteristic stereocilia bundles. The hair-cell-like cells exhibited rapid permeation of FM1-43FX. The whole-cell patch-clamp technique was used to measure the membrane currents of cells differentiated for 7 days on chicken utricle stromal cells and analyze the biophysical properties of the hair-cell-like cells by recording membrane properties of cells. The results suggested that the hair-cell-like cells derived from inner ear multipotent cells were functional following differentiation in an enabling environment.

  10. Male fertility preservation before gonadotoxic therapies

    OpenAIRE

    Wyns, C.

    2010-01-01

    Background: Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, radiotherapy and preparative regimens for bone marrow transplantation can severely affect male germ cells, including spermatogonial stem cells (SSCs), and lead to permanent loss of fertility. Different options for fertility preservation are dependent on the pubertal state of the patient. Methods: Relevant studies were identified by an extens...

  11. CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

    Science.gov (United States)

    Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-12-02

    Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

  12. Membrane elastic properties and cell function.

    Directory of Open Access Journals (Sweden)

    Bruno Pontes

    Full Text Available Recent studies indicate that the cell membrane, interacting with its attached cytoskeleton, is an important regulator of cell function, exerting and responding to forces. We investigate this relationship by looking for connections between cell membrane elastic properties, especially surface tension and bending modulus, and cell function. Those properties are measured by pulling tethers from the cell membrane with optical tweezers. Their values are determined for all major cell types of the central nervous system, as well as for macrophage. Astrocytes and glioblastoma cells, which are considerably more dynamic than neurons, have substantially larger surface tensions. Resting microglia, which continually scan their environment through motility and protrusions, have the highest elastic constants, with values similar to those for resting macrophage. For both microglia and macrophage, we find a sharp softening of bending modulus between their resting and activated forms, which is very advantageous for their acquisition of phagocytic functions upon activation. We also determine the elastic constants of pure cell membrane, with no attached cytoskeleton. For all cell types, the presence of F-actin within tethers, contrary to conventional wisdom, is confirmed. Our findings suggest the existence of a close connection between membrane elastic constants and cell function.

  13. Changes in left ventricular systolic function in patients with chronic heart failure with preserved ejection fraction and cardiorenal anemic syndrome

    Directory of Open Access Journals (Sweden)

    Vasylenko V.A.

    2015-09-01

    Full Text Available The feature of chronic heart failure (CHF in elderly people is increasing incidence of heart failure with preserved left ventricular ejection fraction (LVEF which is associated with age. Such patients account for almost half of the total number of patients with heart failure. Cardiorenal syndrome (CRS is associated with an increased risk of mortality in patients with CHF. The impact of CRS on the structural and functional condition of the heart in these patients is studied insufficiently. The study involved 103 patients with CHF II-IV NYHA with preserved LVEF (>45% and CRS (hemoglobin <120 g/l and function, namely by the increase of end-systolic volume and decrease in the degree of LV fractional shortening size.

  14. Antibody response to a T-cell-independent antigen is preserved after splenic artery embolization for trauma.

    Science.gov (United States)

    Olthof, D C; Lammers, A J J; van Leeuwen, E M M; Hoekstra, J B L; ten Berge, I J M; Goslings, J C

    2014-11-01

    Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function assessed by examining the antibody response to polysaccharide antigens (pneumococcal 23-valent polysaccharide vaccine), B-cell subsets, and the presence of Howell-Jolly bodies (HJB). The data were compared to those obtained from splenectomized patients and healthy controls (HC) who had been included in a previously conducted study. A total of 30 patients were studied: 5 who had proximal SAE, 7 who had distal SAE, 8 who had a splenectomy, and 10 HC. The median vaccine-specific antibody response of the SAE patients (fold increase, 3.97) did not differ significantly from that of the HC (5.29; P = 0.90); however, the median response of the splenectomized patients (2.30) did differ (P = 0.003). In 2 of the proximally embolized patients and none of the distally embolized patients, the ratio of the IgG antibody level postvaccination compared to that prevaccination was splenic immune function of embolized patients was preserved, and therefore routine vaccination appears not to be indicated. Although the median antibody responses did not differ between the patients who underwent proximal SAE and those who underwent distal SAE, 2 of the 5 proximally embolized patients had insufficient responses to vaccination, whereas none of the distally embolized patients exhibited an insufficient response. Further research should be done to confirm this finding. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. In Vivo Functional Selection Identifies Cardiotrophin-1 as a Cardiac Engraftment Factor for Mesenchymal Stromal Cells.

    Science.gov (United States)

    Bortolotti, Francesca; Ruozi, Giulia; Falcione, Antonella; Doimo, Sara; Dal Ferro, Matteo; Lesizza, Pierluigi; Zentilin, Lorena; Banks, Lawrence; Zacchigna, Serena; Giacca, Mauro

    2017-10-17

    Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here, we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell engraftment into the heart both in normal conditions and after myocardial infarction. An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral vectors. Pools from this library were then used for the batch transduction of bone marrow-derived mesenchymal stromal cells ex vivo, followed by intramyocardial cell administration in normal and infarcted mice. Three weeks after injection, vector genomes were recovered from the few persisting cells and identified by sequencing DNA barcodes uniquely labeling each of the tested cytokines. The most effective molecule identified by this competitive engraftment screening was cardiotrophin-1, a member of the interleukin-6 family. Intracardiac injection of mesenchymal stromal cells transiently preconditioned with cardiotrophin-1 preserved cardiac function and reduced infarct size, parallel to the persistence of the transplanted cells in the healing hearts for at least 2 months after injection. Engraftment of cardiotrophin-1-treated mesenchymal stromal cells was consequent to signal transducer and activator of transcription 3-mediated activation of the focal adhesion kinase and its associated focal adhesion complex and the consequent acquisition of adhesive properties by the cells. These results support the feasibility of selecting molecules in vivo for their functional properties with adeno-associated viral vector libraries and identify cardiotrophin-1 as a powerful cytokine promoting cell engraftment and thus improving cell therapy of the infarcted myocardium. © 2017 American Heart Association, Inc.

  16. Testosterone Production is Better Preserved After 16 than 20 Gray Irradiation Treatment Against Testicular Carcinoma In Situ Cells

    International Nuclear Information System (INIS)

    Bang, Anne K.; Petersen, Jorgen H.; Petersen, Peter M.; Andersson, Anna-Maria; Daugaard, Gedske; Jorgensen, Niels

    2009-01-01

    Purpose: To study the effect of 16 Gy radiotherapy (RT) vs. 20 Gy RT on Leydig cell function in men treated with radiotherapy against carcinoma in situ (CIS) of the testis. Methods and Materials: Fifty-one men who were treated between 1985 and 2005 were included. Fourteen men had been treated with 20 Gy and 37 with 16 Gy RT. Measurements of sex hormone-binding globulin and basic and stimulated testosterone, as well as luteinizing hormone levels were performed. Results: The follow-up periods for the patients treated without additional chemotherapy were for the 20 Gy and 16 Gy group mean/median/min-max: 9.0/10.0/1.0-20.3 years and 4.0/3.1/0.4-14.1 years, respectively. During the follow-up period, men treated with 16 Gy RT had stable testosterone levels (-1.1%/year, p = 0.4), whereas men treated with 20 Gy had an annual decrease of 2.4% (p = 0.008). For the latter group, the testosterone decrease was most pronounced in the first 5 years, leveling off during the following 5 years. Additionally, more men treated with 20 Gy needed androgen substitution treatment. Our study showed an increased luteinizing hormone level for the men treated with 16 Gy, although this was not significant (p = 0.5). We anticipated a similar increase in the patients treated with 20 Gy but instead observed a decrease (-3.1%, p = 0.01). Conclusion: RT at 16 and 20 Gy seem to affect Leydig cell function differently, with 16 Gy RT better preserving testosterone levels and thus being preferred from an endocrinological point of view.

  17. The effects of betatron motion on the preservation of FEL microbunching

    Energy Technology Data Exchange (ETDEWEB)

    Geloni, Gianluca [European XFEL GmbH, Hamburg (Germany); Kocharyan, Vitali; Saldin, Evgeni [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2011-05-15

    In some options for circular polarization control at X-ray FELs, a helical radiator is placed a few ten meters distance behind the baseline undulator. If the microbunch structure induced in the baseline (planar) undulator can be preserved, intense coherent radiation is emitted in the helical radiator. The effects of betatron motion on the preservation of micro bunching in such in-line schemes should be accounting for. In this paper we present a comprehensive study of these effects. It is shown that one can work out an analytical expression for the debunching of an electron beam moving in a FODO lattice, strictly valid in the asymptote for a FODO cell much shorter than the betatron function. Further on, numerical studies can be used to demonstrate that the validity of such analytical expression goes beyond the abovementioned asymptote, and can be used in much more a general context. Finally, a comparison with Genesis simulations is given. (orig.)

  18. The effects of betatron motion on the preservation of FEL microbunching

    International Nuclear Information System (INIS)

    Geloni, Gianluca; Kocharyan, Vitali; Saldin, Evgeni

    2011-05-01

    In some options for circular polarization control at X-ray FELs, a helical radiator is placed a few ten meters distance behind the baseline undulator. If the microbunch structure induced in the baseline (planar) undulator can be preserved, intense coherent radiation is emitted in the helical radiator. The effects of betatron motion on the preservation of micro bunching in such in-line schemes should be accounting for. In this paper we present a comprehensive study of these effects. It is shown that one can work out an analytical expression for the debunching of an electron beam moving in a FODO lattice, strictly valid in the asymptote for a FODO cell much shorter than the betatron function. Further on, numerical studies can be used to demonstrate that the validity of such analytical expression goes beyond the abovementioned asymptote, and can be used in much more a general context. Finally, a comparison with Genesis simulations is given. (orig.)

  19. Protecting cells by protecting their vulnerable lysosomes: Identification of a new mechanism for preserving lysosomal functional integrity upon oxidative stress.

    Science.gov (United States)

    Pascua-Maestro, Raquel; Diez-Hermano, Sergio; Lillo, Concepción; Ganfornina, Maria D; Sanchez, Diego

    2017-02-01

    Environmental insults such as oxidative stress can damage cell membranes. Lysosomes are particularly sensitive to membrane permeabilization since their function depends on intraluminal acidic pH and requires stable membrane-dependent proton gradients. Among the catalog of oxidative stress-responsive genes is the Lipocalin Apolipoprotein D (ApoD), an extracellular lipid binding protein endowed with antioxidant capacity. Within the nervous system, cell types in the defense frontline, such as astrocytes, secrete ApoD to help neurons cope with the challenge. The protecting role of ApoD is known from cellular to organism level, and many of its downstream effects, including optimization of autophagy upon neurodegeneration, have been described. However, we still cannot assign a cellular mechanism to ApoD gene that explains how this protection is accomplished. Here we perform a comprehensive analysis of ApoD intracellular traffic and demonstrate its role in lysosomal pH homeostasis upon paraquat-induced oxidative stress. By combining single-lysosome in vivo pH measurements with immunodetection, we demonstrate that ApoD is endocytosed and targeted to a subset of vulnerable lysosomes in a stress-dependent manner. ApoD is functionally stable in this acidic environment, and its presence is sufficient and necessary for lysosomes to recover from oxidation-induced alkalinization, both in astrocytes and neurons. This function is accomplished by preventing lysosomal membrane permeabilization. Two lysosomal-dependent biological processes, myelin phagocytosis by astrocytes and optimization of neurodegeneration-triggered autophagy in a Drosophila in vivo model, require ApoD-related Lipocalins. Our results uncover a previously unknown biological function of ApoD, member of the finely regulated and evolutionary conserved gene family of extracellular Lipocalins. They set a lipoprotein-mediated regulation of lysosomal membrane integrity as a new mechanism at the hub of many cellular

  20. Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration.

    Science.gov (United States)

    Sheard, Michael A; Ghent, Matthew V; Cabral, Daniel J; Lee, Joanne C; Khankaldyyan, Vazgen; Ji, Lingyun; Wu, Samuel Q; Kang, Min H; Sposto, Richard; Asgharzadeh, Shahab; Reynolds, C Patrick

    2015-05-15

    Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival, expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. Copyright © 2015. Published by Elsevier Inc.

  1. Hardwiring Stem Cell Communication through Tissue Structure.

    Science.gov (United States)

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-03-10

    Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function, but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Versatile microsphere attachment of GFP-labeled motors and other tagged proteins with preserved functionality

    Directory of Open Access Journals (Sweden)

    Michael Bugiel

    2015-11-01

    Full Text Available Microspheres are often used as handles for protein purification or force spectroscopy. For example, optical tweezers apply forces on trapped particles to which motor proteins are attached. However, even though many attachment strategies exist, procedures are often limited to a particular biomolecule and prone to non-specific protein or surface attachment. Such interactions may lead to loss of protein functionality or microsphere clustering. Here, we describe a versatile coupling procedure for GFP-tagged proteins via a polyethylene glycol linker preserving the functionality of the coupled proteins. The procedure combines well-established protocols, is highly reproducible, reliable, and can be used for a large variety of proteins. The coupling is efficient and can be tuned to the desired microsphere-to-protein ratio. Moreover, microspheres hardly cluster or adhere to surfaces. Furthermore, the procedure can be adapted to different tags providing flexibility and a promising attachment strategy for any tagged protein.

  3. Activated NKT cells imprint NK-cell differentiation, functionality and education.

    Science.gov (United States)

    Riese, Peggy; Trittel, Stephanie; May, Tobias; Cicin-Sain, Luka; Chambers, Benedict J; Guzmán, Carlos A

    2015-06-01

    NK cells represent a vital component of the innate immune system. The recent discoveries demonstrating that the functionality of NK cells depends on their differentiation and education status underscore their potential as targets for immune intervention. However, to exploit their full potential, a detailed understanding of the cellular interactions involved in these processes is required. In this regard, the cross-talk between NKT cells and NK cells needs to be better understood. Our results provide strong evidence for NKT cell-induced effects on key biological features of NK cells. NKT-cell activation results in the generation of highly active CD27(high) NK cells with improved functionality. In this context, degranulation activity and IFNγ production were mainly detected in the educated subset. In a mCMV infection model, we also demonstrated that NKT-cell stimulation induced the generation of highly functional educated and uneducated NK cells, crucial players in viral control. Thus, our findings reveal new fundamental aspects of the NKT-NK cell axis that provide important hints for the manipulation of NK cells in clinical settings. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Comparison of Tissue Preservation using Formalin and Ethanol as Preservative Formula

    OpenAIRE

    See Woan Shian; Arifin Soenggono; Sawkar Vijay Pramod

    2016-01-01

    Background: Tissue preservation can be performed through embalming, by providing the chemical embalming fluid to the human remains. Formalin’s preservative formula is the foundation for modern methods of embalming. Unfortunately, this preservative formula has several disadvantages. While Ethanol’s preservative formula is a considerable agent to replace formalin’s preservative formula. The aim of this study was to compare the tissue preservation using formalin and ethanol as preservative formu...

  5. Radiosterilization of Tissues Preserved for Clinical Purposes: Effect on Tissue Antigenicity

    International Nuclear Information System (INIS)

    Ostrowski, K.; Kossowska, B.; Moskalewski, S.; Komender, A.; Kurnatowski, W.

    1967-01-01

    The first part of the paper contains practical considerations on the radiosterilization of preserved human bone, human and calf cartilage, cow’s fascia and aponeurosis, based on material from the Tissue Bank which produces about 2500 transplants yearly. The method of preservation and packing of each type of tissue is mentioned briefly. The preserved tissues are irradiated in a cobalt bomb or in a nuclear reactor. The conditions of irradiation and the control of sterility are described. The advantages and disadvantages of radiosterilization are discussed on the basis of the authors’ own experience and clinical reports of surgeons using radiosterilized tissues in practice. In the second part of the paper, experimental studies on the influence of freezing, lyophilization and radiosterilization on tissue antigenicity are reported. The regional lymph node reacts to an antigenic stimulus by an increased production of large, pyroninophylic cells, so-called ''blast'' cells. The rabbits used as recipients received grafts of allogeneic cancellous bone, fresh or subjected to different experimental procedures. Smears from lymph node cell suspension were prepared and the percentage of blast cells was estimated. On the basis of the lymph node response, it appears that freezing and lyophilization, as well as radiosterilization, may abolish the antigenicity of cancellous bone. The practical implication of these results for methods of preservation of tissues for clinical purposes is discussed. (author)

  6. Robust Discontinuity Preserving Optical Flow Methods

    Directory of Open Access Journals (Sweden)

    Nelson Monzón

    2016-11-01

    Full Text Available In this work, we present an implementation of discontinuity-preserving strategies in TV-L1 optical flow methods. These are based on exponential functions that mitigate the regularization at image edges, which usually provide precise flow boundaries. Nevertheless, if the smoothing is not well controlled, it may produce instabilities in the computed motion fields. We present an algorithm that allows three regularization strategies: the first one uses an exponential function together with a TV process; the second one combines this strategy with a small constant that ensures a minimum isotropic smoothing; the third one is a fully automatic approach that adapts the diffusion depending on the histogram of the image gradients. The last two alternatives are aimed at reducing the effect of instabilities. In the experiments, we observe that the pure exponential function is highly unstable while the other strategies preserve accurate motion contours for a large range of parameters.

  7. Preserved functional connectivity in the default mode and salience networks is associated with youthful memory in superaging

    OpenAIRE

    Barrett, Lisa; Zhang, Jiahe; Andreano, Joseph; Dickerson, Bradford; Touroutoglou, Alexandra

    2018-01-01

    'Superagers' are older adults who, despite their advanced age, maintain youthful memory. Previous morphometry studies revealed multiple default mode network (DMN) and salience network (SN) regions whose cortical thickness is preserved in superagers and correlates with memory performance. In this study, we examined the intrinsic functional connectivity within DMN and SN in 41 young (24.5 ± 3.6 years old) and 40 elderly adults (66.9 ± 5.5 years old). As in prior studies, superaging was defined ...

  8. Hearing Preservation in Cochlear Implant Surgery

    Directory of Open Access Journals (Sweden)

    Priscila Carvalho Miranda

    2014-01-01

    Full Text Available In the past, it was thought that hearing loss patients with residual low-frequency hearing would not be good candidates for cochlear implantation since insertion was expected to induce inner ear trauma. Recent advances in electrode design and surgical techniques have made the preservation of residual low-frequency hearing achievable and desirable. The importance of preserving residual low-frequency hearing cannot be underestimated in light of the added benefit of hearing in noisy atmospheres and in music quality. The concept of electrical and acoustic stimulation involves electrically stimulating the nonfunctional, high-frequency region of the cochlea with a cochlear implant and applying a hearing aid in the low-frequency range. The principle of preserving low-frequency hearing by a “soft surgery” cochlear implantation could also be useful to the population of children who might profit from regenerative hair cell therapy in the future. Main aspects of low-frequency hearing preservation surgery are discussed in this review: its brief history, electrode design, principles and advantages of electric-acoustic stimulation, surgical technique, and further implications of this new treatment possibility for hearing impaired patients.

  9. Temperature and oxygenation during organ preservation: friends or foes?

    Science.gov (United States)

    Gilbo, Nicholas; Monbaliu, Diethard

    2017-06-01

    The liberalization of donor selection criteria in organ transplantation, with the increased use of suboptimal grafts, has stimulated interest in ischemia-reperfusion injury prevention and graft reconditioning. Organ preservation technologies are changing considerably, mostly through the reintroduction of dynamic machine preservation. Here, we review the current evidence on the role of temperature and oxygenation during dynamic machine preservation. A large but complex body of evidence exists and comparative studies are few. Oxygenation seems to support an advantageous effect in hypothermic machine preservation and is mandatory in normothermic machine preservation, although in the latter, supraphysiological oxygen tensions should be avoided. High-risk grafts, such as suboptimal organs, may optimally benefit from oxygenated perfusion conditions that support metabolism and activate mechanisms of repair such as subnormothermic machine preservation, controlled oxygenated rewarming, and normothermic machine preservation. For lower risk grafts, oxygenation during hypothermic machine preservation may sufficiently reduce injuries and recharge the cellular energy to secure functional recovery after transplantation. The relationship between temperature and oxygenation in organ preservation is more complex than physiological laws would suggest. Rather than one default perfusion temperature/oxygenation standard, perfusion protocols should be tailored for specific needs of grafts of different quality.

  10. Hybrid cell adhesive material for instant dielectrophoretic cell trapping and long-term cell function assessment.

    Science.gov (United States)

    Reyes, Darwin R; Hong, Jennifer S; Elliott, John T; Gaitan, Michael

    2011-08-16

    Dielectrophoresis (DEP) for cell manipulation has focused, for the most part, on approaches for separation/enrichment of cells of interest. Advancements in cell positioning and immobilization onto substrates for cell culture, either as single cells or as cell aggregates, has benefited from the intensified research efforts in DEP (electrokinetic) manipulation. However, there has yet to be a DEP approach that provides the conditions for cell manipulation while promoting cell function processes such as cell differentiation. Here we present the first demonstration of a system that combines DEP with a hybrid cell adhesive material (hCAM) to allow for cell entrapment and cell function, as demonstrated by cell differentiation into neuronlike cells (NLCs). The hCAM, comprised of polyelectrolytes and fibronectin, was engineered to function as an instantaneous cell adhesive surface after DEP manipulation and to support long-term cell function (cell proliferation, induction, and differentiation). Pluripotent P19 mouse embryonal carcinoma cells flowing within a microchannel were attracted to the DEP electrode surface and remained adhered onto the hCAM coating under a fluid flow field after the DEP forces were removed. Cells remained viable after DEP manipulation for up to 8 d, during which time the P19 cells were induced to differentiate into NLCs. This approach could have further applications in areas such as cell-cell communication, three-dimensional cell aggregates to create cell microenvironments, and cell cocultures.

  11. SPECIFICITY OF SELF-PRESERVATION MOTIVATION IN EXTREME SITUATION

    Directory of Open Access Journals (Sweden)

    Ekaterina Anatolevna Karacheva

    2015-02-01

    Full Text Available The article presents the results of the study motivation of self-preservation in an extreme situation. Usually extreme situation unfold from the point of view of functioning, health, high negative level mental stress and tension. The extreme situation is the situation of human activity to which man acts, carrying out certain activities. The article provides an overview of russian and foreign authors dealing with this problem. Theoretical models of motivation of self-preservation Z. Freud, A. Maslow, G. Murray, M. Magomed-Eminov. The study explores the leading motivation in an extreme situation and analyzed the levels of motivation of self-preservation. The study was conducted in the Afghan veterans, using a method of unfinished sentences and other. Identified two levels of motivation of self-preservation: individual and personal. Revealed that the motivation of self-preservation is the leading motivation in an extreme situation.

  12. Inhibition of WISE preserves renal allograft function.

    Science.gov (United States)

    Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

    2013-01-01

    Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

  13. Modelling OAIS Compliance for Disaggregated Preservation Services

    Directory of Open Access Journals (Sweden)

    Gareth Knight

    2007-07-01

    Full Text Available The reference model for the Open Archival Information System (OAIS is well established in the research community as a method of modelling the functions of a digital repository and as a basis in which to frame digital curation and preservation issues. In reference to the 5th anniversary review of the OAIS, it is timely to consider how it may be interpreted by an institutional repository. The paper examines methods of sharing essential functions and requirements of an OAIS between two or more institutions, outlining the practical considerations of outsourcing. It also details the approach taken by the SHERPA DP Project to introduce a disaggregated service model for institutional repositories that wish to implement preservation services.

  14. Intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation for preservation of facial nerve function in patients with large acoustic neuroma

    Institute of Scientific and Technical Information of China (English)

    LIU Bai-yun; TIAN Yong-ji; LIU Wen; LIU Shu-ling; QIAO Hui; ZHANG Jun-ting; JIA Gui-jun

    2007-01-01

    Background Although various monitoring techniques have been used routinely in the treatment of the lesions in the skull base, iatrogenic facial paresis or paralysis remains a significant clinical problem. The aim of this study was to investigate the effect of intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation on preservation of facial nerve function.Method From January to November 2005, 19 patients with large acoustic neuroma were treated using intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation (TCEMEP) for preservation of facial nerve function. The relationship between the decrease of MEP amplitude after tumor removal and the postoperative function of the facial nerve was analyzed.Results MEP amplitude decreased more than 75% in 11 patients, of which 6 presented significant facial paralysis (H-B grade 3), and 5 had mild facial paralysis (H-B grade 2). In the other 8 patients, whose MEP amplitude decreased less than 75%, 1 experienced significant facial paralysis, 5 had mild facial paralysis, and 2 were normal.Conclusions Intraoperative TCEMEP can be used to predict postoperative function of the facial nerve. The decreased MEP amplitude above 75 % is an alarm point for possible severe facial paralysis.

  15. Structure and function of stem cell pools in mammalian cell renewal systems

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Nothdurft, W.

    1979-01-01

    Stem cells play a key-role in the maintenance of the equilibrium between cell loss and cell production in cell renewal systems as well as in the understanding of the radiation pathophysiology of mammalian organisms. The integrity of mammalian organisms with the need to maintain a constant ''millieu interior'' is depending on the normal functioning of cell renewal systems, especially those of epithelial surfaces and blood cell forming organs. All cell renewal systems of bodies have a very similar functional structure consisting of functional, proliferative - amplifying and stem cell compartments. They differ in transit and cell cycle times and in the number of amplification division - aside from the difference in their functional and biochemical make-up. The stem cell pools are providing the cells capable of differentiation without depleting their own kind. This can be achieved by symmetrical or assymmetrical stem cell division. In normal steady state, 50% of the stem cell division remain in the stem cell pool, while the other 50% leave it to differentiate, proliferate and mature, hemopoietic system is distributed throughout bodies. This is an important factor in the radiation biology of mammalian organisms since the loss of function in one area can be compensated for by more production in other areas, and locally depleted sites can be reseeded with the stem cells migrating in from blood. (Yamashita, S.)

  16. Fertility preservation issues in pediatric hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Balduzzi, A; Dalle, J-H; Jahnukainen, K

    2017-01-01

    Fertility preservation is an urgent challenge in the transplant setting. A panel of transplanters and fertility specialists within the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the International BFM Study Group provides specific guide...

  17. Privacy-preserving data cube for electronic medical records: An experimental evaluation.

    Science.gov (United States)

    Kim, Soohyung; Lee, Hyukki; Chung, Yon Dohn

    2017-01-01

    The aim of this study is to evaluate the effectiveness and efficiency of privacy-preserving data cubes of electronic medical records (EMRs). An EMR data cube is a complex of EMR statistics that are summarized or aggregated by all possible combinations of attributes. Data cubes are widely utilized for efficient big data analysis and also have great potential for EMR analysis. For safe data analysis without privacy breaches, we must consider the privacy preservation characteristics of the EMR data cube. In this paper, we introduce a design for a privacy-preserving EMR data cube and the anonymization methods needed to achieve data privacy. We further focus on changes in efficiency and effectiveness that are caused by the anonymization process for privacy preservation. Thus, we experimentally evaluate various types of privacy-preserving EMR data cubes using several practical metrics and discuss the applicability of each anonymization method with consideration for the EMR analysis environment. We construct privacy-preserving EMR data cubes from anonymized EMR datasets. A real EMR dataset and demographic dataset are used for the evaluation. There are a large number of anonymization methods to preserve EMR privacy, and the methods are classified into three categories (i.e., global generalization, local generalization, and bucketization) by anonymization rules. According to this classification, three types of privacy-preserving EMR data cubes were constructed for the evaluation. We perform a comparative analysis by measuring the data size, cell overlap, and information loss of the EMR data cubes. Global generalization considerably reduced the size of the EMR data cube and did not cause the data cube cells to overlap, but incurred a large amount of information loss. Local generalization maintained the data size and generated only moderate information loss, but there were cell overlaps that could decrease the search performance. Bucketization did not cause cells to overlap

  18. HIV-infected viremic long-term non-progressors and controllers display different immunological mechanisms for preserved CD4+cell counts

    DEFF Research Database (Denmark)

    Gaardbo, J; Ronit, A; Hartling, H

    2012-01-01

    of viral replication cannot explain non-progression in LTNP. Therefore we hypothesized that the immunological mechanism responsible for preserved CD4 counts in LTNP is different from that in VC. Methods: 69 treatment naïve HIV-infected patients were included in a cross-sectional study. A total of 14 LTNP...... ratio in LTNP compared to VC were found (3.8 vs. 5.5, P=0.068) while ratios in LTNP and PR were similar (4.0, P>0.05). Conclusion: LTNP displayed high levels of immune activation, apoptotic cells and reduced Th17/Treg ratio compared to VC, while LTNP were similar to PR. Thus, the immunological mechanism...... responsible for preserved CD4 counts in LTNP is still unclear but seems to be different from that in VC....

  19. Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication.

    Science.gov (United States)

    Uusitalo, Hannu; Chen, Enping; Pfeiffer, Norbert; Brignole-Baudouin, Françoise; Kaarniranta, Kai; Leino, Markku; Puska, Päivi; Palmgren, Elina; Hamacher, Thomas; Hofmann, Günter; Petzold, Gernot; Richter, Ulrich; Riedel, Tobias; Winter, Martin; Ropo, Auli

    2010-05-01

    The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan) treatment. A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits. Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 +/- 2.7 mmHg) as latanoprost at baseline (16.8 +/- 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 +/- 2.5 seconds to 7.8 +/- 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected. Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was

  20. Hybrid Food Preservation Program Improves Food Preservation and Food Safety Knowledge

    Science.gov (United States)

    Francis, Sarah L.

    2014-01-01

    The growing trend in home food preservation raises concerns about whether the resulting food products will be safe to eat. The increased public demand for food preservation information led to the development of the comprehensive food preservation program, Preserve the Taste of Summer (PTTS). PTTS is a comprehensive hybrid food preservation program…

  1. Neuron-glia signaling and the protection of axon function by Schwann cells.

    Science.gov (United States)

    Quintes, Susanne; Goebbels, Sandra; Saher, Gesine; Schwab, Markus H; Nave, Klaus-Armin

    2010-03-01

    The interaction between neurons and glial cells is a feature of all higher nervous systems. In the vertebrate peripheral nervous system, Schwann cells ensheath and myelinate axons thereby allowing rapid saltatory conduction and ensuring axonal integrity. Recently, some of the key molecules in neuron-Schwann cell signaling have been identified. Neuregulin-1 (NRG1) type III presented on the axonal surface determines the myelination fate of axons and controls myelin sheath thickness. Recent observations suggest that NRG1 regulates myelination via the control of Schwann cell cholesterol biosynthesis. This concept is supported by the finding that high cholesterol levels in Schwann cells are a rate-limiting factor for myelin protein production and transport of the major myelin protein P0 from the endoplasmic reticulum into the growing myelin sheath. NRG1 type III activates ErbB receptors on the Schwann cell, which leads to an increase in intracellular PIP3 levels via the PI3-kinase pathway. Surprisingly, enforced elevation of PIP3 levels by inactivation of the phosphatase PTEN in developing and mature Schwann cells does not entirely mimic NRG1 type III stimulated myelin growth, but predominantly causes focal hypermyelination starting at Schmidt-Lanterman incisures and nodes of Ranvier. This indicates that the glial transduction of pro-myelinating signals has to be under tight and life-long control to preserve integrity of the myelinated axon. Understanding the cross talk between neurons and Schwann cells will help to further define the role of glia in preserving axonal integrity and to develop therapeutic strategies for peripheral neuropathies such as CMT1A.

  2. Cryopreservation: a cold look at technology for fertility preservation.

    Science.gov (United States)

    Gosden, Roger

    2011-08-01

    To outline the history of cryopreservation technology and its contributions to reproductive medicine, including fertility preservation. A search of the relevant literature using Medline and other online tools. Research and laboratory protocol development. The biology of preserving cells at low temperatures is complex and still being unraveled. Principles were first established more than half a century ago, with progress being driven empirically and often by trial and error. The protocols vary widely, and practice is still heavily dependent on operator skill, accounting for wide differences in the success rates between centers. No single protocol fits all specimen types, and differential vulnerability to cryoinjury remains a major obstacle. Nevertheless, semen cryopreservation has long been established, embryo banking is now highly effective, and vitrification appears to overcome problems with oocytes. Protocols in the future, although specific to the cell type and tissue, are likely to evolve toward generally acknowledged standards. But heterogeneity between patients and even within samples implies that each cell may have its own peculiar optimum for minimizing cryoinjury; because protocols are therefore compromises, "perfect" preservation may be unattainable. Cryopreservation has become a mainstay in the assisted reproduction laboratory and underpins fertility preservation for patients with cancer and other conditions. The practice is currently evolving from slow freezing methods toward more vitrification, and future technology is likely to reduce dependence on operator skill, which should raise success rates to higher, more uniform levels. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Pricing policy for declining demand using item preservation technology.

    Science.gov (United States)

    Khedlekar, Uttam Kumar; Shukla, Diwakar; Namdeo, Anubhav

    2016-01-01

    We have designed an inventory model for seasonal products in which deterioration can be controlled by item preservation technology investment. Demand for the product is considered price sensitive and decreases linearly. This study has shown that the profit is a concave function of optimal selling price, replenishment time and preservation cost parameter. We simultaneously determined the optimal selling price of the product, the replenishment cycle and the cost of item preservation technology. Additionally, this study has shown that there exists an optimal selling price and optimal preservation investment to maximize the profit for every business set-up. Finally, the model is illustrated by numerical examples and sensitive analysis of the optimal solution with respect to major parameters.

  4. A comparison of cryopreservation methods: Slow-cooling vs. rapid-cooling based on cell viability, oxidative stress, apoptosis, and CD34+ enumeration of human umbilical cord blood mononucleated cells

    Directory of Open Access Journals (Sweden)

    Sandra Ferry

    2011-09-01

    Full Text Available Abstract Background The finding of human umbilical cord blood as one of the most likely sources of hematopoietic stem cells offers a less invasive alternative for the need of hematopoietic stem cell transplantation. Due to the once-in-a-life time chance of collecting it, an optimum cryopreservation method that can preserve the life and function of the cells contained is critically needed. Methods Until now, slow-cooling has been the routine method of cryopreservation; however, rapid-cooling offers a simple, efficient, and harmless method for preserving the life and function of the desired cells. Therefore, this study was conducted to compare the effectiveness of slow- and rapid-cooling to preserve umbilical cord blood of mononucleated cells suspected of containing hematopoietic stem cells. The parameters used in this study were differences in cell viability, malondialdehyde content, and apoptosis level. The identification of hematopoietic stem cells themselves was carried out by enumerating CD34+ in a flow cytometer. Results Our results showed that mononucleated cell viability after rapid-cooling (91.9% was significantly higher than that after slow-cooling (75.5%, with a p value = 0.003. Interestingly, the malondialdehyde level in the mononucleated cell population after rapid-cooling (56.45 μM was also significantly higher than that after slow-cooling (33.25 μM, with a p value p value = 0.138. However, CD34+ enumeration was much higher in the population that underwent slow-cooling (23.32 cell/μl than in the one that underwent rapid-cooling (2.47 cell/μl, with a p value = 0.001. Conclusions Rapid-cooling is a potential cryopreservation method to be used to preserve the umbilical cord blood of mononucleated cells, although further optimization of the number of CD34+ cells after rapid-cooling is critically needed.

  5. Survival or revival: long-term preservation induces a reversible viable but non-culturable state in methane-oxidizing bacteria.

    Directory of Open Access Journals (Sweden)

    Sven Hoefman

    Full Text Available Knowledge on long-term preservation of micro-organisms is limited and research in the field is scarce despite its importance for microbial biodiversity and biotechnological innovation. Preservation of fastidious organisms such as methane-oxidizing bacteria (MOB has proven difficult. Most MOB do not survive lyophilization and only some can be cryopreserved successfully for short periods. A large-scale study was designed for a diverse set of MOB applying fifteen cryopreservation or lyophilization conditions. After three, six and twelve months of preservation, the viability (via live-dead flow cytometry and culturability (via most-probable number analysis and plating of the cells were assessed. All strains could be cryopreserved without a significant loss in culturability using 1% trehalose in 10-fold diluted TSB (TT as preservation medium and 5% DMSO as cryoprotectant. Several other cryopreservation and lyophilization conditions, all of which involved the use of TT medium, also allowed successful preservation but showed a considerable loss in culturability. We demonstrate here that most of these non-culturables survived preservation according to viability assessment indicating that preservation induces a viable but non-culturable (VBNC state in a significant fraction of cells. Since this state is reversible, these findings have major implications shifting the emphasis from survival to revival of cells in a preservation protocol. We showed that MOB cells could be significantly resuscitated from the VBNC state using the TT preservation medium.

  6. Archiving Software Systems: Approaches to Preserve Computational Capabilities

    Science.gov (United States)

    King, T. A.

    2014-12-01

    A great deal of effort is made to preserve scientific data. Not only because data is knowledge, but it is often costly to acquire and is sometimes collected under unique circumstances. Another part of the science enterprise is the development of software to process and analyze the data. Developed software is also a large investment and worthy of preservation. However, the long term preservation of software presents some challenges. Software often requires a specific technology stack to operate. This can include software, operating systems and hardware dependencies. One past approach to preserve computational capabilities is to maintain ancient hardware long past its typical viability. On an archive horizon of 100 years, this is not feasible. Another approach to preserve computational capabilities is to archive source code. While this can preserve details of the implementation and algorithms, it may not be possible to reproduce the technology stack needed to compile and run the resulting applications. This future forward dilemma has a solution. Technology used to create clouds and process big data can also be used to archive and preserve computational capabilities. We explore how basic hardware, virtual machines, containers and appropriate metadata can be used to preserve computational capabilities and to archive functional software systems. In conjunction with data archives, this provides scientist with both the data and capability to reproduce the processing and analysis used to generate past scientific results.

  7. Preservation of sexual function in young prostate cancer patients after radiation therapy: a positive factor in choice of a treatment modality

    International Nuclear Information System (INIS)

    Nicolaou, Nicos; Bruner, Deborah Watkins; Hanks, G.E.; Hanlon, Alex

    1996-01-01

    Purpose/Objective: To assess the effect of definitive radiation therapy (RT) without androgen deprivation, on the sexual function and quality of life of young prostate cancer patients as compared to age matched controls, using the Sexual Adjustment Questionnaire (SAQ), in order to assist future patients in making informed choices when deciding between surgery and radiation therapy. Methods and Materials: Forty five patients between 50 and 65 years of age at time of diagnosis (mean age 60 years), were treated with RT at Fox Chase Cancer Center (FCCC) from 1/1/89 to 12/31/93 for biopsy proven, T1-T3 clinically localized prostatic adenocarcinoma. Mean age at time of present assessment was 63 years. Their pre- and post-treatment sexual function and quality of life were assessed and compared to 47 age matched controls (mean age 60 years) using a modified version of the SAQ. Results: Mean and median follow up of the RT group was 31 months. Potency rate was 85% ((40(47))) in controls and pre-treatment potency rate was 91% ((41(45))) in RT group. Post-treatment overall potency rate in RT group was 67% ((30(45))). Preservation of potency in initially potent patients treated with RT, was 73% ((30(41))). The RT group was significantly inferior to the control group regarding sexual arousal, function and frequency of sexual activity but not in sexual desire and enjoyment or the importance placed on sexual activity. Conclusion: (1) Sexual potency is preserved in 73% of young sexually active men treated with RT for prostate cancer which is at least as good as the best reports after never sparing prostatectomy and far superior to the 0-10% rates of sexual potency preservation after non-nerve sparing prostatectomy. (2) The 27% of patients who lose sexual potency after RT, generally retain sexual desire and enjoyment indicating a favorable situation for rehabilitation. (3) The 27% loss of sexual potency may be artificially high without a known correction factor for those who would

  8. A Method Sustaining the Bioelectric, Biophysical, and Bioenergetic Function of Cultured Rabbit Atrial Cells

    Directory of Open Access Journals (Sweden)

    Noa Kirschner Peretz

    2017-08-01

    Full Text Available Culturing atrial cells leads to a loss in their ability to be externally paced at physiological rates and to maintain their shape. We aim to develop a culture method that sustains the shape of atrial cells along with their biophysical and bioenergetic properties in response to physiological pacing. We hypothesize that adding 2,3-Butanedione 2-monoxime (BDM, which inhibits contraction during the culture period, will preserve these biophysical and bioenergetic properties. Rabbit atrial cells were maintained in culture for 24 h in a medium enriched with a myofilament contraction inhibitor, BDM. The morphology and volume of the cells, including their ability to contract in response to 1–3 Hz electrical pacing, was maintained at the same level as fresh cells. Importantly, the cells could be successfully infected with a GFP adenovirus. Action potentials, Ca2+ transients, and local Ca2+ spark parameters were similar in the cultured and in fresh cells. Finally, these cultured cells' flavoprotein autofluorescence was maintained at a constant level in response to electrical pacing, a response similar to that of fresh cells. Thus, eliminating contraction during the culture period preserves the bioelectric, biophysical and bioenergetic properties of rabbit atrial myocytes. This method therefore has the potential to further improve our understanding of energetic and biochemical regulation in the atria.

  9. Time-dependent density functional theory for open systems with a positivity-preserving decomposition scheme for environment spectral functions

    International Nuclear Information System (INIS)

    Wang, RuLin; Zheng, Xiao; Kwok, YanHo; Xie, Hang; Chen, GuanHua; Yam, ChiYung

    2015-01-01

    Understanding electronic dynamics on material surfaces is fundamentally important for applications including nanoelectronics, inhomogeneous catalysis, and photovoltaics. Practical approaches based on time-dependent density functional theory for open systems have been developed to characterize the dissipative dynamics of electrons in bulk materials. The accuracy and reliability of such approaches depend critically on how the electronic structure and memory effects of surrounding material environment are accounted for. In this work, we develop a novel squared-Lorentzian decomposition scheme, which preserves the positive semi-definiteness of the environment spectral matrix. The resulting electronic dynamics is guaranteed to be both accurate and convergent even in the long-time limit. The long-time stability of electronic dynamics simulation is thus greatly improved within the current decomposition scheme. The validity and usefulness of our new approach are exemplified via two prototypical model systems: quasi-one-dimensional atomic chains and two-dimensional bilayer graphene

  10. Time-dependent density functional theory for open systems with a positivity-preserving decomposition scheme for environment spectral functions.

    Science.gov (United States)

    Wang, RuLin; Zheng, Xiao; Kwok, YanHo; Xie, Hang; Chen, GuanHua; Yam, ChiYung

    2015-04-14

    Understanding electronic dynamics on material surfaces is fundamentally important for applications including nanoelectronics, inhomogeneous catalysis, and photovoltaics. Practical approaches based on time-dependent density functional theory for open systems have been developed to characterize the dissipative dynamics of electrons in bulk materials. The accuracy and reliability of such approaches depend critically on how the electronic structure and memory effects of surrounding material environment are accounted for. In this work, we develop a novel squared-Lorentzian decomposition scheme, which preserves the positive semi-definiteness of the environment spectral matrix. The resulting electronic dynamics is guaranteed to be both accurate and convergent even in the long-time limit. The long-time stability of electronic dynamics simulation is thus greatly improved within the current decomposition scheme. The validity and usefulness of our new approach are exemplified via two prototypical model systems: quasi-one-dimensional atomic chains and two-dimensional bilayer graphene.

  11. The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

    Science.gov (United States)

    Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

    2016-09-01

    Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders. Copyright © 2016. Published by Elsevier Ltd.

  12. Influence of pH on extracellular matrix preservation during lung decellularization.

    Science.gov (United States)

    Tsuchiya, Tomoshi; Balestrini, Jenna L; Mendez, Julio; Calle, Elizabeth A; Zhao, Liping; Niklason, Laura E

    2014-12-01

    The creation of decellularized organs for use in regenerative medicine requires the preservation of the organ extracellular matrix (ECM) as a means to provide critical cues for differentiation and migration of cells that are seeded onto the organ scaffold. The purpose of this study was to assess the influence of varying pH levels on the preservation of key ECM components during the decellularization of rat lungs. Herein, we show that the pH of the 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS)-based decellularization solution influences ECM retention, cell removal, and also the potential for host response upon implantation of acellular lung tissue. The preservation of ECM components, including elastin, fibronectin, and laminin, were better retained in the lower pH conditions that were tested (pH ranges tested: 8, 10, 12); glycosaminoglycans were preserved to a higher extent in the lower pH groups as well. The DNA content following decellularization of the rat lung was inversely correlated with the pH of the decellularization solution. Despite detectible levels of cyotoskeletal proteins and significant residual DNA, tissues decellularized at pH 8 demonstrated the greatest tissue architecture maintenance and the least induction of host response of all acellular conditions. These results highlight the effect of pH on the results obtained by organ decellularization and suggest that altering the pH of the solutions used for decellularization may influence the ability of cells to properly differentiate and home to appropriate locations within the scaffold, based on the preservation of key ECM components and implantation results.

  13. Organ-Preserving Surgical Treatment of a Horseshoe Kidney Occupied by a Large Renal Cell Carcinoma with Extensive Venous Invasion: A Case Report.

    Science.gov (United States)

    Linxweiler, Johannes; Shayesteh-Kheslat, Roushanak; Fries, Peter; Schneider, Günther; Janssen, Martin; Ohlmann, Carsten H; Stöckle, Michael; Siemer, Stefan; Saar, Matthias

    2018-01-01

    The horseshoe kidney is one of the most common congenital disorders affecting the urogenital system. Following a fusion of the lower kidney poles, which in turn lead to the formation of an isthmus, this anatomical variation is accompanied by other characteristic properties like an incomplete ascension, ventral rotation of the pelvices as well as atypical vascular supply. Even though renal carcinoids and Wilms tumors are more common in horseshoe kidneys, the incidence of renal cell carcinomas seems to be unaffected. Here we report the case of a locally advanced renal cell carcinoma with extensive venous invasion occurring in a horseshoe kidney and its complex surgical management. The whole primary tumor as well as a majority of venous tumor thrombi could be removed by a combination of 2/3 nephrectomy and cavotomy with thrombectomy. During 1 year of follow-up, the patient neither suffered from a tumor relapse, nor did he require renal replacement therapy. Thus, we conclude that even in cases of RCC where advanced disease is associated with complex anatomical situations, organ-preserving surgical treatment should be pursued to achieve excellent functional and oncological results. © 2016 S. Karger AG, Basel.

  14. Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using Interrupted Reprogramming

    Directory of Open Access Journals (Sweden)

    Li Guo

    2017-12-01

    Full Text Available Summary: A suitable source of progenitor cells is required to attenuate disease or affect cure. We present an “interrupted reprogramming” strategy to generate “induced progenitor-like (iPL cells” using carefully timed expression of induced pluripotent stem cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc; OSKM from non-proliferative Club cells. Interrupted reprogramming allowed controlled expansion yet preservation of lineage commitment. Under clonogenic conditions, iPL cells expanded and functioned as a bronchiolar progenitor-like population to generate mature Club cells, mucin-producing goblet cells, and cystic fibrosis transmembrane conductance regulator (CFTR-expressing ciliated epithelium. In vivo, iPL cells can repopulate CFTR-deficient epithelium. This interrupted reprogramming process could be metronomically applied to achieve controlled progenitor-like proliferation. By carefully controlling the duration of expression of OSKM, iPL cells do not become pluripotent, and they maintain their memory of origin and retain their ability to efficiently return to their original phenotype. A generic technique to produce highly specified populations may have significant implications for regenerative medicine. : In this article Waddell, Nagy, and colleagues present an “interrupted reprogramming” strategy to produce highly specified functional “induced progenitor-like cells” from mature quiescent cells. They propose that careful control of the duration of transient expression of iPSC reprogramming factors (OSKM allows controlled expansion yet preservation of parental lineage without traversing the pluripotent state. Keywords: generation of induced progenitor-like cells

  15. Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats.

    Science.gov (United States)

    Gu, Qi; Wang, Bing; Zhang, Xiao-Feng; Ma, Yan-Ping; Liu, Jian-Dong; Wang, Xiao-Ze

    2014-08-01

    Aging leads to large vessel arterial stiffening and endothelial dysfunction, which are important determinants of cardiovascular risk. The aim of present work was to assess the effects of chronic aerobic exercise training on aortic stiffening and endothelial dysfunction in aged rats and investigate the underlying mechanism about mitochondrial function. Chronic aerobic exercise training attenuated aortic stiffening with age marked by reduced collagen concentration, increased elastin concentration and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by improved endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Chronic aerobic exercise training abated oxidative stress and nitrosative stress in aortas of aged rats. More importantly, we found that chronic aerobic exercise training in old rats preserved aortic mitochondrial function marked by reduced reactive oxygen species (ROS) formation and mitochondrial swelling, increased ATP formation and mitochondrial DNA content, and restored activities of complexes I and III and electron-coupling capacity between complexes I and III and between complexes II and III. In addition, it was found that chronic aerobic exercise training in old rats enhanced protein expression of uncoupling protein 2 (UCP-2), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), manganese superoxide dismutase (Mn-SOD), aldehyde dehydrogenase 2 (ALDH-2), prohibitin (PHB) and AMP-activated kinase (AMPK) phosphorylation in aortas. In conclusion, chronic aerobic exercise training preserved mitochondrial function in aortas, which, at least in part, explained the aorta-protecting effects of exercise training in aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Pancreatic cancer cell lines as patient-derived avatars: genetic characterisation and functional utility.

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    Knudsen, Erik S; Balaji, Uthra; Mannakee, Brian; Vail, Paris; Eslinger, Cody; Moxom, Christopher; Mansour, John; Witkiewicz, Agnieszka K

    2018-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines. Exome sequencing was performed on the originating tumour and developed models. RNA sequencing, histological and functional analyses were employed to determine the relationship of the patient-derived models to clinical presentation of PDAC. The cohort employed captured the genetic diversity of PDAC. From most cases, both cell lines and xenograft models were developed. Exome sequencing confirmed preservation of the primary tumour mutations in developed cell lines, which remained stable with extended passaging. The level of genetic conservation in the cell lines was comparable to that observed with patient-derived xenograft (PDX) models. Unlike historically established PDAC cancer cell lines, patient-derived models recapitulated the histological architecture of the primary tumour and exhibited metastatic spread similar to that observed clinically. Detailed genetic analyses of tumours and derived models revealed features of ex vivo evolution and the clonal architecture of PDAC. Functional analysis was used to elucidate therapeutic vulnerabilities of relevance to treatment of PDAC. These data illustrate that with the appropriate methods it is possible to develop cell lines that maintain genetic features of PDAC. Such models serve as important substrates for analysing the significance of genetic variants and create a unique biorepository of annotated cell lines and xenografts that were established simultaneously from same primary tumour. These models can be used to infer genetic and empirically determined

  17. Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society.

    Science.gov (United States)

    Mallone, R; Mannering, S I; Brooks-Worrell, B M; Durinovic-Belló, I; Cilio, C M; Wong, F S; Schloot, N C

    2011-01-01

    Autoimmune T cell responses directed against insulin-producing β cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen-specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

  18. American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function.

    Science.gov (United States)

    Folsom, Aaron R; Shah, Amil M; Lutsey, Pamela L; Roetker, Nicholas S; Alonso, Alvaro; Avery, Christy L; Miedema, Michael D; Konety, Suma; Chang, Patricia P; Solomon, Scott D

    2015-09-01

    Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15

    Science.gov (United States)

    Xu, Yang; Zhang, Ming; Ramos, Carlos A.; Durett, April; Liu, Enli; Dakhova, Olga; Liu, Hao; Creighton, Chad J.; Gee, Adrian P.; Heslop, Helen E.; Rooney, Cliona M.; Savoldo, Barbara

    2014-01-01

    Adoptive transfer of T lymphocytes expressing a CD19-specific chimeric antigen receptor (CAR.CD19) induces complete tumor regression in patients with lymphoid malignancies. Although in vivo persistence of CAR-T cells correlates with clinical responses, it remains unknown whether specific cell subsets within the CAR–T-cell product correlate with their subsequent in vivo expansion and persistence. We analyzed 14 patients with B-cell malignancies infused with autologous CAR.CD19-redirected T cells expanded ex vivo using IL-2, and found that their in vivo expansion only correlated with the frequency within the infused product of a CD8+CD45RA+CCR7+ subset, whose phenotype is closest to “T-memory stem cells.” Preclinical models showed that increasing the frequency of CD8+CD45RA+CCR7+ CAR-T cells in the infused line by culturing the cells with IL-7 and IL-15 produced greater antitumor activity of CAR-T cells mediated by increased resistance to cell death, following repetitive encounters with the antigen, while preserving their migration to secondary lymphoid organs. This trial was registered at www.clinicaltrials.gov as #NCT00586391 and #NCT00709033. PMID:24782509

  20. Cell-Intrinsic Roles for Autophagy in Modulating CD4 T Cell Functions

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    Elise Jacquin

    2018-05-01

    Full Text Available The catabolic process of autophagy plays important functions in inflammatory and immune responses by modulating innate immunity and adaptive immunity. Over the last decade, a cell-intrinsic role for autophagy in modulating CD4 T cell functions and differentiation was revealed. After the initial observation of autophagosomes in effector CD4 T cells, further work has shown that not only autophagy levels are modulated in CD4 T cells in response to environmental signals but also that autophagy critically affects the biology of these cells. Mouse models of autophagy deletion in CD4 T cells have indeed shown that autophagy is essential for CD4 T cell survival and homeostasis in peripheral lymphoid organs. Furthermore, autophagy is required for CD4 T cell proliferation and cytokine production in response to T cell receptor activation. Recent developments have uncovered that autophagy controls CD4 T cell differentiation and functions. While autophagy is required for the maintenance of immunosuppressive functions of regulatory T cells, it restrains the differentiation of TH9 effector cells, thus limiting their antitumor and pro-inflammatory properties. We will here discuss these findings that collectively suggest that therapeutic strategies targeting autophagy could be exploited for the treatment of cancer and inflammatory diseases.

  1. Feeder cells support the culture of induced pluripotent stem cells even after chemical fixation.

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    Xiao-Shan Yue

    Full Text Available Chemically fixed mouse embryonic fibroblasts (MEFs, instead of live feeder cells, were applied to the maintenance of mouse induced pluripotent stem (miPS cells. Formaldehyde and glutaraldehyde were used for chemical fixation. The chemically fixed MEF feeders maintained the pluripotency of miPS cells, as well as their undifferentiated state. Furthermore, the chemically fixed MEF feeders were reused several times without affecting their functions. These results indicate that chemical fixation can be applied to modify biological feeders chemically, without losing their original functions. Chemically fixed MEF feeders will be applicable to other stem cell cultures as a reusable extracellular matrix candidate that can be preserved on a long-term basis.

  2. Role of Polyamines in Immune Cell Functions

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    Rebecca S. Hesterberg

    2018-03-01

    Full Text Available The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control the specificity, magnitude and persistence of the immune response. Numerous catabolic and anabolic processes are involved in this process, and prominent roles for l-arginine and l-glutamine catabolism have been described, as these amino acids serve as precursors of nitric oxide, creatine, agmatine, tricarboxylic acid cycle intermediates, nucleotides and other amino acids, as well as for ornithine, which is used to synthesize putrescine and the polyamines spermidine and spermine. Polyamines have several purported roles and high levels of polyamines are manifest in tumor cells as well in autoreactive B- and T-cells in autoimmune diseases. In the tumor microenvironment, l-arginine catabolism by both tumor cells and suppressive myeloid cells is known to dampen cytotoxic T-cell functions suggesting there might be links between polyamines and T-cell suppression. Here, we review studies suggesting roles of polyamines in normal immune cell function and highlight their connections to autoimmunity and anti-tumor immune cell function.

  3. Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

    International Nuclear Information System (INIS)

    Gupta, Tejpal; Jalali, Rakesh; Goswami, Savita; Nair, Vimoj; Moiyadi, Aliasgar; Epari, Sridhar; Sarin, Rajiv

    2012-01-01

    Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children ≥5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5–14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56–70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16–58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

  4. Early Clinical Outcomes Demonstrate Preserved Cognitive Function in Children With Average-Risk Medulloblastoma When Treated With Hyperfractionated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Tejpal, E-mail: tejpalgupta@rediffmail.com [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Jalali, Rakesh [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Goswami, Savita [Department of Clinical Psychology and Psychiatry Unit, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Nair, Vimoj [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Moiyadi, Aliasgar [Division of Neuro-Surgery, Department of Surgical Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Epari, Sridhar [Department of Pathology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India); Sarin, Rajiv [Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer and Tata Memorial Hospital, Mumbai (India)

    2012-08-01

    Purpose: To report on acute toxicity, longitudinal cognitive function, and early clinical outcomes in children with average-risk medulloblastoma. Methods and Materials: Twenty children {>=}5 years of age classified as having average-risk medulloblastoma were accrued on a prospective protocol of hyperfractionated radiation therapy (HFRT) alone. Radiotherapy was delivered with two daily fractions (1 Gy/fraction, 6 to 8 hours apart, 5 days/week), initially to the neuraxis (36 Gy/36 fractions), followed by conformal tumor bed boost (32 Gy/32 fractions) for a total tumor bed dose of 68 Gy/68 fractions over 6 to 7 weeks. Cognitive function was prospectively assessed longitudinally (pretreatment and at specified posttreatment follow-up visits) with the Wechsler Intelligence Scale for Children to give verbal quotient, performance quotient, and full-scale intelligence quotient (FSIQ). Results: The median age of the study cohort was 8 years (range, 5-14 years), representing a slightly older cohort. Acute hematologic toxicity was mild and self-limiting. Eight (40%) children had subnormal intelligence (FSIQ <85), including 3 (15%) with mild mental retardation (FSIQ 56-70) even before radiotherapy. Cognitive functioning for all tested domains was preserved in children evaluable at 3 months, 1 year, and 2 years after completion of HFRT, with no significant decline over time. Age at diagnosis or baseline FSIQ did not have a significant impact on longitudinal cognitive function. At a median follow-up time of 33 months (range, 16-58 months), 3 patients had died (2 of relapse and 1 of accidental burns), resulting in 3-year relapse-free survival and overall survival of 83.5% and 83.2%, respectively. Conclusion: HFRT without upfront chemotherapy has an acceptable acute toxicity profile, without an unduly increased risk of relapse, with preserved cognitive functioning in children with average-risk medulloblastoma.

  5. Functional properties of hepatocytes in vitro are correlated with cell polarity maintenance.

    Science.gov (United States)

    Zeigerer, Anja; Wuttke, Anne; Marsico, Giovanni; Seifert, Sarah; Kalaidzidis, Yannis; Zerial, Marino

    2017-01-01

    Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect the molecular mechanisms underlying the structure and function of the liver in vivo. However, this approach relies on appropriate in vitro cell culture systems that can recapitulate the cell biological and metabolic features of the hepatocytes in the liver whilst being accessible to experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy and quantitative image analysis to compare two primary hepatocyte culture systems, monolayer and collagen sandwich, with respect to the distribution of two distinct populations of early endosomes (APPL1 and EEA1-positive), endocytic capacity, metabolic and signaling activities. In addition to the re-acquisition of hepatocellular polarity, primary hepatocytes grown in collagen sandwich but not in monolayer culture recapitulated the apico-basal distribution of EEA1 endosomes observed in liver tissue. We found that such distribution correlated with the organization of the actin cytoskeleton in vitro and, surprisingly, was dependent on the nutritional state in vivo. Hepatocytes in collagen sandwich also exhibited faster kinetics of low-density lipoprotein (LDL) and epidermal growth factor (EGF) internalization, showed improved insulin sensitivity and preserved their ability for glucose production, compared to hepatocytes in monolayer cultures. Although no in vitro culture system can reproduce the exquisite structural features of liver tissue, our data nevertheless highlight the ability of the collagen sandwich system to recapitulate key structural and functional properties of the hepatocytes in the liver and, therefore, support the usage of this system to study aspects of hepatocellular biology in vitro. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Baculovirus IE2 Stimulates the Expression of Heat Shock Proteins in Insect and Mammalian Cells to Facilitate Its Proper Functioning.

    Science.gov (United States)

    Tung, Hsuan; Wei, Sung-Chan; Lo, Huei-Ru; Chao, Yu-Chan

    2016-01-01

    Baculoviruses have gained popularity as pest control agents and for protein production in insect systems. These viruses are also becoming popular for gene expression, tissue engineering and gene therapy in mammalian systems. Baculovirus infection triggers a heat shock response, and this response is crucial for its successful infection of host insect cells. However, the viral protein(s) or factor(s) that trigger this response are not yet clear. Previously, we revealed that IE2-an early gene product of the baculovirus-could form unique nuclear bodies for the strong trans-activation of various promoters in mammalian cells. Here, we purified IE2 nuclear bodies from Vero E6 cells and investigated the associated proteins by using mass spectrometry. Heat shock proteins (HSPs) were found to be one of the major IE2-associated proteins. Our experiments show that HSPs are greatly induced by IE2 and are crucial for the trans-activation function of IE2. Interestingly, blocking both heat shock protein expression and the proteasome pathway preserved the IE2 protein and its nuclear body structure, and revived its function. These observations reveal that HSPs do not function directly to assist the formation of the nuclear body structure, but may rather protect IE2 from proteasome degradation. Aside from functional studies in mammalian cells, we also show that HSPs were stimulated and required to determine IE2 protein levels, in insect cells infected with baculovirus. Upon inhibiting the expression of heat shock proteins, baculovirus IE2 was substantially suppressed, resulting in a significantly suppressed viral titer. Thus, we demonstrate a unique feature in that IE2 can function in both insect and non-host mammalian cells to stimulate HSPs, which may be associated with IE2 stabilization and lead to the protection of the its strong gene activation function in mammalian cells. On the other hand, during viral infection in insect cells, IE2 could also strongly stimulate HSPs and

  7. Successful Function-Preserving Therapy for Chondroblastoma of the Temporal Bone Involving the Temporomandibular Joint

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    Junkichi Yokoyama

    2011-02-01

    Full Text Available We present a case involving a late diagnosis of chondroblastoma of the temporal skull base involving the temporomandibular joint (TMJ. Following an initial misdiagnosis and unsuccessful treatment over a period of 5 years, the patient was referred to our department for further evaluation and possible surgical intervention for occlusal abnormalities, trismus, clicking of the TMJ, and hearing impairment. Based on preoperative immunochemical studies showing positive reaction of multinucleated giant cells for S-100 protein, the final diagnosis was chondroblastoma. The surgical approach – postauricular incision and total parotidectomy, with complete removal of the temporal bone, including the TMJ via the extended middle fossa – was successful in preserving facial nerves and diminishing clinical manifestations. This study highlights a misdiagnosed case in an effort to underline the importance of medical examinations and accurate differential diagnosis in cases involving any tumor mass in the temporal bone.

  8. Platelet function in stored heparinised autologous blood is not superior to in patient platelet function during routine cardiopulmonary bypass.

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    Rolf C G Gallandat Huet

    Full Text Available BACKGROUND: In cardiac surgery, cardiopulmonary bypass (CPB and unfractionated heparin have negative effects on blood platelet function. In acute normovolemic haemodilution autologous unfractionated heparinised blood is stored ex-vivo and retransfused at the end of the procedure to reduce (allogeneic transfusion requirements. In this observational study we assessed whether platelet function is better preserved in ex vivo stored autologous blood compared to platelet function in the patient during CPB. METHODOLOGY/PRINCIPAL FINDING: We measured platelet aggregation responses pre-CPB, 5 min after the start of CPB, at the end of CPB, and after unfractionated heparin reversal, using multiple electrode aggregometry (Multiplate® with adenosine diphosphate (ADP, thrombin receptor activating peptide (TRAP and ristocetin activated test cells. We compared blood samples taken from the patient with samples taken from 100 ml ex-vivo stored blood, which we took to mimick blood storage during normovolemic haemodilution. Platelet function declined both in ex-vivo stored blood as well as in blood taken from the patient. At the end of CPB there were no differences in platelet aggregation responses between samples from the ex vivo stored blood and the patient. CONCLUSION/SIGNIFICANCE: Ex vivo preservation of autologous blood in unfractionated heparin does not seem to be profitable to preserve platelet function.

  9. Improved biochemical preservation of lung slices during cold storage.

    Science.gov (United States)

    Bull, D A; Connors, R C; Reid, B B; Albanil, A; Stringham, J C; Karwande, S V

    2000-05-15

    Development of lung preservation solutions typically requires whole-organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that lung slices could be used to assess preservation of biochemical function during cold storage. Whole rat lungs were precision cut into slices with a thickness of 500 microm and preserved at 4 degrees C in the following solutions: University of Wisconsin (UW), Euro-Collins (EC), low-potassium-dextran (LPD), Kyoto (K), normal saline (NS), or a novel lung preservation solution (NPS) developed using this model. Lung biochemical function was assessed by ATP content (etamol ATP/mg wet wt) and capacity for protein synthesis (cpm/mg protein) immediately following slicing (0 h) and at 6, 12, 18, and 24 h of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as means +/- SD. ATP content was significantly higher in the lung slices stored in NPS compared with all other solutions at each time point (P cold storage. Copyright 2000 Academic Press.

  10. Preserved C-peptide levels in overweight or obese compared with underweight children upon diagnosis of type 1 diabetes mellitus

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    Hyeoh Won Yu

    2015-06-01

    Full Text Available PurposeWe hypothesized that overweight or obese children might develop type 1 diabetes mellitus (T1DM early despite residual beta-cell function. Factors independently associated with preservation of C-peptide level were analyzed.MethodsWe retrospectively reviewed the medical data of 135 children aged 2.1-16.5 years with autoimmune T1DM. Body mass index (BMI, pubertal stage, and glycosylated hemoglobin (HbA1c and C-peptide levels were evaluated. Patients were assigned to underweight (22.2%, normal weight (63.7%, and overweight or obese (14.1% groups according to their BMI.ResultsPreservation of serum C-peptide levels (≥0.6 ng/mL was found in 43.0% of subjects. With increasing BMI, the proportions of children with preserved C-peptide levels increased from 33.3% to 41.9% to 63.2%, with marginal significance (P=0.051. Interaction analysis indicated no effect of BMI score on age at onset associated with serum C-peptide levels. The lower the C-peptide level, the younger the age of onset (P<0.001, after adjustment for BMI z-score and HbA1c level. However, no significant relationship between BMI z-score or category and onset age was evident. Upon multivariate-adjusted modeling, the odds that the C-peptide level was preserved increased by 1.2 fold (P=0.001 per year of life, by 3.1 folds (P=0.015 in children presenting without (compared to with ketoacidosis, and by 5.0 folds (P=0.042 in overweight or obese (compared to underweight children.ConclusionOverweight or obese children had slightly more residual beta-cell function than did underweight children. However, we found no evidence that obesity temporally accelerates T1DM presentation.

  11. Vascular endothelial dysfunction in β-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO.

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    Ekatherina Stoyanova

    Full Text Available The hereditary β-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of β-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments.Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium-dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of β-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO. While these findings suggest a decrease in NO bioavailability, Western blotting showed heightened expression of aortic endothelial NO synthase (eNOS in β-thalassemia. Vascular remodeling of the common carotid arteries revealed increased medial elastin content. Under isobaric conditions, the carotid arteries of β-thalassemic mice exhibited decreased wall stress and softening due to structural changes of the vessel wall.A complex vasculopathy was identified in untransfused β-thalassemic mice characterized by altered carotid artery structure and endothelial dysfunction of resistance arterioles, likely attributable to reduced NO bioavailability despite enhanced vascular eNOS expression.

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

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    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. Investigation on the suitable pressure for the preservation of astrocyte

    International Nuclear Information System (INIS)

    Sotome, S; Shimizu, A; Nakajima, K; Yoshimura, Y

    2010-01-01

    The effects of pressure on the survival rate of astrocytes in growth medium (DMEM) were investigated at room temperature and at 4 0 C, in an effort to establish the best conditions for the preservation. Survival rate at 4 0 C was found to be higher than that at room temperature. The survival rate of astrocytes preserved for 4 days at 4 0 C increased with increasing pressure up to 1.6 MPa, but decreased with increasing pressure above 1.6 MPa. At 10 MPa, all astrocytes died. The survival rate of cultured astrocytes decreased significantly following pressurization for 2 hours and the subsequent preservation for 2 days at atmospheric pressure. Therefore, it is necessary to maintain pressure when preserving astrocytes. These results indicate that the cells can be stored at 4 0 C under pressurization without freezing and without adding cryoprotective agents. Moreover, it may be possible to use this procedure as a new preservation method when cryopreservation is impractical.

  14. In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel formulation therapy for glaucoma.

    Science.gov (United States)

    Frezzotti, Paolo; Fogagnolo, Paolo; Haka, Gentiana; Motolese, Ilaria; Iester, Michele; Bagaglia, Simone A; Mittica, Pietro; Menicacci, Cristina; Rossetti, Luca; Motolese, Eduardo

    2014-03-01

    To evaluate the effects at 1 year of preservative-free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters. Forty patients with primary open-angle glaucoma or ocular hypertension were randomized to the two treatment groups and compared with 20 healthy age-matched controls. Clinical tests (IOP, Schirmer I test, and lacrimal film break-up time BUT) and in vivo conjunctival confocal microscopy (IVCM) were performed in all patients at baseline and after 12 months. IVCM (HRT II Rostock Cornea Module; Heidelberg Engineering GmbH, Heidelberg, Germany) was performed after topical anaesthesia in the four cardinal locations and at the corresponding limbus to analyse conjunctiva cells. The main IVCM outcomes were goblet cell density and epithelial regularity. IVCM and clinical parameters were similar in the three groups at baseline. After 12 months, intra-epithelial goblet cell density was significantly lower in the preserved (48.25 ± 7.70) than in the preservative-free beta-blocker group (86.83 ± 22.17, p preserved beta-blocker medication group than in the preservative-free beta-blocker group (p preserved timolol (respectively, 11.3 ± 2.97 and 8.12 ± 0.99) compared with preservative-free timolol (16.8 ± 1.83 and 11.27 ± 1.27, p preservative-free beta-blocker gel induces less changes at ocular surface than preserved beta-blockers, a fact that should be considered to obtain less adverse effects and maximal adherence to treatment in a chronic condition such as glaucoma. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. Influence of some physical treatments and natural food preservatives on the diversity of microorganisms in certain egyptian juices

    International Nuclear Information System (INIS)

    Abu El-Naga, M.N.Z.I.

    2009-01-01

    Foods begin to lose their quality from the moment they are harvested.Microorganisms are the main agents responsible for food spoilages . Food preservation prevents deteriorative reaction, extending the shelf life and assuring its safety. The uses of chemical preservatives have harmful effects in long term application. So, the purpose of this article is to use the natural treatments instead of chemical preservatives or application of high temperature which cause losses of some essential nutrients of the juice. In this study the following treatments were investigated: 1. Gamma irradiation . the lethal effect of ionizing radiation on the microorganisms is primarily due to DNA damage, which destroys the reproductive capabilities and other functions of the cell. 2. Pasteurized temperatures(90 degree c).Heat can damage protein, lipids, and nucleic acids of microorganisms and destabilize their membranes.3.The natural preservatives : nisin, citric acid, lactic acid, cinnamon, combination treatments : it was performed between the previous treatments.The best results obtained from our experiments for preserving the fruit juice were performed by combing the pasteurized temperature 90 degree C for 30 sec with gamma irradiation (0.2 K Gy). Or using 200 μg/ml of nisin in combination with 2% (w/v) of citric acid and pasteurized temperature 90 degree C for 30 sec.

  16. Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

    Science.gov (United States)

    Lambertini, Matteo; Cinquini, Michela; Moschetti, Ivan; Peccatori, Fedro A; Anserini, Paola; Valenzano Menada, Mario; Tomirotti, Maurizio; Del Mastro, Lucia

    2017-01-01

    The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Preservation technologies for fresh meat - a review.

    Science.gov (United States)

    Zhou, G H; Xu, X L; Liu, Y

    2010-09-01

    Fresh meat is a highly perishable product due to its biological composition. Many interrelated factors influence the shelf life and freshness of meat such as holding temperature, atmospheric oxygen (O(2)), endogenous enzymes, moisture, light and most importantly, micro-organisms. With the increased demand for high quality, convenience, safety, fresh appearance and an extended shelf life in fresh meat products, alternative non-thermal preservation technologies such as high hydrostatic pressure, superchilling, natural biopreservatives and active packaging have been proposed and investigated. Whilst some of these technologies are efficient at inactivating the micro-organisms most commonly related to food-borne diseases, they are not effective against spores. To increase their efficacy against vegetative cells, a combination of several preservation technologies under the so-called hurdle concept has also been investigated. The objective of this review is to describe current methods and developing technologies for preserving fresh meat. The benefits of some new technologies and their industrial limitations is presented and discussed.

  18. Regulation of Hematopoietic Cell Development and Function Through Phosphoinositides

    Directory of Open Access Journals (Sweden)

    Mila Elich

    2018-05-01

    Full Text Available One of the most paramount receptor-induced signal transduction mechanisms in hematopoietic cells is production of the lipid second messenger phosphatidylinositol(3,4,5trisphosphate (PIP3 by class I phosphoinositide 3 kinases (PI3K. Defective PIP3 signaling impairs almost every aspect of hematopoiesis, including T cell development and function. Limiting PIP3 signaling is particularly important, because excessive PIP3 function in lymphocytes can transform them and cause blood cancers. Here, we review the key functions of PIP3 and related phosphoinositides in hematopoietic cells, with a special focus on those mechanisms dampening PIP3 production, turnover, or function. Recent studies have shown that beyond “canonical” turnover by the PIP3 phosphatases and tumor suppressors phosphatase and tensin homolog (PTEN and SH2 domain-containing inositol-5-phosphatase-1 (SHIP-1/2, PIP3 function in hematopoietic cells can also be dampened through antagonism with the soluble PIP3 analogs inositol(1,3,4,5tetrakisphosphate (IP4 and inositol-heptakisphosphate (IP7. Other evidence suggests that IP4 can promote PIP3 function in thymocytes. Moreover, IP4 or the kinases producing it limit store-operated Ca2+ entry through Orai channels in B cells, T cells, and neutrophils to control cell survival and function. We discuss current models for how soluble inositol phosphates can have such diverse functions and can govern as distinct processes as hematopoietic stem cell homeostasis, neutrophil macrophage and NK cell function, and development and function of B cells and T cells. Finally, we will review the pathological consequences of dysregulated IP4 activity in immune cells and highlight contributions of impaired inositol phosphate functions in disorders such as Kawasaki disease, common variable immunodeficiency, or blood cancer.

  19. Self-preserving cosmetics.

    Science.gov (United States)

    Varvaresou, A; Papageorgiou, S; Tsirivas, E; Protopapa, E; Kintziou, H; Kefala, V; Demetzos, C

    2009-06-01

    Preservatives are added to products for two reasons: first, to prevent microbial spoilage and therefore to prolong the shelf life of the product; second, to protect the consumer from a potential infection. Although chemical preservatives prevent microbial growth, their safety is questioned by a growing segment of consumers. Therefore, there is a considerable interest in the development of preservative-free or self-preserving cosmetics. In these formulations traditional/chemical preservatives have been replaced by other cosmetic ingredients with antimicrobial properties that are not legislated as preservatives according to the Annex VI of the Commission Directive 76/768/EEC and the amending directives (2003/15/EC, 2007/17/EC and 2007/22/EC). 'Hurdle Technology', a technology that has been used for the control of product safety in the food industry since 1970s, has also been applied for the production of self-preserving cosmetics. 'Hurdle Technology' is a term used to describe the intelligent combination of different preservation factors or hurdles to deteriorate the growth of microorganisms. Adherence to current good manufacturing practice, appropriate packaging, careful choice of the form of the emulsion, low water activity and low or high pH values are significant variables for the control of microbial growth in cosmetic formulations. This paper describes the application of the basic principles of 'Hurdle Technology' in the production of self-preserving cosmetics. Multifunctional antimicrobial ingredients and plant-derived essential oils and extracts that are used as alternative or natural preservatives and are not listed in Annex VI of the Cosmetic Directive are also reported.

  20. A small-molecule/cytokine combination enhances hematopoietic stem cell proliferation via inhibition of cell differentiation.

    Science.gov (United States)

    Wang, Lan; Guan, Xin; Wang, Huihui; Shen, Bin; Zhang, Yu; Ren, Zhihua; Ma, Yupo; Ding, Xinxin; Jiang, Yongping

    2017-07-18

    Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34 + cell expansion ex vivo. The extent of cell expansion and the immunophenotype of expanded cells were assessed through flow cytometry. The functional preservation of HSC stemness was confirmed by additional cell and molecular assays in vitro. Subsequently, the expanded cells were transplanted into sublethally irradiated NOD/SCID mice for the assessment of human cell viability and engraftment potential in vivo. Furthermore, the expression of several genes in the cell proliferation and differentiation pathways was analyzed through quantitative polymerase chain reaction (qPCR) during the process of CD34 + cell expansion. The SC cocktail supported the retention of the immunophenotype of hematopoietic stem/progenitor cells remarkably well, by yielding purities of 86.6 ± 11.2% for CD34 + cells and 76.2 ± 10.5% for CD34 + CD38 - cells, respectively, for a 7-day culture. On day 7, the enhancement of expansion of CD34 + cells and CD34 + CD38 - cells reached a maxima of 28.0 ± 5.5-fold and 27.9 ± 4.3-fold, respectively. The SC cocktail-expanded CD34 + cells preserved the characteristics of HSCs by effectively inhibiting their differentiation in vitro and retained the multilineage differentiation potential in primary and secondary in vivo murine xenotransplantation trials. Further gene expression analysis suggested that the small-molecule combination strengthened the ability of the cytokines to enhance the Notch

  1. Spleen-preserving distal pancreatectomy in trauma.

    Science.gov (United States)

    Schellenberg, Morgan; Inaba, Kenji; Cheng, Vincent; Bardes, James M; Lam, Lydia; Benjamin, Elizabeth; Matsushima, Kazuhide; Demetriades, Demetrios

    2018-01-01

    Traumatic injuries to the distal pancreas are infrequent. Universally accepted recommendations about the need for routine splenectomy with distal pancreatectomy do not exist. The aims of this study were to compare outcomes after distal pancreatectomy and splenectomy versus spleen-preserving distal pancreatectomy, and to define the appropriate patient population for splenic preservation. All patients who underwent distal pancreatectomy (January 1, 2007, to December 31, 2014) were identified from the National Trauma Data Bank. Patients with concomitant splenic injury and those who underwent partial splenectomy were excluded. Demographics, clinical data, procedures, and outcomes were collected. Study groups were defined by surgical procedure: distal pancreatectomy and splenectomy versus spleen-preserving distal pancreatectomy. Baseline characteristics between groups were compared with univariate analysis. Multivariate analysis was performed with logistic and linear regression to examine differences in outcomes. Over the 8-year study period, 2,223 patients underwent distal pancreatectomy. After excluding 1,381 patients with concomitant splenic injury (62%) and 8 (pancreatectomy and splenectomy, those who underwent spleen-preserving distal pancreatectomy were younger (p pancreatectomy (p = 0.017). Complications, mortality, and intensive care unit LOS were not significantly different. In young patients after blunt trauma who are not severely injured, a spleen-preserving distal pancreatectomy should be considered to allow for conservation of splenic function and a shorter hospital LOS. In all other patients, the surgeon should not hesitate to remove the spleen with the distal pancreas. Therapy, level IV.

  2. A Method Sustaining the Bioelectric, Biophysical, and Bioenergetic Function of Cultured Rabbit Atrial Cells

    OpenAIRE

    Noa Kirschner Peretz; Sofia Segal; Limor Arbel-Ganon; Ronen Ben Jehuda; Ronen Ben Jehuda; Yuval Shemer; Yuval Shemer; Binyamin Eisen; Binyamin Eisen; Moran Davoodi; Ofer Binah; Ofer Binah; Yael Yaniv

    2017-01-01

    Culturing atrial cells leads to a loss in their ability to be externally paced at physiological rates and to maintain their shape. We aim to develop a culture method that sustains the shape of atrial cells along with their biophysical and bioenergetic properties in response to physiological pacing. We hypothesize that adding 2,3-Butanedione 2-monoxime (BDM), which inhibits contraction during the culture period, will preserve these biophysical and bioenergetic properties. Rabbit atrial cells w...

  3. Recent developments in structure-preserving algorithms for oscillatory differential equations

    CERN Document Server

    Wu, Xinyuan

    2018-01-01

    The main theme of this book is recent progress in structure-preserving algorithms for solving initial value problems of oscillatory differential equations arising in a variety of research areas, such as astronomy, theoretical physics, electronics, quantum mechanics and engineering. It systematically describes the latest advances in the development of structure-preserving integrators for oscillatory differential equations, such as structure-preserving exponential integrators, functionally fitted energy-preserving integrators, exponential Fourier collocation methods, trigonometric collocation methods, and symmetric and arbitrarily high-order time-stepping methods. Most of the material presented here is drawn from the recent literature. Theoretical analysis of the newly developed schemes shows their advantages in the context of structure preservation. All the new methods introduced in this book are proven to be highly effective compared with the well-known codes in the scientific literature. This book also addre...

  4. The Numerology of T Cell Functional Diversity

    OpenAIRE

    Haining, W. Nicholas

    2012-01-01

    Memory T cells are heterogeneous in phenotype and function. In this issue of Immunity Newell et al. (2012) use a new flow cytometry platform to show that the functional heterogeneity in the human T cell compartment is even greater than expected.

  5. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    NARCIS (Netherlands)

    Guadix, Juan Antonio; Orlova, Valeria V.; Giacomelli, Elisa; Bellin, Milena; Ribeiro, Marcelo C.; Mummery, Christine L.; Pérez-Pomares, José M.; Passier, Robert

    2017-01-01

    Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced) to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA)

  6. Status, Antimicrobial Mechanism, and Regulation of Natural Preservatives in Livestock Food Systems.

    Science.gov (United States)

    Lee, Na-Kyoung; Paik, Hyun-Dong

    2016-01-01

    This review discusses the status, antimicrobial mechanisms, application, and regulation of natural preservatives in livestock food systems. Conventional preservatives are synthetic chemical substances including nitrates/nitrites, sulfites, sodium benzoate, propyl gallate, and potassium sorbate. The use of artificial preservatives is being reconsidered because of concerns relating to headache, allergies, and cancer. As the demand for biopreservation in food systems has increased, new natural antimicrobial compounds of various origins are being developed, including plant-derived products (polyphenolics, essential oils, plant antimicrobial peptides (pAMPs)), animal-derived products (lysozymes, lactoperoxidase, lactoferrin, ovotransferrin, antimicrobial peptide (AMP), chitosan and others), and microbial metabolites (nisin, natamycin, pullulan, ε-polylysine, organic acid, and others). These natural preservatives act by inhibiting microbial cell walls/membranes, DNA/RNA replication and transcription, protein synthesis, and metabolism. Natural preservatives have been recognized for their safety; however, these substances can influence color, smell, and toxicity in large amounts while being effective as a food preservative. Therefore, to evaluate the safety and toxicity of natural preservatives, various trials including combinations of other substances or different food preservation systems, and capsulation have been performed. Natamycin and nisin are currently the only natural preservatives being regulated, and other natural preservatives will have to be legally regulated before their widespread use.

  7. Role of Cell-Cell bond for the viability and the function of vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    M. Mura

    2010-01-01

    -matrix interactions and reduces the responsiveness to ATII. Therefore, preserved cell-cell contac may couteract vascular remodeling induced by proatherogenic stimuli.

  8. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis.

    Science.gov (United States)

    Agathocleous, Michalis; Meacham, Corbin E; Burgess, Rebecca J; Piskounova, Elena; Zhao, Zhiyu; Crane, Genevieve M; Cowin, Brianna L; Bruner, Emily; Murphy, Malea M; Chen, Weina; Spangrude, Gerald J; Hu, Zeping; DeBerardinis, Ralph J; Morrison, Sean J

    2017-09-28

    Stem-cell fate can be influenced by metabolite levels in culture, but it is not known whether physiological variations in metabolite levels in normal tissues regulate stem-cell function in vivo. Here we describe a metabolomics method for the analysis of rare cell populations isolated directly from tissues and use it to compare mouse haematopoietic stem cells (HSCs) to restricted haematopoietic progenitors. Each haematopoietic cell type had a distinct metabolic signature. Human and mouse HSCs had unusually high levels of ascorbate, which decreased with differentiation. Systemic ascorbate depletion in mice increased HSC frequency and function, in part by reducing the function of Tet2, a dioxygenase tumour suppressor. Ascorbate depletion cooperated with Flt3 internal tandem duplication (Flt3 ITD ) leukaemic mutations to accelerate leukaemogenesis, through cell-autonomous and possibly non-cell-autonomous mechanisms, in a manner that was reversed by dietary ascorbate. Ascorbate acted cell-autonomously to negatively regulate HSC function and myelopoiesis through Tet2-dependent and Tet2-independent mechanisms. Ascorbate therefore accumulates within HSCs to promote Tet activity in vivo, limiting HSC frequency and suppressing leukaemogenesis.

  9. Clinical dosing regimen of selinexor maintains normal immune homeostasis and T cell effector function in mice: implications for combination with immunotherapy

    Science.gov (United States)

    Tyler, Paul M.; Servos, Mariah M.; de Vries, Romy C.; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K.

    2017-01-01

    Selinexor (KPT-330) is a first in class nuclear transport inhibitor currently in clinical trials as an anti-cancer agent. To determine how selinexor might impact anti-tumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T cell development, a progressive loss of CD8 T cells and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T cell development and function. We determined the minimum concentration of selinexor required to block T cell activation, and showed that T cell inhibitory effects of selinexor occur at levels above 100nM, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 5 day drug holiday led to intratumoral IFNγ+, granzyme B+ cytotoxic CD8 T cells that were comparable to vehicle treated mice. Overall, selinexor treatment leads to transient inhibition of T cell activation but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T cell functioning and development of anti-tumor immunity. PMID:28148714

  10. Improved biochemical preservation of heart slices during cold storage.

    Science.gov (United States)

    Bull, D A; Reid, B B; Connors, R C; Albanil, A; Stringham, J C; Karwande, S V

    2000-01-01

    Development of myocardial preservation solutions requires the use of whole organ models which are animal and labor intensive. These models rely on physiologic rather than biochemical endpoints, making accurate comparison of the relative efficacy of individual solution components difficult. We hypothesized that myocardial slices could be used to assess preservation of biochemical function during cold storage. Whole rat hearts were precision cut into slices with a thickness of 200 microm and preserved at 4 degrees C in one of the following solutions: Columbia University (CU), University of Wisconsin (UW), D5 0.2% normal saline with 20 meq/l KCL (QNS), normal saline (NS), or a novel cardiac preservation solution (NPS) developed using this model. Myocardial biochemical function was assessed by ATP content (etamoles ATP/mg wet weight) and capacity for protein synthesis (counts per minute (cpm)/mg protein) immediately following slicing (0 hours), and at 6, 12, 18, and 24 hours of cold storage. Six slices were assayed at each time point for each solution. The data were analyzed using analysis of variance and are presented as the mean +/- standard deviation. ATP content was higher in the heart slices stored in the NPS compared to all other solutions at 6, 12, 18 and 24 hours of cold storage (p cold storage (p cold storage.

  11. Comparison of contamination rates between preserved and preservative-free fluoroquinolone eyedrops.

    Science.gov (United States)

    Kim, Mo Sae; Kim, Hong Kyun; Kim, Joon Mo; Choi, Chul Young

    2013-03-01

    To evaluate the antimicrobial effectiveness of preservative-free fluoroquinolone products compared with benzalkonium chloride containing fluoroquinolones using the challenge test provided by the United States Pharmacopeia (USP) and the in-use test. 1. Challenge test: to compare the growth of microorganisms between different fluoroquinolone preparations, four test organisms, including Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger were chosen among five microorganisms listed by USP 2004. The inoculated products were sampled for microbial survivors at days 7, 14, and 28 following initial inoculation at room temperature. The number of surviving organisms were calculated as a Log10 reduction from the original inocula. 2. In-use test: a total of 100 bottles were collected after instillation of preservative-free fluoroquinolone eyedrops in volunteer patients after 1 week of use. The remaining fluid and tips of the bottles were cultured. Colonies on the plates were counted at the end of the incubation period. All microorganisms were identified by Gram staining and biochemical assays. 1. Challenge test: preservative-free gatifloxacin and levofloxacin demonstrated a lower log reduction against A. niger than preserved fluoroquinolones and preservative-free moxifloxacin at all time points. 2. In-use test: There was no contamination identified on plates inoculated by preservative-free quinolone bottles after 1 week of use in this study. Physicians should be aware of the lower antifungal preservative effectiveness of some preservative-free fluoroquinolone preparations than preserved ones.

  12. Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

    International Nuclear Information System (INIS)

    Chen, P.-Y.; Huang, Lynn L.H.; Hsieh, H.-J.

    2007-01-01

    For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs

  13. Stem cell function and maintenance

    Indian Academy of Sciences (India)

    Stem cell research holds a promise to treat and prevent age-related degenerative changes in humans. Literature is replete with studies showing that stem cell function declines with aging, especially in highly proliferative tissues/organs. Among others, telomerase and telomere damage is one of the intrinsic physical ...

  14. The effectiveness of BD Vacutainer® Plus Urinalysis Preservative Tubes in preservation of urine for chemical strip analysis and particle counting.

    Science.gov (United States)

    Ekşioğlu, Merve Kaymak; Madenci, Özlem Çakır; Yücel, Nihal; Elçi, Abdullah; Turhan, Bülent; Orhan, Gani; Orçun, Asuman

    2016-01-01

    The aim of this study was to evaluate the stability of urine collected in preservative tubes for chemistry strip analyses and particle counting to determine whether the transport of urine samples with all of their constituents is possible. 275 pathologic urine specimens were included. Each urine sample was evaluated after 4, 8, 12, 24, and 48 hours of storage in BD Vacutainer(®) Plus Urinalysis Preservative (BD UAP) tubes and compared with refrigeration at 4 °C. All analyses were peformed on H-800 and FUS-200 automatic modular urine analyzers (Dirui Industry, Changchun, China). The kappa coefficients (κ), false positive (FP) and false negative (FN) rates were evaluated. κ > 0.8 was accepted as good agreement. Haemoglobin (Hb), leucocyte esterase (LE), and protein (Pro) analyses should be performed within 4 hours, whereas glucose (Glc) was stable until the end of 48 hours in both storage conditions. Nitrite (Nit) was well preserved in BD UAP tubes for 24 hours but was stable only up to 8 hours at 4 °C. Bilirubin (Bil) had very high FN rates even at 4 hours in both conditions. The particle counting showed high FN rates for white blood cells (WBC) and red blood cells (RBC), whereas squamous epithelial cells (EC) were stable up to 8 hours in both conditions. Preanalytical requirements for both urine chemical strip analyses and particle counting in a unique sample were not met in either condition. Thus, the transfer of urine samples for centralization of urinalysis is not yet feasible.

  15. Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

    International Nuclear Information System (INIS)

    Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

    1989-01-01

    This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [ 3 H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

  16. Peroxisome proliferator-activated receptor alpha (PPARalpha) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism

    DEFF Research Database (Denmark)

    Frigerio, F; Brun, T; Bartley, C

    2009-01-01

    and investigated key metabolic pathways and genes responsible for metabolism-secretion coupling during a culture period of 3 days in the presence of 0.4 mmol/l oleate. RESULTS: In INS-1E cells, the secretory dysfunction primarily induced by oleate was aggravated by silencing of PPARalpha. Conversely, PPARalpha...... enzyme pyruvate carboxylase. PPARalpha overproduction increased both beta-oxidation and fatty acid storage in the form of neutral triacylglycerol, revealing overall induction of lipid metabolism. These observations were substantiated by expression levels of associated genes. CONCLUSIONS....../INTERPRETATION: PPARalpha protected INS-1E beta cells from oleate-induced dysfunction, promoting both preservation of glucose metabolic pathways and fatty acid turnover....

  17. Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Cai, Guoping; Lai, Binbin; Hong, Huaxing; Lin, Peng; Chen, Weifu; Zhu, Zhong; Chen, Haixiao

    2017-07-01

    Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin‑1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule‑1 (ICAM‑1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue‑engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post‑cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM‑1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube‑like structure‑forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time‑dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue‑engineered microvascular construction.

  18. Mutual preservation of entanglement

    International Nuclear Information System (INIS)

    Veitia, Andrzej; Jing, Jun; Yu, Ting; Wong, Chee Wei

    2012-01-01

    We study a generalized double Jaynes–Cummings (JC) model where two entangled pairs of two-level atoms interact indirectly. We show that there exist initial states of the qubit system so that two entangled pairs are available at all times. In particular, the minimum entanglement in the pairs as a function of the initial state is studied. Finally, we extend our findings to a model consisting of multi-mode atom–cavity interactions. We use a non-Markovian quantum state diffusion (QSD) equation to obtain the steady-state density matrix for the qubits. We show that the multi-mode model also displays dynamical preservation of entanglement. -- Highlights: ► Entanglement dynamics is studied in a generalized double Jaynes–Cummings model. ► We show that for certain initial states, the atoms remain entangled at all times. ► We extend the results to the case of multi-mode atom–cavity interactions. ► The model suggest that indirect interaction may help to preserve entanglement.

  19. Intact preservation of environmental samples by freezing under an alternating magnetic field.

    Science.gov (United States)

    Morono, Yuki; Terada, Takeshi; Yamamoto, Yuhji; Xiao, Nan; Hirose, Takehiro; Sugeno, Masaya; Ohwada, Norio; Inagaki, Fumio

    2015-04-01

    The study of environmental samples requires a preservation system that stabilizes the sample structure, including cells and biomolecules. To address this fundamental issue, we tested the cell alive system (CAS)-freezing technique for subseafloor sediment core samples. In the CAS-freezing technique, an alternating magnetic field is applied during the freezing process to produce vibration of water molecules and achieve a stable, super-cooled liquid phase. Upon further cooling, the temperature decreases further, achieving a uniform freezing of sample with minimal ice crystal formation. In this study, samples were preserved using the CAS and conventional freezing techniques at 4, -20, -80 and -196 (liquid nitrogen) °C. After 6 months of storage, microbial cell counts by conventional freezing significantly decreased (down to 10.7% of initial), whereas that by CAS-freezing resulted in minimal. When Escherichia coli cells were tested under the same freezing conditions and storage for 2.5 months, CAS-frozen E. coli cells showed higher viability than the other conditions. In addition, an alternating magnetic field does not impact on the direction of remanent magnetization in sediment core samples, although slight partial demagnetization in intensity due to freezing was observed. Consequently, our data indicate that the CAS technique is highly useful for the preservation of environmental samples. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. A new approach to sperm preservation based on bioenergetic theory.

    Science.gov (United States)

    Froman, D P; Feltmann, A J

    2010-04-01

    To date, attempts to preserve chicken sperm have been based on a trial-and-error experimental approach. The present work outlines the development of an alternative approach based on empiricism and bioenergetic theory. In previous work, we found fowl sperm motility to be dependent on mitochondrial calcium cycling, phospholipase A(2), and long-chain fatty acids as an endogenous energy source. It is noteworthy that fowl sperm reside within the sperm storage tubules (SST) of the oviduct over an interval of days to weeks after insemination. In this regard, a model for in vivo sperm storage was developed and tested in additional previous research. Sperm penetration of the SST, sperm residence within the SST, and sperm egress from the SST can be explained in terms mitochondrial function. Understanding sperm function and longevity in terms of bioenergetics presented the possibility that sperm could be inactivated by disrupting mitochondrial calcium cycling and could thereby be preserved. However, this possibility also posed a problem: maintenance of the inner membrane potential of the mitochondrion within inactivated sperm. This report describes a series of experiments in which fowl sperm were inactivated by treatment with the calcium chelator tetrasodium 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, and then reactivated by treatment with calcium ions. The effect of tetrasodium 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid on mitochondrial calcium cycling was confirmed by flow cytometry and confocal microscopy. When treated sperm were cooled to 10 degrees C, inactivated sperm could be reactivated throughout a 5-h storage interval. When stored sperm were held for 3 h before reactivation and insemination, fertility was 88% of the control. Storage did not affect hatchability. In summary, short-term storage was realized by manipulating mitochondrial function. We propose that 1) complex V consumes ATP within inactivated sperm and, by doing so, maintains

  1. Wood preservation

    Science.gov (United States)

    Kevin Archer; Stan Lebow

    2006-01-01

    Wood preservation can be interpreted to mean protection from fire, chemical degradation, mechanical wear, weathering, as well as biological attack. In this chapter, the term preservation is applied more restrictively to protection from biological hazards.

  2. Circadian rhythm of the Leydig cells endocrine function is attenuated during aging.

    Science.gov (United States)

    Baburski, Aleksandar Z; Sokanovic, Srdjan J; Bjelic, Maja M; Radovic, Sava M; Andric, Silvana A; Kostic, Tatjana S

    2016-01-01

    Although age-related hypofunction of Leydig cells is well illustrated across species, its circadian nature has not been analyzed. Here we describe changes in circadian behavior in Leydig cells isolated from adult (3-month) and aged (18- and 24-month) rats. The results showed reduced circadian pattern of testosterone secretion in both groups of aged rats despite unchanged LH circadian secretion. Although arrhythmic, the expression of Insl3, another secretory product of Leydig cells, was decreased in both groups. Intracellular cAMP and most important steroidogenic genes (Star, Cyp11a1 and Cyp17a1), together with positive steroidogenic regulator (Nur77), showed preserved circadian rhythm in aging although rhythm robustness and expression level were attenuated in both aged groups. Aging compromised cholesterol mobilization and uptake by Leydig cells: the oscillatory transcription pattern of genes encoding HDL-receptor (Scarb1), hormone sensitive lipase (Lipe, enzyme that converts cholesterol esters from lipid droplets into free cholesterol) and protein responsible for forming the cholesterol esters (Soat2) were flattened in 24-month group. The majority of examined clock genes displayed circadian behavior in expression but only a few of them (Bmal1, Per1, Per2, Per3 and Rev-Erba) were reduced in 24-month-old group. Furthermore, aging reduced oscillatory expression pattern of Sirt1 and Nampt, genes encoding key enzymes that connect cellular metabolism and circadian network. Altogether circadian amplitude of Leydig cell's endocrine function decreased during aging. The results suggest that clock genes are more resistant to aging than genes involved in steroidogenesis supporting the hypothesis about peripheral clock involvement in rhythm maintenance during aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability.

    Science.gov (United States)

    Magnusson, Mattias; Sierra, Maria I; Sasidharan, Rajkumar; Prashad, Sacha L; Romero, Melissa; Saarikoski, Pamela; Van Handel, Ben; Huang, Andy; Li, Xinmin; Mikkola, Hanna K A

    2013-01-01

    Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.

  4. Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability.

    Directory of Open Access Journals (Sweden)

    Mattias Magnusson

    Full Text Available Lack of HLA-matched hematopoietic stem cells (HSC limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC stroma that protects human hematopoietic stem/progenitor cells (HSPC from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+ characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.

  5. Temporal variation of dielectric properties of preserved blood

    International Nuclear Information System (INIS)

    Hayashi, Yoshihito; Oshige, Ikuya; Katsumoto, Yoichi; Omori, Shinji; Yasuda, Akio; Asami, Koji

    2008-01-01

    Rabbit blood was preserved at 277 K in Alsever's solution for 37 days, and its dielectric permittivity was monitored in a frequency range from 0.05 to 110 MHz throughout the period. The relaxation time and Cole-Cole parameter of the interfacial polarization process for erythrocytes remained nearly constant during the first 20 days and then started to increase and decrease, respectively. On the other hand, the relaxation strength and the cell volume fraction continued to decrease for 37 days, but the decrease rates of both changed discontinuously on about the 20th day. Microscope observation showed that approximately 90% of the erythrocytes were spinous echinocytes at the beginning of preservation and started to be transformed into microspherocytes around the 20th day. Therefore, dielectric spectroscopy is a sensitive tool to monitor the deterioration of preserved blood accompanied by morphological transition of erythrocytes through the temporal variation of their dielectric properties

  6. Effective Application of the Methanol-Based PreservCyt (TM) Fixative and the Cellient (TM) Automated Cell Block Processor to Diagnostic Cytopathology, Immunocytochemistry, and Molecular Biology

    NARCIS (Netherlands)

    van Hemel, Bettien M.; Suurmeijer, Albert J. H.

    We studied the feasibility of immunocytochemistry (ICC), in situ hybridization (ISH), and polymerase chain reaction (PCR) after Cellient automated cell block processing, and tested whether methanol-based PreservCyt fixation could replace formalin fixation, in an attempt to eliminate toxic

  7. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and function......). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially...... and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents...

  8. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    ). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially......Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and function...... and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents...

  9. Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Juan Antonio Guadix

    2017-12-01

    Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

  10. Changes in Ocular Surface Characteristics after Switching from Benzalkonium Chloride-Preserved Latanoprost to Preservative-Free Tafluprost or Benzalkonium Chloride-Preserved Tafluprost

    OpenAIRE

    Tokuda, Naoto; Kitaoka, Yasushi; Matsuzawa, Akiko; Tsukamoto, Ayaka; Sase, Kana; Sakae, Shinsuke; Takagi, Hitoshi

    2017-01-01

    Purpose. The aim of the present study was to examine the effects of switching from Latanoprost ophthalmic solution containing a preservative to preservative-free Tafluprost ophthalmic solution or Tafluprost containing a preservative on ocular surfaces. Materials and Methods. Forty patients (40 eyes) with glaucoma (mean age: 62.0 ± 10.9 years) using Latanoprost with preservative for six months or longer were assigned either to a Tafluprost-containing-preservative group (20 eyes) or preservativ...

  11. [Duodenum-preserving total pancreatic head resection and pancreatic head resection with segmental duodenostomy].

    Science.gov (United States)

    Takada, Tadahiro; Yasuda, Hideki; Nagashima, Ikuo; Amano, Hodaka; Yoshiada, Masahiro; Toyota, Naoyuki

    2003-06-01

    A duodenum-preserving pancreatic head resection (DPPHR) was first reported by Beger et al. in 1980. However, its application has been limited to chronic pancreatitis because of it is a subtotal pancreatic head resection. In 1990, we reported duodenum-preserving total pancreatic head resection (DPTPHR) in 26 cases. This opened the way for total pancreatic head resection, expanding the application of this approach to tumorigenic morbidities such as intraductal papillary mucinous tumor (IMPT), other benign tumors, and small pancreatic cancers. On the other hand, Nakao et al. reported pancreatic head resection with segmental duodenectomy (PHRSD) as an alternative pylorus-preserving pancreatoduodenectomy technique in 24 cases. Hirata et al. also reported this technique as a new pylorus-preserving pancreatoduodenostomy with increased vessel preservation. When performing DPTPHR, the surgeon should ensure adequate duodenal blood supply. Avoidance of duodenal ischemia is very important in this operation, and thus it is necessary to maintain blood flow in the posterior pancreatoduodenal artery and to preserve the mesoduodenal vessels. Postoperative pancreatic functional tests reveal that DPTPHR is superior to PPPD, including PHSRD, because the entire duodenum and duodenal integrity is very important for postoperative pancreatic function.

  12. The preserved autonomic functions may provide the asymptomatic clinical status in heart failure despite advanced left ventricular systolic dysfunction.

    Science.gov (United States)

    Kocaman, Sinan Altan; Taçoy, Gülten; Ozdemir, Murat; Açıkgöz, Sadık Kadri; Cengel, Atiye

    2010-12-01

    Autonomic dysfunction is an important marker of prognosis in congestive heart failure (CHF) and may determine the symptoms and progression of CHF. The aim of our study was to investigate whether preserved autonomic function assessed by heart rate variability (HRV) analyses is related to absence of CHF symptoms despite prominently reduced systolic function. The study had a cross-sectional observational design. Fifty patients with left ventricular ejection fraction (EF) below 40% were enrolled. The patients were divided into two groups according to their CHF symptomatic status as Group 1 (NYHA functional class I, asymptomatic group) and Group 2 (NYHA functional class ≥ II, symptomatic group). Plasma C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-proBNP) levels, echocardiographic parameters and HRV indices were measured while the patients were clinically stable in each group. Possible factors associated with the development of CHF symptoms were assessed by using multiple regression analysis. Baseline clinical characteristics and left ventricular EF were similar in the two groups. Serum CRP (15 ± 21 vs 7 ± 18 mg/L, p=0.011) and NT-proBNP levels (1935 ± 1088 vs 1249 ± 1083 pg/mL, p=0.020) were significantly higher in symptomatic group. The HRV parameters (SDNN: 78 ± 57 vs 122 ± 42 ms, p=0.001; SDANN: 65 ± 55 vs 84 ± 38 ms, p=0.024; SDNNi: 36 ± 41 vs 70 ± 46 ms, pfunction were significantly associated with the asymptomatic status (SDNN, OR: 1.016, 95%CI: 1.002-1.031, p=0.028; SDNNi, OR: 1.030, 95%CI: 1.008-1.052, p=0.006; TI, OR: 1.088, 95%CI: 1.019-1.161, p=0.011). Preserved autonomic functions were shown to be associated with absence of CHF symptoms independently of angiotensin converting enzyme inhibitor/angiotensin receptor blocker's treatment and BNP levels and may be protective against the development of CHF symptoms despite advanced left ventricular systolic dysfunction.

  13. When aging reaches CD4+ T-cells: phenotypic and functional changes

    Directory of Open Access Journals (Sweden)

    Marco Antonio Moro-García

    2013-05-01

    Full Text Available Beyond midlife, the immune system shows aging features and its defensive capability becomes impaired, by a process known as immunosenescence that involves many changes in the innate and adaptive responses. Innate immunity seems to be better preserved globally, while the adaptive immune response exhibits profound age-dependent modifications. Elderly people display a decline in numbers of naïve T-cells in peripheral blood and lymphoid tissues, while, in contrast, their proportion of highly differentiated effector and memory T-cells, such as the CD28null T-cells, increases markedly. Naïve and memory CD4+ T-cells constitute a highly dynamic system with constant homeostatic and antigen-driven proliferation, influx, and loss of T-cells. Thymic activity dwindles with age and essentially ceases in the later decades of life, severely constraining the generation of new T-cells. Homeostatic control mechanisms are very effective at maintaining a large and diverse subset of naïve CD4+ T-cells throughout life, but although later than in CD8+T-cell compartment, these mechanisms ultimately fail with age.

  14. Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

    Science.gov (United States)

    Ammari, Narmeen; Heinrichs, R Walter; Pinnock, Farena; Miles, Ashley A; Muharib, Eva; McDermid Vaz, Stephanie

    2014-05-01

    The main purpose of this investigation was to identify patterns of intellectual performance in schizophrenia patients suggesting preserved, deteriorated, and premorbidly impaired ability, and to determine clinical, cognitive, and functional correlates of these patterns. We assessed 101 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric control participants. The "preserved" performance pattern was defined by average-range estimated premorbid and current IQ with no evidence of decline (premorbid-current IQ difference schizophrenia and general populations, but may not hold true across other cognitive abilities and do not translate into differential functional outcome.

  15. The numerology of T cell functional diversity.

    Science.gov (United States)

    Haining, W Nicholas

    2012-01-27

    Memory T cells are heterogeneous in phenotype and function. In this issue of Immunity, Newell et al. (2012) use a new flow cytometry platform to show that the functional heterogeneity of the human T cell compartment is even greater than previously thought. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Persufflation (gaseous oxygen perfusion) as a method of heart preservation.

    Science.gov (United States)

    Suszynski, Thomas M; Rizzari, Michael D; Scott, William E; Eckman, Peter M; Fonger, James D; John, Ranjit; Chronos, Nicolas; Tempelman, Linda A; Sutherland, David E R; Papas, Klearchos K

    2013-04-22

    Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed.

  17. Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs.

    Science.gov (United States)

    Qazi, Taimoor H; Mooney, David J; Duda, Georg N; Geissler, Sven

    2017-09-01

    Mesenchymal stromal cells (MSCs) secrete paracrine factors that play crucial roles during tissue regeneration. Whether this paracrine function is influenced by the properties of biomaterials in general, and those used for cell delivery in particular, largely remains unexplored. Here, we investigated if three-dimensional culture in distinct microenvironments - nanoporous hydrogels (mean pore size ∼5 nm) and macroporous scaffolds (mean pore size ∼120 μm) - affects the secretion pattern of MSCs, and consequently leads to differential paracrine effects on target progenitor cells such as myoblasts. We report that compared to MSCs encapsulated in hydrogels, scaffold seeded MSCs show an enhanced secretion profile and exert beneficial paracrine effects on various myoblast functions including migration and proliferation. Additionally, we show that the heightened paracrine effects of scaffold seeded cells can in part be attributed to N-cadherin mediated cell-cell interactions during culture. In hydrogels, this physical interaction between cells is prevented by the encapsulating matrix. Functionally blocking N-cadherin negatively affected the secretion profile and paracrine effects of MSCs on myoblasts, with stronger effects observed for scaffold seeded compared to hydrogel encapsulated cells. Together, these findings demonstrate that the therapeutic potency of MSCs can be enhanced by biomaterials that promote cell-cell interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET

    International Nuclear Information System (INIS)

    Suga, Kazuyoshi; Kume, Norihiko; Matsunaga, Naofumi; Ogasawara, Nobuhiko; Motoyama, Kazumi; Hara, Akiko; Matsumoto, Tsuneo

    2000-01-01

    In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic 133 Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster 133 Xe half-clearance time (T 1/2 ) than in central lung (P 1/2 in the peripheral lung area (P 1/2 values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a lower susceptibility of peripheral parenchyma to the development of this disease. (orig.)

  19. Preferential soft-tissue preservation in the Hot Creek carbonate spring deposit, British Columbia, Canada

    Science.gov (United States)

    Rainey, Dustin K.; Jones, Brian

    2010-05-01

    The relict Holocene Hot Creek carbonate spring deposit in southeast British Columbia is characterized by excellent preservation of soft-tissue organisms (e.g. cyanobacteria), but poor preservation of organisms with hard-tissue (e.g. wood, diatoms). The deposit is formed mainly of calcified cyanobacteria, with fewer mineralized macrophytes (plants), bryophytes (mosses), wood, and diatoms. Cyanobacteria grew as solitary filaments ( Lyngbya) and as radiating hemispherical colonies ( Rivularia). Both were preserved by encrustation and encapsulation while alive, and as casts after filament death and decay. Sheath impregnation was rare to absent. Filament encrustation, whereby calcite crystals nucleated on, and grew away from the sheath exterior, produced moulds that replicated external filament morphology, but hastened filament decay. Filament encapsulation, whereby calcite nucleated in the vicinity of, and grew towards the encapsulated filament, promoted sheath preservation even after trichome decay. Subsequent calcite precipitation inside the hollow sheath generated sheath casts. The inability of mineralizing spring water to penetrate durable cell walls meant that bryophytes, macrophytes, and most wood was preserved by encrustation. Some wood resisted complete decay for several thousand years, and its lignified cell walls allowed rare permineralizations. Diatoms were not preserved in the relict deposit because the frustules were dissolved by the basic spring water. Amorphous calcium carbonate produced by photosynthetic CO 2 removal may have acted as nucleation sites for physicochemically precipitated calcite. Thus, metabolic activities of floral organisms probably initiated biotic mineralization, but continuous inorganic calcite precipitation on and in flora ensured that soft tissues were preserved.

  20. nestor Guideline for Preservation Planning – a Process Model

    Directory of Open Access Journals (Sweden)

    Sabine Schrimpf

    2014-02-01

    Full Text Available The nestor guideline for preservation planning is the latest in a series of nestor publications. nestor is the German competence network for digital preservation and it offers all interested parties from the private and public domains the possibility to participate in working groups. The guideline for preservation planning is the result of such a working group, which discussed the conceptual and practical issues of implementing the OAIS Functional Entity “Preservation Planning”.The guideline describes a process model and offers some guidance on potential implementations. It integrates and builds on recognized community concepts like Significant Properties, the OAIS Designated Community, the National Archives of Australia’s Performance Model, the PREMIS concept of Intellectual Entities and Representations, and the PLANET’s approach to preservation planning. Furthermore, it introduces the concepts “intended use” (Nutzungsziele, “information type” (Informationstyp and “preservation group” (Erhaltungsgruppe. The purpose of these new categories is that information objects shall be grouped by information type (e.g., audio, video, text… and intended use (e.g., reading for pleasure, search for specific information… to preservation groups for automatic processing. Significant properties can then be derived for whole preservation groups. The file format alone is considered as not completely sufficient for such categorisation. Some exemplary implementation solutions of the new concepts are presented in an annex.The guideline takes into account that resources for preservation planning and preservation actions are limited and has therefore adopted 4 premises: adequacy, financial viability, automation, and authenticity of archived objects. Its pragmatic approach becomes apparent in the definition and explanation of these dimensions. The guideline is written from the point of view of representatives of memory institutions, i

  1. Temporal variation of dielectric properties of preserved blood

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Yoshihito [Life Science Laboratory, Materials Laboratories, Sony Corporation, Sony Bioinformatics Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510 (Japan); Oshige, Ikuya [Life Science Laboratory, Materials Laboratories, Sony Corporation, Sony Bioinformatics Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510 (Japan); Katsumoto, Yoichi [Life Science Laboratory, Materials Laboratories, Sony Corporation, Sony Bioinformatics Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510 (Japan); Omori, Shinji [Life Science Laboratory, Materials Laboratories, Sony Corporation, Sony Bioinformatics Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510 (Japan); Yasuda, Akio [Life Science Laboratory, Materials Laboratories, Sony Corporation, Sony Bioinformatics Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510 (Japan); Asami, Koji [Laboratory of Molecular Aggregation Analysis, Division of Multidisciplinary Chemistry, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2008-01-07

    Rabbit blood was preserved at 277 K in Alsever's solution for 37 days, and its dielectric permittivity was monitored in a frequency range from 0.05 to 110 MHz throughout the period. The relaxation time and Cole-Cole parameter of the interfacial polarization process for erythrocytes remained nearly constant during the first 20 days and then started to increase and decrease, respectively. On the other hand, the relaxation strength and the cell volume fraction continued to decrease for 37 days, but the decrease rates of both changed discontinuously on about the 20th day. Microscope observation showed that approximately 90% of the erythrocytes were spinous echinocytes at the beginning of preservation and started to be transformed into microspherocytes around the 20th day. Therefore, dielectric spectroscopy is a sensitive tool to monitor the deterioration of preserved blood accompanied by morphological transition of erythrocytes through the temporal variation of their dielectric properties.

  2. Generation of functional eyes from pluripotent cells.

    Directory of Open Access Journals (Sweden)

    Andrea S Viczian

    2009-08-01

    Full Text Available Pluripotent cells such as embryonic stem (ES and induced pluripotent stem (iPS cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.

  3. Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function.

    Science.gov (United States)

    Shah, Prajay T; Stratton, Jo A; Stykel, Morgan Gail; Abbasi, Sepideh; Sharma, Sandeep; Mayr, Kyle A; Koblinger, Kathrin; Whelan, Patrick J; Biernaskie, Jeff

    2018-05-03

    Ependymal cells are multi-ciliated cells that form the brain's ventricular epithelium and a niche for neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ). In addition, ependymal cells are suggested to be latent NSCs with a capacity to acquire neurogenic function. This remains highly controversial due to a lack of prospective in vivo labeling techniques that can effectively distinguish ependymal cells from neighboring V-SVZ NSCs. We describe a transgenic system that allows for targeted labeling of ependymal cells within the V-SVZ. Single-cell RNA-seq revealed that ependymal cells are enriched for cilia-related genes and share several stem-cell-associated genes with neural stem or progenitors. Under in vivo and in vitro neural-stem- or progenitor-stimulating environments, ependymal cells failed to demonstrate any suggestion of latent neural-stem-cell function. These findings suggest remarkable stability of ependymal cell function and provide fundamental insights into the molecular signature of the V-SVZ niche. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Digital preservation

    CERN Document Server

    Deegan, Marilyn

    2013-01-01

    Digital preservation is an issue of huge importance to the library and information profession right now. With the widescale adoption of the internet and the rise of the world wide web, the world has been overwhelmed by digital information. Digital data is being produced on a massive scale by individuals and institutions: some of it is born, lives and dies only in digital form, and it is the potential death of this data, with its impact on the preservation of culture, that is the concern of this book. So how can information professionals try to remedy this? Digital preservation is a complex iss

  5. Expression and function of nicotinic acetylcholine receptors in stem cells

    Directory of Open Access Journals (Sweden)

    Herman S. Cheung

    2016-07-01

    Full Text Available Nicotinic acetylcholine receptors are prototypical ligand gated ion channels typically found in muscular and neuronal tissues. Functional nicotinic acetylcholine receptors, however, have also recently been identified on other cell types, including stem cells. Activation of these receptors by the binding of agonists like choline, acetylcholine, or nicotine has been implicated in many cellular changes. In regards to stem cell function, nicotinic acetylcholine receptor activation leads to changes in stem cell proliferation, migration and differentiation potential. In this review we summarize the expression and function of known nicotinic acetylcholine receptors in different classes of stem cells including: pluripotent stem cells, mesenchymal stem cells, periodontal ligament derived stem cells, and neural progenitor cells and discuss the potential downstream effects of receptor activation on stem cell function.

  6. Ontogeny and function of murine epidermal Langerhans cells.

    Science.gov (United States)

    Kaplan, Daniel H

    2017-09-19

    Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs.

  7. Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy.

    Science.gov (United States)

    Tyler, Paul M; Servos, Mariah M; de Vries, Romy C; Klebanov, Boris; Kashyap, Trinayan; Sacham, Sharon; Landesman, Yosef; Dougan, Michael; Dougan, Stephanie K

    2017-03-01

    Selinexor (KPT-330) is a first-in-class nuclear transport inhibitor currently in clinical trials as an anticancer agent. To determine how selinexor might affect antitumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T-cell development, a progressive loss of CD8 T cells, and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T-cell development and function. We determined the minimum concentration of selinexor required to block T-cell activation and showed that T-cell-inhibitory effects of selinexor occur at levels above 100 nmol/L, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 4-day drug holiday led to intratumoral IFNγ + , granzyme B + cytotoxic CD8 T cells that were comparable with vehicle-treated mice. Overall, selinexor treatment leads to transient inhibition of T-cell activation, but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T-cell functioning and development of antitumor immunity. Mol Cancer Ther; 16(3); 428-39. ©2017 AACR See related article by Farren et al., p. 417 . ©2017 American Association for Cancer Research.

  8. Squamous cell carcinoma of the larynx with subglottic extension: is larynx preservation possible

    Energy Technology Data Exchange (ETDEWEB)

    Levy, A.; Blanchard, P.; Lusinchi, A.; Daly-Schveitzer, N.; Tao, Y. [Gustave Roussy, Department of Radiotherapy, Villejuif (France); Temam, S.; Maison, M.M.; Janot, F.; Mirghani, H. [Gustave Roussy, Department of Otorhinolaryngology - Head and Neck Surgery, Villejuif (France); Bidault, F. [Gustave Roussy, Department of Diagnostic Radiology, Villejuif (France); Guigay, J. [Gustave Roussy, Department of Medical Oncology, Villejuif (France); Bourhis, J. [Gustave Roussy, Department of Radiotherapy, Villejuif (France); University Hospital Lausanne, Department of Radiation Oncology, Lausanne (Switzerland)

    2014-07-15

    Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a rare location described to carry a poor prognosis. The aim of this study was to analyze outcomes and feasibility of larynx preservation in sSCC patients. Between 1996 and 2012, 197 patients with sSCC were treated at our institution and included in the analysis. Stage III-IV tumors accounted for 76 %. Patients received surgery (62 %), radiotherapy (RT) (18 %), or induction chemotherapy (CT) (20 %) as front-line therapy. The 5-year actuarial overall survival (OS), locoregional control (LRC), and distant control rate were 59 % (95 % CI 51-68), 83 % (95 % CI 77-89), and 88 % (95 % CI 83-93), respectively, with a median follow-up of 54.4 months. There was no difference in OS and LRC according to front-line treatments or between primary subglottic cancer and glottosupraglottic cancers with subglottic extension. In the multivariate analysis, age > 60 years and positive N stage were the only predictors for OS (HR 2, 95 % CI 1.2-3.6; HR1.9, 95 % CI 1-3.5, respectively). A lower LRC was observed for T3 patients receiving a larynx preservation protocol as compared with those receiving a front-line surgery (HR 14.1, 95 % CI 2.5-136.7; p = 0.02); however, no difference of ultimate LRC was observed according to the first therapy when including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients receiving a larynx preservation protocol, the 5-year larynx-preservation rate was 55 % (95 % CI 43-68), with 36 % in T3 patients. The 5-year larynx preservation rate was 81 % (95 % CI 65-96) and 35 % (95 % CI 20-51) for patients who received RT or induction CT as a front-line treatment, respectively. Outcomes of sSCC are comparable with other laryngeal cancers when managed with modern therapeutic options. Larynx-preservation protocols could be a suitable option in T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT). (orig.) [German] Plattenepithelkarzinome des Larynx mit

  9. Comparison of manual and automated cell counts in EDTA preserved synovial fluids. Storage has little influence on the results.

    Science.gov (United States)

    Salinas, M; Rosas, J; Iborra, J; Manero, H; Pascual, E

    1997-10-01

    To determine the precision and agreement of synovial fluid (SF) cell counts done manually and with automated counters, and to determine the degree of variability of the counts in SF samples, kept in the tubes used for routine white blood cell (WBC) counts--which use liquid EDTA as anticoagulant--at 24 and 48 hours at 4 degrees C, and at room temperature. To determine precision, cell counts were repeated 10 times--both manually and by an automated counter--in a SF sample of low, medium, and high cellularity. The variances were calculated to determine the interobserver variation in two manual (M1,M2) and two automated cell counts (C1,C2). The agreement between a manual (M1) and automated counter (C1) results, was analysed by the Bland and Altman method and the difference against the mean of the two methods was plotted. Then, the mean difference between the two methods was estimated and the standard deviation of the difference. To determine the effects of storage, SF samples were kept in a refrigerator at 4 degrees C, and at room temperature; cell counts were done manually (M1) and automatically (C1) at 24 and 48 hours and the changes analysed by the Bland and Altman method. The variances were compared using an F test. (1) Precision. With the manual technique, the coefficients of variation were 27.9%, 14%, and 10.7% when used for counting the SF with low (270), medium (6200), and high cellularities (25,000). With the automated technique the coefficients of variation were 20%, 3.4%, and 2.9% in the same SF samples. In the fluids of medium and high cellularity, the variances of the automated cell counts were significatively lower (F test, p automated counter. (4) Influence of storage. The coulter counts of SF samples preserved at 4 degrees C showed less variance (F test, p Automated cell count of the SF offers advantages: it gives higher precision and consumes less time. The stability of the samples preserved in the EDTA tubes used for routine WBC counts is of

  10. Caspase-12 ablation preserves muscle function in the mdx mouse

    Science.gov (United States)

    Moorwood, Catherine; Barton, Elisabeth R.

    2014-01-01

    Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin. Several downstream consequences of dystrophin deficiency are triggers of endoplasmic reticulum (ER) stress, including loss of calcium homeostasis, hypoxia and oxidative stress. During ER stress, misfolded proteins accumulate in the ER lumen and the unfolded protein response (UPR) is triggered, leading to adaptation or apoptosis. We hypothesized that ER stress is heightened in dystrophic muscles and contributes to the pathology of DMD. We observed increases in the ER stress markers BiP and cleaved caspase-4 in DMD patient biopsies, compared with controls, and an increase in multiple UPR pathways in muscles of the dystrophin-deficient mdx mouse. We then crossed mdx mice with mice null for caspase-12, the murine equivalent of human caspase-4, which are resistant to ER stress. We found that deleting caspase-12 preserved mdx muscle function, resulting in a 75% recovery of both specific force generation and resistance to eccentric contractions. The compensatory hypertrophy normally found in mdx muscles was normalized in the absence of caspase-12; this was found to be due to decreased fibre sizes, and not to a fibre type shift or a decrease in fibrosis. Fibre central nucleation was not significantly altered in the absence of caspase-12, but muscle fibre degeneration found in the mdx mouse was reduced almost to wild-type levels. In conclusion, we have identified heightened ER stress and abnormal UPR signalling as novel contributors to the dystrophic phenotype. Caspase-4 is therefore a potential therapeutic target for DMD. PMID:24879640

  11. Neurotransmitters and Neuropeptides: New Players in the Control of Islet of Langerhans' Cell Mass and Function.

    Science.gov (United States)

    Di Cairano, Eliana S; Moretti, Stefania; Marciani, Paola; Sacchi, Vellea Franca; Castagna, Michela; Davalli, Alberto; Folli, Franco; Perego, Carla

    2016-04-01

    Islets of Langerhans control whole body glucose homeostasis, as they respond, releasing hormones, to changes in nutrient concentrations in the blood stream. The regulation of hormone secretion has been the focus of attention for a long time because it is related to many metabolic disorders, including diabetes mellitus. Endocrine cells of the islet use a sophisticate system of endocrine, paracrine and autocrine signals to synchronize their activities. These signals provide a fast and accurate control not only for hormone release but also for cell differentiation and survival, key aspects in islet physiology and pathology. Among the different categories of paracrine/autocrine signals, this review highlights the role of neurotransmitters and neuropeptides. In a manner similar to neurons, endocrine cells synthesize, accumulate, release neurotransmitters in the islet milieu, and possess receptors able to decode these signals. In this review, we provide a comprehensive description of neurotransmitter/neuropetide signaling pathways present within the islet. Then, we focus on evidence supporting the concept that neurotransmitters/neuropeptides and their receptors are interesting new targets to preserve β-cell function and mass. A greater understanding of how this network of signals works in physiological and pathological conditions would advance our knowledge of islet biology and physiology and uncover potentially new areas of pharmacological intervention. J. Cell. Physiol. 231: 756-767, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  12. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  13. Developmental profile of speech-language and communicative functions in an individual with the preserved speech variant of Rett syndrome.

    Science.gov (United States)

    Marschik, Peter B; Vollmann, Ralf; Bartl-Pokorny, Katrin D; Green, Vanessa A; van der Meer, Larah; Wolin, Thomas; Einspieler, Christa

    2014-08-01

    We assessed various aspects of speech-language and communicative functions of an individual with the preserved speech variant of Rett syndrome (RTT) to describe her developmental profile over a period of 11 years. For this study, we incorporated the following data resources and methods to assess speech-language and communicative functions during pre-, peri- and post-regressional development: retrospective video analyses, medical history data, parental checklists and diaries, standardized tests on vocabulary and grammar, spontaneous speech samples and picture stories to elicit narrative competences. Despite achieving speech-language milestones, atypical behaviours were present at all times. We observed a unique developmental speech-language trajectory (including the RTT typical regression) affecting all linguistic and socio-communicative sub-domains in the receptive as well as the expressive modality. Future research should take into consideration a potentially considerable discordance between formal and functional language use by interpreting communicative acts on a more cautionary note.

  14. High Glucose Aggravates the Detrimental Effects of Pancreatic Stellate Cells on Beta-Cell Function

    Directory of Open Access Journals (Sweden)

    Min Zha

    2014-01-01

    Full Text Available Background and Aims. We here assess the effects of PSCs on β-cell function and apoptosis in vivo and in vitro. Materials and Methods. PSCs were transplanted into Wistar and Goto-Kakizaki (GK rats. Sixteen weeks after transplantation, β-cell function, apoptosis, and islet fibrosis were assessed. In vitro the effects of PSCs conditioned medium (PSCs-CM and/or high concentration of glucose on INS-1 cell function was assessed by measuring insulin secretion, INS-1 cell survival, apoptosis, and endoplasmic reticulum stress (ER stress associated CHOP expression. Results. PSCs transplantation exacerbated the impaired β-cell function in GK rats, but had no significant effects in Wistar rats. In vitro, PSCs-CM caused impaired INS-1 cell viability and insulin secretion and increased apoptosis, which were more pronounced in the presence of high glucose. Conclusion. Our study demonstrates that PSCs induce β-cell failure in vitro and in vivo.

  15. [Penis-preserving surgery in patients with primary penile urethral cancer].

    Science.gov (United States)

    Maek, M; Musch, M; Arnold, G; Kröpfl, D

    2014-12-01

    Primary urethral cancer in males is a rare entity with only approximately 800 cases described, which is why it is difficult to formulate evidence-based guidelines for treatment. For tumors in the pT2 stage with a localization distal to the membranous urethra, a penis-preserving operation can be carried out. In the period from November 2006 to February 2014 a total of 4 patients with primary urethral cancer underwent a penis-preserving urethral resection. The tumor characteristics and treatment results were collated retrospectively. Of the four patients one had a transitional cell carcinoma of the mid-penile urethra in stage pT2 G2. In two out of the four patients a squamous cell carcinoma (PEC) was present in the mid-penile urethra in stages pT2 G2 and pT2 G3, respectively, with concomitant carcinoma in situ (CIS). The fourth patient had a PEC of the fossa terminalis in stage pT2 G2. Initially all patients underwent a penis-preserving resection. In one case, despite an initial R0 resection a local recurrence occurred and a complete penectomy was performed. Irradiation and lymphadenectomy were not carried out. At a mean follow-up of 37 months all patients are currently in complete remission. Primary penile urethral cancer can be treated by a penis-preserving operation. Close follow-up is essential because recurrence can arise despite an initial R0 resection.

  16. Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells.

    Science.gov (United States)

    Liu, Hao-Yu; Roos, Stefan; Jonsson, Hans; Ahl, David; Dicksved, Johan; Lindberg, Jan Erik; Lundh, Torbjörn

    2015-04-01

    Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cytoprotective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell-cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  17. Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

    Science.gov (United States)

    Tyler, Lorraine K; Wright, Paul; Randall, Billi; Marslen-Wilson, William D; Stamatakis, Emmanuel A

    2010-11-01

    The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language.

  18. Social cognition in anorexia nervosa: evidence of preserved theory of mind and impaired emotional functioning.

    Science.gov (United States)

    Adenzato, Mauro; Todisco, Patrizia; Ardito, Rita B

    2012-01-01

    The findings of the few studies that have to date investigated the way in which individuals with Anorexia Nervosa (AN) navigate their social environment are somewhat contradictory. We undertook this study to shed new light on the social-cognitive profile of patients with AN, analysing Theory of Mind and emotional functioning. Starting from previous evidence on the role of the amygdala in the neurobiology of AN and in the social cognition, we hypothesise preserved Theory of Mind and impaired emotional functioning in patients with AN. Thirty women diagnosed with AN and thirty-two women matched for education and age were involved in the study. Theory of Mind and emotional functioning were assessed with a set of validated experimental tasks. A measure of perceived social support was also used to test the correlations between this dimension and the social-cognitive profile of AN patients. The performance of patients with AN is significantly worse than that of healthy controls on tasks assessing emotional functioning, whereas patients' performance is comparable to that of healthy controls on the Theory of Mind task. Correlation analyses showed no relationship between scores on any of the social-cognition tasks and either age of onset or duration of illness. A correlation between social support and emotional functioning was found. This latter result seems to suggest a potential role of social support in the treatment and recovery of AN. The pattern of results followed the experimental hypothesis. They may be useful to help us better understand the social-cognitive profile of patients with AN and to contribute to the development of effective interventions based on the ways in which patients with AN actually perceive their social environment.

  19. Klinefelter syndrome and fertility: sperm preservation should not be offered to children with Klinefelter syndrome.

    Science.gov (United States)

    Franik, S; Hoeijmakers, Y; D'Hauwers, K; Braat, D D M; Nelen, W L M; Smeets, D; Claahsen-van der Grinten, H L; Ramos, L; Fleischer, K

    2016-09-01

    (40-70%). Although spermatogonia can be found by TESE in about half of the peri-pubertal adolescents, there are currently no clinically functional techniques for their future use. Children and adolescents need to be informed that early fertility preservation before the age of 16 cannot guarantee fertility later in life and may even reduce the chances for offspring by removing functional immature germ cells which may possibly develop into spermatozoa after puberty. Furthermore, except for the age of patients with KS, there are no identified factors that can reliably be used as a predictive marker for fertility preservation. Most of the evidence presented in this review is based on studies including a small number of adolescents with KS. Therefore, the studies may have been underpowered to detect clinically significant differences for their various outcomes, especially for potential predictive factors for fertility preservation, such as hormone levels. Furthermore, the population of patients with KS diagnosed during childhood might be different from the adult population with KS where the diagnosis is based on infertility. Results based on comparisons between the two groups must be interpreted with caution. Despite the limitations, this review summarizes the current evidence for managing fertility preservation in patients with KS to provide optimal health care. There was no funding for this study. S.F., Y.H., K.D., W.L.M.N., D.S., H.L.C.-v.d.G. and L.R. declare to have no conflicts of interests. D.D.M.B. reports grants from Merck Serono, grants from Ferring and grants from MSD, outside the submitted work. K.F. reports personal fees from MSD (commercial sponsor), personal fees from Ferring (commercial sponsor), grants from Merck-Serono (commercial sponsor), grants from Ferring (commercial sponsor) and grants from MSD (commercial sponsor), outside the submitted work. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human

  20. Modes of fossil preservation

    Science.gov (United States)

    Schopf, J.M.

    1975-01-01

    The processes of geologic preservation are important for understanding the organisms represented by fossils. Some fossil differences are due to basic differences in organization of animals and plants, but the interpretation of fossils has also tended to be influenced by modes of preservation. Four modes of preservation generally can be distinguished: (1) Cellular permineralization ("petrifaction") preserves anatomical detail, and, occasionally, even cytologic structures. (2) Coalified compression, best illustrated by structures from coal but characteristic of many plant fossils in shale, preserves anatomical details in distorted form and produces surface replicas (impressions) on enclosing matrix. (3) Authigenic preservation replicates surface form or outline (molds and casts) prior to distortion by compression and, depending on cementation and timing, may intergrade with fossils that have been subject to compression. (4) Duripartic (hard part) preservation is characteristic of fossil skeletal remains, predominantly animal. Molds, pseudomorphs, or casts may form as bulk replacements following dissolution of the original fossil material, usually by leaching. Classification of the kinds of preservation in fossils will aid in identifying the processes responsible for modifying the fossil remains of both animals and plants. ?? 1975.

  1. Preliminary study of coconut water for graft tissues preservation in transplantation

    Directory of Open Access Journals (Sweden)

    Jorge Miguel Schettino César

    Full Text Available OBJECTIVE: to verify the effectiveness of coconut water in preserving tissues for transplant. METHODS: Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvasted the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exame. The implanted tissues were collected for histopathological examination. RESULTS: The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p <0.001, 4 and 2 (p = 0.03 and 5 and 2 (p = 0.01. The splenic scintigraphy was not different between groups. The ovarian tissue was better preserved in mature coconut water (p <0.007. CONCLUSION: the coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

  2. The Three-Dimensional Culture System with Matrigel and Neurotrophic Factors Preserves the Structure and Function of Spiral Ganglion Neuron In Vitro.

    Science.gov (United States)

    Sun, Gaoying; Liu, Wenwen; Fan, Zhaomin; Zhang, Daogong; Han, Yuechen; Xu, Lei; Qi, Jieyu; Zhang, Shasha; Gao, Bradley T; Bai, Xiaohui; Li, Jianfeng; Chai, Renjie; Wang, Haibo

    2016-01-01

    Whole organ culture of the spiral ganglion region is a resourceful model system facilitating manipulation and analysis of live sprial ganglion neurons (SGNs). Three-dimensional (3D) cultures have been demonstrated to have many biomedical applications, but the effect of 3D culture in maintaining the SGNs structure and function in explant culture remains uninvestigated. In this study, we used the matrigel to encapsulate the spiral ganglion region isolated from neonatal mice. First, we optimized the matrigel concentration for the 3D culture system and found the 3D culture system protected the SGNs against apoptosis, preserved the structure of spiral ganglion region, and promoted the sprouting and outgrowth of SGNs neurites. Next, we found the 3D culture system promoted growth cone growth as evidenced by a higher average number and a longer average length of filopodia and a larger growth cone area. 3D culture system also significantly elevated the synapse density of SGNs. Last, we found that the 3D culture system combined with neurotrophic factors had accumulated effects in promoting the neurites outgrowth compared with 3D culture or NFs treatment only groups. Together, we conclude that the 3D culture system preserves the structure and function of SGN in explant culture.

  3. Splenic implant preservation after conservation in lactated Ringer´s solution.

    Science.gov (United States)

    Matos Filho, Argos Soares DE; Petroianu, Andy; Cardoso, Valbert Nascimento; Vidigal, Paula Vieira Teixeira

    2018-01-01

    to evaluate the morphology and function of autogenous splenic tissue implanted in the greater omentum, 24 hours after storage in Ringer-lactate solution. we divided 35 male rats into seven groups (n=5): Group 1: no splenectomy; Group 2: total splenectomy without implant; Group 3: total splenectomy and immediate autogenous implant; Group 4: total splenectomy, preservation of the spleen in Ringer-lactate at room temperature, then sliced ​​and implanted; Group 5: total splenectomy, ​​spleen sliced and preserved in Ringer-lactate at room temperature before implantation; Group 6: total splenectomy with preservation of the spleen in Ringer-lactate at 4°C and then sliced ​​and implanted; Group 7: total splenectomy and the spleen sliced for preservation in Ringer-lactate at 4°C before implantation. After 90 days, we performed scintigraphic studies with Tc99m-colloidal tin (liver, lung, spleen or implant and clot), haematological exams (erythrogram, leucometry, platelets), biochemical dosages (protein electrophoresis) and anatomopathological studies. regeneration of autogenous splenic implants occurred in the animals of the groups with preservation of the spleen at 4ºC. The uptake of colloidal tin was higher in groups 1, 3, 6 and 7 compared with the others. There was no difference in hematimetric values ​​in the seven groups. Protein electrophoresis showed a decrease in the gamma fraction in the group of splenectomized animals in relation to the operated groups. the splenic tissue preserved in Ringer-lactate solution at 4ºC maintains its morphological structure and allows functional recovery after being implanted on the greater omentum.

  4. Splenic implant preservation after conservation in lactated Ringer´s solution

    Directory of Open Access Journals (Sweden)

    ARGOS SOARES DE MATOS FILHO

    2018-02-01

    Full Text Available ABSTRACT Objective: to evaluate the morphology and function of autogenous splenic tissue implanted in the greater omentum, 24 hours after storage in Ringer-lactate solution. Methods: we divided 35 male rats into seven groups (n=5: Group 1: no splenectomy; Group 2: total splenectomy without implant; Group 3: total splenectomy and immediate autogenous implant; Group 4: total splenectomy, preservation of the spleen in Ringer-lactate at room temperature, then sliced and implanted; Group 5: total splenectomy, spleen sliced and preserved in Ringer-lactate at room temperature before implantation; Group 6: total splenectomy with preservation of the spleen in Ringer-lactate at 4°C and then sliced and implanted; Group 7: total splenectomy and the spleen sliced for preservation in Ringer-lactate at 4°C before implantation. After 90 days, we performed scintigraphic studies with Tc99m-colloidal tin (liver, lung, spleen or implant and clot, haematological exams (erythrogram, leucometry, platelets, biochemical dosages (protein electrophoresis and anatomopathological studies. Results: regeneration of autogenous splenic implants occurred in the animals of the groups with preservation of the spleen at 4ºC. The uptake of colloidal tin was higher in groups 1, 3, 6 and 7 compared with the others. There was no difference in hematimetric values in the seven groups. Protein electrophoresis showed a decrease in the gamma fraction in the group of splenectomized animals in relation to the operated groups. Conclusion: the splenic tissue preserved in Ringer-lactate solution at 4ºC maintains its morphological structure and allows functional recovery after being implanted on the greater omentum.

  5. Developed beverage from roselle calyx and selected fruits modulates β-cell function, improves insulin sensitivity, and attenuates hyperlipidaemia in diabetic rats

    Directory of Open Access Journals (Sweden)

    Ochuko L. Erukainure

    2015-12-01

    Full Text Available The aim of this study is to report the antidiabetic properties of a beverage developed from roselle calyx and selected fruits in male albino rats. The beverage was designed to contain 30% pawpaw (Carica papaya L., 10% grapefruit (Citrus paradisi, 20% guava leaves (Psidium guajava L. and 40% roselle calyx aqueous extracts. Four groups of five rats each were acclimatized on pelletized mouse chow for seven days, after which diabetes was induced by a single ip injection of alloxan in all groups except group 1, which served as control. Group 2 served as negative control while groups 3 and 4 were treated with the beverage at 2.5 and 5 ml/kg bw respectively. Food intake, body weight, and blood glucose levels were monitored. They were sacrificed by cervical dislocation after a 2 week treatment. Blood serum was analysed to evaluate insulin levels, β cell function, insulin resistance and lipid profile. Histological studies were carried out on pancreatic tissues. Treatment with both doses of the beverage led to a significant reduction (p < 0.05 in blood glucose, total cholesterol triglyceride, LDL and increased HDL levels. It also improved serum insulin levels, β cell function, reduced insulin resistance and restored pancreatic beta cells compared to the diabetic group. These antidiabetic properties may be as a consequence of modulation of the β-cell function, reduction of insulin resistance and preservation/restoration of β-cell integrity. However, treatment with the single dose showed signs of hyperinsulinaemia.

  6. Widespread immunological functions of mast cells: fact or fiction?

    Science.gov (United States)

    Rodewald, Hans-Reimer; Feyerabend, Thorsten B

    2012-07-27

    Immunological functions of mast cells are currently considered to be much broader than the original role of mast cells in IgE-driven allergic disease. The spectrum of proposed mast cell functions includes areas as diverse as the regulation of innate and adaptive immune responses, protective immunity against viral, microbial, and parasitic pathogens, autoimmunity, tolerance to graft rejection, promotion of or protection from cancer, wound healing, angiogenesis, cardiovascular diseases, diabetes, obesity, and others. The vast majority of in vivo mast cell data have been based on mast cell-deficient Kit mutant mice. However, work in new mouse mutants with unperturbed Kit function, which have a surprisingly normal immune system, has failed to corroborate some key immunological aspects, formerly attributed to mast cells. Here, we consider the implications of these recent developments for the state of the field as well as for future work, aiming at deciphering the physiological functions of mast cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Preliminary study of coconut water for graft tissues preservation in transplantation.

    Science.gov (United States)

    César, Jorge Miguel Schettino; Petroianu, Andy; Vasconcelos, Leonardo de Souza; Cardoso, Valbert Nascimento; Mota, Luciene das Graças; Barbosa, Alfredo José Afonso; Soares, Cristina Duarte Vianna; de Oliveira, Amanda Lima

    2015-01-01

    to verify the effectiveness of coconut water in preserving tissues for transplant. Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvested the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exam. The implanted tissues were collected for histopathological examination. The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p coconut water (p coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

  8. American Heart Association’s Life’s Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function

    Science.gov (United States)

    Folsom, Aaron R.; Shah, Amil M.; Lutsey, Pamela L.; Roetker, Nicholas S.; Alonso, Alvaro; Avery, Christy L.; Miedema, Michael D.; Konety, Suma; Chang, Patricia P.; Solomon, Scott D.

    2015-01-01

    BACKGROUND Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association’s Life’s Simple 7 guidelines -- on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose -- is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults aged 45-64 years in 1987-89. From the 1987-89 risk factor measurements, we created a Life’s Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2,218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4,855 participants free of clinical cardiovascular disease in 2011-13, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS One in four participants (25.5%) developed heart failure through age 85. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life’s Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life’s Simple 7 score compared with an inadequate score. CONCLUSIONS Greater achievement of American Heart Association’s Life’s Simple 7 in middle-age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. PMID:25908393

  9. Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies

    DEFF Research Database (Denmark)

    La Morgia, C; Ross-Cisneros, F.N.; Sadun, A.A.

    2010-01-01

    Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal...... ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex...... subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case...

  10. Preserving Digital Materials

    CERN Document Server

    Harvey, Ross

    2011-01-01

    This book provides a single-volume introduction to the principles, strategies and practices currently applied by librarians and recordkeeping professionals to the critical issue of preservation of digital information. It incorporates practice from both the recordkeeping and the library communities, taking stock of current knowledge about digital preservation and describing recent and current research, to provide a framework for reflecting on the issues that digital preservation raises in professional practice.

  11. Starved Escherichia coli preserve reducing power under nitric oxide stress

    Energy Technology Data Exchange (ETDEWEB)

    Gowers, Glen-Oliver F. [Department of Molecular Biology, Princeton University, Princeton, NJ (United States); Robinson, Jonathan L. [Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ (United States); Brynildsen, Mark P., E-mail: mbrynild@princeton.edu [Department of Molecular Biology, Princeton University, Princeton, NJ (United States); Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ (United States)

    2016-07-15

    Nitric oxide (NO) detoxification enzymes, such as NO dioxygenase (NOD) and NO reductase (NOR), are important to the virulence of numerous bacteria. Pathogens use these defense systems to ward off immune-generated NO, and they do so in environments that contain additional stressors, such as reactive oxygen species, nutrient deprivation, and acid stress. NOD and NOR both use reducing equivalents to metabolically deactivate NO, which suggests that nutrient deprivation could negatively impact their functionality. To explore the relationship between NO detoxification and nutrient deprivation, we examined the ability of Escherichia coli to detoxify NO under different levels of carbon source availability in aerobic cultures. We observed failure of NO detoxification under both carbon source limitation and starvation, and those failures could have arisen from inabilities to synthesize Hmp (NOD of E. coli) and/or supply it with sufficient NADH (preferred electron donor). We found that when limited quantities of carbon source were provided, NO detoxification failed due to insufficient NADH, whereas starvation prevented Hmp synthesis, which enabled cells to maintain their NADH levels. This maintenance of NADH levels under starvation was confirmed to be dependent on the absence of Hmp. Intriguingly, these data show that under NO stress, carbon-starved E. coli are better positioned with regard to reducing power to cope with other stresses than cells that had consumed an exhaustible amount of carbon. -- Highlights: •Carbon source availability is critical to aerobic E. coli NO detoxification. •Carbon source starvation, under NO stress, preserves intracellular NADH levels. •Preservation of NADH depends on starvation-dependent inhibition of Hmp induction.

  12. Linear maps preserving maximal deviation and the Jordan structure of quantum systems

    International Nuclear Information System (INIS)

    Hamhalter, Jan

    2012-01-01

    In the algebraic approach to quantum theory, a quantum observable is given by an element of a Jordan algebra and a state of the system is modelled by a normalized positive functional on the underlying algebra. Maximal deviation of a quantum observable is the largest statistical deviation one can obtain in a particular state of the system. The main result of the paper shows that each linear bijective transformation between JBW algebras preserving maximal deviations is formed by a Jordan isomorphism or a minus Jordan isomorphism perturbed by a linear functional multiple of an identity. It shows that only one numerical statistical characteristic has the power to determine the Jordan algebraic structure completely. As a consequence, we obtain that only very special maps can preserve the diameter of the spectra of elements. Nonlinear maps preserving the pseudometric given by maximal deviation are also described. The results generalize hitherto known theorems on preservers of maximal deviation in the case of self-adjoint parts of von Neumann algebras proved by Molnár.

  13. Genito-Urinary Function and Quality of Life after Elective Totally Laparoscopic Sigmoidectomy after at Least One Episode of Complicated Diverticular Disease According to Two Different Vascular Approaches: the IMA Low Ligation or the IMA Preservation.

    Science.gov (United States)

    Mari, Giulio; Crippa, Jacopo; Costanzi, Andrea; Mazzola, Michele; Magistro, Carmelo; Ferrari, Giovanni; Maggioni, Dario

    2017-01-01

    The arterial ligation during elective laparoscopic sigmoidectomy for diverticular disease can affect genito-urinary function injuring the superior hypogastric plexus, and can weaken the distal colonic stump arterial perfusion. Ligation of the inferior mesenteric artery distal to the left colic artery or the complete preservation of the inferior mesenteric artery can therefore be compared in terms of preservation of the descending sympathetic fibres running along the aorta to the rectum resulting in a different post operative genito urinary function. From January 2015 to March 2016, 66 patients underwent elective laparoscopic sigmoidectomy for diverticular disease among two enrolling hospitals. In one centre 35 patients underwent laparoscopic sigmoidectomy with the ligation of the inferior mesenteric artery distal to the left colic artery (low ligation). In the other centre 31 patient were operated on the same procedure with complete inferior mesenteric artery preservation (IMA preservation). There was no difference in terms of major complication occurred, first passage of stool and length of hospital stay between the two groups. Time of surgery was significantly shorter in LL group compared to IMA preserving group and intra operative blood loss was significantly lower in the LL group. There were no differences in the genito urinary function between the two group pre operatively, at 1 and 9 months post operatively. Genito urinary function did not significantly change across surgery in each groups. The low ligation and the IMA preserving vascular approach are safe end feasible techniques in elective laparoscopic sigmoidectomy for diverticular disease. They both prevent from genito-urinary post-operative disfunction and allow good post operative quality of life. The low ligation approach is related to shorter operative time and slower intra operative blood loss. Celsius.

  14. Nanothin Coculture Membranes with Tunable Pore Architecture and Thermoresponsive Functionality for Transfer-Printable Stem Cell-Derived Cardiac Sheets.

    Science.gov (United States)

    Ryu, Seungmi; Yoo, Jin; Jang, Yeongseon; Han, Jin; Yu, Seung Jung; Park, Jooyeon; Jung, Seon Yeop; Ahn, Kyung Hyun; Im, Sung Gap; Char, Kookheon; Kim, Byung-Soo

    2015-10-27

    Coculturing stem cells with the desired cell type is an effective method to promote the differentiation of stem cells. The features of the membrane used for coculturing are crucial to achieving the best outcome. Not only should the membrane act as a physical barrier that prevents the mixing of the cocultured cell populations, but it should also allow effective interactions between the cells. Unfortunately, conventional membranes used for coculture do not sufficiently meet these requirements. In addition, cell harvesting using proteolytic enzymes following coculture impairs cell viability and the extracellular matrix (ECM) produced by the cultured cells. To overcome these limitations, we developed nanothin and highly porous (NTHP) membranes, which are ∼20-fold thinner and ∼25-fold more porous than the conventional coculture membranes. The tunable pore size of NTHP membranes at the nanoscale level was found crucial for the formation of direct gap junctions-mediated contacts between the cocultured cells. Differentiation of the cocultured stem cells was dramatically enhanced with the pore size-customized NTHP membrane system compared to conventional coculture methods. This was likely due to effective physical contacts between the cocultured cells and the fast diffusion of bioactive molecules across the membrane. Also, the thermoresponsive functionality of the NTHP membranes enabled the efficient generation of homogeneous, ECM-preserved, highly viable, and transfer-printable sheets of cardiomyogenically differentiated cells. The coculture platform developed in this study would be effective for producing various types of therapeutic multilayered cell sheets that can be differentiated from stem cells.

  15. High oxygen as an additional factor in food preservation

    NARCIS (Netherlands)

    Amanatidou, A.

    2001-01-01

    In this thesis, the efficacy of high oxygen as an additional hurdle for food preservation is studied. At high oxygen conditions and at low temperature, significant impairment of growth and viability of bacterial cells is found to occur as the result of free

  16. Molecular biological features of male germ cell differentiation

    Science.gov (United States)

    HIROSE, MIKA; TOKUHIRO, KEIZO; TAINAKA, HITOSHI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

    2007-01-01

    Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation. (Reprod Med Biol 2007; 6: 1–9) PMID:29699260

  17. Liver-resident NK cells and their potential functions.

    Science.gov (United States)

    Peng, Hui; Sun, Rui

    2017-09-18

    Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells. Here, we present a brief historical perspective on the discovery of liver-resident NK cells and discuss their relationship to cNK cells and other emerging NK cell subsets and their potential functions.Cellular &Molecular Immunology advance online publication, 18 September 2017; doi:10.1038/cmi.2017.72.

  18. CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection.

    Science.gov (United States)

    DiPiazza, Anthony; Laniewski, Nathan; Rattan, Ajitanuj; Topham, David J; Miller, Jim; Sant, Andrea J

    2018-07-01

    Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza virus infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza virus infection in conjunction with intravascular labeling in vivo , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. These studies revealed that tissue-localized CD4 cells were globally distinct from vascular cells in expression of markers associated with transendothelial migration, residency, and micropositioning. Despite these differences, there was little evidence for remodeling of the viral epitope specificity or cytokine potential as cells transition from vasculature to the highly inflamed lung tissue. Our studies also distinguished cells in the pulmonary vasculature from peripheral circulating CD4 T cells, providing support for the concept that the pulmonary vasculature does not simply reflect circulating cells that are trapped within the narrow confines of capillary vessels but rather is enriched in transitional cells primed in the draining lymph node that have specialized potential to enter the lung tissue. IMPORTANCE CD4 T cells convey a multitude of functions in immunity to influenza, including those delivered in the lymph node and others conveyed by CD4 T cells that leave the lymph node, enter the blood, and extravasate into the lung tissue. Here, we show that the transition of recently primed CD4 cells detected in the lung vasculature undergo profound changes in expression of markers associated with tissue localization as

  19. The functional relevance of polyploidization in the skin.

    Science.gov (United States)

    Trakala, Marianna; Malumbres, Marcos

    2014-02-01

    Cell proliferation and differentiation are tightly coupled through the regulation of the cell division cycle. To preserve specific functional properties in differentiated cells, distinct variants of the basic mitotic cell cycle are used in various mammalian tissues, leading to the formation of polyploid cells. In this issue of Experimental Dermatology, Gandarillas and Freije discuss the evidences for polyploidization in keratinocytes, a process whose physiological relevance is now becoming evident. A better evaluation of these unconventional cell cycles is required not only to improve our understanding of the development and structure of the epidermis but also for future therapies against skin diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Mitochondrial function in Müller cells - Does it matter?

    DEFF Research Database (Denmark)

    Toft-Kehler, Anne Katrine; Skytt, Dorte Marie; Svare, Alicia

    2017-01-01

    in the most predominant glial cells of the retina, the Müller cells. Müller cells span the entire thickness of the neuroretina and are in close proximity to retinal cells including the retinal neurons that provides visual signaling to the brain. Among multiple functions, Müller cells are responsible...... for the removal of neurotransmitters, buffering potassium, and providing neurons with essential metabolites. Thus, Müller cells are responsible for a stable metabolic dialogue in the inner retina and their crucial role in supporting retinal neurons is indisputable. Müller cell functions require considerable......Growing evidence suggests that mitochondrial dysfunction might play a key role in the pathogenesis of age-related neurodegenerative inner retinal diseases such as diabetic retinopathy and glaucoma. Therefore, the present review provides a perspective on the impact of functional mitochondria...

  1. Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas

    Science.gov (United States)

    Brooks, Joseph L.; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

    2012-01-01

    Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG. PMID:22947116

  2. High hydrostatic pressure as a method to preserve fresh-cut Hachiya persimmons: A structural approach.

    Science.gov (United States)

    Vázquez-Gutiérrez, José Luis; Quiles, Amparo; Vonasek, Erica; Jernstedt, Judith A; Hernando, Isabel; Nitin, Nitin; Barrett, Diane M

    2016-12-01

    The "Hachiya" persimmon is the most common astringent cultivar grown in California and it is rich in tannins and carotenoids. Changes in the microstructure and some physicochemical properties during high hydrostatic pressure processing (200-400 MPa, 3 min, 25 ℃) and subsequent refrigerated storage were analyzed in this study in order to evaluate the suitability of this non-thermal technology for preservation of fresh-cut Hachiya persimmons. The effects of high-hydrostatic pressure treatment on the integrity and location of carotenoids and tannins during storage were also analyzed. Significant changes, in particular diffusion of soluble compounds which were released as a result of cell wall and membrane damage, were followed using confocal microscopy. The high-hydrostatic pressure process also induced changes in physicochemical properties, e.g. electrolyte leakage, texture, total soluble solids, pH and color, which were a function of the amount of applied hydrostatic pressure and may affect the consumer acceptance of the product. Nevertheless, the results indicate that the application of 200 MPa could be a suitable preservation treatment for Hachiya persimmon. This treatment seems to improve carotenoid extractability and tannin polymerization, which could improve functionality and remove astringency of the fruit, respectively. © The Author(s) 2016.

  3. Privacy-Preserving Verifiability: A Case for an Electronic Exam Protocol

    DEFF Research Database (Denmark)

    Giustolisi, Rosario; Iovino, Vincenzo; Lenzini, Gabriele

    2017-01-01

    We introduce the notion of privacy-preserving verifiability for security protocols. It holds when a protocol admits a verifiability test that does not reveal, to the verifier that runs it, more pieces of information about the protocol’s execution than those required to run the test. Our definition...... of privacy-preserving verifiability is general and applies to cryptographic protocols as well as to human security protocols. In this paper we exemplify it in the domain of e-exams. We prove that the notion is meaningful by studying an existing exam protocol that is verifiable but whose verifiability tests...... are not privacy-preserving. We prove that the notion is applicable: we review the protocol using functional encryption so that it admits a verifiability test that preserves privacy according to our definition. We analyse, in ProVerif, that the verifiability holds despite malicious parties and that the new...

  4. Development of Emu oil-loaded PCL/collagen bioactive nanofibers for proliferation and stemness preservation of human adipose-derived stem cells: possible application in regenerative medicine.

    Science.gov (United States)

    Nejati-Koshki, Kazem; Pilehvar-Soltanahmadi, Younes; Alizadeh, Effat; Ebrahimi-Kalan, Abbas; Mortazavi, Yousef; Zarghami, Nosratollah

    2017-12-01

    Adipose tissue-derived stem cells (ASCs) are promising candidate in stem cell therapies, and maintaining their stemness potential is vital to achieve effective treatment. Natural-based scaffolds have been recently attracted increasing attention in nanomedicine and drug delivery. In the present study, a polymeric nanofibrous scaffold was developed based on the polycaprolactone/Collagen (PCL/Coll) containing Emu oil as a bioactive material to induce the proliferation of ASCs, while simultaneously preserving the stemness property of those cells. Fabrication of the electrospun Emu oil-loaded PCL/Coll nanofibers was confirmed by using FE-SEM, FTIR, and tensile test. ASCs were seeded on two types of nanofibers (PCL/Coll and Emu oil-loaded PCL/Coll) and their proliferation, cell cycle progression, and stemness gene expressions were evaluated using MTT, propidium iodide staining, and qPCR during 14 days, respectively. The results indicated that ASCs displayed improved adhesion capacity with the higher rates of bioactivity and proliferation on the Emu oil-loaded nanofibers than the other groups. The proliferation capacity of ASCs on Emu oil-loaded PCL/Coll nanofibers was further confirmed by the cell cycle progression analysis. It was also found that Emu oil-loaded nanofibers significantly up-regulated the expression of stemness markers including sox-2, nanog, oct4, klf4, and c-Myc. The results demonstrated that the nanofibers containing Emu oil can reinforce the cell adhesion and enhance ASCs proliferation while preserving their stemness; therefore, using scaffolds containing natural products may have a great potential to enhance the in vitro expansion capacity of ASCs in the field of stem cell therapy and regenerative medicine.

  5. Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

    Science.gov (United States)

    Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

    2011-09-01

    Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

  6. TNF-α Regulates Mast Cell Functions by Inhibiting Cell Degranulation

    Directory of Open Access Journals (Sweden)

    Yuwei Gao

    2017-11-01

    Full Text Available Background/Aims: The aim of this study was to investigate the involvement of inducible co-stimulatory ligand (ICOSL expression in stimulation of mast cells (MCs by TNF-α and the ability of TNF-α stimulation of MCs to influence CD4+ T cell differentiation and function. The mechanisms underlying TNF-α stimulation of MCs were also explored. Methods: Mast cells and CD4+ T cells were prepared from C57BL/6 mice (aged 6–8 weeks. ICOSL expression by MCs was measured by real-time PCR and flow cytometry, and levels of IL-4, IL-10 and IFN-γ were measured by ELISA. Results: ICOSL expression by MCs was increased by TNF-α stimulation, and resulted in interaction with CD4+ T cells. The IL-4 and IL-10 levels in the co-culture system increased, while IFN-γ levels decreased. Furthermore, CD4+CD25+Foxp3+ T cell proliferation was induced by co-culture with TNF-α-stimulated MCs. The mechanism by which TNF-α stimulated MCs was dependent on the activation of the MAPK signaling pathway. Conclusion: TNF-α upregulated the expression of ICOSL on mast cells via a mechanism that is dependent on MAPK phosphorylation. TNF-α-treated MCs promoted the differentiation of regulatory T cells and induced a shift in cytokine expression from a Th1 to a Th2 profile by up-regulation ICOSL expression and inhibition of MC degranulation. Our study reveals a novel mechanism by which mast cells regulate T cell function.

  7. Factors That Influence a Mother's Willingness to Preserve Umbilical Cord Blood: A Survey of 5120 Chinese Mothers.

    Directory of Open Access Journals (Sweden)

    Haiyan Lu

    Full Text Available Umbilical Cord blood (UCB, which contains a substantive number of stem cells, could be widely used in transplants to treat a variety of oncologic, genetic, hematologic, and immunodeficiency disorders. However, only a small portion of mothers preserve or donate their UCB in China. The limited availability of UCB has hampered stem cell research and therapy nowadays. To date, no systemic investigations regarding factors that influence a mother's willingness to preserve UCB have been performed in China. In the current study, we are trying to determine those factors which will provide useful information for national health policy development and will raise awareness of the importance of UCB preservation.During 2011 to 2013, 5120 mothers with the average age of 26.1±8.4 years were included in this study. Those mothers participated in a standardized survey. The information gathered consisted of delivery time, occupation, level of education, knowledge of preservation of UCB, willingness to store UCB, and related concerns. The results have been analyzed with SPSS 16.0.The results showed that first-time mothers showed a greater willingness to preserve their UCB (73.3% compared to those having their second (48.9% or third child (40.3%. Mothers who were employed at Government Agencies and Organizations were more willing to preserve their UCB (87.3% than those employed at factories (62.0%, and those who were unemployed (27.3%. Mothers holding master's or college degrees were more willing to preserve their UCB (72.5% and 71.1%, respectively than mothers with high school diplomas (48.7% or those who only went to preliminary school or middle school (40.7%. The two strongest factors that influenced an unwillingness to preserve UCB were the high cost and concerns regarding the safety of the preservation.The results showed that mothers with higher education or those having better occupations are more likely to preserve their UCB in China. These mothers have

  8. Factors That Influence a Mother's Willingness to Preserve Umbilical Cord Blood: A Survey of 5120 Chinese Mothers.

    Science.gov (United States)

    Lu, Haiyan; Chen, Yanwen; Lan, Qiaofen; Liao, Huanjin; Wu, Jing; Xiao, Haiyan; Dickerson, Carol A; Wu, Ping; Pan, Qingjun

    2015-01-01

    Umbilical Cord blood (UCB), which contains a substantive number of stem cells, could be widely used in transplants to treat a variety of oncologic, genetic, hematologic, and immunodeficiency disorders. However, only a small portion of mothers preserve or donate their UCB in China. The limited availability of UCB has hampered stem cell research and therapy nowadays. To date, no systemic investigations regarding factors that influence a mother's willingness to preserve UCB have been performed in China. In the current study, we are trying to determine those factors which will provide useful information for national health policy development and will raise awareness of the importance of UCB preservation. During 2011 to 2013, 5120 mothers with the average age of 26.1±8.4 years were included in this study. Those mothers participated in a standardized survey. The information gathered consisted of delivery time, occupation, level of education, knowledge of preservation of UCB, willingness to store UCB, and related concerns. The results have been analyzed with SPSS 16.0. The results showed that first-time mothers showed a greater willingness to preserve their UCB (73.3%) compared to those having their second (48.9%) or third child (40.3%). Mothers who were employed at Government Agencies and Organizations were more willing to preserve their UCB (87.3%) than those employed at factories (62.0%), and those who were unemployed (27.3%). Mothers holding master's or college degrees were more willing to preserve their UCB (72.5% and 71.1%, respectively) than mothers with high school diplomas (48.7%) or those who only went to preliminary school or middle school (40.7%). The two strongest factors that influenced an unwillingness to preserve UCB were the high cost and concerns regarding the safety of the preservation. The results showed that mothers with higher education or those having better occupations are more likely to preserve their UCB in China. These mothers have related

  9. POSSIBILITIES OF ORGAN-PRESERVING TREATMENT OF PATIENTS WITH MULTIPLE RENAL TUMORS

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2017-01-01

    Full Text Available Renal cell carcinoma (RCC occupies one of the leading places in the world for morbidity among malignant neoplasms of the genitourinary system. The frequency of occurrence of bilateral RCC according to different authors is 2–6% of the total population of patients with RCC. Currently, the only effective method of treatment of bilateral RCC is surgical treatment. Patients with bilateral RCC are at high risk of dev eloping of local recurrence or progression of the disease after organ-preserving surgeries, which is why the surgeon is faced with a choice between a high risk of developing renal failure or relapse and/or progression of the disease, depending on the extent of the surgical intervention. According to the literature, in patients with bilateral RCC there was an increase in the incidence of papillary variant of RCC up to 19% and the presence of multifocal lesion. Surgical treatment of bilateral RCC is the only effective method to achieve satisfactory oncological results at a low incidence of complications. The m ost justified option for the treatment of bilateral RCC is the implementation of bilateral organ-preserving treatment, which allows achieving the optimal functional results. This article presents a clinical case of successful surgical treatment of a patient with bilateral RCC with multiple tumors.

  10. Roles and Functions of the Patani Muslim Religious Committee Council in Propagating and Preserving Islam as a Religion under Thai Constitution

    Directory of Open Access Journals (Sweden)

    Sulaiman Dorloh

    2017-09-01

    Full Text Available This paper examines the roles and the functions that the Islamic committee members play at the Muslim Religious Committee Council in the Patani province in propagating and preserving Islam as a religion under the Thai Constitution. Other councils for example, Narathiwat Muslim Religious Committee Council (NMRCC, Yala Muslim Religious Committee Council (YMRCC and Satul Muslim Religious Committee Council (SMRCC also embarks upon their own roles besides solving the matrimonial disputes among the Muslims in the deep south. This is due to the fact that the sole purpose of the establishment of the Muslim Religious Committee Councils is to propagate the Islamic teachings and monitor the affair of Muslims in those four provinces. Unfortunately, in the recent year, there are some allegations and misunderstandings as to the roles played by the committee. Although there have been attempts to clarify such misconception, no attempt has been made to provide sufficient information and concrete solutions to the above problems. To a large extent those roles and functions are being carried out by the committee since the beginning of the establishment of the councils. Hence, this paper intends to investigate the roles and the functions of the committee in the Patani Muslim Religious Committee Council by exploring the current tasks and responsibilities of the Islamic committee members in the sphere of propagating and preserving the Islamic teachings as well as conducting the dispute resolution mechanism. Finally, the author will provide some possible solutions and suggestions to the current problems faced by PMRCC.

  11. Kupffer cell complement receptor clearance function and host defense.

    Science.gov (United States)

    Loegering, D J

    1986-01-01

    Kupffer cells are well known to be important for normal host defense function. The development of methods to evaluate the in vivo function of specific receptors on Kupffer cells has made it possible to assess the role of these receptors in host defense. The rationale for studying complement receptors is based on the proposed important role of these receptors in host defense and on the observation that the hereditary deficiency of a complement receptor is associated with recurrent severe bacterial infections. The studies reviewed here demonstrate that forms of injury that are associated with depressed host defense including thermal injury, hemorrhagic shock, trauma, and surgery also cause a decrease in complement receptor clearance function. This decrease in Kupffer cell receptor clearance function was shown not to be the result of depressed hepatic blood flow or depletion of complement components. Complement receptor function was also depressed following the phagocytosis of particulates that are known to depress Kupffer cell host defense function. Endotoxemia and bacteremia also were associated with a depression of complement receptor function. Complement receptor function was experimentally depressed in uninjured animals by the phagocytosis of IgG-coated erythrocytes. There was a close association between the depression of complement receptor clearance function and increased susceptibility to the lethal effects of endotoxin and bacterial infection. These studies support the hypotheses that complement receptors on Kupffer cells are important for normal host defense and that depression of the function of these receptors impairs host defense.

  12. Riverscape and Groundwater Preservation: A Choice Experiment

    Science.gov (United States)

    Tempesta, T.; Vecchiato, D.

    2013-12-01

    This study presents a quantitative approach to support policy decision making for the preservation of riverscapes, taking into account the EC Water Framework Directive (2000/60/EC) and the EC Nitrates Directive (91/676/EEC) concerning the protection of waters against nitrate pollution from agricultural sources. A choice experiment was applied to evaluate the benefits, as perceived by inhabitants, of the implementation of policies aiming to reduce the concentration of nitrates in groundwater, preserve the riverscape by maintaining a minimum water flow and increasing hedges and woods along the Serio River in central northern Italy. Findings suggested that people were particularly concerned about groundwater quality, probably because it is strongly linked to human health. Nevertheless, it was interesting to observe that people expressed a high willingness to pay for actions that affect the riverscape as a whole (such as the minimum water flow maintenance plus reforestation). This is probably due to the close connection between the riverscape and the functions of the river area for recreation, health purposes, and biodiversity preservation.

  13. Stem cell mediation of functional recovery after stroke in the rat.

    Directory of Open Access Journals (Sweden)

    Pedro Ramos-Cabrer

    Full Text Available BACKGROUND: Regenerative strategies of stem cell grafting have been demonstrated to be effective in animal models of stroke. In those studies, the effectiveness of stem cells promoting functional recovery was assessed by behavioral testing. These behavioral studies do, however, not provide access to the understanding of the mechanisms underlying the observed functional outcome improvement. METHODOLOGY/PRINCIPAL FINDINGS: In order to address the underlying mechanisms of stem cell mediated functional improvement, this functional improvement after stroke in the rat was investigated for six months after stroke by use of fMRI, somatosensory evoked potentials by electrophysiology, and sensorimotor behavior testing. Stem cells were grafted ipsilateral to the ischemic lesion. Rigorous exclusion of spontaneous recovery as confounding factor permitted to observe graft-related functional improvement beginning after 7 weeks and continuously increasing during the 6-month observation period. The major findings were i functional improvement causally related to the stem cells grafting; ii tissue replacement can be excluded as dominant factor for stem cell mediated functional improvement; iii functional improvement occurs by exclusive restitution of the function in the original representation field, without clear contributions from reorganization processes, and iv stem cells were not detectable any longer after six months. CONCLUSIONS/SIGNIFICANCE: A delayed functional improvement due to stem cell implantation has been documented by electrophysiology, fMRI and behavioral testing. This functional improvement occurred without cells acting as a tissue replacement for the necrotic tissue after the ischemic event. Combination of disappearance of grafted cells after six months on histological sections with persistent functional recovery was interpreted as paracrine effects by the grafted stem cells being the dominant mechanism of cell activity underlying the observed

  14. Human CD8 T cells generated in vitro from hematopoietic stem cells are functionally mature

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    Zúñiga-Pflücker Juan

    2011-03-01

    Full Text Available Abstract Background T cell development occurs within the highly specialized thymus. Cytotoxic CD8 T cells are critical in adaptive immunity by targeting virally infected or tumor cells. In this study, we addressed whether functional CD8 T cells can be generated fully in vitro using human umbilical cord blood (UCB hematopoietic stem cells (HSCs in coculture with OP9-DL1 cells. Results HSC/OP9-DL1 cocultures supported the differentiation of CD8 T cells, which were TCR/CD3hi CD27hi CD1aneg and thus phenotypically resembled mature functional CD8 single positive thymocytes. These in vitro-generated T cells also appeared to be conventional CD8 cells, as they expressed high levels of Eomes and low levels of Plzf, albeit not identical to ex vivo UCB CD8 T cells. Consistent with the phenotypic and molecular characterization, upon TCR-stimulation, in vitro-generated CD8 T cells proliferated, expressed activation markers (MHC-II, CD25, CD38, secreted IFN-γ and expressed Granzyme B, a cytotoxic T-cell effector molecule. Conclusion Taken together, the ability to direct human hematopoietic stem cell or T-progenitor cells towards a mature functional phenotype raises the possibility of establishing cell-based treatments for T-immunodeficiencies by rapidly restoring CD8 effector function, thereby mitigating the risks associated with opportunistic infections.

  15. Fertility preservation in children and young adults undergoing treatment for malignancy

    International Nuclear Information System (INIS)

    Al-Fozan, Haya M.; Tulandi, Togas

    2004-01-01

    Advances in cancer therapy have improved the long term survival of young patients suffering from malignancies. However adverse effects of the treatment are sterlity and loss of gonadal function especially in females. Preservation of fertility in males by sperm freezing is more practical and already established. For young women undergoing cancer treatment , the availability of preserving the gonadal function and fertility has just begun.Today we can crypreserve the oocytes, the embryos or rhe ovarian tissue and those undergoing pelvic irradtion, laparascopic can be cnsidered. Because women with non-gynelical malagnencies seek advice from a general surgeon or a medical onconologist, increasing awawreness of physician and general public is recommended. (author)

  16. Functional heterogeneity and heritability in CHO cell populations.

    Science.gov (United States)

    Davies, Sarah L; Lovelady, Clare S; Grainger, Rhian K; Racher, Andrew J; Young, Robert J; James, David C

    2013-01-01

    In this study, we address the hypothesis that it is possible to exploit genetic/functional variation in parental Chinese hamster ovary (CHO) cell populations to isolate clonal derivatives that exhibit superior, heritable attributes for biomanufacturing--new parental cell lines which are inherently more "fit for purpose." One-hundred and ninety-nine CHOK1SV clones were isolated from a donor CHOK1SV parental population by limiting dilution cloning and microplate image analysis, followed by primary analysis of variation in cell-specific proliferation rate during extended deep-well microplate suspension culture of individual clones to accelerate genetic drift in isolated cultures. A subset of 100 clones were comparatively evaluated for transient production of a recombinant monoclonal antibody (Mab) and green fluorescent protein following transfection of a plasmid vector encoding both genes. The heritability of both cell-specific proliferation rate and Mab production was further assessed using a subset of 23 clones varying in functional capability that were subjected to cell culture regimes involving both cryopreservation and extended sub-culture. These data showed that whilst differences in transient Mab production capability were not heritable per se, clones exhibiting heritable variation in specific proliferation rate, endocytotic transfectability and N-glycan processing were identified. Finally, for clonal populations most "evolved" by extended sub-culture in vitro we investigated the relationship between cellular protein biomass content, specific proliferation rate and cell surface N-glycosylation. Rapid-specific proliferation rate was inversely correlated to CHO cell size and protein content, and positively correlated to cell surface glycan content, although substantial clone-specific variation in ability to accumulate cell biomass was evident. Taken together, our data reveal the dynamic nature of the CHO cell functional genome and the potential to evolve and

  17. Limitation of myocardial infarct size and preservation of left ventricular function by early administration of APSAC in myocardial infarction.

    Science.gov (United States)

    Bassand, J P; Machecourt, J; Cassagnes, J; Lusson, J R; Borel, E; Schiele, F

    1989-07-05

    In cases of acute myocardial infarction (MI), it has been shown that preserving left ventricular function and limiting infarct size with early reperfusion of the occluded artery by means of a thrombolytic agent could eventually result in a reduced mortality rate. The aim of the APSIM study (anisoylated plasminogen streptokinase activator complex [APSAC] dans l'infarctus du Myocarde) was to demonstrate that early administration of APSAC in patients with recent acute MI could limit the infarct size and preserve left ventricular systolic function. In all, 231 patients with a first acute MI were randomly allocated to either APSAC (30 U over 5 minutes) or to conventional heparin therapy (5,000 IU in bolus injection) within 5 hours of the onset of symptoms. Of these patients, 112 received APSAC and 119 received heparin within a mean period of 188 +/- 62 minutes after the onset of symptoms. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC than in the heparin group. This was true for the entire population (0.53 +/- 0.13 vs 0.47 +/- 0.13, p = 0.002) as well as for the subgroups of anterior and inferior wall infarctions (0.47 +/- 0.13 vs 0.4 +/- 0.16, p = 0.004 and 0.56 +/- 0.11 vs 0.51 +/- 0.09, p = 0.02). At 3 weeks, the difference remained significant for patients with anterior MI.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Concise Review: Quiescence in Adult Stem Cells

    DEFF Research Database (Denmark)

    Rumman, M; Dhawan, J; Kassem, Moustapha

    2015-01-01

    Adult stem cells (ASCs) are tissue resident stem cells responsible for tissue homeostasis and regeneration following injury. In uninjured tissues, ASCs exist in a nonproliferating, reversibly cell cycle-arrested state known as quiescence or G0. A key function of the quiescent state is to preserve...... stemness in ASCs by preventing precocious differentiation, and thus maintaining a pool of undifferentiated ASCs. Recent evidences suggest that quiescence is an actively maintained state and that excessive or defective quiescence may lead to compromised tissue regeneration or tumorigenesis. The aim...

  19. Potential of bursa-immigrated hematopoietic precursor cells to differentiate to functional B and T cells

    International Nuclear Information System (INIS)

    Weber, W.T.; Alexander, J.E.

    1978-01-01

    The potential of hematopoietic precursor cells, recently immigrated into the 13- and 14-day-old embryonic bursa, to migrate to the thymus and to differentiate to functional T cells was investigated. Chromosomally marked cell populations obtained from 13- and 14-day-old embryonic bursas were transferred i.v. to 780 R γ-irradiated chick embryos of equivalent age. When appropriate chimeras were examined at 4 to 12 weeks after cell transfer, donor cells were found to proliferate primarily in the bursa. Significant donor cell influx into the thymus was not detected. In correlation with these findings, Con A- and PHA-responsive T cells in thymus and spleen cell cultures of recipients remained of host origin whereas the number of anti-CIg responsive B cells of donor type increased gradually in the spleens of recipients. An initial lag period preceded the accumulation of functional donor B cells in the spleens of recipients, despite the predominant presence of dividing donor cells in the bursa. This suggests that the transferred bursal cell population required substantially longer to mature and emigrate from the bursa as functional B cells than the host cell population remaining in the irradiated bursas at time of cell transfer. The failure to detect significant influx of donor cells into the thymus and their failure to differentiate to functional T cells suggest that the recently bursa-immigrated hematopoietic stem cells of 13- and 14-day-old embryos may not be pluripotential cells, but rather cells already committed to the B cell line of differentiation

  20. Determinants of midterm functional outcomes, wound healing, and resources used in a hospital-based limb preservation program.

    Science.gov (United States)

    Ramanan, Bala; Ahmed, Ayman; Wu, Bian; Causey, Marlin W; Gasper, Warren J; Vartanian, Shant M; Reyzelman, Alexander M; Hiramoto, Jade S; Conte, Michael S

    2017-12-01

    The objective of this study was to assess midterm functional status, wound healing, and in-hospital resource use among a prospective cohort of patients treated in a tertiary hospital, multidisciplinary Center for Limb Preservation. Data were prospectively gathered on all consecutive admissions to the Center for Limb Preservation from July 2013 to October 2014 with follow-up data collection through January 2016. Limbs were staged using the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) threatened limb classification scheme at the time of hospital admission. Patients with nonatherosclerotic vascular disorders, acute limb ischemia, and trauma were excluded. The cohort included 128 patients with 157 threatened limbs; 8 limbs with unstageable disease were excluded. Mean age (±standard deviation [SD]) was 66 (±13) years, and median follow-up duration (interquartile range) was 395 (80-635) days. Fifty percent (n = 64/128) of patients were readmitted at least once, with a readmission rate of 20% within 30 days of the index admission. Mean total number of admissions per patient (±SD) was 1.9 ± 1.2, with mean (±SD) cumulative length of stay (cLOS) of 17.1 (±17.9) days. During follow-up, 25% of limbs required a vascular reintervention, and 45% developed recurrent wounds. There was no difference in the rate of readmission, vascular reintervention, or wound recurrence by initial WIfI stage (P > .05). At the end of the study period, 23 (26%) were alive and nonambulatory; in 20%, functional status was missing. On both univariate and multivariate analysis, end-stage renal disease and prior functional status predicted ability to ambulate independently (P wound healing. Direct hospital (inpatient) cost per limb saved was significantly higher in stage 4 patients (P wound healing, or wound recurrence. Patients presenting with limb-threatening conditions require significant inpatient care, have a high frequency of repeated hospitalizations, and are at

  1. GAIN RATIO BASED FEATURE SELECTION METHOD FOR PRIVACY PRESERVATION

    Directory of Open Access Journals (Sweden)

    R. Praveena Priyadarsini

    2011-04-01

    Full Text Available Privacy-preservation is a step in data mining that tries to safeguard sensitive information from unsanctioned disclosure and hence protecting individual data records and their privacy. There are various privacy preservation techniques like k-anonymity, l-diversity and t-closeness and data perturbation. In this paper k-anonymity privacy protection technique is applied to high dimensional datasets like adult and census. since, both the data sets are high dimensional, feature subset selection method like Gain Ratio is applied and the attributes of the datasets are ranked and low ranking attributes are filtered to form new reduced data subsets. K-anonymization privacy preservation technique is then applied on reduced datasets. The accuracy of the privacy preserved reduced datasets and the original datasets are compared for their accuracy on the two functionalities of data mining namely classification and clustering using naïve Bayesian and k-means algorithm respectively. Experimental results show that classification and clustering accuracy are comparatively the same for reduced k-anonym zed datasets and the original data sets.

  2. A review of preserved and preservative-free prostaglandin analogues for the treatment of open-angle glaucoma and ocular hypertension.

    Science.gov (United States)

    Hommer, A

    2010-06-01

    Glaucoma affects an increasing number of people worldwide and is the second leading cause of blindness. The aim of antiglaucoma therapy is to maintain a patient's visual function and quality of life. Prostaglandin analogues are first-line topical antiglaucoma therapy. They are effective at lowering intraocular pressure (IOP) and are generally well tolerated, with fewer systemic adverse events compared with the other classes. However, the use of prostaglandin analogues can be associated with ocular adverse effects, such as stinging/burning sensation, dry eyes, iris and periocular hyperpigmentation, and eye lash growth, which can affect patient compliance. Preservatives used in antiglaucoma preparations can have dose-dependent toxic effects, which contribute to adverse effects. The development of preservative-free preparations may reduce such adverse effects and therefore improve patient compliance. Tafluprost is a prostaglandin analogue in a preservative-free formulation that was recently approved for the reduction of elevated IOP in open-angle glaucoma and ocular hypertension. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  3. Functionality of liquid smoke as an all-natural antimicrobial in food preservation.

    Science.gov (United States)

    Lingbeck, Jody M; Cordero, Paola; O'Bryan, Corliss A; Johnson, Michael G; Ricke, Steven C; Crandall, Philip G

    2014-06-01

    The smoking of foods, especially meats, has been used as a preservation technique for centuries. Today, smoking methods often involve the use of wood smoke condensates, commonly known as liquid smoke. Liquid smoke is produced by condensing wood smoke created by the pyrolysis of sawdust or wood chips followed by removal of the carcinogenic polyaromatic hydrocarbons. The main products of wood pyrolysis are phenols, carbonyls and organic acids which are responsible for the flavor, color and antimicrobial properties of liquid smoke. Several common food-borne pathogens such as Listeria monocytogenes, Salmonella, pathogenic Escherichia coli and Staphylococcus have shown sensitivity to liquid smoke in vitro and in food systems. Therefore liquid smoke has potential for use as an all-natural antimicrobial in commercial applications where smoke flavor is desired. This review will cover the application and effectiveness of liquid smoke and fractions of liquid smoke as an all-natural food preservative. This review will be valuable for the industrial and research communities in the food science and technology areas. Copyright © 2014. Published by Elsevier Ltd.

  4. Functional duality of the cell wall.

    Science.gov (United States)

    Latgé, Jean-Paul; Beauvais, Anne

    2014-08-01

    The polysaccharide cell wall is the extracellular armour of the fungal cell. Although essential in the protection of the fungal cell against aggressive external stresses, the biosynthesis of the polysaccharide core is poorly understood. For a long time it was considered that this cell wall skeleton was a fixed structure whose role was only to be sensed as non-self by the host and consequently trigger the defence response. It is now known that the cell wall polysaccharide composition and localization continuously change to adapt to their environment and that these modifications help the fungus to escape from the immune system. Moreover, cell wall polysaccharides could function as true virulence factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Identification of a soluble guanylate cyclase in RBCs: preserved activity in patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Miriam M. Cortese-Krott

    2018-04-01

    Full Text Available Endothelial dysfunction is associated with decreased NO bioavailability and impaired activation of the NO receptor soluble guanylate cyclase (sGC in the vasculature and in platelets. Red blood cells (RBCs are known to produce NO under hypoxic and normoxic conditions; however evidence of expression and/or activity of sGC and downstream signaling pathway including phopshodiesterase (PDE-5 and protein kinase G (PKG in RBCs is still controversial. In the present study, we aimed to investigate whether RBCs carry a functional sGC signaling pathway and to address whether this pathway is compromised in coronary artery disease (CAD. Using two independent chromatographic procedures, we here demonstrate that human and murine RBCs carry a catalytically active α1β1-sGC (isoform 1, which converts 32P-GTP into 32P-cGMP, as well as PDE5 and PKG. Specific sGC stimulation by NO+BAY 41-2272 increases intracellular cGMP-levels up to 1000-fold with concomitant activation of the canonical PKG/VASP-signaling pathway. This response to NO is blunted in α1-sGC knockout (KO RBCs, but fully preserved in α2-sGC KO. In patients with stable CAD and endothelial dysfunction red cell eNOS expression is decreased as compared to aged-matched controls; by contrast, red cell sGC expression/activity and responsiveness to NO are fully preserved, although sGC oxidation is increased in both groups. Collectively, our data demonstrate that an intact sGC/PDE5/PKG-dependent signaling pathway exists in RBCs, which remains fully responsive to NO and sGC stimulators/activators in patients with endothelial dysfunction. Targeting this pathway may be helpful in diseases with NO deficiency in the microcirculation like sickle cell anemia, pulmonary hypertension, and heart failure. Keywords: cGMP, Nitric oxide, Protein kinase G, Signaling, Non -canonical functions of RBCs

  6. Stem Cells from Cryopreserved Human Dental Pulp Tissues Sequentially Differentiate into Definitive Endoderm and Hepatocyte-Like Cells in vitro.

    Science.gov (United States)

    Han, Young-Jin; Kang, Young-Hoon; Shivakumar, Sarath Belame; Bharti, Dinesh; Son, Young-Bum; Choi, Yong-Ho; Park, Won-Uk; Byun, June-Ho; Rho, Gyu-Jin; Park, Bong-Wook

    2017-01-01

    We previously described a novel tissue cryopreservation protocol to enable the safe preservation of various autologous stem cell sources. The present study characterized the stem cells derived from long-term cryopreserved dental pulp tissues (hDPSCs-cryo) and analyzed their differentiation into definitive endoderm (DE) and hepatocyte-like cells (HLCs) in vitro . Human dental pulp tissues from extracted wisdom teeth were cryopreserved as per a slow freezing tissue cryopreservation protocol for at least a year. Characteristics of hDPSCs-cryo were compared to those of stem cells from fresh dental pulps (hDPSCs-fresh). hDPSCs-cryo were differentiated into DE cells in vitro with Activin A as per the Wnt3a protocol for 6 days. These cells were further differentiated into HLCs in the presence of growth factors until day 30. hDPSCs-fresh and hDPSCs-cryo displayed similar cell growth morphology, cell proliferation rates, and mesenchymal stem cell character. During differentiation into DE and HLCs in vitro , the cells flattened and became polygonal in shape, and finally adopted a hepatocyte-like shape. The differentiated DE cells at day 6 and HLCs at day 30 displayed significantly increased DE- and hepatocyte-specific markers at the mRNA and protein level, respectively. In addition, the differentiated HLCs showed detoxification and glycogen storage capacities, indicating they could share multiple functions with real hepatocytes. These data conclusively show that hPDSCs-cryo derived from long-term cryopreserved dental pulp tissues can be successfully differentiated into DE and functional hepatocytes in vitro . Thus, preservation of dental tissues could provide a valuable source of autologous stem cells for tissue engineering.

  7. Comparative histochemical study of Bowen’s disease and actinic keratosis: preserved normal basal cells in Bowen’s disease

    Directory of Open Access Journals (Sweden)

    H Ishida

    2009-12-01

    indicate that the basal cells in Bowen’s disease are normal. In support of this conclusion, the same cells showed normal morphology on electron microscopy with preserved basement membrane, although the latter was often damaged in actinic keratosis.

  8. Pre-ischemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischemia-reperfusion

    DEFF Research Database (Denmark)

    Jespersen, Nichlas Riise; Yokota, Takashi; Støttrup, Nicolaj Brejnholt

    2017-01-01

    KEY POINTS: Pre-ischaemic administration of aminooxiacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against ischaemia-reperfusion injury. The underlying mechanism remains unknown. We examined whether transient inhibition of the MAS during ischaemia......, but not IPC, reduced the myocardial interstitial concentration of tricarboxylic acid cycle intermediates at the onset of reperfusion. The results obtained in the present study demonstrate that metabolic regulation by inhibition of the MAS at the onset of reperfusion may be beneficial for the preservation...... of mitochondrial function during late reperfusion in an IR-injured heart. ABSTRACT: Mitochondrial dysfunction plays a central role in ischaemia-reperfusion (IR) injury. Pre-ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against IR...

  9. Direct Reprogramming of Human Bone Marrow Stromal Cells into Functional Renal Cells Using Cell-free Extracts

    Directory of Open Access Journals (Sweden)

    Evangelia Papadimou

    2015-04-01

    Full Text Available The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs, also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes—formation of “domes” and tubule-like structures—and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy.

  10. The Effect of Disinfection on Viability and Function of Baboon Red Blood Cells and Platelets

    Science.gov (United States)

    1997-07-11

    blood cells was evaluated by their ability to transport oxygen as assessed by measurement of 2,3 diphosphoglycerate (DPG)14 and red blood cell p50,15...Blood collected from the bleeding time site (referred to as "shed blood") had a significantly reduced thromboxane A2 level . The ability of the...preserved or treated platelets to increase the shed blood thromboxane A2 level and reduce the 8; extended bleeding time is the measure of their

  11. Development of Domestic Cat Embryo Produced by Preserved Sperms

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    KARTINI ERIANI

    2008-12-01

    Full Text Available The ability to mature and fertilize oocytes of endangered species may allow us to sustain genetic and global biodiversity. Epididymis sperms may be the last chance to ensure preservation of genetic materials after injury or death of a valuable animal. Studies have been conducted to determine wether both epididymis sperms and oocytes can be used to produce viable embryos and offspring. The purpose of this study was to determine how long cats sperms contained in epididymis were remain motile and had intact membranes when preserved at 4 ° C, and to determine whether such those preserved sperms are able to fertilize oocytes. Epididymis was preserved immediately in phosphate buffer saline at 4 ° C for 1, 3, and 6 days. The observation of sperm quality and viability after preservation was performed by vital staining acrosom and Hoechst-Propidium Iodine. Biological functions of sperms were evaluated by in vitro culture technique for fertilization, micro fertilization and embryonic development rate in CR1aa medium. The results showed that average motility of sperms collected from ductus deferens, cauda and corpus epididymis decreased not significantly (P > 0.05 from 0, 1, 3, and 6 days of preservation times (from 83.0%, 80.2%, 79.0%; 80.9%, 75.0%, 75.5%; 52.0%, 63.2%, 55.0% to 34.6%, 34.6%, 33.3%, respectively. The general results showed that sperms from epididymis preserved for 1, 3, and 6 days can be used for IVF. The rate of embryonal cleavage produced by IVF technique using sperms collected from epididymis preserved for 1-, 3- and 6-days were 33.3, 26.7, and 20.0%, respectively and significantly different (p < 0.05 from that of controll (50.0%. In conclusion, sperms contained in epididyimis preserved at 4 ° C in PBS (Phospate Buffer Saline for 1-6 days can be used to IVF and in vitro production of cat embryos.

  12. Technical aspects of preservation of architectural heritage of Modern in Serbia

    OpenAIRE

    Kuzović Duško

    2016-01-01

    This paper analyzes the technical and technological problems of preserving architecture from the period 1945-1990. Complex social and economic conditions hinder the proper approach to the preservation of Modernist architecture. Modern functions that are inserted into objects of Modern require complex changes to the building. If changes are not made in accordance with the principles of profession risk to completely lose the architectural value of the buildings. It is necessary to specify the t...

  13. Potential roles of self-reactive T cells in autoimmunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2014-01-01

    The immune system is a complex arrangement of cells and molecules that preserve the integrity of the organism by eliminating all elements judged to be dangerous. Several regulatory mechanisms function to terminate immune responses to antigens, return the immune system to a basal state after the a...

  14. Chronopolis Digital Preservation Network

    Directory of Open Access Journals (Sweden)

    David Minor

    2010-07-01

    Full Text Available The Chronopolis Digital Preservation Initiative, one of the Library of Congress’ latest efforts to collect and preserve at-risk digital information, has completed its first year of service as a multi-member partnership to meet the archival needs of a wide range of domains.Chronopolis is a digital preservation data grid framework developed by the San Diego Supercomputer Center (SDSC at UC San Diego, the UC San Diego Libraries (UCSDL, and their partners at the National Center for Atmospheric Research (NCAR in Colorado and the University of Maryland's Institute for Advanced Computer Studies (UMIACS.Chronopolis addresses a critical problem by providing a comprehensive model for the cyberinfrastructure of collection management, in which preserved intellectual capital is easily accessible, and research results, education material, and new knowledge can be incorporated smoothly over the long term. Integrating digital library, data grid,