Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats

This chapter examines the importance of surface characteristics such as microstructure, composition, crystallographic texture, and surface free energy in achieving desired biocompatibility and tribological properties thereby improving in vivo life of artificial articulating implants. Current implants often fail prematurely due to inadequate mechanical, tribological, biocompatibility, and osseointegration properties, apart from issues related to design and surgical procedures. For long-term in vivo stability, artificial implants intended for articulating joint replacement must exhibit long-term stable articulation surface without stimulating undesirable in vivo effects. Since the implant's surface plays a vital and decisive role in their response to biological environment, and vice versa, surface modification of implants assumes a significant importance. Therefore, overview on important surface modification techniques, their capabilities, properties of modified surfaces/implants are presented in the chapter. The clinical performance of surface modified implants and new surfaces for potential next-generation articulating implant applications are discussed at the end.

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Glucose regulates lipid metabolism in fasting king penguins

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00094.2003 ◽

2003 ◽

Vol 285 (2) ◽

pp. R313-R320 ◽

Cited By ~ 9

Author(s):

Servane F. Bernard ◽

Jord Orvoine ◽

René Groscolas

Keyword(s):

Lipid Metabolism ◽

Plasma Concentration ◽

Energy Production ◽

Important Determinant ◽

Plasma Concentrations ◽

Glucose Infusion ◽

Nonesterified Fatty Acids ◽

Fat Stores

This study aims to determine whether glucose intervenes in the regulation of lipid metabolism in long-term fasting birds, using the king penguin as an animal model. Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo before, during, and after a 2-h glucose infusion under field conditions. All the birds were in the phase II fasting status (large fat stores, protein sparing) but differed by their metabolic and hormonal statuses, being either nonstressed (NSB; n = 5) or stressed (SB; n = 5). In both groups, glucose infusion at 5 mg·kg-1·min-1 induced a twofold increase in glycemia. In NSB, glucose had no effect on lipolysis (maintenance of plasma concentrations and rates of appearance of glycerol and nonesterified fatty acids) and no effect on the plasma concentrations of triacylglycerols (TAG), glucagon, insulin, or corticosterone. However, it limited fatty acid (FA) oxidation, as indicated by a 25% decrease in the plasma level of β-hydroxybutyrate (β-OHB). In SB, glucose infusion induced an ∼2.5-fold decrease in lipolytic fluxes and a large decrease in FA oxidation, as reflected by a 64% decrease in the plasma concentration of β-OHB. There were also a 35% decrease in plasma TAG, a 6.5- and 2.8-fold decrease in plasma glucagon and corticosterone, respectively, and a threefold increase in insulinemia. These data show that in fasting king penguins, glucose regulates lipid metabolism (inhibition of lipolysis and/or of FA oxidation) and affects hormonal status differently in stressed vs. nonstressed individuals. The results also suggest that in birds, as in humans, the availability of glucose, not of FA, is an important determinant of the substrate mix (glucose vs. FA) that is oxidized for energy production.

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Lithium Restores Abnormal Platelet 5-HT Transport in Patients with Affective Disorders

The British Journal of Psychiatry ◽

10.1192/bjp.136.3.235 ◽

1980 ◽

Vol 136 (3) ◽

pp. 235-238 ◽

Cited By ~ 58

Author(s):

Alec Coppen ◽

Cynthia Swade ◽

Keith Wood

Keyword(s):

Blood Platelets ◽

Lithium Treatment ◽

Before And After ◽

Short And Long Term ◽

5 Ht Uptake ◽

Depressive Patients ◽

Rate Of Accumulation

SummaryKinetic analysis of the transport of 5-HT into the blood platelets of depressed patients and recovered depressive patients has shown that the rate of accumulation of 5-hydroxytryptamine (5-HT) is significantly decreased both before and after recovery from the illness. This abnormality is corrected by both short and long-term lithium treatment. As a corollary to these studies, the effect of lithium in vitro on 5-HT uptake has been studied and the results are opposite to those reported in vivo. These findings suggest that lithium acts indirectly, and possible mechanisms of its action are discussed.

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Short- and Long-Term Multilineage Repopulating Hematopoietic Stem Cells in Late Fetal and Newborn Mice: Models for Human Umbilical Cord Blood

Blood ◽

10.1182/blood.v90.1.174 ◽

1997 ◽

Vol 90 (1) ◽

pp. 174-181 ◽

Cited By ~ 50

Author(s):

David E. Harrison ◽

Clinton M. Astle

Keyword(s):

Stem Cells ◽

Cord Blood ◽

Umbilical Cord Blood ◽

Functional Abilities ◽

Newborn Mice ◽

Hematopoietic Stem ◽

Short And Long Term ◽

Marrow Cells

Abstract Blood from late fetal and newborn mice is similar to umbilical cord blood obtained at birth in human beings, an important source of stem cells for clinical transplantation. The mouse model is useful because long-term functions can be readily assayed in vivo. To evaluate the functions of hematopoietic precursors in the blood and other tissues of late fetal and newborn mice, short- and long-term multilineage repopulating abilities were measured in vivo by competitive repopulation. Manipulations that might affect cell function, such as enrichment, tissue culture, or retroviral marking, were avoided. Hematopoietic stem cell functions of late fetal or newborn blood, liver, and spleen, were assayed as myeloid and lymphoid repopulating abilities relative to standard adult marrow cells. Donor cells from these tissues as well as adult control donor marrow cells were all of the same genotype. Cells from each donor tissue were mixed with portions from a pool of standard adult “competitor” marrow distinguished from the donors by genetic differences in hemoglobin and glucosephosphate isomerase. After 21 to 413 days, percentages of donor type myeloid and lymphoid cells in recipient blood were measured to assay the functional abilities of donor precursors relative to the standard. These relative measures are expressed as repopulating units, where each unit is equivalent to the repopulating ability found in 100,000 standard adult marrow cells. Thus, measures of repopulating units do not compare single cells but overall repopulating abilities of donor cell populations. Relative functional abilities in 1 million nucleated cells from late fetal or newborn blood were several times less than those found in adult marrow, but far more than in normal adult blood, and appeared to include long-term functional primitive hematopoietic stem cells (PHSC) similar to those in marrow. To estimate functional abilities of individual PHSC, variances among large groups of identical recipients were analyzed using both the binomial model and competitive dilution, a new model based on the Poisson distribution. The data best fit the hypothesis that individual PHSC from adult marrow, late fetal blood, or newborn blood each produce similar fractions of the total lymphoid and erythroid cells found in the recipient for many months.

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Ex Vivo Expansion of Genetically Marked Rhesus Peripheral Blood Progenitor Cells Results in Diminished Long-Term Repopulating Ability

Blood ◽

10.1182/blood.v92.4.1131 ◽

1998 ◽

Vol 92 (4) ◽

pp. 1131-1141 ◽

Cited By ~ 208

Author(s):

J.F. Tisdale ◽

Y. Hanazono ◽

S.E. Sellers ◽

B.A. Agricola ◽

M.E. Metzger ◽

...

Keyword(s):

Peripheral Blood ◽

Ex Vivo ◽

Retroviral Vectors ◽

Ex Vivo Expansion ◽

Us Government ◽

Government Work ◽

Stromal Support ◽

Short And Long Term

Abstract The possibility of primitive hematopoietic cell ex vivo expansion is of interest for both gene therapy and transplantation applications. The engraftment of autologous rhesus peripheral blood (PB) progenitors expanded 10 to 14 days were tracked in vivo using genetic marking. Stem cell factor (SCF)/granulocyte colony-stimulating factor (G-CSF)–mobilized and CD34-enriched PB cells were divided into two equal aliquots and transduced with one of two retroviral vectors carrying the neomycin-resistance gene (neo) for 4 days in the presence of interleukin-3 (IL-3), IL-6, and SCF in the first 5 animals, IL-3/IL-6/SCF/Flt-3 ligand (FLT) in 2 subsequent animals, or IL-3/IL-6/SCF/FLT plus an autologous stromal monolayer (STR) in the final 2. At the end of transduction period, one aliquot (nonexpanded) from each animal was frozen, whereas the other was expanded under the same conditions but without vector for a total of 14 days before freezing. After total body irradiation, both the nonexpanded and expanded transduced cells were reinfused. Despite 5- to 13-fold higher cell and colony-forming unit (CFU) doses from the expanded fraction of marked cells, there was greater short- and long-term marking from the nonexpanded cells in all animals. In animals receiving cells transduced and expanded in the presence of IL-3/IL-6/SCF/FLT, engraftment by the marked expanded cells was further diminished. This discrepancy was even more pronounced in the animals who received cells transduced and expanded in the presence of FLT and autologous stroma, with no marking detectable from the expanded cells. Despite lack of evidence for expansion of engrafting cells, we found that the addition of FLT and especially STR during the initial brief transduction period increased engraftment with marked cells into a clinically relevant range. Levels of marked progeny cells originating from the nonexpanded aliqouts were significantly higher than that seen in previous 4 animals receiving cells transduced in the presence of IL-3/IL-6/SCF, with levels of 10% to 20% confirmed by Southern blotting from the nonexpanded IL-3/IL-6/SCF/FLT/STR graft compared with 0.01% in the original IL-3/IL-6/SCF cohort. These results suggest that, although expansion of PB progenitors is feasible ex vivo, their contribution towards both short- and long-term engraftment is markedly impaired. However, a brief transduction in the presence of specific cytokines and stromal support allows engraftment with an encouraging number of retrovirally modified cells. This is a US government work. There are no restrictions on its use.

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Mesoporous Silicon: Short and Long Term, In Vitro and In Vivo Correlations of Cellular and Tissue Responses to Mesoporous Silicon Nanovectors (Small 9-10/2013)

Small ◽

10.1002/smll.201370058 ◽

2013 ◽

Vol 9 (9-10) ◽

pp. 1721-1721

Author(s):

Jonathan O. Martinez ◽

Christian Boada ◽

Iman K. Yazdi ◽

Michael Evangelopoulos ◽

Brandon S. Brown ◽

...

Keyword(s):

Mesoporous Silicon ◽

Tissue Responses ◽

Short And Long Term

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Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves: An in vivo study in swine

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2008.01.045 ◽

2008 ◽

Vol 136 (4) ◽

pp. 908-914 ◽

Cited By ~ 14

Author(s):

Stephen H. McKellar ◽

Jess L. Thompson ◽

Raul F. Garcia-Rinaldi ◽

Ryan J. MacDonald ◽

Thoralf M. Sundt ◽

...

Keyword(s):

Heart Valves ◽

Mechanical Heart Valves ◽

In Vivo Study ◽

Term Efficacy ◽

Short And Long Term

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Short- and long-term neurobehavioral toxicity of fluorene after a nose-only exposure during the lactating period (14 days) in F1 Wistar rats

Neurotoxicology and Teratology ◽

10.1016/j.ntt.2015.04.148 ◽

2015 ◽

Vol 49 ◽

pp. 146-147

Author(s):

Julie Peiffer ◽

Marie-Josèphe Decret ◽

Hervé Nunge ◽

Guido Rychen ◽

Frédéric Cosnier ◽

...

Keyword(s):

Wistar Rats ◽

Short And Long Term

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Exploring Mechanistic Toxicity of Mixtures Using PBPK Modeling and Computational Systems Biology

Toxicological Sciences ◽

10.1093/toxsci/kfz243 ◽

2019 ◽

Vol 174 (1) ◽

pp. 38-50 ◽

Cited By ~ 1

Author(s):

Patricia Ruiz ◽

Claude Emond ◽

Eva D McLanahan ◽

Shivanjali Joshi-Barr ◽

Moiz Mumtaz

Keyword(s):

Risk Assessment ◽

Current Knowledge ◽

Pbpk Modeling ◽

Toxic Substances ◽

Computational Systems Biology ◽

Stream Data ◽

Short And Long Term

Abstract Mixtures risk assessment needs an efficient integration of in vivo, in vitro, and in silico data with epidemiology and human studies data. This involves several approaches, some in current use and others under development. This work extends the Agency for Toxic Substances and Disease Registry physiologically based pharmacokinetic (PBPK) toolkit, available for risk assessors, to include a mixture PBPK model of benzene, toluene, ethylbenzene, and xylenes. The recoded model was evaluated and applied to exposure scenarios to evaluate the validity of dose additivity for mixtures. In the second part of this work, we studied toluene, ethylbenzene, and xylene (TEX)-gene-disease associations using Comparative Toxicogenomics Database, pathway analysis and published microarray data from human gene expression changes in blood samples after short- and long-term exposures. Collectively, this information was used to establish hypotheses on potential linkages between TEX exposures and human health. The results show that 236 genes expressed were common between the short- and long-term exposures. These genes could be central for the interconnecting biological pathways potentially stimulated by TEX exposure, likely related to respiratory and neuro diseases. Using publicly available data we propose a conceptual framework to study pathway perturbations leading to toxicity of chemical mixtures. This proposed methodology lends mechanistic insights of the toxicity of mixtures and when experimentally validated will allow data gaps filling for mixtures’ toxicity assessment. This work proposes an approach using current knowledge, available multiple stream data and applying computational methods to advance mixtures risk assessment.

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