scholarly journals The Regulation of Haemocyanin Oxygen Affinity during Emersion of the Crayfish Austropotamobius Pallipes: II. An Investigation of in Vivo changes in Oxygen Affinity

1986 ◽  
Vol 121 (1) ◽  
pp. 327-337 ◽  
Author(s):  
S. MORRIS ◽  
R. TYLER-JONES ◽  
C. R. BRIDGES ◽  
E. W. TAYLOR
Keyword(s):  
Oxygen Affinity ◽  
Physiological Significance ◽  
Aerial Exposure ◽  
Austropotamobius Pallipes ◽  
Short And Long Term ◽  
Vitro Data ◽  
In Vitro Data

The oxygen-transporting properties of the haemolymph from the crayfish Austropotamobius pallipes were investigated. The haemolymph concentrations of K+, Mg2+ and Ca2+ ions, together with the concentration of L-lactate were measured in crayfish before, during and after 24 h emersion. The concentrations of K+ and Mg2+ increased during aerial exposure and returned to pre-emersion levels during immersed recovery. Large increases in the level of circulating L-lactate and Ca2+ were correlated with short- and long-term aerial exposure respectively. Changes in the concentrations of these ions could also be correlated with changes in haemocyanin oxygen affinity. Reimmersion and recovery returned all parameters to near control values. The effect, on haemocyanin oxygen affinity, of the Bohr shift alone was calculated and compared with the change in oxygen affinity (ΔP50) actually determined during aerial exposure. These data were also compared with predictions, calculated from in vitro data, for the potentiation of haemocyanin oxygen affinity by Ca2+ and L-lactate ions in aerially exposed crayfish. The physiological significance of the regulation of haemocyanin oxygen affinity by these ions is discussed.

Cbfa-1 (Runx-2) and Osteocalcin Expression by Human Osteoblasts in Heparin Osteoporosis in Vitro

2006 ◽  
Vol 12 (4) ◽  
pp. 465-472 ◽  
Author(s):  
Alexander E. Handschin ◽  
Marcus Egermann ◽  
Otmar Trentz ◽  
Guido A. Wanner ◽  
Hans-Jürgen Kock ◽  
...  
Keyword(s):  
Bone Formation ◽  
Significant Inhibition ◽  
Osteoblast Function ◽  
Culture Model ◽  
High Doses ◽  
Vitro Data ◽  
In Vitro Data

Heparin may cause adverse effects on bone formation following long-term application. The exact pathomechanism is unclear, but in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 ( Runx-2) and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo. We used a human osteoblast cell culture model to further investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on the expression of these two regulators of osteoblast differentiation. At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro. Our data support the hypothesis of a direct inhibition of osteoblast function underlying heparin osteoporosis.

scholarly journals Durability of Anti-Infective Effect of Long-Term Silicone Sheath Catheters Impregnated with Antimicrobial Agents

2001 ◽  
Vol 45 (7) ◽  
pp. 1990-1993 ◽  
Author(s):  
Robert K. Tcholakian ◽  
Issam I. Raad
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Cost Effective ◽  
Cost Effective Alternative ◽  
Vitro Data ◽  
Gradual Release ◽  
In Vitro Data

ABSTRACT This study was performed to test the long-term antimicrobial efficacy of impregnated silicone catheters comprising an antimicrobial layer sandwiched between an external surface sheath and a luminal surface silicone sheath. The design of the catheter permits the introduction of various antimicrobials in addition to anticoagulants or antifibrins in the antimicrobial layer and allows their gradual release over a period of months after insertion. The in vitro data presented show that the catheter can provide antimicrobial activity for 90 days, after being replated for 15 7-day cycles of replating. When the catheters were immersed in human serum and incubated at 37°C, they demonstrated significant antimicrobial activity after more than 325 days of incubation. The significant long-term in vitro antimicrobial activity observed may imply effective in vivo activity for almost 1 year after insertion and could serve as a cost-effective alternative to surgically implantable silicone catheters.

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

scholarly journals MATURATION OF HEMOLYSIN-PRODUCING CELL CLONES

1970 ◽  
Vol 131 (6) ◽  
pp. 1261-1270 ◽  
Author(s):  
George C. Saunders ◽  
Douglas Swartzendruber
Keyword(s):  
Bone Marrow ◽  
Doubling Time ◽  
Sheep Erythrocyte ◽  
Mature Animal ◽  
Cell Clones ◽  
Initial Appearance ◽  
Vitro Data ◽  
In Vitro Data

Cells capable of reacting with sheep erythrocyte (SRBC) antigen to maturate and produce hemolysin appear simultaneously in the bone marrow and spleen of 1-day old Swiss-Webster mice. However, hemolysin-producing cell clones (HPCC) do not result. Complete functional precursor units generally appear in the spleens of mice older than 3 days. In vivo and in vitro data correlate well in this regard. Complete precursor units are not seen in the bone marrow and only very rarely in the thymus. The efficiency of precursor units of neonatal mice when they become functional approximates that of the mature animal when based on the doubling time of plaque-forming cells (PFC). Possible explanations of the initial appearance of incomplete precursor units have been discussed.

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

1980 ◽  
Vol 136 (3) ◽  
pp. 235-238 ◽  
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.

Identification of human cytochrome P 450 s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data

2003 ◽  
Vol 59 (5-6) ◽  
pp. 429-442 ◽  
Author(s):  
Xue-Qing Li ◽  
Anders Bj�rkman ◽  
Tommy B. Andersson ◽  
Lars L. Gustafsson ◽  
Collen M. Masimirembwa
Keyword(s):  
Hepatic Clearance ◽  
Human Cytochrome ◽  
Cytochrome P 450 ◽  
Vitro Data ◽  
In Vitro Data

scholarly journals 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 ◽  
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

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

2019 ◽  
Vol 174 (1) ◽  
pp. 38-50 ◽  
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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