Combining in vitro data and modelling to predict in vivo animal response

2006 ◽  
Vol 34 ◽  
pp. 135-144
Author(s):  
Jan Dijkstra ◽  
James France
Keyword(s):  
Quantitative Description ◽  
Gas Production ◽  
Biological Data ◽  
Mathematical Methods ◽  
Passage Rate ◽  
Fractional Rate ◽  
Microbial Efficiency ◽  
Definition Of

SummaryExisting feed evaluation systems for ruminants assess the feed value in a rather empirical way, with a limited ability to integrate metabolism in a meaningful framework. For the quantitative description of the mechanisms, appropriate biological data can be obtained using in vitro methods. The aim of this paper is to examine the use of modelling and in vitro data to predict digestion processes in vivo. Suitable mathematical methods are required to describe and interpret substrate disappearance profiles or gas production profiles. The derivation of such models is important since this allows a clear definition of the underlying assumptions made. Such assumptions are related to the change in fractional rate of degradation (kd) during incubation that will determine the shape of the profile. Furthermore, the value of the fractional passage rate (kp) is of crucial importance in the prediction of extent of degradation in the rumen. The development and application of models, based on classic microbial growth equations, clearly shows that observed variation in microbial efficiency in batch cultures (including the gas production technique) is not necessarily related to that in vivo. Rather, kp is again a major factor contributing to explanation of variation in microbial efficiency. Similarly, the end products of fermentation (VFA) and the VFA molar proportions can be estimated in vitro, but its direct applicability to the in vivo situation is limited. It is concluded that some potential uses of in vitro techniques are ultimately misleading. Mechanistic models indicate that mechanisms governing microbial efficiency and VFA molar proportions in vitro are not necessarily valid for the in vivo situation. Therefore, the in vitro data cannot be used directly for a uniform system of feed evaluation to predict animal responses. Rather, the in vitro data obtained for substrate degradation may be used in whole rumen models as a basal input value to indicate the degradation potential.

scholarly journals Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adriana M. De Mendoza ◽  
Soňa Michlíková ◽  
Johann Berger ◽  
Jens Karschau ◽  
Leoni A. Kunz-Schughart ◽  
...  
Keyword(s):  
Protein Denaturation ◽  
Collateral Damage ◽  
Hyperthermia Treatment ◽  
Reversible Process ◽  
Technological Advances ◽  
Thermal Enhancement ◽  
Main Driver ◽  
Definition Of

AbstractRadiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

Turnover of total proteins and ornithine aminotransferase during liver regeneration in rats

1980 ◽  
Vol 238 (1) ◽  
pp. E46-E52
Author(s):  
S. L. Augustine ◽  
R. W. Swick
Keyword(s):  
Amino Acids ◽  
Liver Regeneration ◽  
Protein Degradation ◽  
Partial Hepatectomy ◽  
Free Amino ◽  
Liver Protein ◽  
Ornithine Aminotransferase ◽  
Fractional Rate

The recovery of approximately 40% of the total liver protein during the first day after partial hepatectomy was shown to be due to the near cessation of protein breakdown rather than to an increase in protein synthesis. The decrease in degradation of total protein was less if rats were adrenalectomized or protein-depleted prior to partial hepatectomy. The effect of these treatments originally suggested that changes in free amino acid levels in liver might be related to the rate of protein degradation. However, no correlation was found between levels of total free amino acids and rates of breakdown. Measurements of individual amino acids during liver regeneration suggested that levels of free methionine and phenylalanine, amino acids that have been found to lower rates of protein degradation in vitro, are not correlated with rates of breakdown in vivo. The difference between the fractional rate of ornithine aminotransferase degradation (0.68/day and 0.28/day in sham-hepatectomized and partially hepatectomized rats, respectively) was sufficient to account for the higher level of this protein 3 days after surgery in the latter group.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

scholarly journals Definition of a minimal munc18c domain that interacts with syntaxin 4

2000 ◽  
Vol 350 (3) ◽  
pp. 741-746 ◽  
Author(s):  
Julian GRUSOVIN ◽  
Violet STOICHEVSKA ◽  
Keith H. GOUGH ◽  
Katrina NUNAN ◽  
Colin W. WARD ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Full Length ◽  
Yeast Two Hybrid ◽  
Protein Protein Interaction ◽  
Interaction Studies ◽  
Syntaxin 4 ◽  
Definition Of ◽  
Two Hybrid

munc18c is a critical protein involved in trafficking events associated with syntaxin 4 and which also mediates inhibitory effects on vesicle docking and/or fusion. To investigate the domains of munc18c responsible for its interaction with syntaxin 4, fragments of munc18c were generated and their interaction with syntaxin 4 examined in vivo by the yeast two-hybrid assay. In vitro protein–protein interaction studies were then used to confirm that the interaction between the proteins was direct. Full-length munc18c1–592, munc18c1–139 and munc18c1–225, but not munc18c226–592, munc18c1–100, munc18c43–139 or munc18c66–139, interacted with the cytoplasmic portion of syntaxin 4, Stx42–273, as assessed by yeast two-hybrid assay of growth on nutritionally deficient media and by β-galactosidase reporter induction. The N-terminal predicted helix-a-helix-b-helix-c region of syntaxin 4, Stx429–157, failed to interact with full-length munc18c1–592, indicating that a larger portion of syntaxin 4 is necessary for the interaction. The yeast two-hybrid results were confirmed by protein–protein interaction studies between Stx42–273 and glutathione S-transferase fusion proteins of munc18c. Full-length munc18c1–592, munc18c1–139 and munc18c1–225 interacted with Stx42–273 whereas munc18c1–100 did not, consistent with the yeast two-hybrid data. These data thus identify a region of munc18c between residues 1 and 139 as a minimal domain for its interaction with syntaxin 4.

scholarly journals BIOGENESIS OF MITOCHONDRIA

1969 ◽  
Vol 42 (2) ◽  
pp. 377-391 ◽  
Author(s):  
G. M. Kellerman ◽  
D. R. Biggs ◽  
Anthony W. Linnane
Keyword(s):  
Unsaturated Fatty Acids ◽  
Mitochondrial Protein ◽  
Mitochondrial Membranes ◽  
Phylogenetic Implications ◽  
Obligate Aerobic ◽  
Biogenesis Of Mitochondria ◽  
Citric Acid Cycle Enzymes ◽  
Definition Of

Growth under conditions of oxygen restriction results in a generalized decrease in the definition of the mitochondrial membranes, a decrease in the mitochondrial cytochromes, and a decrease in citric acid cycle enzymes of the obligate aerobic yeast Candida parapsilosis. Addition of unsaturated fatty acids and ergosterol to cultures exposed to limited oxygen results in improved definition of the mitochondrial membranes and an increase in the total mitochondrial cytochrome content of the cells. Euflavine completely inhibits mitochondrial protein synthesis in vitro. Its in vivo effect is to cause the formation of giant mitochondrial profiles with apparently intact outer membranes and modified internal membranes; the cristae (in-folds) appear only as apparently disorganized remnants while the remainder of the inner membrane seems intact. Cytochromes a, a3, b, and c1 are not synthesized by the cells in the presence of euflavine. Ethidium appears to have effects identical to those of euflavine, whereas chloramphenicol, lincomycin, and erythromycin have similar effects in principle but they are less marked. The effects of all the inhibitors are freely reversible after removal of the drugs. The results are discussed in terms of a functionally three-membrane model of the mitochondrion. In addition, the phylogenetic implications of the observed differences between this organism and the facultative anaerobic yeasts are considered.

Effect of non-digestible oligosaccharides in diets for weaner pigs on in vitro fermentation

1998 ◽  
Vol 1998 ◽  
pp. 30-30 ◽  
Author(s):  
J.G.M. Houdijk ◽  
B.A. Williams ◽  
S. Tamminga ◽  
M.W.A. Verstegen
Keyword(s):  
Gas Production ◽  
Production Technique ◽  
In Vitro Fermentation ◽  
Weaner Pigs

Dietary fructooligosaccharides (FOS) shifted the proportion of propionate (↑) and acetate (↓) compared to transgalactooligosaccharides (TOS) in weaner pigs' ileal digesta, both in vivo and in vitro (Houdijk et al., 1997). This could be related to different fermentation rates between these so-called non-digestible oligosaccharides (NDOs). These rates were studied via the cumulative gas production technique comparing FOS, TOS, and glucose.

scholarly journals Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

2020 ◽  
Vol 8 (1) ◽  
pp. e000337 ◽  
Author(s):  
Lorenzo Galluzzi ◽  
Ilio Vitale ◽  
Sarah Warren ◽  
Sandy Adjemian ◽  
Patrizia Agostinis ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Adaptive Immune Response ◽  
Operational Definition ◽  
Immunogenic Cell Death ◽  
Adaptive Immune ◽  
Regulated Cell Death ◽  
Definition Of

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Glucose homeostasis and hypothalamic-pituitary-adrenocortical axis during development in rats

1990 ◽  
Vol 259 (5) ◽  
pp. E601-E613 ◽  
Author(s):  
E. P. Widmaier
Keyword(s):  
Stress Responses ◽  
Adrenocorticotropic Hormone ◽  
Glucose Sensor ◽  
Adult Life ◽  
Glucose Sensing ◽  
Physiological Data ◽  
Compensatory Mechanisms ◽  
Definition Of

Glucoprivation represents a model stress in which activation of different stress responses at different ages can be monitored both in vivo and in vitro. Physiological data indicate rat brain contains a liver/pancreas-type glucose sensor, yet no biochemical or immunocytochemical evidence exists for such a sensor. Young rats appear to lack normal hypothalamic glucose-sensing ability and do not show typical secretory patterns of corticotropin-releasing factor, adrenocorticotropic hormone, or corticosterone after experimentally induced glucoprivation. However, they hypersecrete catecholamines and glucagon (compared with adults) and thrive on fuel sources other than glucose that are abundant after birth. High steroid levels during the first 24 h after birth may be critical for inducing gluconeogenic enzymes and promoting differentiation of tissues like pancreas. Neonatal rats also have unique control systems to combat the damaging effects of other stresses like hypoxia; these systems may disappear in adults. Thus the definition of stress may change during development, and the compensatory mechanisms employed to combat stress change from neonatal to adult life and are intricately related to the metabolic needs of the animal.

scholarly journals PSVIII-7 In vitro fermentation of different dietary fibers selectively changed sow gut microbiota composition

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 283-283
Author(s):  
Xiong Xia ◽  
Lingling Hu ◽  
Jian Peng
Keyword(s):  
Gut Microbiota ◽  
Guar Gum ◽  
Gas Production ◽  
Modified Starch ◽  
Microbiota Composition ◽  
Kinetics Parameters ◽  
In Vitro Fermentation ◽  
Fractional Rate ◽  
Konjac Flour

Abstract In vitro fermentation experiments with modified starch 1 (MS1), modified starch 2 (MS2), guar gum (GG), xanthan gum (XG), konjac flour (KF), wheat brain (WB), and inulin (I) were conducted for 48 h to investigate the effects on gilt gut microbiota. Fecal examples were obtained from three gilts; the fermentation kinetics parameters were analysed in Logistic-Exponential (LE) model such as the final asymptotic gas volume (Vf, ml/g), initial fractional rate of degradation at t-value=0 (FDR0, h-1), fractional rate of gas production at particular time (k, h-1) and half-time to asymptote (T1/2, h). Samples were collected after fermentation for short chain fatty acids (SCFAs) and 16S rDNA microbial analysis. MS1, MS2, and I had the highest Vf (P < 0.01). The k of GG and I were significant higher (P < 0.01). FDR0 of MS2, GG, and I were the lowest following KF, MS1, WB, and XG, successively (P < 0.01). T1/2 of MS1, KF, WB, and GG were lower (P < 0.01). MS1, MS2, and GG produced more acetate (P < 0.05) and total SCFAs (P < 0.01), and butyrate produced by MS2 was significant higher (P < 0.01). The microbiota composition changed dramatically after fermentation, decreasing bacteria abundance and alpha-diversity (P < 0.01). The relative abundance of phyla Firmicutes and Bacteroidetes decreased, while phyla Spirochaetes, Proteobacteria, Kiritimatiellaeota, and Fusobacteria were selectively promoted by DF. The LEfSe analysis showed Proteobacteria, Gammaproteobacteria, and Aeromonadales were enriched in MS1 treatment; Clostridiales, Clostridia, and Anaerosporobacter were enriched in MS2 treatment; Bacteroidales, Bacteroidia, and Bacteroidetes were enriched in GG treatment; Ruminococcaceae and Ruminococcaceae_UCG_013 were enriched in XG treatment; Lachnospiraceae, Lachnospiraceae_NK4A136_group, and Ruminiclostridium were enriched in KF treatment; Enterobacteriales, Enterobacteriaceae, and Lactobacillales, were enriched in I treatment. In conclusion, different type of DFs may play a specific role in gilt gut microbiota changing and composition.

scholarly journals 133 Porcine in vitro degradation and fermentation characteristics of heat-pretreated and multi-enzyme-supplemented soybean hulls

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 114-115
Author(s):  
Cienna J Boss ◽  
Jung Wook Lee ◽  
Rob Patterson ◽  
Tofuko A Woyengo
Keyword(s):  
In Vitro Digestion ◽  
Gas Production ◽  
In Vitro Digestibility ◽  
Soybean Hulls ◽  
In Vitro Fermentation ◽  
Heat Pretreatment ◽  
Fractional Rate ◽  
Enzyme Supplementation ◽  
Kinetics Of

Abstract A study was conducted to determine effects of pretreating and supplementing soybean hulls with multi-enzyme on porcine in vitro digestion and fermentation characteristics. Treatments were untreated and heat-pretreated (160 °C and 70 psi for 20 min) soybean hulls without or with multi-enzyme in a 2 × 2 factorial arrangement. The multi-enzyme supplied 2,800 U of cellulase, 1,800 U of pectinase, 400 U of mannanase, 1,000 U of xylanase, 600 U of glucanase, and 200 U of protease/kilogram of feedstuff. Feedstuffs were subjected to in vitro digestion with porcine pepsin and pancreatin, followed by in vitro fermentation for 72 h. Accumulated gas production was recorded and modeled to estimate kinetics of gas production. On DM basis, untreated and pretreated soybean hulls contained 10.4 and 10.6% CP, and 63.2 and 49.5% ADF, respectively. Pretreatment and multi-enzyme supplementation did not interact on in vitro digestibility of DM (IVDDM). Untreated and pretreated soybean hulls did not differ in IVDDM (24.8 vs. 25.7%). Multi-enzyme increased (P < 0.05) IVDDM of soybean hulls by a mean of 45.5%. Pretreatment and multi-enzyme unaffected total gas production. Pretreatment and multi-enzyme interacted (P < 0.05) on fractional rate of degradation such that the fractional rate of degradation for pretreated soybean hulls was greater (P < 0.05) than that of untreated soybean hulls when soybean hulls were supplemented with multi-enzyme (0.045 vs. 0.062 h-1), but not when soybean hulls were unsupplemented with multi-enzyme (0.053 vs. 0.059 h-1). In conclusion, multi-enzyme supplementation increased IVDDM, implying that the multi-enzyme used in the study can be used to enhance utilization of soybean hulls. Heat pretreatment increased the rate of fermentation of multi-enzyme-supplemented soybean hulls, implying that the rate of fermentation of soybean hulls in the hindgut of pigs can be enhanced by a combination of heat pretreatment and multi-enzyme supplementation.

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