Cell kinetics in the liver of rats under normal and abnormal dietary conditions

Blikkendaal-Lieftinck, L.F.; Kooij, M. van der; Kramer, M. F.; Otter, W. Den

doi:10.1016/0014-4800(77)90048-x

Cited by 27 publications

(9 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Six differential equations were obtained which were subsequently solved using the Matlab software [23], and biological parameters previously described and used by others [24]–[26], [28], [29], [37] when modeling HBV infection. The obtained numerical solutions were consistent with those previously reported by others considering the HBV infection alone [19], [20], [24], [28].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of Mathematical Models for the Analysis of Hepatitis Delta Virus Viral Dynamics

Sousa

Cunha

2010

PLoS ONE

View full text Add to dashboard Cite

BackgroundMathematical models have shown to be extremely helpful in understanding the dynamics of different virus diseases, including hepatitis B. Hepatitis D virus (HDV) is a satellite virus of the hepatitis B virus (HBV). In the liver, production of new HDV virions depends on the presence of HBV. There are two ways in which HDV can occur in an individual: co-infection and super-infection. Co-infection occurs when an individual is simultaneously infected by HBV and HDV, while super-infection occurs in persons with an existing chronic HBV infection.Methodology/Principal FindingsIn this work a mathematical model based on differential equations is proposed for the viral dynamics of the hepatitis D virus (HDV) across different scenarios. This model takes into consideration the knowledge of the biology of the virus and its interaction with the host. In this work we will present the results of a simulation study where two scenarios were considered, co-infection and super-infection, together with different antiviral therapies. Although, in general the predicted course of HDV infection is similar to that observed for HBV, we observe a faster increase in the number of HBV infected cells and viral load. In most tested scenarios, the number of HDV infected cells and viral load values remain below corresponding predicted values for HBV.Conclusions/SignificanceThe simulation study shows that, under the most commonly used and generally accepted therapy approaches for HDV infection, such as lamivudine (LMV) or ribavirine, peggylated alpha-interferon (IFN) or a combination of both, LMV monotherapy and combination therapy of LMV and IFN were predicted to more effectively reduce the HBV and HDV viral loads in the case of super-infection scenarios when compared with the co-infection. In contrast, IFN monotherapy was found to reduce the HDV viral load more efficiently in the case of super-infection while the effect on the HBV viral load was more pronounced during co-infection. The results suggest that there is a need for development of high efficacy therapeutic approaches towards the specific inhibition of HDV replication. These approaches may additionally be directed to the reduction of the half-life of infected cells and life-span of newly produced circulating virions.

show abstract

Section: Discussionmentioning

confidence: 99%

“…From [25] and [26] approximately 0.3% of the liver cells in rats go through mitosis every day. Assuming the same for humans, the constant rate at which uninfected cells are generated, , can be estimated by cells/mL per day.…”

Section: Methodsmentioning

confidence: 99%

Development of Mathematical Models for the Analysis of Hepatitis Delta Virus Viral Dynamics

Sousa

Cunha

2010

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…4, 1999 radioactively labeled with thymidine after partial hepatectomy. 23,26 However, when the dividing hepatocytes were stably marked with a reporter gene (using retroviruses or transgenic mice), continued streaming toward the central vein could not be observed, even in long-term experiments. 27,28 Instead, hepatocytes are removed by apoptosis in a wide pericentral region.…”

Section: All Hepatocytes Can Express the Same Spectrum Of Genesmentioning

confidence: 99%

A Mechanistic Model for the Development and Maintenance of Portocentral Gradients in Gene Expression in the Liver

et al. 1999

View full text Add to dashboard Cite

In the liver, genes are expressed along a portocentral gradient. Based on their adaptive behavior, a gradient versus compartment type, and a dynamic versus stable type of gradient have been recognized. To understand at least in principle the development and maintenance of these gradients in gene expression in relation to the limited number of signal gradients, we propose a simple and testable model. The model uses portocentral gradients of signal molecules as input, while the output depends on two gene-specific variables, viz., the affinity of the gene for its regulatory factors and the degree of cooperativity that determines the response in the signal-transduction pathways. As a preliminary validity test for its performance, the model was tested on control and hormonally induced expression patterns of phosphoenolpyruvate carboxykinase (PCK), carbamoylphosphate synthetase I (CPS), and glutamine synthetase (GS). Affinity was found to determine the overall steepness of the gradient, whereas cooperativity causes these gradients to steepen locally, as is necessary for a compartment-like expression pattern. Interaction between two or more different signal gradients is necessary to ensure a stable expression pattern under different conditions. The diversity in sequence and arrangement of related DNA-response elements of genes appears to account for the gene-specific shape of the portocentral gradients in expression. The feasibility of testing the function of hepatocyte-specific DNA-response units in vivo is demonstrated by integrating such units into a ubiquitously active promoter/enhancer and analyzing the pattern of expression of these constructs in transgenic mice. (HEPATOLOGY 1999;29:1180-1192

show abstract

“…Obviously since non-anatomical radii may not be projected into the second dimension their mapping is more difficult. In the studies which were mentioned above, hepatocytes were sampled only along a "standard plate" extending between the portal space and terminal hepatic vein (4). The present study utilizes a novel sampling approach which is more precise than those used previously.…”

Section: The Tissue Radiusmentioning

confidence: 99%

The streaming liver

Zajicek

Oren

Weinreb

1985

Liver

247

View full text Add to dashboard Cite

ABSTRACT— Twenty male adult rats weighing 200 g were injected with tritiated thymidine (3HTdR). The animals were then killed in groups of five, at the following times: 1 h, 1, 3 and 5 weeks. Autoradiograms of sections through the liver were prepared. The distances between labelled cells and the portal space rim were measured. One hour after labelling most labelled cells were confined to a region extending from the portal space rim up to a distance of 700 μm, which roughly corresponds to Rappaport's hepatic acinus zones‐1 and ‐2. Throughout the experiment lasting 5 weeks labelled cells entered zone‐3 and advanced toward the terminal hepatic vein. Hepatocytes travelled at a daily velocity of 1.44 μm, covering daily 0.324% of the acinus diameter. During the experiment acinus size did not change appreciably. The estimated mean hepatocyte cell cycle time was 37 days and its life expectation, 201 days. These experiments show that the liver is essentially a slowly renewing cell population. Hepatocytes nascent at the portal space gradually stream toward the terminal hepatic vein where they are probably eliminated by apoptosis. Their journey lasts 201 days. Since hepatocytes are glued together with tight junctions, all have to advance toward their terminal hepatic veins en masse. During their voyage, they traverse the three acinus zones, and since in each they produce different enzymes, each zone represents a differentiation state of the advancing cell. It is suggested further that the streaming hepatocyte carries with it its nerve supply and is accompanied by sinusoidal endothelium and Kupffer cells.

show abstract

Cell kinetics in the liver of rats under normal and abnormal dietary conditions

Cited by 27 publications

References 12 publications

Development of Mathematical Models for the Analysis of Hepatitis Delta Virus Viral Dynamics

Development of Mathematical Models for the Analysis of Hepatitis Delta Virus Viral Dynamics

A Mechanistic Model for the Development and Maintenance of Portocentral Gradients in Gene Expression in the Liver

The streaming liver

Contact Info

Product

Resources

About