Exercise-Induced Release of Pharmacologically Active Substances and Their Relevance for Therapy of Hepatic Injury

Chronic liver disease features constant parenchymal injury and repair together with an increasing hepatic impairment, finally leading to fibrosis and cirrhosis and a heightened risk of hepatocellular carcinoma. Closely related to the rise in obesity, the worldwide prevalence of nonalcoholic fatty liver disease, the most common form of chronic liver disease, has reached an epidemic dimension and is estimated to afflict up to 46 percent of the general population, including more than one out of three U.S. citizens. Up to now there is no effective drug treatment available, which is why recommendations encompass both exercise programs and changes in dietary habits. Exercise is well-known for unleashing potent anti-inflammatory effects, which can principally counteract liver inflammation and chronic low-grade inflammation. This review article summarizes the underlying mechanisms responsible for the exercise-mediated anti-inflammatory effects, illustrates the application in animal models as well as in humans, and highlights the therapeutic value when possible. Based on the available results there is no doubt that exercise can even be beneficial in an advanced stage of liver disease and it is the goal of this review article to provide evidence for the therapeutic impact on fibrosis, cirrhosis, and hepatocellular carcinoma and to assess whether exercise might be of value as adjuvant therapy in the treatment of chronic liver disease. In principle, all exercise programs carried out in these high-risk patients should be guided and observed by qualified healthcare professionals to guarantee the patients' safety. Nevertheless, it is also necessary to additionally determine the optimal amount and intensity of exercise to maximize its value, which is why further studies are essential

Cysteine-rich protein family of highly related LIM domain proteins

Journal ArticleHere we describe a family of closely related LIM domain proteins in avian cells. The LIM motif defines a zinc-binding domain that is found in a variety of transcriptional regulators, proto-oncogene products, and proteins associated with sites of cell-substratum contact. One type of LIM-domain protein

Comparative evaluation of gene delivery devices in primary cultures of rat hepatic stellate cells and rat myofibroblasts

BACKGROUND: The hepatic stellate cell is the primary cell type responsible for the excessive formation and deposition of connective tissue elements during the development of hepatic fibrosis in chronically injured liver. Culturing quiescent hepatic stellate cells on plastic causes spontaneous activation leading to a myofibroblastic phenotype similar to that seen in vivo. This provides a simple model system for studying activation and transdifferentiation of these cells. The introduction of exogenous DNA into these cells is discussed controversially mainly due to the lack of systematic analysis. Therefore, we examined comparatively five nonviral, lipid-mediated gene transfer methods and adenoviral based infection, as potential tools for efficient delivery of DNA to rat hepatic stellate cells and their transdifferentiated counterpart, i.e. myofibroblasts. Transfection conditions were determined using enhanced green fluorescent protein as a reporter expressed under the transcriptional control of the human cytomegalovirus immediate early gene 1 promoter/enhancer. RESULTS: With the use of chemically enhanced transfection methods, the highest relative efficiency was obtained with FuGENE™6 gene mediated DNA transfer. Quantitative evaluation of representative transfection experiments by flow cytometry revealed that approximately 6% of the rat hepatic stellate cells were transfected. None of the transfection methods tested was able to mediate gene delivery to rat myofibroblasts. To analyze if rat hepatic stellate cells and myofibroblasts are susceptible to adenoviral infection, we have inserted the transgenic expression cassette into a recombinant adenoviral type 5 genome as replacement for the E1 region. Viral particles of this replication-deficient Ad5-based reporter are able to infect 100% of rat hepatic stellate cells and myofibroblasts, respectively. CONCLUSIONS: Our results indicate that FuGENE™6-based methods may be optimized sufficiently to offer a feasible approach for gene transfer into rat hepatic stellate cells. The data further demonstrate that adenoviral mediated transfer is a promising approach for gene delivery to these hepatic cells

Standardization and Normalization of Data from Laser Ablation Inductively Coupled Plasma Mass Spectrometry

Laser ablation inductively coupled plasma mass spectrometry is a useful technique for the precise determination of major, minor and trace element distributions or isotope ratios in solid samples and biological tissue sections. However, measured ion intensities of selected mass-to-charge ratios, may vary considerably from run to run and might also underlie non-linear drift within a run. Therefore, beside the calibration of the measurement, normalization of ion intensities to a reference such as an internal standard is necessary. Other strategies use an endogenous reference element of which a homogenous distribution in the sample is assumed, or derive a more complex reference parameter from a given dataset. Generally, normalization methods depend on the experimental setup and sample material and are usually based on one or few isotopes or the total ion current. This chapter reports different normalization methods that either used a separate reference value for each data point – constituting a pixel in the isotope image – or used a constant normalization factor per measurement run. In conclusion, normalization is essential to minimize deviations of element concentrations due to measurement-related fluctuations. Normalization and definition of an area of interest are powerful tools to obtain high-contrast isotope images with absolute element concentrations

Vitamin A: too good to be bad?

Vitamin A is a micronutrient important for vision, cell growth, reproduction and immunity. Both deficiency and excess consuming of vitamin A cause severe health consequences. Although discovered as the first lipophilic vitamin already more than a century ago and the definition of precise biological roles of vitamin A in the setting of health and disease, there are still many unresolved issues related to that vitamin. Prototypically, the liver that plays a key role in the storage, metabolism and homeostasis of vitamin A critically responds to the vitamin A status. Acute and chronic excess vitamin A is associated with liver damage and fibrosis, while also hypovitaminosis A is associated with alterations in liver morphology and function. Hepatic stellate cells are the main storage site of vitamin A. These cells have multiple physiological roles from balancing retinol content of the body to mediating inflammatory responses in the liver. Strikingly, different animal disease models also respond to vitamin A statuses differently or even opposing. In this review, we discuss some of these controversial issues in understanding vitamin A biology. More studies of the interactions of vitamin A with animal genomes and epigenetic settings are anticipated in the future

Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts [version 1; referees: 2 approved]

Hepatic fibrosis is characterized by the formation and deposition of excess fibrous connective tissue, leading to progressive architectural tissue remodeling. Irrespective of the underlying noxious trigger, tissue damage induces an inflammatory response involving the local vascular system and the immune system and a systemic mobilization of endocrine and neurological mediators, ultimately leading to the activation of matrix-producing cell populations. Genetic disorders, chronic viral infection, alcohol abuse, autoimmune attacks, metabolic disorders, cholestasis, alterations in bile acid composition or concentration, venous obstruction, and parasite infections are well-established factors that predispose one to hepatic fibrosis. In addition, excess fat and other lipotoxic mediators provoking endoplasmic reticulum stress, alteration of mitochondrial function, oxidative stress, and modifications in the microbiota are associated with non-alcoholic fatty liver disease and, subsequently, the initiation and progression of hepatic fibrosis. Multidisciplinary panels of experts have developed practice guidelines, including recommendations of preferred therapeutic approaches to a specific cause of hepatic disease, stage of fibrosis, or occurring co-morbidities associated with ongoing loss of hepatic function. Here, we summarize the factors leading to liver fibrosis and the current concepts in anti-fibrotic therapies

Editorial: Macrophages in Liver Disease

Macrophages constitute a key component of our immune system and play an important role in immune surveillance. Hepatic macrophages are a heterogeneous population of immune cells that mainly comprises of embryonically-derived resident Kupffer cells (KCs), and circulating monocyte-derived macrophages (MoMFs). They play a critical role in disease initiation and progression as well as contribute to disease resolution. Traditionally, macrophages were defined by two broad subsets: classically-activated pro-inflammatory M1 or alternatively-activated anti-inflammatory M2 macrophages. However, it has been recognized that macrophages can differentiate into multiple phenotypes with distinct functions based on the tissue microenvironment

Электропривод питателя сырого концентрата

Объект исследований - электропривод питателя. Цель работы – модернизация электропривода шнекового питателя сырого концентрата с использованием имеющегося оборудования.Object of researches - the feeder electric drive. The work purpose – upgrade of the electric drive of the screw feeder of a crude concentrate with use of the available equipment