Comparison of in vitro and in vivo modulation of myelopoiesis by biological response modifiers

1984 ◽  
Vol 18 (3) ◽  
Author(s):  
Erich Schlick ◽  
Klaus Hartung ◽  
MichaelA. Chirigos
Keyword(s):  
Biological Response ◽  
Biological Response Modifiers

scholarly journals Biological Response Modifiers and Parasitic Infections: Experimental Aspects of Toxoplasmosis

1994 ◽  
Vol 5 (suppl a) ◽  
pp. 47A-50A
Author(s):  
Miles H Beaman
Keyword(s):  
Critical Role ◽  
Biological Response ◽  
Biological Response Modifiers ◽  
Toxoplasmic Encephalitis ◽  
Current Therapy ◽  
Mouse Strains ◽  
Parasitic Infections ◽  
Ifn Γ

Parasitic infections are important causes of disease in the developing world and, since the advent of AIDS, the developed world. Over the past decade, in vitro and in vivo studies have established the important role that biological response modifiers play in pathogenesis of parasitic disease. These basic studies have resulted in successful clinical trials of interferon gamma (IFN-γ) in human leishmaniasis. Toxoplasmic encephalitis is a major opportunistic infection in patients with AIDS. and current therapy is often problematic. IFN-γ has been shown in in vitro and in vivo animal studies to be critical for host defence against Toxoplasma gondii. Tumour necrosis factor alpha plays a critical role in mediating IFN-γ effect in vitro, but its role in vivo is under further study. lnterleukin (1L)-6 and IL-10 have both recently been shown to enhance T gondii replication in vitro and to antagonize the beneficial effects of IPN-γ. In addition, in certain mouse strains. IL-6 has been shown to worsen mortality from T gondii infection. Future strategies for therapy of T gondii may include administration of exogenous IFN-γ or IL-12 with or without antibody to antagonistic cytokines such as IL-6 (or possibly IL-10).

scholarly journals An Historic Overview of Biological Response Modifiers as Antiviral Agents

1992 ◽  
Vol 3 (suppl b) ◽  
pp. 34-40 ◽  
Author(s):  
Page S Morahan ◽  
Aangelo J Pinto
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Antiviral Agents ◽  
Biological Response ◽  
Natural Resistance ◽  
Biological Response Modifiers ◽  
Protective Effects ◽  
Small Molecular Weight

A wide variety ofimmunomodulators/biological response modifiers (BRMs) has been demonstrated to provide broad spectrum antiviral activity against both RNA and DNA viruses in several animal species. Dramatic decreases in mortality, reduced virus titres in tissues and reduced histopathology can be produced. The antivirally effective agents include microbially derived materials, polyanions, cytokines and chemically diverse small molecular weight chemicals. The greatest protective effects are observed with prophylactic treatment. although early therapeutic treatment can also be effective. Little direct antiviral activity can be observed in vitro. The findings suggest induction by BRMs of antiviral mediators in vivo early in the course of viral pathogenesis, before the virus has become sequestered in a privileged site or too much infectious virus has been produced for natural resistance to have an impact, immunomodulators are pleiotropic in their immunomodulatory effects, and it has been difficult to establish whether one cell type or mediator is critical for the observed broad spectrum antiviral activity. Therefore, the mechanisms of antiviral action of immunomodulators remain unclear for most systems, but probably involve enhancement of natural immune responses. While no unified antiviral mechanism among different immunomodulators has yet emerged, interferon induction remains a major hypothesis.

scholarly journals Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors

1999 ◽  
Vol 19 (6) ◽  
pp. 4028-4038 ◽  
Author(s):  
Shen-Hsi Yang ◽  
Alex Galanis ◽  
Andrew D. Sharrocks
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Map Kinases ◽  
Biological Response ◽  
Extracellular Signals ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in the conversion of extracellular signals into a cellular response. However, the existence of multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses a problem in maintaining substrate specificity and hence the correct biological response. Both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of MAP kinases use a second specificity determinant and require docking to their transcription factor substrates to achieve maximal substrate activation. In this study, we demonstrate that among the different MAP kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38α and p38β2. The efficiency of phosphorylation in vitro and transcriptional activation in vivo of MEF2A and MEF2C by these p38 subtypes requires the presence of a kinase docking domain (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38 responsiveness on different transcription factors, and reciprocal effects are observed upon the introduction of alternative D-domains into MEF2A. These results therefore contribute to our understanding of signalling to MEF2 transcription factors and demonstrate that the requirement for substrate binding by MAP kinases is an important facet of three different subclasses of MAP kinases (ERK, JNK, and p38).

scholarly journals Self-organized cell migration across scales – from single cell movement to tissue formation

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
pp. dev191767
Author(s):  
Jessica Stock ◽  
Andrea Pauli
Keyword(s):  
Cell Migration ◽  
Multiple Scales ◽  
Single Cells ◽  
Cell Movement ◽  
Biological Response ◽  
Collective Cell Migration ◽  
Theoretical Concepts ◽  
Self Organizing

ABSTRACTSelf-organization is a key feature of many biological and developmental processes, including cell migration. Although cell migration has traditionally been viewed as a biological response to extrinsic signals, advances within the past two decades have highlighted the importance of intrinsic self-organizing properties to direct cell migration on multiple scales. In this Review, we will explore self-organizing mechanisms that lay the foundation for both single and collective cell migration. Based on in vitro and in vivo examples, we will discuss theoretical concepts that underlie the persistent migration of single cells in the absence of directional guidance cues, and the formation of an autonomous cell collective that drives coordinated migration. Finally, we highlight the general implications of self-organizing principles guiding cell migration for biological and medical research.

What can we Predict Before it's Implanted?

1985 ◽  
Vol 55 ◽  
Author(s):  
Donald F. Gibbons
Keyword(s):  
Biological Response ◽  
High Sensitivity ◽  
Biological Pathways ◽  
Surface Topology ◽  
Dystrophic Calcification ◽  
Vitro Assay ◽  
In Vivo Assays ◽  
Tissue Interface

ABSTRACTThe material factors which relate to the degradation and/or leaching of ions or molecules are described and the possible biological pathways which they may activate are described, i.e. cytotoxic, immune, tumor and nonspecific inflammatory response. Cytotoxicity is the only biological response which may be measured with high sensitivity by an in vitro assay prior to implantation. All other biological pathways require some degree of in vivo involvement. Three examples of biological response to material factors associated with devices which require evaluation by in vivo assays are discussed, namely: surface topology (texture), mechanically induced factors at the device/tissue interface caused by differences in compliance, and dystrophic calcification in connective tissue and vascular devices.

Pre-Clinical Biocompatibility Testing of Peritoneal Dialysis Solutions

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 5-9 ◽  
Author(s):  
C.J. Holmes
Keyword(s):  
Peritoneal Dialysis ◽  
Screening Program ◽  
Ex Vivo ◽  
Biological Response ◽  
Cell Types ◽  
Hierarchical Level ◽  
Clinical Phase ◽  
Biocompatibility Testing

Pre-clinical biocompatibility testing of peritoneal dialysis (PD) solutions has become an integral part of new solution development. The construction of a pre-clinical screening program for solution biocompatibility should take a hierarchical approach, starting with in vitro cell viability and function assays. The selection of cell types and assay systems for the in vitro studies should be broad enough to permit a balanced interpretation. Whenever possible, animal models are recommended for the next hierarchical level of testing, followed by human ex vivo study designs. Designs of the latter sort provide evidence that a new solution formulation is exerting an altered biological response in vivo; the response is not purely an in vitro artifact or restricted to a given animal species. This article discusses the various approaches available for biocompatibility testing during the pre-clinical phase of solution development, with an emphasis on the advantages and drawbacks of each method.

scholarly journals Targeting of the Pilosebaceous Follicle by Liquid Crystal Nanocarriers: In Vitro and In Vivo Effects of the Entrapped Minoxidil

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1127
Author(s):  
Massimo Fresta ◽  
Antonia Mancuso ◽  
Maria Chiara Cristiano ◽  
Konrad Urbanek ◽  
Felisa Cilurzo ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Biological Effects ◽  
Biological Response ◽  
Response Duration ◽  
Topical Administration ◽  
Active Compounds ◽  
Biological Responses ◽  
Negative Surface

The topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments/diseases.

Mechanical Properties and Microarchitecture of Nanoporous Hydroxyapatite Bioceramic Nanoparticle Coatings on Ti and TiN

2006 ◽  
Vol 975 ◽  
Author(s):  
Andrei Stanishevsky ◽  
Shafiul Chowdhury ◽  
Nathaniel Greenstein ◽  
Helene Yockell-Lelievre ◽  
Jari Koskinen
Keyword(s):  
Mechanical Properties ◽  
Young’S Modulus ◽  
Young's Modulus ◽  
Biological Response ◽  
Dip Coating ◽  
Nano Crystalline ◽  
Ceramic Manufacturing ◽  
Nanoparticle Coatings

ABSTRACTThe hydroxyapatite (HA) based bioceramic materials are usually prepared at high sintering temperatures to attain suitable mechanical properties. The sintering process usually results in a material which is compositionally and morphologically different from nonstoichiometric nano-crystalline HA phase of hard tissue. At the same time, HA particulates used as precursors in ceramic manufacturing are often very similar to the natural HA nanocrystals. It has been shown that synthetic nanoparticle HA (nanoHA) based materials improve the biological response in vitro and in vivo, but the information on mechanical properties of these materials is scarce.In this work we studied the HA nanoparticle (10 – 80 nm mean size) coatings with 30 – 70% porosity prepared by a dip-coating technique on Ti and TiN substrates. It has been found that the mechanical properties of HA nanoparticle coatings are strongly influenced by the initial size, morphology, and surface treatment of nanoparticles. The nanoindentation Young's modulus and hardness of as–deposited nanoHA coatings were in the range of 2.5 – 6.9 GPa and 80 – 230 MPa, respectively. The coatings were stable after annealing up to at least 600 °C, reaching the Young's modulus up to 23 GPa and hardness up to 540 MPa, as well as in simulated body fluids.

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