scholarly journals Biomimetic Model of Articular Cartilage Based on In Vitro Experiments

Author(s):  
Patrick A. Smyth ◽  
Itzhak Green ◽  
Robert L. Jackson ◽  
R. Reid Hanson

Articular cartilage is a complicated material to model for a variety of reasons: its biphasic/triphasic properties, heterogeneous structure, compressibility, unique geometry, and variance between samples. However, the applications for a biomimetic, cartilage-like material are numerous and include: porous bearings, viscous dampers, robotic linkages, artificial joints, etc. This work reports experimental results on the stress-relaxation of equine articular cartilage in unconfined compression. The response is consistent with simple spring and damper systems, and gives a storage and loss moduli. This model is proposed for use in evaluating biomimetic materials, and can be incorporated into large-scale dynamic analyses to account for motion or impact. The proposed characterization is suited for high-level analysis of multi-phase materials, where separating the contribution of each phase is not desired.

2019 ◽  
Vol 36 (3) ◽  
pp. 391-415 ◽  
Author(s):  
Carolin Krautz ◽  
Stefan Hoffmann

Purpose Extant research shows that acquiescence response style (ARS) is culture-bound and may bias the results of comparative cross-cultural studies. Conventional measures of ARS are difficult to apply in practice. To overcome this limitation, the purpose of this paper is to propose an alternative, practice-oriented measure, namely, pARS. The authors apply Hofstede’s cultural dimensions (Hofstede et al., 2010) to test whether pARS is culture-bound. The cross-cultural study provides a high level of cross-cultural generalisability due to the extensive number of surveyed countries (n=30) and subjects (n=236.089). The authors run multi-level analysis to identify within- and between-country-level predictors. Design/methodology/approach On the individual level, the authors use data of a large-scale cross-cultural study, including 236.089 consumers from 30 countries worldwide. The authors apply several methods to test for the culture-boundness of pARS. First, they apply correlation analysis to replicate existing cross-cultural results and to ensure nomological validity. Second, applying ordinary least square regression, the authors simultaneously test the six Hofstede cultural dimensions (Hofstede et al., 2010) and investigate interactions between the dimensions. Finally, they use multi-level analysis to confirm the stability of culture-bound results, controlling for individual- and country-level variability. Findings The paper introduces an alternative measure for acquiescence (pARS), which is particularly suitable for shorter questionnaires. A large-scale consumer study with 236.089 respondents in 30 countries supports the culture-bound validity of pARS. The authors confirm construct validity and the nomological network of pARS. Contrasting existing studies, multi-level analysis demonstrates that a high level of power distance majorly leads to ARS. Therefore, cross-cultural researchers need to control for ARS in countries high in power distance, especially when paired with high uncertainty avoidance. Originality/value A large-scale consumer study with 236.089 respondents from 30 countries shows that respondents from various countries differ significantly in their level of acquiescence. The study confirms that power distance is the most relevant cultural dimension to explain these differences. Although ARS may bias the results of comparative cross-cultural studies, it is rarely controlled by market research studies outside the academic realm. The present work proposes and establishes the validity of a practice-oriented measure of acquiescence, namely, pARS. pARS is particularly suitable for shorter questionnaires. In contrast to prior approaches, applying pARS does not require adding non-substantive items to the questionnaire.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1018
Author(s):  
James E. K. Hildreth ◽  
Jon D. Moulton ◽  
Donald J. Alcendor

Therapeutic modalities designed specifically to inhibit COVID-19 infection and replication would limit progressive COVID-19-associated pulmonary disease in infected patients and prevent or limit systemic disease. If effective, antivirals could reduce viral transmission rates by reducing viral burden and allow time for immune clearance. For individuals infected with acute-stage disease, antivirals in support of the existing vaccines could reduce COVID-19 hospitalizations and deaths. Here, we evaluate MRCV-19, a phosphorodiamidate morpholino oligo with delivery dendrimer (Vivo-Morpholino), to prevent coronavirus infection in a cell culture model. This is a novel antiviral that effectively inhibits SARS-CoV-2 replication in vitro. By design, MRCV-19 targets the SARS-CoV-2 5’UTR and overlaps the pp1a start site of translation in order to block access of the translation initiation complex to the start. MRCV-19 testing is conducted in a high-throughput, 384-well plate format with a 10-point dose-response curve (common ratio of 2) assayed in duplicate with parallel cytotoxicity evaluations. MRCV-19 was shown to be more effective than hydroxychloroquine and remdesivir in our CPE reduction assay with low toxicity. The clinical translational impact of this study is providing the basis for evaluating MRCV-19 on a large scale in an appropriate infection model for toxicity and systemic high-level inhibition of SARS-CoV-2, which could lead in time to phase I testing in humans.


2021 ◽  
pp. 12-18
Author(s):  
Sergey Baranov ◽  
Lyudmila Derevshchikova ◽  
Alina Samitova ◽  
Pavel Krylov

Articular cartilage is a highly specialized dense connective tissue, and can be considered as a composite gel with a relatively low content (5%) of cells, chondrocytes, embedded in the extracellular matrix. Chondrocytes are the only cell type in articular cartilage and are responsible for the biosynthesis and catabolism of the extracellular matrix. Osteoarthritis, the most common cartilage disease, has many independent risk factors, among which is diabetes mellitus, which allows us to hypothesize that different glucose concentrations have a huge effect on the morfunctional properties of chondrocytes in general and on the formation of osteoarthritis in particular. Despite numerous studies, the question of the effect of glucose on cartilage function is still open. In this regard, the study of morphofunctional changes in chondrocytes under the influence of various glucose concentrations is an urgent problem. The following results were obtained: an increase in the concentration of glucose in cell culture has a positive effect on cell viability and proteoglycan synthesis, but at an external glucose concentration of 25 мМ, cells die, while the synthesis of proteoglycans remains at a high level. The higher the concentration of glucose in the nutrient medium, the larger the cell size, which is probably due to hypertrophy of chondrocytes. In the future, the results obtained will be useful for understanding the process of hypertrophy and identifying ways to control it, as well as for a detailed study of other biochemical processes.


1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.


Author(s):  
Georgi Derluguian

The author develops ideas about the origin of social inequality during the evolution of human societies and reflects on the possibilities of its overcoming. What makes human beings different from other primates is a high level of egalitarianism and altruism, which contributed to more successful adaptability of human collectives at early stages of the development of society. The transition to agriculture, coupled with substantially increasing population density, was marked by the emergence and institutionalisation of social inequality based on the inequality of tangible assets and symbolic wealth. Then, new institutions of warfare came into existence, and they were aimed at conquering and enslaving the neighbours engaged in productive labour. While exercising control over nature, people also established and strengthened their power over other people. Chiefdom as a new type of polity came into being. Elementary forms of power (political, economic and ideological) served as a basis for the formation of early states. The societies in those states were characterised by social inequality and cruelties, including slavery, mass violence and numerous victims. Nowadays, the old elementary forms of power that are inherent in personalistic chiefdom are still functioning along with modern institutions of public and private bureaucracy. This constitutes the key contradiction of our time, which is the juxtaposition of individual despotic power and public infrastructural one. However, society is evolving towards an ever more efficient combination of social initiatives with the sustainability and viability of large-scale organisations.


2020 ◽  
Vol 26 ◽  
Author(s):  
Luíza Dantas-Pereira ◽  
Edézio F. Cunha-Junior ◽  
Valter V. Andrade-Neto ◽  
John F. Bower ◽  
Guilherme A. M. Jardim ◽  
...  

: Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo are essential for the development of a novel, specific and safe derivative, minimizing adverse effects.


2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.


Author(s):  
Anchal Trivedi ◽  
Aparna Misra ◽  
Esha Sarkar ◽  
Anil K. Balapure

Background: In recent years, great progress has been made in reducing the high level of malaria suffering worldwide. There is a great need to evaluate drug resistance reversers and consider new medicines against malaria. There are many approaches to the development of antimalarial drugs. Specific concerns must be taken in to account in these approaches, in particular there requirement for very in expensive and simple use of new therapies and the need to limit drug discovery expenses. Important ongoing efforts are the optimisation of treatment with available medications, including the use of combination therapy. The production of analogs of known agents and the identification of natural products, the use of compounds originally developed against other diseases, the assessment of overcoming drug resistance and the consideration of new therapeutic targets. Liver and spleen are the important organs which are directly associated with malarial complications. Aim: An analysis the Activity of Adenosine Triphosphatase, Aryl Hyrocarbon Hydroxylase Enzymes and Malondialdehyde in spleen Explant Culture. Objective: To determine in-Vitro Effect of Chlorquine and Picroliv on Plasmodium Berghei Induced Alterations in the Activity of Adenosine Triphosphatase, Aryl Hyrocarbon Hydroxylase Enzymes and Malondialdehyde in spleen Explant Culture. Material and method: 1-Histological preparation of spleen explants for paraplast embedding 2-Biochemicalstudies (Enzymes (Atpase, ALP&GST) and the level of protein, Malondialdehyde (MDA). Result: Splenomegalyis one of the three main diagnostic parameters of malaria infection besides fever and anaemia. Many enzymes present in the liver and spleen may also be altered or liberated under different pathological conditions. Enzymes (ATPase, ALP&GST) and the level of protein, Malondialdehyde (MDA) content was found to increase in the liver and spleen explants during malarial infection. In the liver and spleen derived from parasitized CQ treated animals, the activity of all the above enzymes (ATPase, ALP&GST) and the level of protein & MDA of liver/spleen reversed towards the normal for all the 4or3 days of incubations. Picroliv efficacy decreased with the increment of parasitaemia and at 60%parasitaemia. Conclusion: Alkalinephosphatase (ALP) was found to increase with increasing parasitaemia. After the addition of Picroliv to the medium, a decrement in the activity was observed up to day 4 of culture.A similar positive effect of Picroliv was observed on the ATPase and ALP activity of spleen explants.DNA and protein contents also increased in the parasitized liver cultured in the presence of picroliv.On the contrary, in the spleen explants DNA, protein and MDA content were found to decrease after Picroliv supplementation to the culture medium.


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