Cathepsin B is a lysosomal cysteine proteinase, thought to be involved in the degradation of connective tissue breakdown products internalized by endocytosis. It has also been implicated in the extracellular matrix degradation of collagens and proteoglycans in disease states such as tumour invasion, rheumatoid arthritis and osteoarthritis. To date it is still unclear which factors can potentially modulate the release and/or activation of this enzyme.

OBJECTIVE:To measure levels of cytokines, proteases, and glycosaminoglycans (GAG) in synovial fluid (SF) from the knees of animals with experimental osteoarthritis (OA) and from their contralateral (control) knees, and to compare and correlate these values with each other as well as with measures of proteoglycan synthesis in the corresponding articular cartilage. This study will help to identify cytokines of potential importance in the early stages of the development of OA.METHODS:OA was induced in 12 mature animals by sectioning the anterior cruciate ligament. After 3 months, SF from the operated and contralateral (control) knee joints was assayed for interleukin-6 (IL-6), tumor necrosis factor (TNF), IL-1, latent metalloproteinase, and sulfated GAG. Proteoglycan synthesis in the corresponding articular cartilage was also measured.RESULTS:IL-6 levels in SF from the operated joint compared with the control joint were significantly elevated in 11 of 12 animals. TNF levels were also elevated in 10 of 11 SF samples from operated joints, but to a lesser extent than those of IL-6. IL-1 and IL-1 inhibitors were undetectable in either the operated or control joint SF. The GAG concentration was elevated in SF from experimental OA joints. This elevation correlated with that of TNF, but not IL-6. There was no significant difference in the concentration of APMA-activatable metalloproteinase. The rate of proteoglycan synthesis was higher in the cartilage from the operated joint in 8 of 12 animals, and the mean rate of synthesis was significantly higher than in the control joint. There was a positive correlation between this increase in cartilage proteoglycan synthesis (operated versus control) and the increase in SF IL-6, but there was no correlation with the levels of TNF or GAG.CONCLUSION:This is the first study of SF levels of cytokines in early experimental OA. Our results show surprisingly high levels of IL-6 in operated joints, where the cytokine could act directly on the chondrocytes, and thus play a role in mediating their responses to cartilage injury.

The COVID-19 global incidence rate among young adults (age 19-40) drastically increased since summer 2020, and young adults were often portrayed by popular media as the "main spreader" of the pandemic. However, young adults faced unique challenges during the pandemic due to working in high-risk, low-paying essential service occupations, as well as having higher levels of financial insecurity and mental burden. This qualitative study aims to examine the attitudes and perceptions of health orders of young adults to better inform public health messaging to reach this demographic and increase compliance to public health orders. A total of 50 young adults residing in British Columbia, Canada, were recruited to participate in focus group in groups of four to six. Focus group discussions were conducted via teleconferencing. Thematic analysis revealed four major themes: 1) risks of contracting the disease, 2) the perceived impact of COVID-19, 3) responsibility of institutions, 4) and effective public health messaging. Contrary to existing literature, our findings suggest young adults feel highly responsible for protecting themselves and others. They face a higher risk of depression and anxiety compared to other age groups, especially when they take on multiple social roles such as caregivers and parents. Our findings suggest young adults face confusion due to inconsistent messaging and are not reached due to the ineffectiveness of existing strategies. We recommend using evidence-based strategies proven to promote behaviour change to address the barriers identified by young adults through tailoring public health messages, specifically by using positive messaging, messaging that considers the context of the intended audiences, and utilizing digital platforms to facilitate two-way communication.

2-[4-(1,1-Dimethylethyl)phenyl]thiophene 12 was carboxylated using butyllithium and carbon dioxide to give 5-[4-(1,1-dimethylethyl)phenyl]thiophene-2-carboxylic acid 13. Conversion of the acid 13 using diphenyl phosphazidate and triethylamine gave 5-[4-(1,1-dimethylethyl)phenyl]thiophene-2-carbonyl azide 14, which was rearranged in toluene at 110-degrees-C with loss of nitrogen to give the isocyanate 15; this in turn was treated with sodium 1-cyanoprop-1-ene 2-oxide 16 in tetrahydrofuran to give 2-cyano-N-{5-[4-(1,1-dimethylethyl)phenyl]thiophen-2-yl}-3-hydroxybut-2-enamide 17. Analogous chemistry has been utilised to synthesize both phenylheteroarylbutenamides and phenylbutenamides which display immunosuppressive activity towards proliferating concanavalin A-stimulated T-lymphocytes.

Monoclonal antibodies to certain cell surface constituents on lymphocytes, monocytes and macrophages have been administered to Lewis rats with developing, established or adoptively transferred arthritis, to determine any immunomodulatory properties. Anti-CD4 antibodies against helper T-lymphocytes produced a dose related inhibition of developing arthritis; high dose levels completely suppressed all symptoms of arthritis and these rats were resistant to further attempts to induce arthritis. Anti-Ia (MHCII) antibodies also inhibited arthritis in a dose related manner; anti-pan T antibodies delayed the onset of arthritis, but antibodies against CD8 and IL-2 receptor positive cells were without effect. Development of type II collagen-induced arthritis was also inhibited by anti-CD4 treatment. Established arthritis could be temporatily inhibited by anti-CD4 antibodies, but rebound of arthritis invariably occurred after stopping treatment, as is the case with cyclosporin A. Similar results with anti-CD4 antibodies were obtained during treatment of arthritis adoptively transferred by arthritogenic T-lymphocytes. From these experiments it is clear that CD4 positive T-lymphocytes have a major role in the induction of adjuvant arthritis and that interaction between CD4 and Ia bearing cells is important. The rebound of arthritis that occurred after withdrawal of anti-CD4 treatment during established disease infers that cells in addition to helper T-lymphocytes are involved in the chronicity of arthritis, but these remain to be elucidated. These findings are discussed in relation to results with monoclonal antibodies in other models of arthritis and human rheumatoid arthritis; the prospects for human therapy are also discussed.

To be of real value, models of arthritis should be close enough to the human diseases to enable rational drug discovery for halting or even reversing these crippling afflictions. Unfortunately this is not yet totally so, and our existing models of arthritis are frequently criticized for both their failure to replicate the human condition, and to reliably demonstrate the disease-modifying qualities of gold and penicillamine, the mainstays of human therapy. Clearly we live in an imperfect world; nevertheless penicillamine has been found active in one model of arthritis, after considerable, patient experimentation1, and clobuzarit (Clozic® ICI), a molecule with the ability to slow down the erosive progression of rheumatoid arthritis, is active in various models of polyarthritis in the rat2. Precedent has therefore been set, and this success, though limited, is sufficient to justify optimism that further refinement of arthritis models will lead to disease-modifying therapy for arthritic disease.

It has been shown that some of the controversy over the structure of articular cartilage may be due to slight differences in the orientation of the sample that has been studied. As our decisive criterion we have used the simple physical fact that elongate proteins, such as collagen micelles, that can exhibit form-birefringence, had to show virtually straight extinction when viewed under crossed polars. The use of a variably adjustable microtome chuck facilitated small adjustments in the orientation of the cartilage to meet this criterion. Under these conditions, the collagen of the matrix has been shown to be aligned mainly perpendicularly to the surface which was bounded by a thin lamina in which the collagen showed birefringence at 90 degrees to that of the matrix. The conventionally described zonation of articular cartilage has been shown to be inadequate for that of the dog tibial plateau. The conventional Zone 2 has been shown to consist of two zones, Zones 2a and 2b, with different cell sizes, cell concentrations, and concentration of matrix components.

Articular cartilage is generally considered to be an homogeneous tissue. It has now been shown that, although different regions of the medial tibial cartilage of the dog have very similar oxidative enzymic activities, each region is heterogeneous with respect to these activities. The conventional histological delineation of this cartilage has been modified, to take into account a narrow band (designated zone 2a), just below the most superficial spindle-shaped cells, that has higher oxidative enzymic activity than any other. Changes in the activity in this zone might be diluted by the lack of change in other zones if measured by conventional biochemical procedures which could not measure the activities of the different zones separately.

Changes in the cellularity and in the nature of the matrix were studied in the cartilages of the tibial plateau in experimentally induced arthritis in the dog, 7 and 14 days after section of the anterior cruciate ligament. Samples from the different regions of these cartilages were chilled and sectioned in a cryostat, with a variable microtome chuck to allow precise orientation of the specimens. The samples were examined by normal light microscopy, by microscopic interferometry, and by quantitative polarized light microscopy. The orientation of the glycosaminoglycans was assessed by the new “induced birefringence” method. The results indicated that only the region of the medial tibial cartilage that was unprotected by the meniscus was affected, showing increased water content, loss of superfical cells, and a decrease in orientation of the glycosaminoglycans. Whereas the birefringence of the collagen was markedly increased: this may be a useful indicator of early osteoarthritic changes.

Conference Abstract| January 01 1985 Induced Birefringence for Measuring Changed Orientation of Glycosaminoglycans in Cartilage in Experimental Canine Osteoarthritis Jane Dunham; Jane Dunham 1Kennedy Institute of Rheumatology, London W6 7DW Search for other works by this author on: This Site PubMed Google Scholar D.R. Shackleton; D.R. Shackleton 1Kennedy Institute of Rheumatology, London W6 7DW Search for other works by this author on: This Site PubMed Google Scholar M. E. J. Billingham; M. E. J. Billingham †I.C.I., Pharmaceuticals Division, Macclesfield Search for other works by this author on: This Site PubMed Google Scholar Lucille Bitensky; Lucille Bitensky 1Kennedy Institute of Rheumatology, London W6 7DW Search for other works by this author on: This Site PubMed Google Scholar J. Chayen; J. Chayen 1Kennedy Institute of Rheumatology, London W6 7DW Search for other works by this author on: This Site PubMed Google Scholar Helen Muir Helen Muir *Divisions of Cellular Biology and Biochemistry Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1985) 68 (s11): 72P. https://doi.org/10.1042/cs068072Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation Jane Dunham, D.R. Shackleton, M. E. J. Billingham, Lucille Bitensky, J. Chayen, Helen Muir; Induced Birefringence for Measuring Changed Orientation of Glycosaminoglycans in Cartilage in Experimental Canine Osteoarthritis. Clin Sci (Lond) 1 January 1985; 68 (s11): 72P. doi: https://doi.org/10.1042/cs068072Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1985 The Biochemical Society and the Medical Research Society1985 Article PDF first page preview Close Modal You do not currently have access to this content.

Conference Abstract| February 01 1984 The Lamina Splendens of Articular Cartilage: Fact or Artifact D.R. Shackleton; D.R. Shackleton 1Divisions of Cellular Biology and Biochemistry, Kennedy Institute, Bute Gardens, London W6 7DW and Pharmaceuticals Division, I.C.I., Macclesfield Search for other works by this author on: This Site PubMed Google Scholar A. M. Nahir; A. M. Nahir 1Divisions of Cellular Biology and Biochemistry, Kennedy Institute, Bute Gardens, London W6 7DW and Pharmaceuticals Division, I.C.I., Macclesfield Search for other works by this author on: This Site PubMed Google Scholar M. E. J. Billingham; M. E. J. Billingham 1Divisions of Cellular Biology and Biochemistry, Kennedy Institute, Bute Gardens, London W6 7DW and Pharmaceuticals Division, I.C.I., Macclesfield Search for other works by this author on: This Site PubMed Google Scholar Lucille Bitensky; Lucille Bitensky 1Divisions of Cellular Biology and Biochemistry, Kennedy Institute, Bute Gardens, London W6 7DW and Pharmaceuticals Division, I.C.I., Macclesfield Search for other works by this author on: This Site PubMed Google Scholar J. Chayen; J. Chayen 1Divisions of Cellular Biology and Biochemistry, Kennedy Institute, Bute Gardens, London W6 7DW and Pharmaceuticals Division, I.C.I., Macclesfield Search for other works by this author on: This Site PubMed Google Scholar I. Helen Muir I. Helen Muir 1Divisions of Cellular Biology and Biochemistry, Kennedy Institute, Bute Gardens, London W6 7DW and Pharmaceuticals Division, I.C.I., Macclesfield Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1984) 66 (2): 22P. https://doi.org/10.1042/cs066022P_pt2 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation D.R. Shackleton, A. M. Nahir, M. E. J. Billingham, Lucille Bitensky, J. Chayen, I. Helen Muir; The Lamina Splendens of Articular Cartilage: Fact or Artifact. Clin Sci (Lond) 1 February 1984; 66 (2): 22P. doi: https://doi.org/10.1042/cs066022P_pt2 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1984 The Biochemical Society and the Medical Research Society1984 Article PDF first page preview Close Modal You do not currently have access to this content.

Inflammation and injury to tissue results in a variety of local and systemic events, however although the local events of oedema formation and cellular infiltration have received considerably more attention the systemic response to inflammation is no less profound. The particular systemic event which forms the substance of this communication is the change in the circulating levels of plasma proteins which occurs after imflammatory injury, and the manner in which these changes in plasma concentration are controlled by changes in the rate of synthesis. A discussion of the role of the liver in controlling inflammatory events, in relation to the synthesis of an anti-inflammatory protein has been given; the present work is an extension of this and describes the changes in concentration and synthesis rate of albumin, fibrinogen andα1 acid glycoprotein during adjuvant arthritis in the rat. The changes which occur are regulated at the liver by alteration of the rate of synthesis of the individual protein. For example albumin at the height of adjuvant arthritis falls to a third of its normal plasma level whereas the level ofα1 acid glycoprotein increases up to twenty-fold; these changes are reflected by similar changes in their synthesis rate by the liver.

THE belief that the venom of the common honey bee, Apis mellifira, is beneficial in certain arthritic and rheumatoid conditions goes back to antiquity1. In a study of phospholi-pase-A2,3 we have fractionated nearly 1 kg of freeze-dried bee venom and tested all the fractions for anti-inflammatory activity. Preliminary experiments showed activity to be associated with the basic peptide fraction. The peptides were separated using ‘Sephadex’ G25 and G50 followed by ion-exchange chromatography using either CM ‘Sephadex’ C25 (pH 4.7) or SE ‘Sephadex’ C25 (pH 4.2).

INFLAMMATION leads to the appearance in plasma and inflammatory exudates of a protein with anti-inflammatory properties1–4. The greatest concentration of this anti-inflammatory protein (AIP) occurs relatively late after injury2, which suggests that it plays a role in the later stages of the inflammatory reaction and during healing. The synthesis of the protein is shown here to be similar to that of most other plasma proteins in that it occurs in the liver, which raises the question of the extent to which inflammation is influenced or controlled by the rates of synthesis of plasma proteins.