The control of syphilis, a contemporary problem: a historical perspective.

The control of syphilis in the United Kingdom and United States has been managed in different ways in each country over the course of the last century. Older more established measures including contact tracing, serological surveillance, and health education strategies together with effective antibiotic therapy have had some success. However, changing social structures on both sides of the Atlantic Ocean have brought newer mathematical and epidemiological methods to the fore. This review looks at the past management of syphilis control in the United Kingdom and United States, and speculates on future prospects for disease management in these countries.

Cyclooxygenase-2 is upregulated in inflamed gingival tissues.

BACKGROUND: Increased release of prostaglandins (PG) within periodontal tissues is considered to play a pathogenetic role during periodontal disease progression. The rate-limiting step in the formation of PG from arachidonic acid is catalyzed by cyclooxygenase (COX). Currently there are 2 known isoforms of the enzyme. COX-1 is constitutively expressed in various tissues whereas COX-2 is an inducible enzyme believed to be responsible for PG synthesis at sites of inflammation. The purpose of this study was to compare COX-2 expression in inflamed and healthy human gingiva and further explore some of the pathogenetic mechanisms which may lead to elevated COX-2 expression in vivo. METHODS: Thirty-two gingival biopsies were obtained during routine oral surgical procedures and were processed histologically using hematoxylin and eosin to determine the degree of inflammation. Of these biopsies, 7 with low and 7 with high histological levels of inflammation were further processed immunohistochemically in order to assess the levels of COX-2 expression in situ. To explore some potential mechanisms of COX-2 upregulation, gingival connective tissue primary cell cultures were established and challenged with periodontal bacteria or proinflammatory cytokines in vitro. The levels of COX-2 expression were analyzed by Western blot of cell lysates. COX-2 activity was assessed by quantifying prostaglandin E2 (PGE2) levels in culture supernatants by competitive EIA. RESULTS: We have shown by immunohistochemistry that COX-2 expression was significantly higher (P < 0.01) in tissues with higher levels of inflammatory infiltrates. Expression of COX-2 was detected in gingival epithelium, endothelial cells as well as cells with fibroblast morphology. In vitro studies indicated that gingival fibroblasts (GF) did not express COX-2 constitutively. However, when these cells were challenged with interleukin (IL)-1 beta or bacterial cells (A. actinomycetemcomitans JP2 or B. forsythus ATCC 43037), COX-2 expression as well as COX-2 activity were upregulated. COX-2 expression was upregulated as early as 2 hours post IL-1 beta challenge and was accompanied by a sustained PGE2 release in the culture supernatants. Cyclosporin A (CsA) did not inhibit COX-2 expression induced by bacterial challenge. In contrast, NS-398, a selective inhibitor of COX-2 activity, almost completely abolished PGE2 synthesis by these cells in response to bacterial or cytokine challenge. CONCLUSIONS: We conclude that COX-2 expression is significantly upregulated in inflamed periodontal tissues. Both inflammatory cytokines such as IL-1 beta and bacterial constituents may be responsible for the enhanced COX-2 expression and PGE2 synthesis in vivo.

Regulation of gingival fibroblast interleukin-6 secretion by cyclosporine A.

BACKGROUND: Cyclosporine A (CsA) is a widely used immunosuppressant, with clinical applications ranging from organ transplants to chronic inflammatory diseases. One of the side effects associated with CsA treatment is the development of gingival overgrowth. Exuberant growth of connective tissue within the periodontium can result from hyperactivity of resident fibroblasts. Fibroblasts are capable of secreting interleukin-6 (IL-6), which has been shown to enhance proliferation as well as collagen and glycosaminoglycan synthesis by these cells. We tested the hypothesis that one of the pathogenetic mechanisms underlying CsA-induced fibrosis is an enhanced IL-6 secretion by gingival fibroblasts (GF) in response to this drug. METHODS: The ability of CsA to upregulate GF IL-6 secretion alone or in combination with bacterial challenge or other inflammatory cytokines was tested in an in vitro system. Fibroblast cultures were established from systemically healthy gingival tissue donors and were challenged with CsA in the absence or presence of bacteria, IL-1beta, or tumor necrosis factor (TNF) alpha as co-stimulants. Nifedipine and phenytoin were also tested to further support findings with CsA. After 72 hours of incubation, culture supernatants were collected and analyzed for IL-6 content by ELISA. RESULTS: We have shown that GF respond to CsA with an increase in IL-6 secretion. The magnitude of this response varies among cultures derived from different tissue donors. We have also demonstrated that GF IL-6 responses to bacterial challenge or TNFalpha are downregulated by CsA. However, CsA synergizes with IL-1beta to further upregulate IL-6 secretion, and this effect is shared by phenytoin and nifedipine. CONCLUSIONS: We conclude that one of the pathogenetic mechanisms underlying drug-induced gingival overgrowth may be enhanced secretion of IL-6 by GF in response to these medications. This is the first report on direct and indirect effects of gingival overgrowth-related medications on GF IL-6 metabolism. This work will lay the foundation for future studies directed towards the development of prevention or treatment modalities for gingival overgrowth based on blocking the fibrogenic activities of IL-6 at the cellular level.

Genitourinary chlamydial infection: a reappraisal and hypothesis.

Our understanding of genitourinary chlamydial infection and disease remains limited. That natural defences and/or apparently adequate treatments leave some patients with latent disease is suspected. There is, however, no consensus as to its nature. Furthermore, many patients, most obviously males, presenting with similar or identical symptoms and signs remain unexplained in microbiological terms; this in spite of many years of dedicated research endeavour. The recent trend towards an impasse has coincided with a growing acquaintance with the immunobiology and immunopathology of chlamydial infections. The time would seem to have arrived for a reappraisal of available clinical and laboratory observations. A hypothesis with research suggestions is presented for discussion.

Role of fever in infection: has induced fever any therapeutic potential in HIV infection?

Ancient societies had no rational understanding of fever. The Greeks were the first to recognise that it may be part of nature's method of effecting cure in some diseases. How best to assist nature went through many trials and errors. Appreciation of the prognostic value of fever and how it may be controlled was slow to appear. That there was a place in the therapeutic arsenal for induced fever came only with the 20th century. Finding a suitable, safe, and satisfactory means came slowly. The curative power of well controlled and reproducible levels of fever was proved by the arrest of one deadly and incurable complication of a sexually transmitted disease in the first half of this century. The purpose of this review is to promote discussion and, hopefully, well ordered laboratory and clinical trials aimed at learning whether or not induced fevers have a place in the care of patients with HIV/AIDS.

Sexual attitudes, preferences and infections in Ancient Egypt.

This socio-sexual review of Ancient Egyptian society aims to increase awareness that the prevalence of sexually transmitted diseases (STDs) is largely determined by the way a society is structured and how that structure functions. The prevalence of STDs in Ancient Egypt has been found to be low. This state of affairs was maintained for centuries. Although the structure of their society was rigidly hierarchical, Egyptian people made it function in an acceptable way. What might be learned is concerned more with prevention than cure. Whether this has any relevance today is discussed.

Did Catherine the Great of Russia have syphilis?

Catherine the Great (1729-96) ruled Russia for the last 34 years of her life. She pursued many reforms with energy, intelligence and political shrewdness. Not least amongst her activities was a serious interest in matters of public health which extended to personal involvement in the care of the venereally infected. This paper suggests that perhaps her zeal in this last was based on more than social awareness.

Sexual attitudes, preferences and infections in Ancient Greece: has antiquity anything useful for us today?

Modern society bears a heavy burden of medico-social pathology particularly amongst its young. The size, nature and costs of the sexually transmitted disease element is now considerable and dwarfs such successes as have been achieved. In the belief that the structure of a society and the way that structure functions determines the size of its STD problem, a review of Ancient Greek society has been undertaken. Greek society, not least concerning all aspects of sex, was well ordered, frank and tolerant. Some of the areas of Greek society's structure and functioning which differ most markedly from ours, and seem to have determined a modest STD problem, are highlighted and discussed. Greek ideas that might be adapted to match today's needs are presented for consideration.

Syphilis in art: an entertainment in four parts. Part 1.

It is widely recognised that the history of art reveals the contemporary attitudes of societies and artists to changing patterns of social and sexual behaviour. This collection of artistic creations shows that representations of syphilis in art, over more than five centuries, are consistent with this view. The first quarter century of the morbus gallicus in Europe, starting in 1493, coincided with the spread of Renaissance influence, including printing. A host of pamphlets with woodcut illustrations reflected public alarm at the epidemic proportions and severity of the new disease, with its disabling and sometimes deadly consequences. Also revealed in these early works are the astrological and theological beliefs of disease causation as well as identifiable and serious attempts at public education. These twinned themes of understanding and educational endeavour recur together throughout the centuries and take many forms as man attempts to outline and influence attitudes and so improve his medico-social health. Attitudes to causation changed with experience so that by the beginning of the 17th century the morbus gallicus is no longer a mere contagion but recognised socially and represented artistically, as a morbus venereus. Its clinical presentation had changed remarkably from the alarming early days; and so too had its prevalence--from epidemic to endemic proportions. We find that the artists of both the 16th and 17th centuries, while somewhat reticent about syphilis, are nonetheless at pains to suggest that sex is not without its serious side effects. Their artistic exhortations suggest women as the source of the disease, so that we find Venus shown as both ideal love and the source of contamination. Such attitudes contrast strikingly with what follows. The 18th century is characterised by the sophisticated elements of European societies taking an irreverent or satirical view of sex and syphilis. In England this is reflected in the works of Hogarth and other notable caricaturists. The fierce castigation of men and their follies is matched by more understand and rational attitudes towards women. But it does not last. Indeed it seems almost to invite the studied censoriousness of the 19th centrury with women again stigmatised as a source of degradation and disease. In essence this collection of examples of syphilis in art illustrates wide variations in attitude and behaviour from alarm to tolerance and from intolerance through liberality to licence and much the same again, over nearly five centuries. Just occasionally an artist seems to be ahead of his times.