Editorial Special Section: “Commemorating Leading Inflammo-Pharmacologists”

This Special Editorial Section of the Journal is dedicated to the lifetime contributions by an outstanding multidisciplinary scientist, academic scholar, colleague, and friend to many throughout the world. To describe Michael’s field of specialization in a single term, would be a gross understatement of his training, skills and scholarship.

Throughout about 70 years of academic life, Michael has accrued a great thirst for knowledge whether scientific, scholastic or cultural. He is anything but selective or exclusive in his approach to acquiring knowledge or focus as an academic. I have had the great pleasure of knowing Michael both as a research and scholastic colleague as well as being close friend for the best part of half a century! From the beginning of our working relationship, I have found that Michael has that special kind of quality in a natural ‘meeting of the minds’. Many occasions when we have worked together on research projects or writing manuscripts, I have thought that we sense the others’ intuition and thoughts. This is a very special quality for which I am immensely grateful. It is not to say we have been uncritical of one another’s ideas, but we have a special way of inter-weaving our ideas and working together for what many would say is ‘for the common good’. I find that many of Michael’s colleagues from different disciplines, lives and backgrounds also have great respect for him, his ideas and thoughts. Basically, Michael gets on very well with all and manages to bring out the best in so many of his lifetime of contacts. Some of the contributions from colleagues and friends shown at the end of this article attest to these views and show how much he has given to many of those with whom he has had contacts through his life.

Michael was born 90 years ago in Hendon (formerly an ancient parish of Middlesex, now part of Greater London) and grew up in Sheffield (South Yorkshire) and later in Wigan (Lancashire) where he went to Wigan Grammar School, Then, he went to Alsop High School in Liverpool and Highgate School (North London). The period of his school and later higher education at Oxford must have been very trying as this was during the 1930s recession and then World War II with the bombing in and around the areas where he lived with his parents. He moved around quite extensively during his secondary education with his father who was a leading secondary school modern languages teacher. I sometimes wonder if Michael’s undoubted skills in writing and English expression came from his father.

Certainly, he had a very high standard of education in wartime and immediate post-war conditions, which must have been very challenging. In 1948, he won a scholarship to Keble College, Oxford University where he read Chemistry and Biochemistry, graduating with a 1st Class honours degree with distinction in biochemistry. Keble College must have been a stimulating environment, not only for learning the sciences, but also cultural as the first Oxford College of “the modern era” founded in memory of John Keble who was a key member of the “Oxford Movement” that sought to recover some Catholic heritage of the Church of England. It was well supported in its foundation by being endowed by the Gibbs Banking Company who made money from a monopoly on imports of bird droppings from the Galapagos Islands as a source of fertiliser in Victorian times. The college has particularly attractive chromatic brickwork described as Butterfield Architecture.

While at Oxford, Michael undertook studies to be admitted as an Associate Member, followed later in 1962 as a Fellow, of the Royal Institute of Chemistry (London) which qualified him as a professional chemist. This has enabled him to analyse biological and medical problems through the eyes of a chemist so giving him privileged insight into the molecular aspects of diseases, development of therapeutic agents and as well as the potential properties of biological agents. Michael can be regarded as one of the unique class of “biological chemists” (following the approach of the classical journal [Journal of Biological Chemistry] and the textbook of the same title by Lubert Stryer). His post-doctoral experience (1955–9, supported by the English Speaking Union) ranged from biochemistry at the University of Pennsylvania, and University of Stockholm (1960; as Geigy Travelling Fellow of the Empire Rheumatism Council, now the British Society of Rheumatology), where he had a particularly productive period working with Dr. Harry Bostrom at the latter university. His early period involved work with the famous biochemist, Dr. Paul Kent, as Drs. Lash, Zilliken, Denko, Kritchevsky, Dean, Skidmore among others working on the chemistry, biochemistry of liver and mitochondrial metabolism of lipids (including those in bile), cholesterol, polysaccharides, sialic acids, glycoproteins, and effects of anti-inflammatory drugs on intermediary and polysaccharide metabolism. He undertook research while a Lecturer in the Biochemistry Department (headed by Prof Hans Krebs) at the University of Oxford (1960–1966), as well as being the Staines Medical Research Fellow of Exeter College, and Tutor in Physiology and Biochemistry at Keble College and St Peter’s Hall, Oxford. Several of his outstanding publications of the time appeared in Nature, leading biochemical, medicinal chemistry and pharmacological journals. It was this and later work on the diverse molecular aspects of drugs used to control inflammation and immunity to which I was particularly attracted. Michael and I first met and started to work together when he was a Visiting Research Fellow (1966–1967) and had a Commonwealth Travelling Bursary funded by the Royal Society) and later Senior Research Fellow (1973–1981) at the prestigious, John Curtin School of Medical Research (JCSMR) at the Australian National University in the Australian national capital of Canberra, during the 1970s when I was a Lecturer/Senior Lecturer in Biochemistry at the University of Tasmania Medical School, Hobart, Tasmania, as well as being a Visiting Fellow in the JCSMR. This was among the many productive periods of our collaboration which has extended now for over half a century.

In between the two periods (1967–1973) in Canberra, Michael was Associate Professor of Medicinal Chemistry, Ohio State University, Columbus and Full Professor in Medicine/Rheumatology at the University of California at Los Angeles (UCLA) where he worked with the late Carl Pearson, Frances Beck (see later contribution) and others on some of the key immunological aspects of chronic inflammatory diseases especially the roles of adjuvants and lymphocytes.

Since we first started to collaborate in 1975, we have had a very productive and stimulating friendship. Sometimes this was accompanied with intense discussions and critical encounters, but these had very positive outcomes. A few occasions this led to an agreement to disagree, but from my side an immense respect and deep appreciation of Michael’s breath of knowledge and his intellect. We collaborated in our research not only on a broad range of projects focussing on exploring and modifying the actions of salicylates, and other NSAIDs and analgesics in attempts to make these drugs safer, especially to the gastro-intestinal tract, as well as to be more effective therapeutically.

We tried hard over the years to encourage clinical exploitation of these key findings and observations. Most notable was with leading pharmaceutical companies, some of the principal scientists, medical directors and clinicians, as well as with management and laboratory staff. Many of these associations were very useful insights into industrial approaches and the requirements and difficulties in meeting the diverse regulatory and clinical requirements for getting drugs into clinical use, as well as that strange entity known as the market. We did achieve some success, but it has to be said there were many disappointments (to put it mildly). Overall, our experiences in working with the pharma industry could be summarized (in hindsight) as being profoundly negative even though in many cases we had very strong support from rank and file, researchers and clinicians. Often, we hit a log-jam with mostly middle-order managers and marketers with deeply entrenches views, many of which were based on arcane concepts and ideas. A key point was, however, that in many cases our discoveries and developments were made on their own company products, especially on aspirin and other salicylates. We and our own scientific advisors and colleagues genuinely believed these would benefit both, the company and us. With one or two exceptions these proved not to be the case as senior management (often who had little understanding of the clinical benefits or knowledge of the fields in which the discoveries were made or their benefits to patients) often actively blocked or connived to derail exploitation and development of the innovative forms of the drugs either because (a) it would be a counter-development to the company’s existing products or product range, (b) the risk commercially could not be redirected from disadvantages to advantages. Most managers in the pharmacy industry are inherently risk-averse and have one eye on the shareholders (who in most cases are non-scientists, non-physicians and don’t even have the vaguest understanding of the drugs in development) or the complexity of the deep-seated politics in big pharma, or (c) the attitudes, poor scientific quality and background as well as attitudes, intrinsic risk-adverse negativity of national and multinational (especially in the European Union and its member states) of the regulatory agencies that govern approval of new products. While very occasionally encounters or interactions with a few members of these agencies have been positive, they are governed by negative pressures from political and bureaucratic masters. Thus, the whole process of taking a promising (often very promising) new discovery or development through company and drug-regulatory processes is rather like seeing horses jumping over and falling at a grand national steeplechase (especially like that of the annual event in Aintree, UK).

We did go through many exhaustive processes including getting university committee or administrative approvals, patent applications, many of which were very challenging and intellectually unique exercises in themselves (writing a patent specification is in my view a somewhat arcane art–science form, wrapped in its own legalese, but which can be very rewarding, especially when the patent is finally approved and in some cases an elaborate document and certificate is produced by the Patent Office or agency concerned. Working with patents attorneys can be both an intellectually challenging and a satisfactory experience that proves you have to know your invention, competitive other discoveries and developments.

Finally, there is the ever-expanding involvement of university administrators and deans. In a number of cases we had some encouragement and support from these senior officers. However, a few of the middle order management seem to see us a ‘cash cows’ with rapacious appetites for money and royalties to be siphoned off into their coffers and without recognition of the hard work done by those who have been the creators, fund-raisers and who have done everything to create novel drugs. As Michael and I know only too well, the foot soldiers never receive any gratitude—maybe the odd award and promotion but not without dripping envy and jealousy. We have the T-shirts but they are all blank.

The next entrepreneurial venture which Michael and I have been involved in over the years is the communication of our science as well as ideas and criticisms, and that of our highly valued colleagues. This has taken the form of the development of a journal devoted to the broad subject area which up to the late 1980s had been somewhat neglected or left to other journals with less specialized expertise, focus or scope. Enter ‘Inflammopharmacology’, a journal dedicated to the pharmacology of inflammatory diseases and their associated aches and pains, their clinical treatment and pharmacotherapy. The history of the development and achievements of this journal since its inception in 1991 has been told elsewhere (Rainsford 2016). Since its inception, the journal has benefited over the years from many ideas, commentaries, publications and concepts initiated and developed by Michael. Among the many significant concepts begun by Michael was that of ‘Conditional Pharmacology’ which he pioneered (Whitehouse 1987, 1991) and developed with the late Professor Barrie Vernon-Roberts (University of Adelaide, Australia) (Whitehouse and Vernon Roberts 1991) and Dr. Michael Powanda (M/C Biomedical Consultants LLC, Mill Valley, CA, USA) (Powanda 1995).

In essence, this concept states that (a) inflammatory processes may alter the basis for the actions of drugs that have been designed to act on these processes by means of altering the receptors, enzyme activities, drug metabolism or other physio-pathological mechanisms that are affected by these agents, and (b) that through these actions, the alteration of these inflammatory processes they may in turn affect those mechanisms (e.g. drug metabolic enzymes) that influence their mode of action.

This elegant, if little appreciated, concept may be summarized as the vicious cycle of drug actions and influences of their consequences; elements of this vicious cycle may have positive therapeutic consequences and possibly negative or positive toxicological impact.

Another part of our collaboration has been in the contribution to the ethos and development of the International Conference series which initially began (in collaboration with the late Professor Giampaolo Velo, Verona, Italy) as the “Side Effects of Anti-inflammatory/Analgesic Drugs” conferences and then progressed to the “International Conference on Inflammopharmacology with the symposium on Side Effects of Anti-inflammatory Drugs” and also Safety and Efficacy of Non-Prescription (OTC) Analgesics and NSAIDs which was held in collaboration with Dr. Michael Powanda. These were followed with the conference series on “Inflammopharmacology”, held in collaboration with Dr. Brian Callingham (University of Cambridge and Queens’ College, Cambridge) (Rainsford 2016). Not only did Michael make presentations of major significance to these conferences, but also challenged many of the arguments and data that were presented and contributed to the ideas and planning of these conferences.

It is interesting to reflect back to the earliest conference that we organized in 1975 which was held on “Aspirin and Related Drugs. Their Actions and Uses” (Rainsford et al. 1977). Here we presented concepts of how aspirin and related drugs produced their anti-inflammatory actions as well as causing side-effects. Notably, presented data on salicylates that were derived from natural products and how these might produce anti-inflammatory effects and have differing actions (or inactions) on platelet aggregation. Strikingly, these observations are relevant today and may still be worth consideration in the pharmacotherapy of inflammatory conditions.

From these early observations on salicylates derived from natural products, Michael and his colleagues have continued to have interests in natural products as anti-inflammatory and analgesic activities. Among the most notable of these has been the ethanolic extract of the celery seed derived from Amritsar (India) which has proven clinical activity as well as gastro-intestinal protection (Rainsford et al. 2015). The latter extends to an important and unique action found in a phthalate component of celery seed oil which has since been found to have anti-helicobacter activity (Zhou et al. 2009). Our interests and research work in this and many other natural products, as well as development of derivatives thereof would not have been possible without the initial and continued interest by Michael.

Like so many research collaborations, the unique and highly significant results come from a meeting of minds, personal relationships and long-standing friendship. We owe an immense debt of gratitude to Michael for all these especial qualities.

References

• Powanda MP (1995) The concept of conditional pharmacology and toxicology. Inflammopharmacology 3:363–371.

• Rainsford KD (2016) Origins of Inflammopharmacology: twenty-five years on. Inflammopharmacology 24:297–302

• Rainsford KD, Brune K, Whitehouse MW (eds) (1977) Aspirin and related drugs. their actions and uses, agents and actions, suppl. no 1. Birkhäuser Verlag, Basel.

• Rainsford KD, Powanda MC, Whitehouse MW (2015) Novel natural products in pain, arthritis and gastro-intestinal diseases. Progress in drug research, vol 70. Springer, Basel.

• Whitehouse MW (1991) Disease–drug interactions: significance or insignificance of the ED-50 value for anti-inflammatory agents. Inflammopharmacology 1:143–149.

• Whitehouse MW, Vernon-Roberts B (1991) Conditional pharmacology. Inflammopharmacology 1:61–68.

• Zhou Y, Liu ZP, Taylor B, Smith TJ, Clench M, Davies N, Rainsford KD (2009) A novel compound found from celery seed with bactericidal effects against Helicobacter pylori. J Pharm Pharmacol 61:1061–1077.

Mini Symposium ‘Commemorating Life and Works of Leading Australian Scientists in the Fields of Inflammation and Pharmacotherapy of Inflammatory Diseases’

Garry G. Graham

Department of Pharmacology and Toxicology, St Vincent’s Hospital, University of New South Wales, Darlinghurst, NSW, Australia

The reviews are based on a small symposium held in Adelaide on July 5, 2019. The symposium was organized by Professor Kim Rainsford, Sheffield Hallam University, Sheffield and University of Adelaide and Professor David Haynes, University of Adelaide.

As outlined during this symposium, Professor Michael Whitehouse has freely given his time and valuable research advice to all presenters at the symposium. As outlined below, Professor Whitehouse has published over a wide range of research areas. Not surprisingly, he has a considerable publication record. Reference to Google Scholar indicates that he has published 422 papers with 9324 citations. His h-index, a measure of interest in his publications is 53.

Studying Chemistry and Biochemistry at Oxford started Professor Whitehouse off on a line of research that led through various aspects of molecular medicine; including chemistry of animal polysaccharides, sterol metabolism and ischemic heart disease, cartilage degradation and osteoarthritis, toxicity of adrenocorticoid hormones, non-steroidal anti-inflammatory drugs and natural products. Professor Whitehouse has conducted many studies on the evaluation of the anti-inflammatory activity of compounds in experimental animals and is an expert on the details of these often-difficult studies. In research management, Professor Whitehouse was very much involved in the establishment of committees for the ethical examination of animal-based research.

To Professor Whitehouse, the world is chemical in nature and cannot be understood without knowledge of the chemical properties of compounds under study. His initial studies in pathology were on mucins in the gastrointestinal tract and, because of his interest in the relevant chemistry, was a co-author of a book on the constituent amino-sugars (Kent, Whitehouse 1955). This book is still being referenced.

Professor Whitehouse has conducted much research in Australia, starting in the Department of Experimental Pathology, John Curtin School of Medical Research, the Australian National University, Canberra, with the initial assistance of Professor Sir Howard Florey in 1966–1967 and again 1973–1981. In the intervening period (1968–73), Professor Whitehouse was Professor of Medicine and Acting Professor of Pharmacology at University of California, Los Angeles (UCLA). From 1981 to 1994, Professor Whitehouse was a senior researcher successively at three South Australian institutions, Flinders University of South Australia, the Department of Pathology and Institute of Medical & Veterinary Science, University of Adelaide, and the University of South Australia. He has also worked for several years with Professor Michael Roberts, School of Pharmacy, University of Queensland. Currently, he is an Honorary Research Professor in Experimental Medicine at Griffith University in Queensland.

While at UCLA, Professor Whitehouse was a consultant to Riker Laboratories with a particular interest in the anti-inflammatory drugs used in the treatment of rheumatoid arthritis. At the time, Riker Laboratories were developing an unusual anti-rheumatic drug and because of his expertise in chemistry, Professor Whitehouse rapidly and correctly identified the drug as reacting with sulfydryl (thiol) groups.

Professor Whitehouse has published many papers on the anti-inflammatory and anti-cancer activity of metals, including complexes of zinc, copper, silver, platinum, and gold. He has also shown that colloidal gold has anti-inflammatory activity. This work was published from the 1970s onwards but is still being referenced, an indication of the novelty and value of Professor Whitehouse’s research approach. Professor Whitehouse’s two papers on colloidal gold are of note. Metallic gold is generally considered to be inert. However, Professor Whitehouse showed that colloidal gold is not inert but has anti-inflammatory activity (Brown et al. 2007, 2008).

Consistent with these findings, gold pellets also have anti-inflammatory activity and have continued use and investigational studies as local injections for anti-inflammatory action in hip dysplasia in dogs (Jaeger et al. 2016). This activity is due to dissolution of gold from the surface of the pellets which may be increased with greater pharmacological effect due to the greater surface/mass ratio of colloidal gold than gold pellets.

Other notable and widely cited work of Professor Whitehouse includes his finding that thiocyanate, SCN-, a normal body constituent, has pro-inflammatory activity in rats (Whitehouse and Jones 2009) but, on the other hand, may decrease neutrophil-induced tissue damage (van Dahlen et al. 1997). Professor Whitehouse was responsible for the introduction of the term, ‘Conditional Pharmacology’ which is defined as the modification of the pharmacological actions of a drug changing pathophysiological conditions or the addition of a compound which is not a drug. Professor Whitehouse et al. (2013) first discussed this concept on how thiocyanate modifies the activity of silver and the anti-rheumatic gold complexes. Further work on conditional pharmacology, particularly with thiocyanate, is warranted from the work of Professor Whitehouse.

Another example of early work of Professor Whitehouse was his studies of emu oil which is reviewed elsewhere (Whitehouse et al. 1998) which has been widely applied to the skin by Australian aboriginals. The anti-inflammatory activity of topical emu oil was quickly realized by Professor Whitehouse (1998) Unfortunately, Professor Whitehouse could not continue this work due to patenting questions and consequent lack of support by funding organisations. However, his work has been confirmed by several other groups and is a further example of research studies initiated by the work of Professor Whitehouse.

Professor Whitehouse is now 90 but is still an active researcher putting forward novel ideas in pharmacology and toxicology, particularly with his wife, Desley.

References

• Brown CL, Bushell G, Whitehouse MW et al. (2007) Nanogold pharmaceutics. Gold Bull 40(3):245–250 (citation count 114)

• Brown CL, Whitehouse MW, Tiekink ERT, Bushell GR (2008) Colloidal metallic gold is not bio-inert. Inflammopharmacology 16(3):133–137 (citation count 77)

• Jaeger GT, Larsen S, Soli N, Moe L (2006) Double-blind, placebo-controlled trial of the pain-relieving effects of the implantation of gold beads into dogs with hip dysplasia. Vet Rec 158(21):722–726

• Kent PW, Whitehouse MW (1955) Biochemistry of the aminosugars. Butterworths, London (citation count 202)

• van Dalen JC, Whitehouse MW, Winterbourn CC, Kettle JA (1997) Thiocyanate and chloride as competing substrates for myeloperoxidase. Biochem J 327(2):487–492 (citation count 349)

• Whitehouse M, Butters D, Vernon-Roberts B (2013) Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (Myocrysin) and metallic silver. Inflammopharmacology 21(4):291–300

• Whitehouse MW, Jones M (2009) Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke. Inflamm Res 58:693–704

• Whitehouse MW, Turner AG, Davis CKC, Roberts MS (1998) Emu oil(s): a source of non-toxic transdermal anti-inflammatory agents in aboriginal medicine. Inflammopharmacology 6(1):1–8 (citation count 93)

The evolution of conditional pharmacology

M. C. Powanda

M/P Biomedical Consultants LLC, 435 Marin Avenue, Mill Valley, CA 94941, USA

The concept of conditional pharmacology and toxicology originates in the studies of drug-disease interactions in inflammation done by Dr. Whitehouse and his colleagues (Whitehouse 1985, 1991; Whitehouse and Vernon-Roberts 1991). The concept originally focused on how expression of anti-inflammatory activity may require pre-existent inflammatory mediators/hormones. A few years later I commented on how broad the implications of conditional pharmacology might be, even extending the concept to preclinical toxicology studies (Powanda 1995).

As I stated then and now recapitulate, “Conditional pharmacology/toxicology involves employing the physiological or metabolic activity, the genetic and/or molecular structure of the host, of the disease process and/or of the parasite to activate and target the drug or biologic, as well as to regulate and delimit its activity. This definition emphasizes the multifactorial aspects of the approach and sets the stage for a listing of some existing as well as proposed examples of use of the concept in the treatment of inflammatory diseases and in the treatment of neoplastic and infectious diseases. This concept is also an underlying assumption, and expected consequence, of successful gene therapy.”

Almost three decades later, there are a number of drugs and biologics whose actions depend on the presence of a receptor or an overactive gene. In breast cancer, a gene called HER2 makes too many copies of itself in about 20% of people with breast cancer. Trastuzumab (Herceptin), an antibody, is the standard treatment for this type of breast cancer apparently acting by sticking to certain areas on cancer cells, stopping them from growing, as well as signalling the body’s immune system to attack cancer cells (Romão et al. 2017).

About 2 out of 3 breast cancers are hormone receptor-positive. Their cells have receptors (proteins) for the hormones estrogen (ER-positive cancers) and/or progesterone (PR-positive cancers) which help the cancer cells grow and spread. Tamoxifen blocks estrogen receptors on breast cancer cells. It stops estrogen from connecting to the cancer cells and telling them to grow and divide. While tamoxifen acts like an anti-estrogen in breast cells, it acts like an estrogen in other tissues, like the uterus and the bones. Because of this, it is called a selective estrogen receptor modulator (SERM). It can be used to treat women with breast cancer who have or have not gone through menopause (Kahlenberg and Fox 2011).

In the case of rheumatoid arthritis, there are a series of biologics that work by interfering with the activity of tumor necrosis factor. This is a key immune system cytokine. These drugs include: adalimumab, etanercept, infliximab and golimumab. Another cytokine target is interleukin-1 (IL-1); Anakinra blocks the action of interleukin-1. Tocilizumab is a biologic that works by blocking the cytokine interleukin 6 (IL-6). In contrast, Abatacept is a selective T cell co-stimulation modulator, while Rituximab, a CD20-directed cytolytic antibody, appears to help control RA by destroying another category of immune system cells called B cells.

In November 2012, the U.S. Food and Drug Administration (FDA) approved tofacitinib citrate, a drug “to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to, or who are intolerant of, methotrexate.” Tofacitinib is a Janus-associated kinase (JAK) inhibitor. It works by blocking a cellular signalling pathway inside cells. It can be taken orally.

The above drugs/biologics all depend on some factor/factors related to the disease being present in the extra or intracellular milieu, as ‘conditional pharmacology’ would predict. Despite this array of drugs and biologics for breast cancer and rheumatoid arthritis, it is clear that these agents may be ineffective or less effective in some cases (5–7). Also, none of these is a cure. Plus, virtually all these agents display toxicities (8). It remains to be seen whether other disease related factors can be identified and targeted so as to increase efficacy and decrease toxicity of cancer and arthritis treatments.

In the case of drugs, safety and efficacy may be related to drug–drug interactions, either metabolism mediated drug interactions or transporter mediated drug interactions. In concert with metabolizing enzymes, transporters can govern a drug’s disposition and pharmacological action. The US Food and Drug Administration has recently published a final guidance document to assist investigators in determining whether drugs are affected by metabolism and or transporter interactions (9).

The continuing hope inherent in the concept of ‘conditional pharmacology’ is that the discovery of new, even more highly specific disease related targets may help in the development of drugs and biologics that are both more efficacious and, if possible, less toxic.

References

• 1. Whitehouse MW (1967) Disease-drug interactions: utility of the conditional concept for experimental pharmacology and toxicology in the context of inflammation. In: Rainsford KD, Velo GP (eds) Side-effects of anti-inflammatory drugs, vol 1. MTP Press, Lancaster, pp 259–274.

• 2. Whitehouse MW, Vernon-Roberts B (1991) Conditional pharmacology. Inflammopharmacology 1:61–68.

• 3. Whitehouse MW (1991) Disease–drug interactions: significance or insignificance of the ED50 value for anti-inflammatory agents. Inflammopharmacology 1:143–149.

• 4. Powanda MC (1995) The concept of conditional pharmacology and toxicology. Inflammopharmacology 3:363–371.

• 5. https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html.

• 6. https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html.

• 7. Romão VC, Vital EM, Fonseca JE et al. (2017) Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis? Arthritis Res Ther 19:239

• 8. Kahlenberg JM, Fox DA (2011) Advances in the medical treatment of rheumatoid arthritis. Hand Clin 27(1):11–20.

• 9. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/vitro-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions. January 2020, Docket Number: FDA-2017-D-5961.

A personal appreciation of Professor Michael W. Whitehouse

Frances J. W. Beck

Department of Medicine, School of Medicine, Wayne State University, Detroit, Michigan, USA

Early in the decade of 1970 at the University of California, Los Angeles (UCLA), one found Professor Michael W. Whitehouse investigating mediators of inflammation and their pathological importance in rheumatoid arthritis at a time when the new field of Immunology was at its rudimentary beginning. In addition, he was a research consultant to the late Dr. Louis Levy at Riker Laboratories (now 3 M) in Northridge, California where questions concerning effectiveness of anti-inflammatory compounds were also being addressed. At Riker, where compounds were both manufactured and evaluated, the question asked was: “Are these compounds effective in reducing the inflammatory response?”. However, most testing was done using healthy animals. Several years later, I was honoured to join Professor Whitehouse at UCLA where the question was turned around: “Does the physiological state (healthy/unhealthy {disease}) of the subject alter the ultimate efficacy of the drug being administered”. At the time, it was an interesting exercise in experimental research, but eventually, over time, it became clear that the answer would be a resounding “YES!” and is the central theme of today’s concept of ‘Conditional Pharmacology’ applied in nutrition, drug development, ageing studies and particularly in cancer research as well as in other disciplines. Thus, Professor Whitehouse had at that time laid the groundwork for both of our individual careers in academic research even though our respective careers would soon diverge. Two years later, Professor Whitehouse relocated to Australia where he would continue to investigate this subject in search of better treatments for arthritis for the rest of his academic career. However, before leaving, he was instrumental in providing arrangements with the late Dr. Carl Pearson that would allow me to continue our research at UCLA for the interim between his exit and the appointment of a new investigator to his former position. This provided for me an unprecedented opportunity to be an independent investigator responsible for the design and execution of experiments leading to several publication years before I was able to obtain advanced degrees. It was the grand initiation into an interesting, enjoyable and successful career in academic research.

In Australia, Professor Whitehouse continues to define the mechanisms by which adverse physiological conditions would affect drug efficacy using unique animal models that were developed during his time at UCLA. For his extensive research into the treatment of arthritis and inflammation, he was elected to Life Membership of the Australasian Society and the Australian Rheumatism Association of Clinical and Experimental Pharmacologist and Toxicologists. Although unaware of each other’s work, Professor Whitehouse’s research into the effect of zinc on the inflammatory response in a compromised system paralleled our similar studies at Wayne State University School of Medicine, Detroit, Michigan under the direction of Dr. Ananda Prasad. There, we demonstrated that multiple molecular mechanisms involved in the production and expression of inflammatory cytokines as well as the regulation of target receptors were altered in the physiological zinc deficient state whether zinc deficiency was nutritionally, experimentally or disease induced or genetically inherited. Later, in collaboration with the University of Queensland, Professor Whitehouse founded and managed research at Pharma Quest, a Consultancy to promote research on natural medicines. Near the same time, my work at the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan with Drs. Ramzi Mohammad and Ayad Al-Katib, was centered in evaluating the efficacy of anti-cancer compounds also isolated from natural sources. That cancer cells respond to specific drugs quite differently from that of normal cells is possibly the most complex form of the ‘Conditional Pharmacology’ concept embraced at UCLA 45 years earlier and now requires investigative research be executed at the molecular level. The search for compounds that modulate specific intracellular molecules aberrantly expressed in cancer cells but not in normal cells is at the core of cancer research pharmacology.

Before Professor Whitehouse became semi-retired from active research, our paths would cross once again. It was a privilege to share results of our respective research careers with each other and with his colleagues at the University of Queensland in 2002. Conversations concerning all manner of things discussed within the “Whitehouse Research Family” at UCLA years ago were easily continued as if it were but yesterday. Old acquaintances were remembered (Drs. Peter Fowler, J. P. Famaey, Carson Dick, Kim Rainsford to name a few) and new ones established. Sprinkled between seminars, conferences, presentations and experiments were short trips to explore nearby surrounding Australia with his dear wife and colleague, Desley Butters. Recently, he was awarded Chevalier of the Hospitalier of St. John’s of Jerusalem, one of many accolades he has received throughout his lifetime. On behalf of the many, many individuals who have benefited from Professor Whitehouse’s support and friendship we say “Congratulations on your many contributions to science, medicine and humanity, the honours are well deserved.” To Professor Whitehouse, the true honour for each of us, however, is to have been and continue to be your colleague and friend.

Some biographical reflections

Prof. M. W. Whitehouse

Griffith University, School of Medicine (Gold Coast Campus), and School of Biomedical Sciences (Nathan Campus), Queensland, Australia

Michael was born in Middlesex, North London, in 1930, both his parents being schoolteachers. He was raised first in Sheffield (Yorkshire), Wigan (Lancashire) and finally in Liverpool (Merseyside) from where he was twice evacuated to Wales, before heading south, first to Highgate School (North London) and then Oxford University.

After studying Chemistry and Biochemistry at Oxford he went off on a line of research that led through various aspects of molecular medicine; including chemistry of animal polysaccharides, sterol metabolism and ischaemic heart disease, cartilage degradation and osteoarthritis, toxicity of the adrenocorticoid hormones and non-steroidal anti-inflammatory drugs, including complexes of the coinage ‘noble metals’ Cu, Ag & Au used as ‘novel’ drugs to control inflammation. Resulting from a long-standing interest in immunological adjuvants as aetiologic agents in (poly)-arthritis, he undertook a search for environmental arthritogens (oils, bacteria) and for natural anti-inflammatories. These included those sourced from Aboriginal (Australia), Maori (New Zealand), Melanesian and Ayurvedic (India) traditions of healing. Recently he has returned to nutritional medicine, believing that low cost ‘Preventative Medicine’ is the most needed item for helping people world-wide to increase their wellbeing—without recourse to the expensive and/or labile (i.e. those needing refrigeration) medications promoted by the Western pharmaceutical industry.

For personal support he successively taught organic chemistry, biochemistry, endocrinology, molecular pharmacology, immunology, molecular pathology and toxicology in six medical schools (Oxford, Pennsylvania, Ohio State, California Los Angeles, Adelaide, Flinders South Australia), and worked in six hospitals (Serafima, Stockholm, University of California at Los Angeles, Royal North Shore, Sydney, Royal Newcastle, NSW, Christchurch, NZ, and Princess Alexandra, Brisbane). He reckons his best teaching (and stimulating learning) experiences were located outside the norm: particularly in the South Australian College of Natural Therapies (Adelaide, Australia) and the Canberra College of Advanced Education—all with eager mature students but regrettably little in the way of relevant textbooks.

One of the highlights of his early career was having the Australian pathologist Howard Florey OM, Nobel Laureate, President of the Royal Society UK and Professor of Pathology at Oxford as his ‘technical assistant’ (!) while doing research for the D.Phil degree at Oxford. This happened because Florey was rather fearful that cortisone, the new wonder drug for arthritis and septic shock, would damage the production of protective gastrointestinal mucins, just as it could severely damage the production of other carbohydrate polymers present in cartilage, skin, the vasculature, etc. Cortisone then being in extremely short supply in the UK (1954), the Medical Research Council would only provide small quantities to qualified investigators who would personally administer the drug, either to patients or for animal studies. So Florey began the experimental work by injecting duodenal-cannulated rabbits and Michael then measured intestinal mucin production (using the incorporation of ³⁵S-sulphate as a new tool to monitor mucin biodynamics). Outcomes from this early experience were learning to use radiotracers for metabolic studies and that toxicology was a most important aspect of therapeutics. Furthermore, personal status should be no hindrance to scientific collaboration. Subsequently, when the opportunity came to take sabbatical leave from Oxford (1966) to be a Visiting Fellow at the Australian National University, Canberra, Florey kindly facilitated this visit.

Another instructive experience was learning that if you saw a need for, or discovered a new research tool, you were then either ignored for an unwarranted period or almost immediately overwhelmed by other editors and authors who felt challenged to out-publish you. When Paul Kent and Michael wrote a book on the amino sugars in 1954, the first since PA Levene’s monograph on hexosamine and muco-proteins published in 1925, very soon thereafter a four volume compendium on glycosaminoglycan was produced by E. Balasz for Academic Press. Subsequently Bob Scherrer (then at the 3 M Research Minneapolis) and Michael prepared and edited a two volume treatise on Anti-Inflammatory Agents in 1974 (Academic Press NY). This was a monumental effort bringing together an immense literature on the medicinal chemistry of non-steroidal and steroidal anti-inflammatory drugs. This book is remarkable in that its contents are still current today. In 1967, Peter Ghosh and Michael serendipitously discovered the fluorigenic reagent, NBD chloride for detecting and labelling amino acids and peptides. It is still in use today, having been exploited and cited in over 2000 publications. Later, a look-alike NBD fluoride was patented, duly promoted and became undoubtedly profitable.

Another highlight was collecting and collating the supportive data for seven labour-intensive publications that gave him particular satisfaction. These were:

• 1964. Uncoupling of oxidative phosphorylation by salicylate analogues: relationship of structure to activity. Biochem Pharmacol 13:319–336.

• 1969. Passive transfer of adjuvant-induced arthritis and allergic encephalomyelitis in rats using thoracic duct lymphocytes. Nature 224:1322.

• 1974. Freund’s Adjuvant: relationship of arthritogenicity and adjuvanticity in rats to vehicle composition. Immunology 27:311–330.

• 1982. Rat polyarthritis: induction with adjuvants composed of various mycobacteria (and oils) from the environment. J Rheumatol 9:494–501.

• 2009. Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke. Inflamm Res 58:696–704.

• 2010. Questioning the safe use of vaccines containing squalene. Immunol Cell Biol 88:497–499.

• 2015. Silver pharmacology: past, present and questions for the future. Progr Drug Res 70:237–273.

The passage of time is still affording judgement and (re)appraisal of these publications.

Michael particularly appreciated being awarded research scholarships/fellowships throughout his career, particularly from the Medical Research Council UK, the English-Speaking Union, the Royal Society UK, Empire Rheumatism Council (now Arthritis UK) London, Exeter College Oxford, the Australian National University (ANU) Canberra, the National Academy of Sciences and National Institute of Health, Washington DC and the 3D Centre, University of Queensland. Currently he is Honorary Professor of Experimental Medicine at Griffith University, Gold Coast, Queensland, Australia, still particularly interested in alternative/neglected anti-inflammatories.

None of this would have been possible without the moral support of various heads of departments, colleagues and the able assistance of many storekeepers and animal attendants.

After-thoughts

• Nowadays, free thinkers and bench workers are being stifled with demands for frequent reports, changes in thinking and inability to discuss ideas outside the immediate group, etc. Gone are the days where a disparate group of researchers could sit drinking tea or having a beer together, discussing what they were doing and especially in sharing ideas.

• Its almost impossible to believe that the head of a pharmaceutical company would give one a cheque to assist travel expense and say, “Come back in 12 months and tell me what you’ve found out.” The ‘bean counters’ and ethics committees would be unable to relate to such a happening. Yet, this is precisely what Lou Sarett of Merck USA did in 1966. After 10 months Michael hadn’t found the golden elixir but had shown that methyl glyoxal (pyruvaldehyde) and cortisol aldehyde were potential endogenous metabolites that might behave as pseudo-NSAIDs in regulating lymphoid and epithelial cells (J Pharm Pharmacol 1967; 19:590–595).

• In 1992 while working in Adelaide he was asked by Peter Ghosh (then in Sydney) to help investigate the therapeutic potential of emu oil. Since European settlement in Australia, stories abound about the successful treatment of muscular ailments with emu oil as practised by the First Peoples of Australia. The West Australian Aboriginal community at Wiluna, with enlightened support from friends in Perth WA commissioned this work. So began an adventure learning about the life cycle and productivity of emus. [A case of pharming for farmaceuticals?] A provisional patent (PP) was lodged from Western Australia to protect their intellectual property. However, for some inexplicable reason the Australian Patents Office released the PP. An Aboriginal community in Queensland then claimed priority for the intellectual property but had never demonstrated its validity. The end result was that the good work and knowledge obtained was unable to be further financed.

• He was rather surprised on returning to Australia in 1973 to find that few, if any, universities had established animal ethics committees. In the UK and USA he had always worked within the guidelines of such committees. So with the help of two veterinarians, he set down some guidelines for working with animals in Australia, responding to a request from the National Health and Medical Research Council (NH&MRC). These guidelines, largely based on those in the UK, were written in a user-friendly style—unlike the very restrictive guidelines issued today.

• Later on, he was even more surprised when the Australian Government, having set up a Department of Productivity and Innovation, then awarded support for development of non-gastrotoxic aspirin formulations in collaboration with Kim Rainsford; only to have it rejected by the ANU on the grounds that they might be providing scarce facilities to promote a commercial enterprise!! [Good sense eventually prevailed: but it was an uncomfortable experience being branded a pariah by the ‘pathology establishment’ and initially denied approved government support.]

• Commercial collaborations within Australian university laboratories during the early 1970s were not generally encouraged. Yet, within 12 months of his leaving ANU the medical school was actively promoting such activities. Such a contrast to today when universities are encouraged to undertake research work for pharmaceutical and other organisation with shared patent rights and a business office to supervise negotiations.

• While at UCLA the then Californian governor (R Reagan) ordered the university’s closure in response to a vigorous student protest about extending the Vietnamese war into Cambodia. This lock-out also affected the university’s peripheral research and medical research on campus. No provision had been made for the welfare of animals under treatment. It was enforced by the presence of armed police, who had no interest in conducting further dialogues. So Michael used to crawl through the bushes to gain entry to the laboratory by the fire escape in order to feed, care for and treat his animals. This all had to be done by daylight, as anyone moving around at night was asking for serious trouble (police policy then being shoot first, ask questions later). This injustice/melodrama was further extended to the teaching staff who were then denied their incremental pay-rise that year—these extra funds being distributed to others who were no more deserving. In fact, the floor cleaner got a double bonus! The medical school teaching staff voluntarily repeated interrupted courses as students reappeared, being brave enough to try to continue ‘as normal’. Michael taught his contribution to the pharmacology and toxicology course three times over and had accordingly to conduct three sets of examinations. This determination to continue the education of medical students was never recognised by the State authorities. In fact, for supporting student rights to object, many teaching staff were ‘punished’ by being denied agreed prospects of promotion or tenure, as the University of California’s five-year plan was then junked/torn up by the State legislature. This was yet another re-enactment of the serious divide between politicians and educators. Consider the fate of Socrates 399 BCE “refusing to recognize the gods recognized by the state” and of “corrupting the youth.” (http://www.eyewitnesstohistory.com)

• An ill-mix of politics and science had got him into trouble previously in Czechoslovakia in the 1960s. While attending the International Congress of Rheumatology in Prague he found his way to the home of a Dr. X, a geneticist who had taught at the famed Charles University but who, unbeknownst to Michael, was apparently under house arrest. [His crime: pointing out that T.D Lysenko (a Russian)’s neo-genetics, as approved by Stalin, was false and that G. Mendel (a Slovak)’s theory should still be taught. For this, he was stripped of Czech citizenship, declared an enemy of the State, and therefore ineligible for a job and receipt of food rations.] Michael’s visit was on behalf of a supporter in London who was trying to find Dr. X a job in the UK; but meanwhile asked him to check on his welfare and give him $US50. The State police apparently knew of this visit and subsequently followed Michael around because his visitor’s visa was peremptorily terminated. The president of the Congress and Professor of Balneology in Prague, Franz Lenoch, spoke to Michael, insisting the conversation be in Latin; a somewhat arduous task for Michael not having used this classical language for 17 years. Very fortunately Milan Adam, a medical physiologist, took care of him as, no longer having a valid visa, he had to leave the country the next day. Milan made sure he was delivered to the airport where he had a body search and was stripped of all cash on his person, quite a memorable visit! Michael was able to add ‘persona non grata in the CSSR’ to his CV! As it so happened when he next applied for a Czech visa to attend a pharmacology congress, he had no trouble; the visa having been completed in the Czech language.

Publications—M. W. Whitehouse

Journal Publications

• Kent PW, Whitehouse MW (1953) 2,4,5-Trimethyl d-arabonamide. J Chem Soc 1953:2501–2502.

• Whitehouse MW, Kent PW, Peters RA, Foulkes EC (1954) Factors influencing the utilization of citrate by yeast. Biochem J 58:437–440.

• Whitehouse MW, Pasternak CA, Kent PW (1954) Acyclic derivatives of amino sugars. J Chem Soc 1954:2315–2318.

• Kent PW, Whitehouse MW (1955) Micro-determination of ester sulphates and free sulphate ions. Analyst 30:630–631.

• Kent PW, Whitehouse MW, Jennings MA, Florey HW (1956) Observations on the incorporation of 35S into duodenal mucosubstances. Q J Exp Physiol 41:230–246.

• Whitehouse MW, Moeksi H, Gurin S (1957) Synthesis and properties of fatty acyl adenylates. J Biol Chem 226:813–819.

• Whitehouse MW, Bresler AE, Staple E (1958) The use of iodine for the detection of lipids. J Chromatogr 1:385–386.

• Briggs T, Whitehouse MW, Staple E (1958) Moving acid-boundary (pH gradient) paper ionophoresis of bile salts. Nature 182:394.

• Zilliken Z, Whitehouse MW (1958) The nonulosaminic acids: neuraminic acids and related compounds. Adv Carbohyd Chem 13:237–263.

• Whitehouse MW, Kent PW (1958) Synthesis of methyl 2-acetamido-2-deoxy-d-glucofuranoside. Tetrahedron 4:425–429.

• Kritchevsky D, Whitehouse MW, Staple E (1959) Influence of dietary fat on the oxidation of cholesterol by rat liver mitochondria. Arch Biochem Biophys 30:221–222.

• Whitehouse MW, Staple E, Gurin S (1959) Catabolism in vitro of cholesterol: 1. Oxidation of the terminal methyl groups of cholesterol to carbon dioxide by rat liver preparations. J Biol Chem 234:276–281.

• Staple E, Whitehouse MW (1959) Synthesis of coprostane-3α, 7α, 12α-triol-27-C14 coprostane-3α, 7α, 12α triol-24-one-27-C14 and coprostane-3α, 7α, 12α, 24-tetrol-27-C14. J Org Chem 24:433–434.

• Staple E, Whitehouse MW (1959) Recent aspects of cholesterol biosynthesis and catabolism. Ann N Y Acad Sci 72:803–812.

• Whitehouse MW, Staple E (1959) Regulation of cholesterol oxidation by the liver in vitro. Proc Soc Exp Biol Med 101:439–441.

• Kritchevsky D, Kolman RR, Whitehouse MW, Cottrell MC, Staple E (1959) Oxidation of cholesterol by rat liver mitochondria; effect of dietary fat. J Lipid Res 1:83–89.

• Briggs T, Whitehouse MW, Staple E (1959) Formation of bile acids from cholesterol in the alligator. Arch Biochem Biophys 85:275–277.

• Kritchevsky D, Whitehouse MW, Staple E (1960) Oxidation of cholesterol by rat liver mitochondria; effect of nicotinic acid. J Lipid Res 1:154–158.

• Whitehouse MW, Zilliken F (1960) Isolation and determination of neuraminic (sialic) acids. Methods Biochem Anal 8:199–220.

• Whitehouse MW, Kritchevsky D, Staple E (1960) Oxidation of cholesterol by rat liver mitochondria; effect of metal ions. Arch Biochem Biophys 87:193–197.

• Lash JW, Whitehouse MW (1960) An unusual polysaccharide in chondroid tissue of the snail Busycon; Polyglucose sulphate. Biochem J 74:351–355.

• Whitehouse MW, Rabinowitz JL, Staple E, Gurin S (1960) Formation of acetone and acetoacetate from cholesterol by rat and mouse liver mitochondria. Biochem Biophys Acta 37:382–384

• Lash JW, Holtzer H, Whitehouse MW (1960) Studies on in vitro chondrogenesis; The uptake of radio-active sulphate during cartilage induction. Dev Biol 2:76–89.

• Kritchevsky D, Staple E, Whitehouse MW (1960) Regulation of cholesterol biosynthesis and catabolism. Am J Clin Nutr 8:411–423.

• Whitehouse MW, Lash JW (1960) Variation in polysaccharide composition of cartilage with age. Arch Biochem Biophys 90:159–161.

• Kritchevsky D, Langan J, Whitehouse MW (1960) Distribution of cholesterol amongst liver sub-cellular fractions. Experientia 1645:24–53.

• Whitehouse MW, Lash JW (1961) Effect of cortisone and related compounds on the biogenesis of cartilage. Nature 109:37–39.

• Whitehouse MW, Staple E, Gurin S (1961) Catabolism in vitro of cholesterol II. Further studies on the oxidation of cholesterol by rat liver mitochondria. J Biol Chem 236:68–72.

• Whitehouse MW, Staple E, Gurin S (1961) Catabolism in vitro of cholesterol III,- Oxidation of 3α, 7α, 12α- trihydroxycoprostane and 3α, 7α, 12α, 24-tetrahydroxycoprostane by rat liver mitochondria. J Biol Chem 236:73–75.

• Briggs T, Whitehouse MW, Staple E (1961) Metabolism of trihyroxycoprostanic acid; formation from cholesterol in the alligator and conversion to cholic acid and carbon dioxide in vitro by rat liver mitochondria. J Biol Chem 236:688–691.

• Lash JW, Whitehouse MW (1961) Effect of steroid hormones and some anti-inflammatory agents upon in vitro chondrogenesis. Lab Investig 10:388–396.

• Kritchevsky D, Staple E, Rabinowitz JL, Whitehouse MW (1961) Differences in cholesterol oxidation and biosynthesis in liver of male and female rats. Am J Physiol 200:519–522.

• Whitehouse MW, Bostrom H (1961) Studies on the action of some anti-inflammatory agents in inhibiting the biosynthesis of mucopolysaccharide sulphates. Biochem Pharmacol 7:135–150.

• Kritchevsky D, Staple E, Whitehouse MW (1961) Oxidation of ergosterol by rat and mouse liver mitochondria. Proc Soc Exp Biol Med 106:704–708.

• Whitehouse MW, Kritchevsky D (1962) Lack of correlation between serum cholesterol levels and cholesterol catabolism in rats. Atheroscler Res 2:47–49.

• Whitehouse MW (1962) Structure-action relationships among drugs acting on connective tissues (anti-rheumatic agents). Nature 194:984–985.

• Whitehouse MW, Briggs T, Cottrell MC, Staple E (1962) Catabolism in vitro of cholesterol; some comparative aspects. Arch Biochem Biophys 98:305–311.

• Whitehouse MW, Bostrom H (1962) Biochemical properties of anti-inflammatory drugs I. The effect of some anti-inflammatory (antirheumatic) drugs on the metabolism of connective tissues. Biochem Pharmacol 11:1175–1201.

• Whitehouse MW, Haslam JM (1962) Ability of some antirheumatic drugs to uncouple oxidative phosphorylation. Nature 196:1323–1324.

• Whitehouse MW, Kritchevsky D, Tepper SA, Staple E (1963) Influence of sex and sex hormones on the oxidation of cholesterol-26-14C by rat liver mitochondria. J Lipid Res 4:188–191.

• Moretti A, Whitehouse MW (1963) Changes in the mucopolysaccharide composition of bovine heart valves with age. Biochem J 87:396–402.

• Whitehouse MW (1963) A biochemical distinction between non-steroid anti-inflammatory and analgesic drugs. J Pharm Pharmacol 15:556–557.

• Lee MJ, Whitehouse MW (1963) The effect of bile salts and some bile salt analogues on the oxidation of cholesterol by liver mitochondria. Biochem J 89:189–195.

• Bostrom H, Moretti A, Whitehouse MW (1963) Studies on the biochemistry of heart valves 1. On the biosynthesis of mucopolysaccharides in bovine heart valves. Biochem Biophys Acta 74:213–221.

• Whitehouse MW (1964) Uncoupling of oxidative phosphorylation by some arylacetic acids (anti-inflammatory or hypocholesterolemic drugs). Nature 201:629–630.

• Bostrom H, Berntsen K, Whitehouse MW (1964) Biochemical properties of anti-inflammatory drugs II. Some effects on sulphate–35S metabolism in vivo. Biochem Pharmacol 13:413–420.

• Whitehouse MW (1964) Biochemical properties of anti-inflammatory drugs III. Uncoupling of oxidative phosphorylation in a connective tissue (cartilage) and liver mitochondria by salicylate analogues: relationship of structure of activity. Biochem Pharmacol 13:319–336.

• Whitehouse MW (1964) Uncoupling of oxidative phosphorylation by some inorganic compounds of pharmaceutical interest. Biochem J 92:36P.

• Smith GM, Parsons ME, Whitehouse MW (1964) Biochemical and pharmacological properties of some amidopyrine metabolites. J Pharm Pharmacol 16:830–831.

• Skidmore IF, Whitehouse MW (1965) Biochemical properties of anti-inflammatory drugs IV. Uncoupling of oxidative phosphorylation by resorcinols, tropolones and diones. Biochem Pharmacol 14:547–555.

• Whitehouse MW, Dean PDG (1965) Biochemical properties of anti-inflammatory drugs V. Uncoupling of oxidative phosphorylation by some gamma-resorcyl and other dihyroxybenzoyl compounds. Biochem Pharmacol 14:557–567.

• Lee MJ, Whitehouse MW (1965) Inhibition of electron transport and coupled phosphorylation in liver mitochondria by cholanic (bile) acids and their conjugates. Biochem Biophys Acta 100:317–328.

• Burke JF, Whitehouse MW (1965) Some biochemical properties of thio analogues of salicylic acid. Biochem Pharmacol 14:1039–1048.

• Whitehouse MW, Bostrom H (1965) Biochemical properties of anti-inflammatory drugs VI. The effects of chloroquine (resochin), mepacrine (quinacrine) and some of their potential metabolites on cartilage metabolism and oxidative phosphorylation. Biochem Pharmacol 14:1173–1184.

• Whitehouse MW, Skidmore IP (1965) Concerning the regulation of some diverse biochemical reactions, underlying the inflammatory response by salicylic acid, phenylbutazone and other acidic anti-rheumatic drugs. J Pharm Pharmacol 17:668–671.

• Skidmore IF, Whitehouse MW (1965) Effect of non-steroid anti-inflammatory drugs on aldehyde binding to plasma albumin. A novel in vitro assay for potential anti-inflammatory activity. J Pharm Pharmacol 17:671–673.

• Lee MJ, Parke DV, Whitehouse MW (1965) Regulation of cholesterol catabolism by bile salts and glycyrrhetic acid in vivo. Proc Soc Exp Biol Med 120:6–8.

• Dean PDG, Whitehouse MW (1965) The chemical synthesis and biological oxidation of 7a-¬hydroxy (26-14C) cholesterol, 7-dehydro (26-14C) cholesterol and 26-hydroxy (26-14C) cholesterol. Biochem J 98:410–419.

• Cowey FK, Whitehouse MW (1966) Biochemical properties of anti-inflammatory drugs VII: Inhibition of proteolytic enzymes in connective tissue by Chloroquine (resochin) and related antimalaria/anti-rheumatic drugs. Biochem Pharmacol 15:1071–1084.

• Leader JE, Whitehouse MW (1966) Uncoupling of oxidative phosphorylation by some salicylamide derivatives. Biochem Pharmacol 15:1379–1387.

• Skidmore IF, Whitehouse MW (1966) Concerning the regulation of some diverse biochemical reactions underlying the inflammatory response by salicylic acid, phenylbutazone and other acidic anti-rheumatic drugs (2nd communication). J Pharm Pharmacol 18:558–560.

• Dean PDG, Whitehouse MW (1966) Catabolism of 2-methyloctanoic acid and 3α-hydroxycholest–5-en-26-oic acid. Biochem J 101:632–635.

• Raggatt PR, Whitehouse MW (1966) Substrate and inhibitor specificity of the cholesterol oxidase in bovine adrenal cortex. Biochem J 101:819–830.

• Skidmore IF, Whitehouse MW (1966) Biochemical properties of anti-inflammatory drugs VIII: inhibition of histamine formation catalysed by substrate -specific mammalian histidine decarboxylases. Drug antagonism of aldehyde-binding to protein amino groups. Biochem Pharmacol 15:1965–1983.

• Fisher D, Whitehouse MW, Kent PW (1967) α-Xylosidase and β-galactosidase activities of mammalian connective tissues and other sources. Nature 213:204–205.

• Burke JF, Whitehouse MW (1967) Concerning the differences in uncoupling activity of isomeric dinitrophenols. Biochem Pharmacol 16:209–211.

• Dean PDG, Whitehouse MW (1967) The effects of mepyrapone (Su-4885) and some hypocholesterolaemic drugs on hepatic sterol and fatty acid oxidation. Biochem Pharmacol 16:441–446.

• Whitehouse MW, Leader JE (1967) Biochemical properties of anti-inflammatory drugs IX: uncoupling of oxidative phosphorylation and inhibition of a thiol enzyme (papain) by some cyclic α-diones and ninhydrin. Biochem Pharmacol 16:537–551.

• Dean PDG, Whitehouse MW (1967) Inhibition of hepatic sterol oxidation by cholanic (bile) acids and their conjugates. Biochem Biophys Acta 137:328–334.

• Skidmore IF, Whitehouse MW (1967) Biochemical properties of anti-inflammatory drugs X: the inhibition of serotonin formation in vitro and inhibition of the esterase activity of α-chymotrypsin. Biochem Pharmacol 16:737–751.

• Whitehouse MW (1967) Biochemical properties of anti-inflammatory drugs XI: structure-action relationship for the uncoupling of oxidative phosphorylation and inhibition of chymotrypsin by N-substituted anthranilates and related compounds. Biochem Pharmacol 16:753–760.

• Whitehouse MW, Skidmore IF (1967) Uncoupling of oxidative phosphorylation by some fluoro-compounds, notably perfluoropinacol. Biochem Pharmacol 16:911–915.

• Whitehouse MW, Dean PDG, Halsall TG (1967) Uncoupling of oxidative phosphorylation by glycyrrhetic acid, fusidic acid and some related triterpenoid acids. J Pharm Pharmacol 19:533–544.

• Whitehouse MW (1967) Evaluation of potential antirheumatic drugs in vitro using lymphocytes and epithelial cells. The selective action of indoxole, methyl glyoxal and chloroquine. J Pharm Pharmacol 19:590–595.

• Dean PDG, Halsall TG, Whitehouse MW (1967) Preparation of some derivatives of glycyrrhetic acid and oleanolic acid. J Pharm Pharmacol 19:682–689.

• Mitropoulos KA, Dean PDG, Whitehouse MW, Myant NB (1967) Conversion of 3α-hydroxycholest-5-en-26-oic acid into bile acids in vivo. Biochem J 105:31P.

• Whitehouse MW, Ghosh PB (1968) 4-Nitrobenzfurazans and 4-nitrobenzfuroxans: a new class of thiol-neutralising agents and potent inhibitors of nucleic acid synthesis in leucocytes. Biochem Pharmacol 17:158–161.

• Ghosh PB, Whitehouse MW (1968) Potential antileukemic and immunosuppressive drugs I: Preparation and in vitro pharmacological activity of some benzo-2,1,3-oxadiazoles (benzofurazans) and their N-oxides (benzofuroxans). J Med Chem 11:305–311.

• Ghosh PB, Whitehouse MW (1968) 7-Chloro-4-nitrobenzo-2-oxa-1, 3-diazole: a new fluorigenic reagent for amino acids and other amines. Biochem J 108:155–156.

• Kier LB, Whitehouse MW (1968) Similarities in the interatomic distances of some anti-inflammatory agents and inflammogenic amines: a possible insight into their common receptors. J Pharm Pharmacol 20:793–795.

• Witiak DT, Whitehouse MW (1969) Species differences in the albumin binding of 2,4,6-trinitrobenzaldehyde, chlorophenoxyacetic acids, 2-(4′-hydroxybenzene-azo)-benzoic acid (HBABA) and some other acidic drugs: the unique behaviour of rat plasma albumin. Biochem Pharmacol 18:971–977.

• Ghosh PB, Whitehouse MW (1969) Potential antileukemic and immunosuppressive drugs II: further studies with benzo-2,1,3-oxadiazoles (benzofurazans) and their N-oxides (benzofuroxans). J Med Chem 12:505–507.

• Whitehouse MW, Doskotch RW (1969) Selective inhibition of thymidine incorporation into lymphocytes by cucurbitacins B and D. Biochem Pharmacol 18:1790–1793.

• Witiak DT, Sokoloski TD, Whitehouse MW, Hermann P (1969) Species difference in the competitive binding of 2–(4′-hydroxybenzeneazo)-benzoic acid (HBABA) and α(4-chlorophenoxy)-β-methylpropionic acid (CPMPA) to serum albumin; a possible model system for studying allosteric transitions. J Med Chem 12:754–761.

• Witiak DT, Hackney RE, Whitehouse MW (1969) Inhibition of cholesterologenesis in vitro by chlorophenoxyacetic acids: effect of a-methyl groups. J Med Chem 12:697–699.

• Whitehouse DJ, Whitehouse MW, Pearson CM (1969) Passive transfer of adjuvant-induced arthritis and allergic encephalomyelitis in rats using thoracic duct lymphocytes. Nature 224:1322.

• Denko CW, Whitehouse MW (1970) Effects of colchicine in rats with urate crystal-induced inflammation. Pharmacology 3:229–242.

• Whitehouse MW, Bluestone R, Kippen I, Klinenberg JR (1970) When is a drug inactive? Concerning the uricosuric activity of some anti-inflammatory drugs. J Pharm Pharmacol 22:134–135.

• Bluestone R, Kippen I, Klinenberg JR, Whitehouse MW (1970) Effect of some uricosuric and anti-inflammatory drugs on the binding of uric acid to human serum albumin in vitro. J Lab Clin Med 76:85–90.

• Whitehouse MW (1971) Biochemical studies of flumefenine HCl (R-760), a novel anti-inflammatory drug. Proc West Pharmacol Soc 14:55–58.

• Whitehouse MW, Kippen I, Klinenberg JR (1971) Biochemical properties of anti-inflammatory drugs XII: inhibition of urate binding to human albumin by salicylate and phenylbutazone analogues and some novel anti-inflammatory drugs. Biochem Pharmacol 20:3309–3320.

• Ghosh PB, Ternai B, Whitehouse MW (1972) Potential anti-leukemic and immunosuppressive drugs III. Effects of homocyclic ring substitution on the in vitro drug activity of 4-Nitrobenzo-2,1,3,oxadiazoles (4-nitrobenzofurazans) and their N-oxides (4-Nitrobenzofuroxans). J Med Chem 15:255–260.

• Whitehouse MW, Droge MM, Struck RF (1972) Lymphocyte deactivation by cyclophosphamide metabolites and mannomustine. Proc West Pharmacol Soc 15:195–198.

• Levy L, Whitehouse MW, Beck FJ (1972) Effect of drugs on the host-response to parental lymphocytes in rats. Proc West Pharmacol Soc 15:200–202.

• Gerber RC, Whitehouse MW, Orr KJ (1972) Effect of gold preparations on the development and passive transfer of experimental allergic encephalomyelitis in rats. Proc Soc Exp Biol Med 140:1379–1384.

• Paulus HE, Machleder H, Bangert R, Stratton A, Goldberg L, Yu D, Whitehouse MW, Pearson CM (1973) Thoracic duct lymphocyte drainage in rheumatoid arthritis. Clin Immunol Immunopathol 1:173–175.

• Schlosstein LH, Kippen I, Whitehouse MW, Bluestone R, Paulus HE, Klinenberg JR (1973) Studies with some novel uricosuric agents and their metabolites: correlation between clinical activity and drug-induced displacement of urate from its albumin-binding sites’. J Lab Clin Med 82:412–418.

• Whitehouse MW, Levy L, Beck FJ (1973) Effect of cyclophosphamide on a local graft versus host reaction in the rat: influence of sex, disease and different dosage regimens. Agents Actions 3:53–60.

• Beck FJ, Whitehouse MW (1973) Effect of adjuvant disease in rats on cyclophosphamide and isophosphamide metabolism. Biochem Pharmacol 22:2453–2468.

• Beck FJ, Levy L, Whitehouse MW (1973) The local graft versus host reaction in the rat as a tool for drug mechanism studies. Br J Pharmacol 49:293–302.

• Whitehouse MW, Kippen I, Klinenberg JR, Schlosstein L, Campion DS, Bluestone R (1973) Increasing excretion of urate with displacing agents in man. Ann N Y Acad Sci 226:309–318.

• Famaey JP, Whitehouse MW (1973) Interactions between non-steroidal anti-inflammatory drugs and biological membranes II. Swelling and membrane permeability changes induced in some immunocompetent cells by various non-steroidal anti-inflammatory drugs. Biochem Pharmacol 22:2707–2717.

• Whitehouse MW, Famaey JP (1973) Concerning the pharmacological activity of non-steroid anti-inflammatory drugs; is the acidic function essential? Agents Actions 3:217–220.

• Whitehouse MW, Yu DTY (1974) Effect of some nitrogen mustards and thoracic duct drainage on lymphocyte distributions in rats. Int Arch Allergy 46:172–182.

• Beck FJ, Whitehouse MW (1974) Impaired drug metabolism in rats associated with acute inflammation: a possible assay for anti-injury agents. Proc Soc Exp Biol Med 145:135–140.

• Baumgartner WA, Beck FWJ, Lorber A, Whitehouse MW, Pearson CM (1974) Adjuvant disease in rats: biochemical criteria for distinguishing several phases of inflammation and arthritis. Proc Soc Exp Biol Med 145:625–630.

• Whitehouse MW, Beck FJ, Kacena A (1974) Some (pharmacological) properties of chloracetaldehyde, an oxidation product and potential metabolite of cyclophosphamide. Agents Actions 4:34–43.

• Levy L, Whitehouse MW (1974) Selective stimulation of a cellular immune response by methotrexate. Agents Actions 4:113–116.

• Whitehouse MW, Beck FWJ, Droge MM, Struck RP (1974) Lymphocyte deactivation by (potential immunosuppressant) alkylating metabolites of cyclophosphamide. Agents Actions 4:117–124.

• Bluestone R, Kippen I, Whitehouse MW, Campion D, Klinenberg J (1974) Urate binding: a clue to the pathogenesis of gout. J Rheumatol 1:230–233.

• Beck FWJ, Whitehouse MW (1974) Drug sensitivity of rat adjuvant arthritis induced with ‘Adjuvants’ containing no mineral oil components. Proc Soc Exp Biol Med 146:665–559.

• Beck FWJ, Whitehouse MW (1974) Modified assay for anti-arthritic drugs. Proc West Pharmacol Soc 17:284–287.

• Whitehouse MW, Orr KJ, Beck FWJ, Pearson CM (1974) Freund’s Adjuvants: Relationship of arthritogenicity and adjuvanticity in rats to vehicle composition. Immunology 27:311–330.

• Whitehouse MW, Schlosstein L, Kippen I, Bluestone R, Klinenberg JR (1974) Association between hypouricemia and jaundice. Ann Rheum Dis 33:308.

• Kippen IF, Whitehouse MW, Klinenberg JR (1974) Pharmacology of uricosuric drugs. Ann Rheum Dis 33:391–396.

• Famaey JP, Whitehouse MW (1974) About some biochemical properties of dimethyl sulfoxide and three of its homologues: is the acidic function essential for nonsteroidal anti-inflammatory activities? Agents Actions 4:259–263.

• Famaey JP, Whitehouse MW, Dick WC (1975) Interactions between nonsteroidal anti-inflammatory drugs and biological membranes III. Effect of non-steroidal anti-inflammatory drugs on bound mitochondrial bromothymol blue and possible intramitochondrial pH variations induced by these drugs. Biochem Pharmacol 24:267–275.

• Beck FWJ, Whitehouse MW (1975) Modified EAE as an assay for immunosuppressant drugs. Proc West Pharmacol Soc 18:136–140.

• Famaey JP, Whitehouse MW (1975) Some possible anti-inflammatory properties of various membrane permeant agents. Agents Actions 5:133–136.

• Famaey JP, Whitehouse MW (1975) Interaction between nonsteroidal anti-inflammatory drugs and biological membranes IV. Effects of non-steroidal anti-inflammatory drugs and of various ions on the availability of sulphydryl groups on lymphoid cells and mitochondrial membrane. Biochem Pharmacol 24:1609–1615.

• Whitehouse MW, Beck FWJ (1975) Irritancy of cyclophosphamide-derived aldehydes (acrolein, chloracetaldehyde) and their effect on lymphocyte distribution in vivo: Protective effect of thiols and bisulphite ions. Agents Actions 5:541–548.

• Rainsford KD, Whitehouse MW (1976) Concerning the merits of copper aspirin as a potential anti-inflammatory drug. J Pharm Pharmacol 28:83–86.

• Beck FWJ, Whitehouse MW, Pearson CM (1976) A simplified technique for inducing experimental allergic encephalomyelitis in rats. Proc Soc Exp Biol Med 151:615–620.

• Beck FWJ, Whitehouse MW (1976) Modifications in the establishment of allergic encephalomyelitis in rats: an improved assay for immunosuppressant drugs. Agents Actions 6:460–467.

• Denko CW, Whitehouse MW (1976) Experimental inflammation induced by naturally occurring microcrystalline calcium salts. J Rheumatol 3:54–62.

• Rainsford KD, Whitehouse MW (1976) Gastric irritancy of aspirin and its congeners: anti-inflammatory activity without this side effect. J Pharm Pharmacol 28:599–601.

• Rainsford KD, Whitehouse MW (1976) Gastric mucus effusion elicited by oral copper compounds: potential anti-ulcer activity. Experientia 32:1172–1173.

• Famaey JP, Whitehouse MW (1976) Effects of non-steroid anti-inflammatory drugs on the uptake of various cations by lymphoid cells. Arch Int Physiol Biochem 84:719–734.

• Barritt GJ, Whitehouse MW (1977) Pathobiodynamics: effects of extrahepatic inflammation on calcium transport and drug metabolism by rat liver mitochondria in vitro I. Biochem Med 17:99–115.

• Whitehouse MW, Rainsford KD (1977) Aspirin as a pathogen: some possible solutions for this problem. Drugs Exp Clin Res 2:133–137.

• Fujihira E, Whitehouse MW (1977) Pathobiodynamics: Reduced ascorbate excretion by rats with severe inflammation I. Proc Soc Exp Biol Med 155:361–364.

• Rainsford KD, Whitehouse MW (1977) Non-steroid anti-inflammatory drugs: Combined assay for anti-edemic potency and gastric ulcerogenesis in the same animal. Life Sci 21:371–377.

• Poon PYW, Whitehouse MW (1978) Pathobiodynamics: changes in ascorbate metabolism in rats with peripheral inflammation. Biochem Med 20:81–86.

• Famaey JP, Whitehouse MW (1978) Some common biochemical and pharmacological properties of bile salts and non-steroidal anti-inflammatory drugs. Arch Int Physiol Biochem 86:577–591.

• Fujihira E, Sandeman VA, Whitehouse MW (1979) Pathobiodynamics: reduction in hepatic and intestinal ligandin (glutathione S-transferase) level in rats with severe acute and chronic inflammation. Biochem Med 22:175–191.

• Rainsford KD, Whitehouse MW (1980) Are all aspirins really alike? A comparison of gastric ulcerogenicity with bio-efficacy in rats. Pharmacol Res Commun 12:85–95.

• Rainsford KD, Whitehouse MW (1980) Biochemical gastro-protection from acute ulceration induced by aspirin and related drugs. Biochem Pharmacol 29:1281–1289.

• Beveridge SJ, Whitehouse MW (1980) Anti-inflammatory activity of a dermally applied copper salicylate preparation (Alcusal™). Agents Actions 10:38–47.

• Broomhead JA, Fairlie DP, Whitehouse MW (1980) Cis-platinum (II) amine complexes: some structure–activity relationships for immunosuppressive nephrotoxic and gastrointestinal (side) effects in rats. Chem Biol Interact 31:113–132.

• Aggarwal SK, Broomhead JA, Fairlie DP, Whitehouse MW (1980) Platinum drugs: Combined anti-lymphoproliferative and nephrotoxicity assay in rats. Cancer Chemother Pharmacol 4:249–258.

• Beveridge SJ, Walker WR, Whitehouse MW (1980) Anti-inflammatory activity of copper salicylates applied to rats percutaneously in dimethylsulphoxide with glycerol. J Pharm Pharmacol 32:425–427.

• Rainsford KD, Whitehouse MW (1980) Gastroprotective and anti-inflammatory properties of a green-lipped mussel (Perna canaliculus) preparation. Arzneim-Forsch 30:2128–2132.

• Rainsford KD, Whitehouse KD (1980) Anti-inflammatory/antipyretic salicylic acid esters with low gastric ulcerogenic activity. Agents Actions 10:451–456.

• Rainsford KD, Schweitzer A, Green P, Whitehouse MW, Brune K (1980) Biodistribution in rats of some non-gastrotoxic salicylates. Agents Actions 10:457–464.

• Whitehouse MW, Rainsford KD (1980) Esterification of acidic anti-inflammatory drugs suppresses their gastrotoxicity without adversely affecting their anti-inflammatory activities in rats. J Pharm Pharmacol 32:795–796.

• Roos IA, Fairlie DP, Whitehouse MW (1980) A peculiar toxicity manifested by platinum (II) amines in rats: gastric distension after intraperitoneal administration. Chem Biol Interact 35:111–117.

• Denko CW, Petricevic M, Whitehouse MW (1981) Inflammation in relation to dietary intake of zinc and copper. Int J Tissue React 3:73–76.

• Denko CW, Petricevic M, Whitehouse MW (1981) 35S Incorporation in rats in relation to deprivation of copper and zinc in the diet. Int J Tissue React 3:121–125.

• Beveridge SJ, Whitehouse MW, Walker WR (1982) Lipophilic copper (II) formulations: Some correlations between their composition and anti-inflammatory/anti-arthritic activity when applied to the skin of rats. Agents Actions 12:225–231.

• Andrews JL, Ghosh P, Ternai B, Whitehouse MW (1982) Ammonium 4-chloro-7-sulphobenzofurazan (Sbf-Cl): a new fluorigenic thiol-specific reagent. Arch Biochem 214:386–396.

• Fairlie DP, Whitehouse MW (1982) Lymphoid suppression by cis platinum (II) amines: What are the active agents? Biochem Pharmacol 31:933–939.

• Whitehouse MW (1982) Rat polyarthritis: induction with adjuvants composed of various mycobacteria (and oils) from the environment. J Rheumatol 9:494–501.

• Burkhardt D, Ghosh P, Ternai B, Whitehouse MW (1982) Effects of 4-nitro and 4-sulpho-7-substituted benzofurazans on nucleic acid and protein synthesis of a malignant fibrosarcoma cell line in combination with mild hyperthermia. Chem Biol Interact 42:195–207.

• Whitehouse MW, Edwards L, Ghosh PB, Ternai B (1982) 7-chloro-4-sulfobenzofurazan: a novel fluorigen to assay glutathione-transferase/ligandin levels. Clin Exp Pharmacol Physiol 9:455.

• Whitehouse MW, Rainsford KD (1983) Prevention of the gastrotoxicity of aspirin and related drugs in rats by lithium salts and sodium thiocyanate. Toxicol Appl Pharmacol 68:323–323.

• Miners J, Fearnley I, Smith KJ, Birkett DJ, Brooks PM, Whitehouse MW (1983) Analyses of D-pencillamine in plasma by fluorescence derivatisation with N-(p-(2-Benzoxazolyl)-phenyl) maleimide and high performance liquid chromatography. J Chromatogr 275:89–96.

• Beveridge SJ, Boettcher B, Walker WR, Whitehouse MW (1984) Biodistribution of 64Cu in rats after topical application of two lipophilic anti-inflammatory Cu(II) formulations. Agents Actions 14:291–295.

• Betts WH, Cleland LG, Gee DJ, Whitehouse MW (1984) Effects of D-Penicillamine on a model of oxygen-derived free radical-mediated tissue damage. Agents Actions 14:283–290.

• Garrett IR, Whitehouse MW, Vernon-Roberts B (1985) Ambivalent properties of gold drugs in adjuvant-induced polyarthritis in rats. J Rheumatol 12:1079–1082.

• Beveridge SJ, Garrett IR, Whitehouse MW, Vernon-Roberts B, Brooks PM (1985) Biodistribution of 64Cu in inflamed rats following administration of two anti-inflammatory copper complexes. Agents Actions 17:104–111.

• Cleland LG, Whitehouse MW, Betts WH (1985) Gentisate, a salicylate metabolite with antioxidant properties. Drugs Expt Clin Res 11:463–467.

• Whitehouse MW, Rainsford KD (1985) A model of peripheral microvascular injury: Irreversible caudal necrosis in carrageenan-inflamed rats treated with anti-inflammatory drugs and mild chilling. Int J Tissue React 7:127–131.

• Whitehouse MW, Cleland LG (1985) Reactive oxygen species and drug therapy for inflammatory diseases. Agents Actions Suppl 17:177–188.

• Whitehouse MW, Betts WM, Cleland LG, Vernon-Roberts B (1985) In vitro antioxidant properties of potential biotransformation products of salicylate, sulphasalazine and amidopyrine. J Free Radic Biol Med 1:273–280.

• Whitehouse MW (1986) Oxicams: relative safety and anti-injury effects in rats. Brit J Clin Pharmacol 22(Suppl 2):111S–116S.

• Fairlie DP, Whitehouse MW, Broomhead JA (1987) Irritancy and anti-inflammatory activity of bis (cyclopentadienyl)-titanium (IV) complexes in rats. Chem Biol Interact 61:277–291.

• McColl SR, Cleland LG, Whitehouse MW, Vernon-Roberts B (1987) Effect of dietary polyunsaturated fatty acid supplementation on adjuvant-induced polyarthritis in rats. J Rheumatol 14:197–201.

• Haynes DR, Garrett IR, Whitehouse MW, Vernon Roberts B (1988) Do gold drugs inhibit IL-1? Evidence from an in vitro (LAF) assay. J Rheumatol 15:775–778.

• Forbes IJ, Zalewski PD, Hurst NP, Gionnakis C, Whitehouse MW (1989) Zinc increases phorbol ester receptors in intact B cells, neutrophil polymorphs and platelets. FEBS Lett 247:445–447.

• Rofe AM, Whitehouse MW, Bourgeois CS, Haynes DR, Vernon-Roberts B (1990) Prevention of adjuvant-induced cachexia in rats by cyclosporin-A. Immunol Cell Biol 68:63–69.

• Whitehouse MW, Rainsford KD, Taylor RM, Vernon-Roberts B (1990) Zinc monoglycerolate: a slow-release source of zinc with anti-arthritic activity in rats. Agents Actions 31:47–58.

• Whitehouse MW, Hann C, Ford G, Vernon-Roberts B (1990) Polyunsaturated fatty acids are pharmacoactive when given transdermally: anti-inflammatory activity in polyarthritic rats. Proc Nutr Soc Austr 15:28.

• Haynes DR, Wright PF, Whitehouse MW, Vernon-Roberts B (1990) The cyclo-oxygenase inhibitor, Piroxicam, enhances cytokine-induced lymphocyte proliferation in vitro and in vivo. Immunol Cell Biol 68:225–230.

• Haynes DR, Whitehouse MW, Vernon-Roberts B (1991) The effects of some anti-arthritic drugs and cytokines on the shape and function of rodent macrophages. Int J Exp Pathol 72:9–22.

• Whitehouse MW (1991) Trace element supplements for inflammatory disease. In: Dixon J, Furst D (eds) Second line agents in the rheumatic diseases. Marcel Dekker, New York, pp 549–578.

• Whitehouse MW (1991) Disease-drug interaction: significance or insignificance of the ED50 value for anti-inflammatory agents. Inflammopharmacology 1:143–149.

• Harker CSW, Tiekink ERT, Whitehouse MW (1991) Studies on the interaction of Gold (l) phosphines with 2-thiouracil. Inorg Chim Acta 181:23–30.

• Fairlie DP, Whitehouse MW, Taylor RM (1992) Zinc monoglycerolate, a slow release source of zinc and glycerol: solubilisation by bioconstitutent ligands. Agents Actions 36:152–158.

• Rainsford KD, Whitehouse MW (1992) Anti-ulcer activity of a slow-release zinc complex, zinc monoglycerolate (GlyzincR). J Pharm Pharmacol 44:476–482.

• Haynes DR, Whitehouse MW, Vernon-Roberts B (1992) The prostaglandin E1 analogue, Misoprostol, regulates inflammatory cytokines and immune functions in vitro like the natural Prostaglandins E1, E2 and E3. Immunology 76:251–257.

• Taylor RM, Slade PG, Aldous GL, Wilding IR, Whitehouse MW, Siddiqui (1992) Preparation and properties of a glycerolato-calcium complex. Aust J Chem 45:1179–1185.

• Whitehouse MW, Gadd SJ, Vernon-Roberts B (1992) Conditional Pharmacology II: ambivalent effects of aurocyanide, a putative active metabolite of anti-arthritic gold drugs, on human and rat PMN Leukocytes. Inflammopharmacology 1:305–314.

• Rofe AM, Philcox JC, Haynes DR, Whitehouse MW, Coyle P (1992) Changes in plasma, zinc, copper, iron and hepatic metallothionein in adjuvant-induced arthritis treated with cyclosporin. Biol Trace Element Res 34:237–248.

• Haynes DR, Wright PFA, Gadd SJ, Whitehouse MW, Vernon-Roberts B (1993) Is aspirin a prodrug for antioxidant and cytokine-modulating oxymetabolites. Agents Actions 39:49–58.

• Bolton M, Haritos VS, Whitehouse MW, Ahokas JT (1994) Ammonium 4-Chloro-7-Sulfobenzofurazan—a fluorescent substrate highly specific for rat glutathione-S-Transferase subunit-3. Analyt Biochem 216:418–423.

• Cookson PD, Tiekink ERT, Whitehouse MW (1994) Phosphinegold (I) complexes containing the purine-6-thiolate anion and their antiarthritic activity. Aust J Chem 47:577–586.

• Whitehouse MW, Fairlie DP, Thong YH (1994) Anti-inflammatory activity of the isoquinoline alkaloid, tetrandrine, against established adjuvant arthritis in rats. Agents Actions 42:123–127.

• Whitehouse MW, Fairlie DP (1994) Anti-inflammatory activity of a holothurian (sea cucumber) food supplement in rats. Inflammopharmacology 2:411–417.

• Whitehouse MW, Sun D, Ghosh P (1995) A deer cartilage preparation (Cervusen R) contains type II collagen and is orally active in the rat adjuvant arthritis model (Abstract). Aust N Z J Med 25:400.

• Rainsford KD, Whitehouse MW, Vernon-Roberts B (1995) Effects of the prostaglandin E1 analogue, misoprostol, on the development of adjuvant arthritis in rats. Inflammopharmacology 3:49–63.

• Haynes DR, Gadd SJ, Whitehouse MW, Mayrhofer G, Vernon-Roberts B (1996) Complete prevention of the clinical expression of adjuvant-induced arthritis in rats by cyclosporine-A and lobenzarit. The regulation of lymph node cell populations and cytokine production. Inflamm Res 45:159–165.

• Whitehouse MW, Graham GG (1996) Is local biotransformation the key to understanding the pharmacological activity of salicylates and gold drugs? Inflamm Res 45:579–582.

• Snowden JM, Whitehouse MW (1997) Anti-inflammatory action of emu oil. Inflammopharmacology 5:127–132.

• van Dalen CJ, Whitehouse MW, Winterbourne CC, Kettle AJ (1997) Thiocyanate and chloride as competing substrates for myeloperoxidase. Biochem J 327:487–492.

• Whitehouse MW, Macrides TA, Kalafatis N, Betts WH, Haynes DR, Broadbent J (1997) Anti-inflammatory activity of a lipid fraction (Lyprinol) from the NZ green-lipped mussel. Inflammopharmacology 5:237–246.

• Whitehouse MW, Turner AG, Davis CKC, Roberts MS (1998) Emu Oil(s): a source of non-toxic transdermal anti-inflammatory agents in Aboriginal medicine. Inflammopharmacology 6:1–8.

• Whitehouse MW, Cookson PD, Siasios G, Tiekink ERT (1998) Anti-arthritic activity in rats of some phosphine-gold(I) thionucleobases and related thiolates. Metal-based Drugs 5:245–249.

• Hung DY, Mellick GD, Masci PP, Whitaker AN, Whitehouse MW, Roberts MS (1998) Focused antithrombotic therapy: novel anti-platelet salicylates with reduced ulcerogenic potential and higher first-pass detoxification than aspirin in rats. J Lab Clin Med 132:469–477.

• Whitehouse MW, McGeary RP (1999) Concerning the anti-arthritic action of cetyl myristoleate in rats: an interim report. Inflammopharmacology 7:303–310.

• Megwa SA, Cross SE, Whitehouse MW, Benson HAE, Roberts MS (2000) Effect of ion pairing with alkylamines on the in vitro and in vivo dermal penetration of salicylates. J Pharm Pharmacol 52:929–940.

• Harbison SJ, Whitehouse MW (2000) Possible steroid-sparing effect in asthma of Lyprinol, a shellfish lipid extract. Med J Aust 173:560.

• Shiels IA, Whitehouse MW (2000) Lyprinol: anti-inflammatory and uterine-relaxant activities in rats, with special reference to a model for Dysmenorrhoea. Allergie et Immunologie, Paris 32:279–283.

• Whitehouse MW, Butters DE, Clarke ML, Rainsford KD (2001) NSAID gastropathy: prevention by celery seed extracts in disease-stressed rats. Inflammopharmacology 9:201–209.

• Whitehouse MW, Butters DE (2003) Combination anti-inflammatory therapy: synergism in rats of NSAIDs/corticosteroids with some herbal/animal products. Inflammopharmacology 11:453–464.

• Hansford KA, Reid RC, Clark CI, Tyndall JDA, Whitehouse MW, Guthrie T, McGeary RP, Schafer K, Martin JL, Fairlie DP (2003) d-Tyrosine as a chiral precusor to potent inhibitors of human nonpancreatic secretory phospholipase A2 (IIa) with anti-inflammatory activity. Chem Biol Chem 4:181–185.

• Whitehouse MW (2005) Prostanoids as friends, not foes: further evidence from the interference by cyclooxygenase-inhibitory drugs when inducing tolerance to experimental arthritigens in rats. Inflammopharmacology 12:481–492.

• Rainsford KD, Whitehouse MW (2006) Paracetamol [acetaminophen]-induced gastrotoxicity: revealed by induced hyperacidity in combination with acute or chronic inflammation. Inflammopharmacology 14:150–154.

• Ghosh P, Shimmon S, Whitehouse MW (2006) Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: a novel approach to therapy. Inflammopharmacology 14:155–162.

• Hung DY, Siebert GA, Chang P, Whitehouse MW, Fletcher L, Crawford DHG, Roberts MS (2006) Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation. Am J Physiol Gastroint Liver Physiol 290:G343–G351.

• Mo Y-K, Kankavi O, Masci PP, Mellick GD, Whitehouse MW, Boyle GM, Parsons PG, Roberts MS, Cross SE (2007) Surfactant protein expression in skin: evidence and implication. J Investig Dermatol 127:381–386.

• Sheean PD, Hodges LD, Kalafatis N, Wright PFA, Wynne PM, Whitehouse MW, Macrides TA (2007) Bioactivity of extracts from gonadal tissue of the edible Australian purple sea urchin Heliocidaris erythrogramma. J Sci Food Agric 87:694–702.

• Graham GG, Whitehouse MW, Bushell GR (2008) Aurocyanide, dicyano-aurate(I), a pharmacologically active metabolite of medicinal gold complexes. Inflammopharmacology 16:126–132.

• Brown CR, Whitehouse MW, Tiekink ERT, Bushell GR (2008) Colloidal metallic gold is not bio-inert. Inflammopharmacology 16:133–137.

• Whitehouse MW, Jones M (2009) Pro-inflammatory activity in rats of thiocyanate, a metabolite of the hydrocyanic acid inhaled from tobacco smoke. Inflamm Res 58:693–710.

• Roberts MS, Liu X, Zou Y, Siebert GA, Chang P, Whitehouse MW, Fletcher L, Crawford DH (2011) Effect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate. Am J Physiol Gastrointest Liver Physiol 300:G130–G136.

• Khan MA, El-Khatib R, Rainsford KD, Whitehouse MW (2012) Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids. Bioorg Chem 40:30–38.

• Newbould BB, Pearson CM, Whitehouse MW (2019) Passive transfer of allergic encephalomyelitis in rats: a tool for drug mechanism studies and detecting late-acting immunosuppressants. Inflammopharmacology. https://doi.org/10.1007/s10787-019-00565-w.

• Whitehouse MW (2019) Conditional nutrition (I): concerning zinc as a beneficial but variable regulator of inflammation and experimental arthritis. Inflammopharmacology. https://doi.org/10.1007/s10787-019-00669-3.

Reviews and chapters in books

• Kent PW, Whitehouse MW (1955) Biochemistry of the amino-sugars Butterworths Scientific Publications, London and New York: Academic Press, pp 311–350.

• Zilliken Z, Whitehouse MW (1958) The nonulosaminic acids: neuraminic acids and related compounds. Adv Carbohyd Chem 13:237–263.

• Staple E, Whitehouse MW (1959) Recent aspects of cholesterol biosynthesis and catabolism. Ann N Y Acad Sci 72:803–812.

• Whitehouse MW (1962) Enzymes of lipid metabolism. Desnuelle P (ed) Pergamon Press, Oxford, pp 69–73.

• Whitehouse MW (1963) Some effects of salicylates upon connective tissue metabolism. In: Dixon A, St J, Martin BK, Smith MJH, Wood PHN (eds) Salicylates, an international symposium. J & A. Churchill, London, pp 55–64.

• Kritchevsky D, Whitehouse MW, Staple E (1963) Oxidation of cholesterol-26-14C by rat liver mitochondria; influence of sex hormones. In: Horning E (ed) Proceedings of the first international pharmacology meeting, vol 2. Pergamon Press, Oxford, p. 23.

• Whitehouse MW (1964) Drugs, hormones and other factors influencing steroid and sterol metabolism. In: Paoletti R (ed) Lipid pharmacology. Academic Press, New York, pp 185–210.

• Whitehouse MW (1964) Some biochemical and pharmacological properties of anti-inflammatory drugs. In: Jucker E (ed) Arzneimittel. Forsch. [Progr. Drug Res.], vol 8. Birkhäuser, Basel, pp 321–429.

• Whitehouse MW, Dean PDG, Raggatt PR (1966) Drugs and other regulators of cholesterol catabolism. Progr Biochem Pharmacol 2:30–36.

• Whitehouse MW (1965) Some biochemical properties of non-steroid anti-inflammatory drugs which may determine their clinical activity. In: Garattini S, Dukes MGN (eds) Non-steroid anti-inflammatory drugs. Excerpta Medica Fnd., Amsterdam, pp 52–56.

• Whitehouse MW (1966) Wirkungsmechamismus entzundungshemmender Arzneimittel auf molekularer Ebene. In: Heister R, Hofmann RHF (eds) Die Entzundung. Urban and Schwarzenberg, Munich, pp 239–243.

• Whitehouse MW (1968) Molecular pharmacology of anti-inflammatory drugs: some possible mechanisms of action at the biochemical level. Biochem. Pharmacol., supplement—chemical biology of inflammation, pp 293–307.

• Whitehouse MW (1969) Concerning the design of anti-inflammatory drugs: some considerations based on pessimism, molecular pharmacology and cellular pathology. Pure Appl Chem 19:35–47.

• Whitehouse MW (1970) Contributions from pharmacological studies at the cellular and supramolecular level. In: Proc. symp. investigation of antirheumatic drug activity: a critical approach to traditional and potential experimental models. Proc. IVth International Congress of Pharmacology, Basel 1969, vol IV. Schwabe and Co., Basel, pp 203–207.

• Whitehouse MW (1971) The mediators of inflammation and their pathogenetic importance in rheumatoid arthritis—with special reference to lymphocytes and their regulation. In: Muller W, Harwerth HG, Fehr K (eds) Rheumatoid arthritis: pathogenetic mechanisms and consequences in therapeutics. Academic Press, London, pp 197–208.

• Whitehouse MW, Paulus HE (1972) Drugs for chronic inflammatory disease. In: Rubin A (ed) Search for new drugs. Marcel Dekker, New York, pp 1–114.

• Whitehouse MW (1972) Biochemistry of heavy metal toxicity. Ann Intern Med 76:787–791.

• Whitehouse MW, Pearson CM, Paulus HE (1972) Animal models for rheumatoid arthritis and their extension to man. In: Proceedings of the Carlo Erba Symposium on Rheumatoid Arthritis, San Remo: A Medical Summit Monograph.

• Paulus HE, Whitehouse MW (1973) Non-steroid anti-inflammatory agents. Annu Rev Pharmacol 13:107–125.

• Whitehouse MW (1973) Search for novel uricosuric agents. Ann Intern Med 78:102–104.

• Whitehouse MW, Beck FJ (1973) Impaired drug metabolism in rats with adjuvant-induced arthritis: a brief review. Drug Metab Dispos 1:251–255.

• Whitehouse MW, Floersheim GF (1973) A problem of nomenclature: Immunopharmacology (editorial). Agents Actions 3:52.

• Whitehouse MW (1973/4) Search for new drugs. Info 6(4) Winter, 1973/4.

• Whitehouse MW (1973) A problem of nomenclature (II): Freund’s adjuvants (editorial). Agents Actions 3:221–222.

• Whitehouse MW (1973) Abnormal drug metabolism in rats after an inflammatory insult. Agents Actions 3:312–316.

• Whitehouse MW, Beck FJ (1973) Impaired drug metabolism in rats with adjuvant-induced arthritis: a brief review. In: Estabrook RW, Gillette JR, Leibman KC (eds) Microsomes and drug oxidations. Williams and Wilkins Co., Philadelphia, p 251.

• Klinenberg JR, Bluestone R, Whitehouse MW, Campion D (1974) Binding of urate to plasma protein. Int. Symp. Purine Metab. in Man, Tel-Aviv 1973. Adv Exp Med Biol 41B:557–561.

• Whitehouse MW (1974) Soft immunodepressants: drugs to disarm over enthusiastic leucocytes. In: Velo GP, Willoughby DA, Giroud JP (eds) Future trends in. inflammation. Piccin Medical Books, Padua and London, pp 365–379.

• Whitehouse MW, Scherrer RA (eds) (1974) Anti-inflammatory agents (Chemistry and Pharmacology). In: de Stevens G (ed) A monograph 2 vols. Medicinal Chemistry Series. Academic Press, New York.

• Whitehouse MW (1974) Introduction and background to the regulation of inflammation and the immune response. In: Anti-inflammatory agents (chemistry and pharmacology), vol II. Academic Press, New York, pp 1–31.

• Whitehouse MW, Beck FWJ (1974) (Editorial) Standardisation of arthritogenic adjuvants for evaluating anti-inflammatory and immunosuppressant drugs. Agents Actions 4:227–229.

• Whitehouse MW, Levy J (1975) Experimental evaluation of immunosuppressive drugs in the context of connective tissue diseases. In: Buchanan WW, Dick WC (eds) Recent advances in rheumatology, vol 2. Churchill-Livingstone, Edinburgh.

• Whitehouse MW (1975) Timely appraisal: ectopic (exocellular) nucleic acid as a drug target, especially in rheumatoid arthritis and certain cancers. Agents Actions 5:508–511.

• Whitehouse MW (1975) Problems of nomenclature III: ambiguous abbreviations and catchwords. Agents Actions 5:181–182.

• Whitehouse MW (1976) Some problems and pitfalls in inflammation research. Agents Actions 6:44–49.

• Whitehouse MW (1976) Ambivalent role of copper in inflammatory disorders. Agents Actions 6:201–206.

• Whitehouse MW, Rainsford KD, Ardlie NG, Young IG, Brune K (1976) Alternatives to aspirin, derived from biological sources. In: Actions and uses of aspirin and related drugs. Agents Actions, Suppl. 1. Birkhäuser Verlag, Basel, pp 43–57.

• Whitehouse MW (1977) Biochemical complexities of inflammatory disease affecting drug action. In: Recent developments in the pharmacology of inflammatory mediators. Agents Actions Suppl. 2:135–147.

• Whitehouse MW, Rainsford KD (1977) Side effects of anti-inflammatory drugs. Are they essential or can they be circumvented? In: Inflammation mechanisms and their impact on therapy. Agents Actions, Suppl. 3. Birkhäuser, Basel, pp 171–187.

• Whitehouse MW (1977) Immunological adjuvants: help still needed here (Editorial). Agents Actions 7:251–253.

• Whitehouse MW, Field L, Hanley WS (1977) A potential hazard: the toxicity of zinc with penicillamine (Letter). Arthritis Rheumatol 20:1035.

• Whitehouse MW (1977) Biochemical complexities of inflammatory disease affecting drug action. In: Recent developments in the pharmacology of inflammatory mediators. Agents Actions, Suppl. 2. Birkhäuser, Basel, pp 135–147.

• Whitehouse MW, Walker WR (1977) The copper bracelet for arthritis (Letter). Med J Aust 1:938.

• Whitehouse MW (1978) The chemical nature of adjuvants. In: Glynn LE, Steward MW (eds) Wiley, London, pp 571–605.

• Whitehouse MW, Walker WR (1978) Copper and inflammation. Agents Actions 8:85–90.

• Whitehouse MW (1978) Some chemical aspects of inflammation: a brief overview. Aust N Z J Med 8(Suppl. 1):89–93.

• Whitehouse MW (1978) Restorative chemotherapy in degenerative hip disease (Editorial). Agents Actions 8:280–281.

• Whitehouse MW (1978). The chemical nature of adjuvants. In: Glynn LE, Steward MW (eds) Immuno-chemistry. Wiley, London, pp 571–605.

• Whitehouse MW (1978) Salicylates 1977: a centennial colloquium (book review). Agents Actions 8:576–577.

• Whitehouse MW (1978) Some Chemical aspects of inflammation: a brief overview. Aust N Z J Med 8(Suppl. 1):89–93.

• Brune K, Whitehouse MW (1979) Cytostats with effects in chronic inflammation. In: Ferreira SH, Vane JR (eds) Handbook of experimental pharmacology: inflammation and anti-inflammatory drugs, vol 50, pt II. Springer, Heidelberg, pp 531–578.

• Whitehouse MW (1979) Anti-inflammatory drugs 1977 (Book review). Agents Actions 9:232–233.

• Perrin DD, Whitehouse MW (1980) Metal ion therapy: some fundamental considerations. In: Rainsford KD, Brune K, Whitehouse MW (eds) Trace elements in the pathogenesis and treatment of inflammation. Agents Actions Suppl 8. Birkhäuser Verlag, Basel, pp 261–290.

• Rainsford KD, Brune K, Whitehouse MW (eds) (1980) Trace elements in the pathogenesis and treatment of inflammation. Agents Actions, Suppl 8. Birkhäuser Verlag, Basel.

• Walker WR, Beveridge SJ, Whitehouse MW (1980) Dermal copper drugs: the copper bracelet and Cu(II) salicylate complexes. In: Rainsford KD, Brune K, Whitehouse MW (eds) Trace elements in the pathogenesis and treatment of inflammation. Birkhäuser Verlag, Basel. Agents Actions Suppl. 8:359–367.

• Fairlie DP, Whitehouse MW (1980) cis-Platinum (II) amines: toxicities and immunosuppressant/anti-arthritic activities. In: Rainsford KD, Brune K, Whitehouse MW (eds) Trace elements in the pathogenesis and treatment of inflammation. Birkhäuser Verlag, Basel. Agents Actions. Suppl 8:399–434.

• Perrin DD, Whitehouse MW (1980) Copper and inflammation: dynamic equilibria and potential therapeutic effects. CSIRO symposium, the importance of copper in biology and medicine. Commonwealth Scientific and Research Organisation, Canberra, pp 27–31.

• Aggarwal SK, Ramchandran C, Whitehouse MW (1980) Ultrastructural effects of cisplatin. In: Prestayko AW, Crooke ST, Carter SK (eds) Cisplatin. Current status and new developments. Academic Press, New York, pp 79–111.

• Whitehouse MW, Walker WR, Beveridge SJ (1980) Anti-inflammatory action of dermally applied copper salicylate preparations. Agents Actions Suppl. 8:36–41.

• Ghosh P, Ternai B, Whitehouse MW (1981) Benzofurazans and Benzofuroxans: biochemical and pharmacological properties. Med Res Rev I:159–187.

• Walker WR, Whitehouse MW, Beveridge SJ (1981) Dermally applied copper salicylates as anti-inflammatory agents I. In: Howell MJ, Gawthorne JM, White CL, Howell MJ, Gawthorne JM, White CL (eds) Trace element metabolism in man and animals. Australian Academy of Sciences, Canberra, pp 502–505.

• Whitehouse MW, Rainsford MW (1982) A comparison of gastric ulcerogenic activities of different salicylates. In: CRC handbook: drugs and peptic ulcer, vol II. CRC Press, Boca Raton, pp 127–142.

• Whitehouse MW, Garrett IR (1983) Heavy metal (Au, Hg) nephropathy: studies in normal and inflamed rats. In: Sorenson JRH (ed) Inflammatory disease and copper. Humana Press, Clifton, pp 291–294.

• Betts WH, Cleland LG, Whitehouse MW, Gee DJ (1983) Iron-associated hydroxyl radical production: influence of metal chelators, copper (II) and thiols. In: Cohen G, Greenwald RA (eds) Oxy radicals and their scavenger systems, vol 1. CRC Press, Boca Raton, pp 95–100.

• Whitehouse MW, Rainsford-Koechli V, Rainsford KD (1984) Aspirin gastrotoxicity: protection by various strategems. In: Rainsford KD, Velo GP (eds) Side-effects of anti-inflammatory/analgesic drugs. Raven Press, New York, pp 77–87.

• Betts WH, Garrett IR, Whitehouse MW (1985) Therapy with metal complexes. In: Rainsford KD (ed) Anti-rheumatic and anti-inflammatory drugs, vol III. CRC Press, Boca Raton, pp 65–103.

• Whitehouse MW, Cleland LG (1985) Reactive oxygen species and drug therapy for inflammatory diseases. Agents Actions, Suppl 17. Birkhäuser, Basel, pp 177–188.

• Whitehouse MW (1986) Rheumatoid arthritis and tuberculosis. Lancet II:688–689.

• Whitehouse MW (1987) Disease and drug interactions: utility of the conditional concept for experimental pharmacology and toxicology in the context of inflammation. In: Rainsford KD, Velo GP (eds) Side effects of anti-inflammatory drugs, part 1. MTP Press, Lancaster, pp 259–271.

• Whitehouse MW, Rainsford KD (1987) Why are non-steroidal anti-inflammatory drugs so toxic, even when given orally as solubilized salt formulations, or parenterally. In: Rainsford KD, Velo GP (eds) Side effects of anti-inflammatory analgesic drugs. Part 2. MTP Press, Lancaster, pp 55–65.

• Whitehouse MW, Garrett IR (1987) Copper and inflammation. In: Howell MJ, Gawthorne J (eds) Copper in animals and man, vol II. CRC Press, Boca Raton, pp 107–122.

• McColl SR, Cleland LG, Whitehouse MW, Vernon-Roberts B (1987) Effect of dietary polyunsaturated fatty acid supplementation on adjuvant-induced polyarthritis in rats. J Rheumatol 14:197–201.

• Whitehouse MW (1988) Adjuvant-induced polyarthritis in rats. In: Greenwald RM, Diamond H (eds) Handbook of animal models for the rheumatic diseases, vol I. CRC Press, Boca Raton, pp 3–16.

• Whitehouse MW, Horewood AH, Vernon-Roberts B (1988) Variable response to gold 1-thiolates (chrysotherapy) in two models of rat polyarthritis. Agents Actions, Suppl 24. Birkhäuser Verlag, Basel, pp 184–188.

• Whitehouse MW, Bolt AG, Ford GL, Vernon-Roberts B (1988) Anti-arthritic activity of PUFA derivatives in adjuvant arthritic rats. In: Wahlquist M, MacLean A (eds) Recent advances in clinical nutrition, vol 3. J. Liddy, London, pp 101–103.

• Haynes DR, Whitehouse MW (1989) Gold (I)-thiolates: slow acting anti-arthritic drugs. In: Rainsford KD (ed) New developments in anti-rheumatic therapy. MTP Press, Lancaster, pp 207–234.

• Tiekink ERT, Whitehouse MW(1990) The use of gold compounds in medicine. Chemistry in Australia 57:346–348.

• Fairlie DP, Whitehouse MW (1991) Transdermal delivery of inorganic complexes as metal drugs or nutritional supplements. Drug Design Deliv 8:83–102.

• Whitehouse MW, Vernon-Roberts B (1991) Conditional pharmacology: expression of anti-inflammatory activity may require pre-existent inflammatory mediators/hormones. Inflammopharmacology 1:61–68.

• Whitehouse MW (1991) Trace element supplements for inflammatory disease. In: Dixon J, Furst D (eds) Marcel Dekker, New York, pp 549–578.

• Whitehouse MW (1995) Inflammation, stress and environmental factors as determinants of NSAID efficacy and toxicity. Inflammopharmacology 3:373–377.

• Whitehouse MW, Tiekink ER, Dekker M(1995) Gold in medicine. In: Berthon G (ed) Handbook of metal–ligand interactions in biological fluids, vol 2. CRC Press/Taylor & Francis, Boca Raton, pp 1266–1273.

• Rainsford KD, Whitehouse MW, Vernon-Roberts B (1995) Effects of the prostaglandin E1 analogue, misoprostol, on the development of adjuvant arthritis in rats. Inflammopharmacology 3:49–63.

• Snowden JM, Whitehouse MW (1997) Anti-inflammatory action of emu oil. Inflammopharmacology 5:127–132.

• Whitehouse MW, Roberts MS (1998) Drugs for pain and inflammation. In: Roberts MS, Walters KA (eds) Dermal absorption and toxicity assessment. Marcel Dekker, New York, pp 327–352.

• Whitehouse MW (1999) Celery seed for arthritis. Melbourne: The Herbal Doctor 2:9–10.

• Whitehouse MW, Butters DE (1999) Non-NSAID over the counter (OTC) remedies for arthritis: good, bad or indifferent? Inflammopharmacology 7:227–247.

• Whitehouse MW (2002) Call for a trial of Lyprinol, an over the counter 5-lipoxygenase inhibitor. Arthritis Rheumatol 45.

• Whitehouse M (2002) Anti-inflammatory activity of a complementary medicine (FYI). Parma: Progress in Nutrition 4, suppl. 1:55–61.

• Whitehouse MW (2004) (Point of View) Anti-TNF-α for chronic inflammation: reconsidering pentoxifylline as an alternative to therapeutic protein drugs. Inflammopharmacology 12:223–227.

• Whitehouse MW (2004) Tumour necrosis factor alpha inhibitor for the treatment of adult rheumatoid arthritis (Letter). Australian Prescriber.

• Whitehouse MW (2005) In memory of Derek Willoughby. Inflammopharmacology 12:461–462.

• Whitehouse MW (2005) Prostanoids as friends, not foes: further evidence from the interference by cyclooxygenase-inhibitory drugs when inducing tolerance to experimental arthritigens in rats. Inflammopharmacology 12:481–492.

• Whitehouse MW (2005) Efficacy and safety of dermal oils: particularly in the context of experimental arthritis. Proc. Conf. Dermal delivery Down-Under, Brisbane. March 2005;10.

• Whitehouse MW (2005) Coxibs and their aftermath: an opinionated commentary based on some historical viewpoints. Inflammopharmacology 13:403–417.

• Whitehouse MW. Rainsford KD (2006) Lipoxygenase inhibition: the neglected frontier for regulating chronic inflammation and pain. Inflammopharmacology 14:99–102.

• Whitehouse MW (2005) Drugs to treat inflammation: a historical introduction. Curr Med Chem 12:2931–2942.

• Ghosh P, Shimmon S, Whitehouse MW (2005) The immunological basis for inflammation and cartilage destruction in osteoarthritis. New opportunities for therapeutic intervention. Reumatismo 2005; 57: Speciale 1:110–112.

• Ghosh P, Shimmon S, Whitehouse MW (2006) Arthritic disease suppression and cartilage protection with glycosaminoglycan polypeptide complexes (Peptacans) derived from the cartilage extracellular matrix: a novel approach to therapy. Inflammopharmacology 14:155–162.

• Whitehouse MW, Sarkar M, Roberts MS (2007) Drugs for pain and inflammation. In: Roberts MS, Walters KA (eds) Dermatological and cosmeceutical development: absorption, efficacy and toxicity. Taylor & Francis, New York.

• Brown C, Bushell G, Whitehouse MW, Agrawal DS, Tupe SG, Paknakar KM, Tiekink ERT (2007) Nanogold pharmaceutics: (i) the use of colloidal gold to treat experimentally-induced arthritis in rat models; (ii) characterisation of the gold in Swarna bhasma, a microparticulate used in traditional Indian medicine. Gold Bull 40:245–250.

• Whitehouse MW (2008) Therapeutic gold: is it due for a comeback? Inflammopharmacology, 16:107–109.

• Whitehouse MW (2007) Adjuvant arthritis 50 years on. Inflamm Res 56:133–138.

• Whitehouse MW (2011) Anti-inflammatory glucocorticoid drugs: reflections after 60 years. Inflammopharmacology 19:1–19.

• Whitehouse MW, Butters DE (2014) Paracetamol (acetaminophen): a blessing or a hidden curse? Inflammopharmacology 22:63–65.

• Rainsford KD, Powanda MC, Whitehouse MW (2015) Preface. Novel natural products: therapeutic effects in pain arthritis and gastro-intestinal diseases. Prog Drug Res 70:v.

• Powanda MC, Whitehouse MW, Rainsford KD (2015) Celery seed and related extracts with antiarthritic, antiulcer, and antimicrobial activities. In: Rainsford KD, Powanda MC, Whitehouse MW (eds) Novel natural products: therapeutic effects in pain arthritis and gastro-intestinal diseases. Prog Drug Res 70:133–153.

• Whitehouse MW (2015) Silver Pharmacology: past, present and questions for the future. In: Rainsford KD, Powanda MC (eds) Novel natural products: therapeutic effects in pain arthritis and gastro-intestinal diseases. Whitehouse, MW. Prog Drug Res 70:237–73.

• Whitehouse MW (2012) Oily adjuvants and autoimmunity: now time for reconsideration? Lupus 21:217–222

• Cock I, Mohanty S, White A, Whitehouse MW (2012) Colloidal Silver (CS) as an antiseptic: two opposing viewpoints. Pharmacogn Commun 2:47–56

• Whitehouse M (2013) Book review: Ben Goldacre: bad pharma. How drug companies mislead doctors and harm patients. New York Faber & Faber, 2013, (also a paperback edition 2012). Pharmacogn Commun 3:426

• Disaanayake DMBT, Faoagali, J, Laroo H, Hancock G, Whitehouse M (2014) Efficacy of some colloidal silver preparations and silver salts against Proteus bacteria, one possible cause of rheumatoid arthritis. Inflammopharmacology 22:73–77

• Turner A, Hancock, G, Wells J, Whitehouse M (2015) Traditional medicinal oils sourced from birds: anti-inflammatories and potential immunoregulants. In: Rainsford KD, Whitehouse MW, Powanda MC (eds) Novel natural products: therapeutic effects in pain, arthritis and gastro-intestinal diseases. Progr Drug Res, vol 70. Springer, Basel, pp 155–178

• Powanda MC, Whitehouse MC, Rainsford KD (2015) Celery seed and related extracts with antiarthritic, antiulcer and antimicrobial activities. In: Rainsford KD, Whitehouse MW, Powanda MC (eds) Novel natural products: therapeutic effects in pain, arthritis and gastro-intestinal diseases. Progr Drug Res, vol 70. Springer, Basel, pp 133–153

• Whitehouse MW (2015) Microbes as trigger/sustainers of chronic immuno-mediated inflammatory diseases. Inflammopharmacology 23:371–374

• Whitehouse MW (2016) Our silver jubilee/anniversary 1991–2016. Inflammopharmacology. 24:295–296

• Laroo H, Whitehouse M (2017) “Colloidal silver”: recommendations to remove this misleading term for describing nanoparticulate silver antimicrobial agents. Pharmacogn Commun 7:98–101

• Whitehouse MW, Butters DE (2018) Lest we forget: the darker side of the hypocholesterolemic statin drugs. Pharmacogn Commun 8:2–7

• Whitehouse M (2018) Book review. medical myths and lies that are killing us by Peter Dingle 2014. Pharmacogn Commun 8:132–134

• Whitehouse MW (2019) Conditional nutrition (I): concerning zinc as a beneficial but variable regulator of inflammation and experimental arthritis. Inflammopharmacology 2019. https://doi.org/10.1007/s10787-019-00669-3

• Newbould BB, Pearson CM,Whitehouse MW (2019) Passive transfer of allergic encephalomyelitis in rats: a tool for drug mechanism studies and detecting lateacting immunosuppressants. Inflammopharmacology 2019. https://doi.org/10.1007/s10787-019-00565-w

Patents

• 1. Rainsford KD, Whitehouse MW (1982) Composition with reduced gastro-intestinal damage—contains dibromo-aspirin, solubilising agent e.g. sodium carboxylate, and a gastro-protectant e.g. d-glucose. EP 13783, ES 4440762, DE 2966867.

• 2. Rainsford KD, Whitehouse MW (1982) Composition of analgesic and carbohydrate. Australian Patent No. 511, 852. 23 December 1982.

• 3. Rainsford KD, Whitehouse MW (1984) Protection of the gastric mucosal lining from damage by aspirin and related drugs, U.S. Patent No. 4,440,762, 3 April 1984.

• 4. Rainsford KD, Whitehouse MW (1984) Protection of the gastric mucosal lining from damage by aspirin and related drugs (originally assigned to Australian National University, then later on 1st March 1984 back to the inventors) European Patent No. 0013783 (U.K., France, W. Germany, Switzerland).

• 5. Rainsford KD, Whitehouse MW (1985) A pharmaceutical formulation containing azapropazone. EP 85301395, GB 846055 (5 February 198), US 89368100, ES 541054.

• 6. Rainsford KD, Whitehouse MW (1985) Anti-inflammatory azapropazone compositions containing carbohydrate and carboxylic acid salt to prevent gastric erosion. GB Patent 2155329 (25 September 1985) European Patent 154523 (22 March 1989), US Patent 5034379 (23 July 1991).

• 7. Rainsford KD, Whitehouse MW (1986) A pharmaceutical formulation containing indomethacin. U.K. Patent No. 8607662. EP 239332, AU 8770713, NO 8701187, ZA 8702137, DK 8701548, JP 63022017, PT 84580, US 4885279, DE 3768110, CA 1285488, ES 2038658.

• 8. Rainsford KD, Hunt RH, Goldie VJ (1994) Treatment for gastric disorders. Australian Patent. PM 4568, 18th March 1994.

• 9. Rainsford KD, Story MJ, Whitehouse MW (1994) Novel salicylic acid and aspirin formulations. WPI Acc No. 95-170033/199522. PCT/EP/94/03363, 12th October 1994; WO 9511030, AU 9479909; ZA 9408192.

• 10. Ghosh P, Whitehouse MW, Dawson M, Turner AG (1995) Anti-inflammatory composition derived from emu oil. U.S. Patent 5, 431, 922.

• 11. Butters DE, Davis CKC, McGeary RP, Powanda MC, Rainsford KD, Whitehouse MW (2002) Extracts of celery seed for the prevention and treatment of pain, inflammation and gastrointestinal irritation. WO 00/40258. 3 November 1999. US Patent 6,352,728 (March 5, 2002 and Continuation in part as US Patent 6,761,913 (July 13, 2004). European Patent (Application No. 99961567.7) February 9, 2005.

• 12. Taylor S, Shiels IA, Brown L, Whitehouse MW (2006) Use of C-5A receptor Q antagonist in the treatment of fibrosis. US Patent 10/510614.